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Sample records for cell chymase limits

  1. Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo

    OpenAIRE

    He, Shaoheng; Walls, Andrew F.

    1998-01-01

    The roles of chymase in acute allergic responses are not clear, despite the relative abundance of this serine proteinase in the secretory granules of human mast cells. We have isolated chymase to high purity from human skin tissue by heparin-agarose affinity chromatography and Sephacryl S-200 gel filtration procedures, and have investigated the ability of human mast cell chymase to stimulate cell accumulation following injection into laboratory animals.Injection of chymase provoked marked neu...

  2. Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs.

    OpenAIRE

    Rubinstein, I; Nadel, J A; Graf, P D; Caughey, G H

    1990-01-01

    Skin mast cells release the neutral protease chymase along with histamine during degranulation. To test the hypothesis that chymase modulates histamine-induced plasma extravasation, we measured wheal formation following intradermal injection of purified mast cell chymase and histamine into the skin of ragweed-allergic dogs. We found that chymase greatly augments histamine-induced wheal formation. The magnitude of the potentiating effect increases with increasing doses of chymase and becomes m...

  3. GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Zhuo [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, 105 Jiefang Road, Jinan, 250013 (China); Wang, Hao; Lin, Marina [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Groban, Leanne, E-mail: lgroban@wakehealth.edu [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Hypertension and Vascular Disease Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States); Office of Women in Medicine and Science, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States)

    2015-03-27

    Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, and immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression.

  4. GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

    International Nuclear Information System (INIS)

    Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, and immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression

  5. Inhibition of tryptase and chymase induced nucleated cell infiltration by proteinase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Han-qiu CHEN; Jian ZHENG

    2004-01-01

    AIM: To investigate the ability of proteinase inhibitors to modulate nucleated cell infiltration into the peritoneum of mice induced by tryptase and chymase. METHODS: Human lung tryptase and skin chymase were purified by a similar procedure involving high salt extraction, heparin agarose affinity chromatography followed by S-200 Sephacryl gel filtration chromatography. The actions of proteinase inhibitors on tryptase and chymase induced nucleated cell accumulation were examined with a mouse peritoneum model. RESULTS: A selective chymase inhibitor Z-Ile-GluPro-Phe-CO2Me (ZIGPPF) was able to inhibit approximately 90% neutrophil, 73% eosinophil, 87% lymphocyte and 60% macrophage accumulation induced by chymase at 16 h following injection. Soy bean trypsin inhibitor (SBTI), chymostatin, and α1-antitrypsin showed slightly less potency than ZIGPPF in inhibition of the actions of chymase. While all tryptase inhibitors tested were able to inhibit neutrophil, eosinophil, and macrophage accumulation provoked by tryptase at 16 h following injection, only leupeptin, APC366, and aprotinin were capable of inhibiting tryptase induced lymphocyte accumulation. The inhibitiors of tryptase tested were also able to inhibit tryptase induced neutrophil and eosinophil accumulation at 6 h following injection. When being injected alone, all inhibitors of chymase and tryptase at the concentrations tested by themselves had no significant effect on the accumulation of nucleated cells in the peritoneum of mice at both 6 h and 16 h. CONCLUSION: Proteinase inhibitors significantly inhibited tryptase and chymase-induced nucleated cell accumulation in vivo, and therefore they are likely to be developed as a novel class of anti-inflammatory drugs.

  6. Possible roles of mast cell-derived chymase for skin rejuvenation.

    Science.gov (United States)

    Amano, Nobuyuki; Takai, Shinji; Jin, Denan; Ueda, Koichi; Miyazaki, Mizuo

    2009-03-01

    The relationships between mast cell-derived chymase, angiotensin II, and extracellular matrix production in the skin after intense pulsed light (IPL) were clarified in hamsters. Dorsal areas of the hamsters were irradiated once or twice a week by IPL. The index of extracellular matrix production in the skin was defined as the depth stained with Azan-Mallory stain from the epidermis to the dermis at the point of maximum thickness. The index had significantly increased 7 days after IPL irradiation in sections treated once or twice with IPL compared with that of untreated control sections. The numbers of mast cells, chymase-positive cells, and angiotensin II-positive cells had also significantly increased in IPL-irradiated areas. Significant increases in chymase and angiotensin II activities were observed in the extracts obtained from IPL-irradiated skin. Mast cell-derived chymase may be involved via angiotensin II formation in the dermal extracellular matrix production that occurs after IPL irradiation. PMID:18408985

  7. Inhibition of histamine release from human mast cells by natural chymase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Hua XIE; Xiao-jun ZHANG; Xian-jie WANG

    2004-01-01

    AIM: To investigate the ability of natural chymase inhibitors to modulate histamine release from human mast cells.METHODS: Enzymatically dispersed cells from human lung, tonsil, and skin were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of the natural chymase inhibitors secretory leukocyte protease inhibitor (SLPI) and α1-antitrypsin, then histamine release was determined. RESULTS: IgE-dependent histamine release from lung, tonsil, and skin mast cells were inhibited by up to 70 %, 61%, and 62%, respectively following incubation with α1-antitrypsin (5000 nmol/L). SLPI 5000 nmol/L was also able to inhibit anti-IgEdependent histamine released from lung, tonsil and skin mast cells by up to approximately 72%, 67%, and 58%,respectively. While neither α1-antitrypsin nor SLPI by themselves altered histamine release from lung, tonsil and skin mast cells, they were able to inhibit calcium ionophore-induced histamine release from lung and tonsil mast cells. CONCLUSION: Both α1-antitrypsin and SLPI could potently inhibit IgE-dependent and calcium ionophoreinduced histamine release from dispersed human lung, tonsil, and skin mast cells in a concentration-dependent manner, which suggested that they were likely to play a protective role in mast cell associated diseases including allergy.

  8. The Chymase, Mouse Mast Cell Protease 4, Constitutes the Major Chymotrypsin-like Activity in Peritoneum and Ear Tissue. A Role for Mouse Mast Cell Protease 4 in Thrombin Regulation and Fibronectin Turnover

    OpenAIRE

    Tchougounova, Elena; Pejler, Gunnar; Åbrink, Magnus

    2003-01-01

    To gain insight into the biological role of mast cell chymase we have generated a mouse strain with a targeted deletion in the gene for mast cell protease 4 (mMCP-4), the mouse chymase that has the closest relationship to the human chymase in terms of tissue localization and functional properties. The inactivation of mMCP-4 did not affect the storage of other mast cell proteases and did not affect the number of mast cells or the mast cell morphology. However, mMCP-4 inactivation resulted in c...

  9. Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation

    DEFF Research Database (Denmark)

    Sverrild, Asger; Bergqvist, Anders; Baines, Katherine J;

    2016-01-01

    tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. METHODS: Airway hyperresponsiveness to inhaled mannitol was measured in 23 non......BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway......-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. RESULTS...

  10. Predomination of IL-17-producing tryptase-positive/chymase-positive mast cells in azoospermic chronic testicular inflammation.

    Science.gov (United States)

    Chen, S-J; Duan, Y-G; Haidl, G; Allam, J-P

    2016-08-01

    Chronic testicular inflammation and infection have been regarded as important factors in the pathogenesis of azoospermia. As key effector cells in innate and adaptive immune system, mast cells (MCs) were observed in inflammation and autoimmune disease. Furthermore, increased expression of tryptase-positive MCs has been reported in testicular disorders associated with male infertility/subfertility. However, little is known about the potential relationship between MCs and chronic testicular inflammation in azoospermic patients. Moreover, the preferential expression of MCs' subtypes in testis of these patients is still far from being understood. Thus, this study aimed to investigate characteristics of testicular MCs as well as their subtypes in azoospermic men with chronic testicular inflammation (AZI, n = 5) by immunohistochemical techniques. Our results showed significant increase of MCs in AZI, and more importantly, considerable numbers of tryptase-positive/chymase-positive MCs could also be demonstrated in AZI, when compared to control groups representing azoospermia without chronic testicular inflammation (AZW, n = 5) and normal spermatogenesis (NT, n = 5) respectively. Most interestingly, immunofluorescence staining revealed autoimmune-associated interleukin (IL)-17-producing MCs in AZI, whereas co-expression of MC markers with tumour necrosis factor (TNF)-α, IL-10 and IL-1β could not be detected. In conclusion, AZI is associated with significant increase of tryptase-positive/chymase-positive MCs expressing IL-17, and these MCs might contribute to the pathogenesis of AZI. PMID:26420243

  11. Degradation of human anaphylatoxin C3a by rat peritoneal mast cells: a role for the secretory granule enzyme chymase and heparin proteoglycan

    International Nuclear Information System (INIS)

    Purified human C3a was iodinated (125I-C3a) and used to study the interaction of labeled peptide with rat peritoneal mast cells (RMC). Cellular binding of 125I-C3a occurred within 30 sec, followed by a rapid dissociation from the cell. Both the binding of 125I-C3a and the rate of dissociation from the cell were temperature dependent. At 00C, the binding of 125I-C3a was increased and the rate of dissociation reduced, as compared to 370C. Once 125I-C3a was exposed to RMC, it lost the ability to rebind to a second batch of RMC. Analysis of the supernatants by trichloroacetic acid (TCA) precipitation and electrophoresis in sodium dodecyl sulfate polyacrylamide gels (SDS PAGE) revealed a decrease in the fraction of 125I precipitable by TCA and the appearance of 125I-C3a cleavage fragments. Pretreatment of RMC with enzyme inhibitors specific for chymotrypsin, but not trypsin, abrogated the degradation of 125I-C3a. Treatment of RMC bearing 125I-C3a with Bis (sulfosuccinimidyl) suberate (BS3) covalently crosslinked the 125I-Ca to chymase, the predominant enzyme found in the secretory granules. Indirect immunofluorescence of RMC using the IgG fraction of goat anti-rat chymase showed that chymase is present on the surface of unstimulated cells. The results indicate that 125I-C3a binds to RMC and is promptly degraded by chymase in the presence of heparin proteoglycan. In addition, this proteolysis of 125I-C3a by chymase must be blocked in order to detect plasma membrane C3a binding components on RMC

  12. The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis

    Directory of Open Access Journals (Sweden)

    Jianping Li

    2016-03-01

    Results and conclusion: The results indicate the presence of PAR-2 on MCs and that tryptase inhibition and nedocromil prevented TAC-induced fibrosis and increases in MC density, activation, and chymase release. Tryptase also significantly increased chymase concentration in ventricular slice culture media, which was prevented by the tryptase inhibitor. Hydroxyproline concentration in culture media was significantly increased with tryptase incubation as compared to the control group and the tryptase group incubated with nafamostat mesilate or chymostatin. We conclude that tryptase contributes to TAC-induced cardiac fibrosis primarily via activation of MCs and the amplified release of chymase.

  13. Effect of chymase on intraocular pressure in rabbits.

    Science.gov (United States)

    Konno, Takashi; Maruichi, Midori; Takai, Shinji; Oku, Hidehiro; Sugiyama, Tetsuya; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Ikeda, Tsunehiko; Miyazaki, Mizuo

    2005-11-01

    Chymase is a chymotrypsin-like serine protease that is stored exclusively in the secretory granules of mast cells and converts big endothelins to endothelin-1 (1-31). The aim of this study was to evaluate the effect of chymase on intraocular pressure in rabbits. Chymase injection (3 and 10 mU) resulted in a trend toward increased intraocular pressure and a significant increase in intraocular pressure at a dose of 10 mU compared with the control. A specific chymase inhibitor, Suc-Val-Pro-Phe(P)(OPh)(2), attenuated the ocular hypertension induced by chymase. Endothelin-1 (1-31) also caused ocular hypertension, which was inhibited by a selective endothelin ET(A) receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123). Moreover, chymase-induced ocular hypertension was inhibited by BQ-123. These results suggest that chymase influences the regulation of intraocular pressure, and it is likely that the formation of endothelin-1 (1-31) and subsequent activation of endothelin ET(A) receptors are involved in the development of ocular hypertension induced by chymase. PMID:16253233

  14. The expression of mast cells chymase activity in keloid tissue%肥大细胞糜蛋白酶在瘢痕疙瘩组织的活性表达

    Institute of Scientific and Technical Information of China (English)

    徐涛; 董祥林

    2015-01-01

    目的:探讨肥大细胞糜蛋白酶在人瘢痕疙瘩组织中的表达活性。方法采用免疫组织化学法检测瘢痕疙瘩组织和正常皮肤中肥大细胞的数量和糜蛋白酶的表达,并以 RT-PCR 和放免法检测瘢痕疙瘩和正常皮肤组织中糜蛋白酶 mRNA 表达活性变化。结果瘢痕疙瘩组织中肥大细胞数量与糜蛋白酶阳性表达评分为(10±0.25)个/HP、(6.2±0.23)mm2,明显高于正常皮肤组织的(4±0.22)个/HP、(2.5±0.12)mm2(P <0.01);RT-PCR结果显示瘢痕疙瘩组织中肥大细胞 mRNA 和糜蛋白酶 mRNA 表达水平较正常皮肤组织明显增高。结论肥大细胞糜蛋白酶存在于瘢痕疙瘩中且活性表达明显高于正常皮肤组织。%Objective To explore the expressed activity of mast cells chymase exist in human keloid tissues. Methods The number of mast cell and chymase expression in keloid and normal skin were assessed by im-munohistochemical methods.Quantitative real-time PCR and Radio immunity method were conducted to measure the change of mRNA expressed activity of chymase in keloid and normal skin tissues.Results Com-pared with normal skin tissue,the number of mast cells and chymase expression were higher in keloid tissues [(10 ±0.25)/hp vs (4±0.22)/hp,and (6.2±0.23)mm2 vs (2.5±0.12)mm2 ,P <0.01)].The results of RT-PCR showed mast cell mRNA expression levels and chymase mRNA level were also significantly higher in keloid tissues than those of normal skin tissues (P <0.05).Conclusion The chymase of mast cells exists in keloids and the expressed activity of chymase is statistically higher than those of normal skin tissues.

  15. Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice

    OpenAIRE

    Ju, Haisong; Gros, Robert; You, Xiaomang; Tsang, Sarah; Husain, Mansoor; Rabinovitch, Marlene

    2001-01-01

    We cloned a rat vascular chymase (RVCH) from smooth muscle cells (SMCs) that converts angiotensin I to II and is up-regulated in SMC from spontaneously hypertensive vs. normotensive rats. To determine whether increased activity of RVCH is sufficient to cause hypertension, transgenic mice were generated with targeted conditional expression of RVCH to SMC, with the use of the tetracycline-controlled transactivator (tTA). We confirmed conditional expression of RVCH by mRNA, protein, and chymase ...

  16. Recent chymase inhibitors and their effects in in vivo models.

    Science.gov (United States)

    Muto, Tsuyoshi; Fukami, Harukazu

    2002-12-01

    Recent efforts to discover novel chymase inhibitors have produced orally bioavailable compounds. Studies using such inhibitors have shed light on the pathophysiological roles of chymase, eg, a chymase inhibitor has prevented atherosclerosis, restenosis and myocardial infarction in respective animal models. In these cardiovascular diseases, angiotensin I is likely involved as a substrate for chymase. The studies using chymase inhibitors have also shown the potential role of chymase in other diseases, including atopic dermatitis, tissue fibrosis and rheumatoid arthritis; a chymase inhibitor also reduced ischemic reperfusion injury in the small intestine. These results suggest the existence of physiological substrates for chymase other than angiotensin I. Chymase inhibitors are promising for the treatment of cardiovascular as well as inflammatory diseases. PMID:12800055

  17. Role of chymase in the local renin-angiotensin system in keloids: inhibition of chymase may be an effective therapeutic approach to treat keloids

    Directory of Open Access Journals (Sweden)

    Wang R

    2015-08-01

    Full Text Available Ru Wang, Junjie Chen, Zhenyu Zhang, Ying CenDepartment of Burn and Plastic Surgery, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaBackground: Histologically, keloids contain excess fibroblasts and an overabundance of dermal collagen. Recently, it was reported that chymase induced a profibrotic response via transforming growth factor-β1 (TGF-β1/Smad activation in keloid fibroblasts (KFs. However, the role of chymase in the local renin-angiotensin system (RAS in keloids has not been elucidated. This study aims to determine whether chymase plays an important role in the local RAS in keloids.Methods: We compared the expression and activity of chymase in keloids and normal skin tissues using Western blotting and radioimmunoassay, and studied the expression of TGF-β1, interleukin-1β, collagen I, hydroxyproline, and angiotensin II in KFs after chymase and inhibitors’ treatment.Results: The results revealed an increased activity of chymase in keloid tissues, and that chymase enhanced the expression of angiotensin II, collagen I, TGF-β1, and interleukin-1β in KFs. Blockade of the chymase pathway involved in the local RAS lowered the expression of these signaling factors.Conclusion: This research suggests that inhibition of chymase might be an effective therapeutic approach to improve the clinical treatment of keloids.Keywords: pathological scar, chymase, angiotensin II, therapy

  18. Inhibitors of human heart chymase based on a peptide library.

    OpenAIRE

    Bastos, M; Maeji, N J; Abeles, R H

    1995-01-01

    We have synthesized two sets of noncleavable peptide-inhibitor libraries to map the S and S' subsites of human heart chymase. Human heart chymase is a chymotrypsin-like enzyme that converts angiotensin I to angiotensin II. The first library consists of peptides with 3-fluorobenzylpyruvamides in the P1 position. (Amino acid residues of substrates numbered P1, P2, etc., are toward the N-terminal direction, and P'1, P'2, etc., are toward the C-terminal direction from the scissile bond.) The P'1 ...

  19. Molecular modeling study for inhibition mechanism of human chymase and its application in inhibitor design.

    Directory of Open Access Journals (Sweden)

    Mahreen Arooj

    Full Text Available Human chymase catalyzes the hydrolysis of peptide bonds. Three chymase inhibitors with very similar chemical structures but highly different inhibitory profiles towards the hydrolase function of chymase were selected with the aim of elucidating the origin of disparities in their biological activities. As a substrate (angiotensin-I bound crystal structure is not available, molecular docking was performed to dock the substrate into the active site. Molecular dynamics simulations of chymase complexes with inhibitors and substrate were performed to calculate the binding orientation of inhibitors and substrate as well as to characterize conformational changes in the active site. The results elucidate details of the 3D chymase structure as well as the importance of K40 in hydrolase function. Binding mode analysis showed that substitution of a heavier Cl atom at the phenyl ring of most active inhibitor produced a great deal of variation in its orientation causing the phosphinate group to interact strongly with residue K40. Dynamics simulations revealed the conformational variation in region of V36-F41 upon substrate and inhibitor binding induced a shift in the location of K40 thus changing its interactions with them. Chymase complexes with the most active compound and substrate were used for development of a hybrid pharmacophore model which was applied in databases screening. Finally, hits which bound well at the active site, exhibited key interactions and favorable electronic properties were identified as possible inhibitors for chymase. This study not only elucidates inhibitory mechanism of chymase inhibitors but also provides key structural insights which will aid in the rational design of novel potent inhibitors of the enzyme. In general, the strategy applied in the current study could be a promising computational approach and may be generally applicable to drug design for other enzymes.

  20. Interaction of human chymase with ginkgolides, terpene trilactones of Ginkgo biloba investigated by molecular docking simulations.

    Science.gov (United States)

    Dubey, Amit; Marabotti, Anna; Ramteke, Pramod W; Facchiano, Angelo

    2016-04-29

    The search for natural chymase inhibitors has a good potential to provide a novel therapeutic approach against the cardiovascular diseases and other heart ailments. We selected from literature 20 promising Ginkgo biloba compounds, and tested them for their potential ability to bind chymase enzyme using docking and a deep analysis of surface pocket features. Docking results indicated that the compounds may interact with the active site of human chymase, with favorable distinct interactions with important residues Lys40, His57, Lys192, Phe191, Val146, Ser218, Gly216, and Ser195. In particular, proanthocyanidin is the one with the best-predicted binding energy, with seven hydrogen bonds. Interestingly, all active G. biloba compounds have formed the hydrogen bond interactions with the positively charged Lys192 residue at the active site, involved in the mechanism of pH enhancement for the cleavage of angiotensin I site. Ginkgolic acid and proanthocyanidin have better predicted binding energy towards chymase than other serine proteases, i.e kallikrein, tryptase and elastase, suggesting specificity for chymase inhibition. Our study suggests these G. biloba compounds are a promising starting point for developing chymase inhibitors for the potential development of future drugs. PMID:26975469

  1. Function of chymase in the heart angiotensin Ⅱ forma- tion in transgenic mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The myosin light chain 2 promoter-human heart chymase (MLC2-hChymase) transgenic mice founded by our laboratory were used as the model to study the function of chymase in the heart angiotension Ⅱ (Ang Ⅱ) formation and heart remodeling. Tissue-specific expression of human heart chymase gene and transcriptional expression of typeⅠ and type Ⅲ collagens genes were analyzed by RT-PCR. Activities of chymase, ACE and the levels of AngⅡ in heart and plasma were determined with radioimmunoassay (RIA) kit. Activity of heart matrix metalloproteinase-9 (MMP-9) was detected using gelatin zymography. The cardiac hypertrophic phenotypes were also observed with the physiological and morphological methods. The results in the MLC2-hChymase transgenic mice indicated: (ⅰ) human heart chymase gene was expressed specially in the heart; (ⅱ) heart chymase activity increased markedly in the transgenic mice vs non-transgenic mice (control) (0.27±0.07 U/mg vs. 0.15±0.02 U/mg, P<0.05) with no significant difference in ACE activity (0.17±0.03 U/mg vs. 0.18±0.02 U/mg); (ⅲ) heart AngⅡ content increased 3-fold (1984±184 vs. 568±88 pg/g protein, P<0.05) but was unchanged in plasma (218±106 vs. 234±66 pg/mL); (ⅳ) both MMP-9 activity and collagen Ⅰ mRNA level increased significantly in the heart (P<0.05) but there was neither significant increase in colla-gen Ⅲ mRNA nor in the ratio of Ⅰ/ Ⅲ collagen mRNA levels; (ⅴ) the MLC2-hChymase transgenic mice showed no significant changes in blood pressure, heart-rate, ratio of heart/body weight and cardiomyocyte diameter compared to the control. This suggests that heart AngⅡ formation cata-lyzed through overexpression of human heart chymase gene in the heart of transgenic mice might activate MMP-9 to influence collagen metabolism in cardiac interstitial and to be involved in the process of heart remodeling.

  2. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders;

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by...... stabilizing the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes...

  3. Crystal structure of a complex of human chymase with its benzimidazole derived inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Yoshiyuki; Kakuda, Shinji; Koizumi, Masahiro; Mizuno, Tsuyoshi; Muroga, Yumiko; Kawamura, Takashi; Takimoto-Kamimura, Midori, E-mail: m.kamimura@teijin.co.jp [Teijin Institute for Bio-medical Research, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512 (Japan)

    2013-11-01

    The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. The present study shows that the benzimidazole ring of the inhibitor takes the stable stacking interaction with the protonated His57 in the catalytic domain of human chymase. The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. The X-ray crystallographic study shows that the benzimidazole inhibitor forms a non-covalent interaction with the catalytic domain of human chymase. The hydrophobic fragment of the inhibitor occupies the S1 pocket. The carboxylic acid group of the inhibitor forms hydrogen bonds with the imidazole N(∊) atom of His57 and/or the O(γ) atom of Ser195 which are members of the catalytic triad. This imidazole ring of His57 induces π–π stacking to the benzene ring of the benzimidazole scaffold as P2 moiety. Fragment molecular orbital calculation of the atomic coordinates by X-ray crystallography shows that this imidazole ring of His57 could be protonated with the carboxyl group of Asp102 or hydroxyl group of Ser195 and the stacking interaction is stabilized. A new drug design strategy is proposed where the stacking to the protonated imidazole of the drug target protein with the benzimidazole scaffold inhibitor causes unpredicted potent inhibitory activity for some enzymes.

  4. 3D QSAR Pharmacophore Modeling, in Silico Screening, and Density Functional Theory (DFT Approaches for Identification of Human Chymase Inhibitors

    Directory of Open Access Journals (Sweden)

    Keun Woo Lee

    2011-12-01

    Full Text Available Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942 pharmacophore model (Hypo1 with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating “Hypo1”, it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC50 data thus successfully validating “Hypo1” by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors.

  5. Atick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation

    Czech Academy of Sciences Publication Activity Database

    Chmelař, Jindřich; Oliveira, C. J.; Řezáčová, Pavlína; Francischetti, I.M.B.; Kovářová, Zuzana; Pejler, G.; Kopáček, Petr; Ribeiro, J.M.C.; Mareš, Michael; Kopecký, Jan; Kotsyfakis, Michalis

    2011-01-01

    Roč. 117, č. 2 (2011), s. 736-744. ISSN 0006-4971 R&D Projects: GA AV ČR IAA600960811; GA MŠk(CZ) LC06009; GA ČR(CZ) GAP207/10/2183 Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z40550506 Keywords : parasite serpin * IRS-2 * tick * Ixodes ricinus * platelet aggregation * inflammation * cathepsin G * chymase Subject RIV: EC - Immunology Impact factor: 9.898, year: 2011

  6. Limited small cell lung cancer

    International Nuclear Information System (INIS)

    This paper assesses the prognosis of patients with limited small cell lung cancer (LSCLC) not achieving complete response (CR) to induction combination chemotherapy (ICC) but who achieve CR after thoracic irradiation (TI). Twenty-four patients had CRs to ICC (CR- ICC) of two cycles of cytoxan, Adriamycin, and vincristine alternating with two cycles of cisplatin with VP-16. Another 24 had CR after consolidation with subsequent T1 (CR-T1): 45 Gy in daily fractions of 2.5 Gy or twice-daily fractions of 1.5 Gy. The CR-ICC and CR-TI patients had similar prognostic factors and treatment. Comparing CR-ICC and CR-TI, survival was 40% versus 26% at 2 years and 35% versus 4% at 5 years (P < .05). There were eight (33%) long-term survivors (≥3 years) in the CR-ICC group versus three (13%) in the CR-TI group. Local control for CR-ICC patients was 59% at 5 years versus 21% for the CR-TI patients (not significant). Freedom from DM for the CR-ICC patients was 41% at 5 years versus 8% for the CR-TI patients (P < .05)

  7. Mast cell heterogeneity in the gastrointestinal tract: variable expression of mouse mast cell protease-1 (mMCP-1) in intraepithelial mucosal mast cells in nematode-infected and normal BALB/c mice.

    OpenAIRE

    Scudamore, C. L.; McMillan, L; Thornton, E. M.; Wright, S H; Newlands, G. F.; Miller, H. R.

    1997-01-01

    Soluble granule chymases in rodent intestinal mucosal mast cells (IMMCs) may play an important role in altering epithelial permeability during immediate hypersensitivity reactions. Using a monoclonal antibody against the chymase mouse mast cell protease-1 (mMCP-1), we have shown that it is constitutively expressed in < or = 20% of esterase-positive (esterase+) IMMCs but not in esterase+ gastric mucosal mast cells (GMMCs) in normal BALB/c mice. Intestinal infection with mouse- or rat-adapted s...

  8. Limit Cycle Oscillations in Pacemaker Cells

    CERN Document Server

    Endresen, L P; Endresen, Lars Petter; Skarland, Nils

    1999-01-01

    In recent decades, several mathematical models describing the pacemaker activity of the rabbit sinoatrial node have been developed. We demonstrate that it is not possible to establish the existence, uniqueness, and stability of a limit cycle oscillation in those models. Instead we observe an infinite number of limit cycles. We then display numerical results from a new model, with a limit cycle that can be reached from many different initial conditions.

  9. Phenotypic variability in human skin mast cells.

    Science.gov (United States)

    Babina, Magda; Guhl, Sven; Artuc, Metin; Trivedi, Neil N; Zuberbier, Torsten

    2016-06-01

    Mast cells (MCs) are unique constituents of the human body. While inter-individual differences may influence the ways by which MCs operate in their skin habitat, they have not been surveyed in a comprehensive manner so far. We therefore set out to quantify skin MC variability in a large cohort of subjects. Pathophysiologically relevant key features were quantified and correlated: transcripts of c-kit, FcεRIα, FcεRIβ, FcεRIγ, histidine decarboxylase, tryptase, and chymase; surface expression of c-Kit, FcεRIα; activity of tryptase, and chymase; histamine content and release triggered by FcεRI and Ca(2+) ionophore. While there was substantial variability among subjects, it strongly depended on the feature under study (coefficient of variation 33-386%). Surface expression of FcεRI was positively associated with FcεRIα mRNA content, histamine content with HDC mRNA, and chymase activity with chymase mRNA. Also, MC signature genes were co-regulated in distinct patterns. Intriguingly, histamine levels were positively linked to tryptase and chymase activity, whereas tryptase and chymase activity appeared to be uncorrelated. FcεRI triggered histamine release was highly variable and was unrelated to FcεRI expression but unexpectedly tightly correlated with histamine release elicited by Ca(2+) ionophore. This most comprehensive and systematic work of its kind provides not only detailed insights into inter-individual variability in MCs, but also uncovers unexpected patterns of co-regulation among signature attributes of the lineage. Differences in MCs among humans may well underlie clinical responses in settings of allergic reactions and complex skin disorders alike. PMID:26706922

  10. Cell Reprogramming, IPS Limitations, and Overcoming Strategies in Dental Bioengineering

    Directory of Open Access Journals (Sweden)

    Gaskon Ibarretxe

    2012-01-01

    Full Text Available The procurement of induced pluripotent stem cells, or IPS cells, from adult differentiated animal cells has the potential to revolutionize future medicine, where reprogrammed IPS cells may be used to repair disease-affected tissues on demand. The potential of IPS cell technology is tremendous, but it will be essential to improve the methodologies for IPS cell generation and to precisely evaluate each clone and subclone of IPS cells for their safety and efficacy. Additionally, the current state of knowledge on IPS cells advises that research on their regenerative properties is carried out in appropriate tissue and organ systems that permit a safe assessment of the long-term behavior of these reprogrammed cells. In the present paper, we discuss the mechanisms of cell reprogramming, current technical limitations of IPS cells for their use in human tissue engineering, and possibilities to overcome them in the particular case of dental regeneration.

  11. Efficiency limits for single-junction and tandem solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Meillaud, F.; Shah, A.; Droz, C.; Vallat-Sauvain, E.; Miazza, C. [Institute of Microtechnology (IMT), University of Neuchatel, A.-L Breguet 2, 2000 Neuchatel (Switzerland)

    2006-11-23

    Basic limitations of single-junction and tandem p-n and p-i-n diodes are established from thermodynamical considerations on radiative recombination and semi-empirical considerations on the classical diode equations. These limits are compared to actual values of short-circuit current, open-circuit voltage, fill factor and efficiency for amorphous (a-Si:H) and microcrystalline ({mu}c-Si:H) silicon solar cells. For single-junction cells, major efficiency gains should be achievable by increasing the short-circuit current density by better light trapping. The limitations of p-i-n junctions are estimated from recombination effects in the intrinsic layer. The efficiency of double-junction cells is presented as a function of the energy gap of top and bottom cells, confirming the 'micromorph' tandem (a-Si:H/{mu}c-Si:H) as an optimum combination of tandem solar cells. (author)

  12. The Shockley-Queisser limit for nanostructured solar cells

    CERN Document Server

    Xu, Yunlu; Munday, Jeremy N

    2014-01-01

    The Shockley-Queisser limit describes the maximum solar energy conversion efficiency achievable for a particular material and is the standard by which new photovoltaic technologies are compared. This limit is based on the principle of detailed balance, which equates the photon flux into a device to the particle flux (photons or electrons) out of that device. Nanostructured solar cells represent a new class of photovoltaic devices, and questions have been raised about whether or not they can exceed the Shockley-Queisser limit. Here we show that single-junction nanostructured solar cells have a theoretical maximum efficiency of 42% under AM 1.5 solar illumination. While this exceeds the efficiency of a non- concentrating planar device, it does not exceed the Shockley-Queisser limit for a planar device with optical concentration. We conclude that nanostructured solar cells offer an important route towards higher efficiency photovoltaic devices through a built-in optical concentration.

  13. Inhibition of tryptase release from human colon mast cells by protease inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of protease inhibitors to modulate tryptase release from human colon mast cells.METHODS: Enzymatically dispersed cells from human colon were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of tryptase and chymase inhibitors,and tryptase release was determined.RESULTS: IgE dependent tryptase release from colon mast cells was inhibited by up to approximately 37%, 40% and 36.6% by chymase inhibitors Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPFM), N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK), and α1-antitrypsin, respectively. Similarly, the inhibitors of tryptase leupeptin, N-tosyl-L-lysine chloromethyl ketone (TLCK) and lactoferrin were also able to inhibit anti-IgE induced tryptase release by a maximum of 39.4%,47.6% and 36.6%, respectively. The inhibitory actions of chymase inhibitors, but not tryptase inhibitors on colon mast cells were enhanced by preincubation of them with cells for 20 min before challenged with anti-IgE. At a concentration of 10 μg/mL, protamine was able to inhibit anti-IgE and calcium ionophore induced tryptase release. However, at 100 μg/mL, protamine elevated tryptase levels in supernatants.A specific inhibitor of aminopeptidase amastatin had no effect on anti-IgE induced tryptase release. The significant inhibition of calcium ionophore induced tryptase release was also observed with the inhibitors of tryptase and chymase examined. The inhibitors tested by themselves did not stimulate tryptase release from colon mast cells.CONCLUSION: It was demonstrated for the first time that both tryptase and chymase inhibitors could inhibit IgE dependent and calcium ionophore induced tryptase release from dispersed colon mast cells in a concentration dependent of manner, which suggest that they are likely to be developed as a novel class of anti-inflammatory drugs to treat chronic of colitis in man.

  14. Limitations of fitting angular scattering from single cells (Conference Presentation)

    Science.gov (United States)

    Fan, Xing; Cannaday, Ashley E.; Berger, Andrew J.

    2016-04-01

    The literature contains several reports of Mie-like fits to angular-domain elastic scattering measurements from multiple cells or isolated mitochondria. In these studies, the sampling volume typically contains hundreds or thousands of mitochondria, allowing for the size distribution of mitochondria to be modeled as a smooth function, (e.g. Gaussian or log-normal) with a small number of free parameters. In the case of a single-cell volume containing significantly fewer mitochondria, the true size distribution will no longer be as smooth. Increasing the number of free parameters can lead to unstable fits, however, as the forward-directed angular scattering pattern from such a population illuminated with 785 nm light is a monotonically decaying radial function with few distinct features. Using simulations, we have investigated the limitations of modeling single-cell mitochondrial scattering using smooth population distributions of Mie scatterers. In different instances, the fidelity of the estimated size information can be limited by the number of organelles, the angular detection range, or the non-ideality of the data (both speckle and shot noise). We will describe the conditions under which each of these effects dominates. We will also discuss whether mean and standard deviation are the best sizes to report from such Mie modeling, or if there are other size parameters that have greater fidelity to the true, non-smooth size distributions.

  15. Complete and limited proteolysis in cell cycle progression.

    Science.gov (United States)

    Goulet, Brigitte; Nepveu, Alain

    2004-08-01

    An important mechanism of regulation that controls progression through the cell cycle involves the timely degradation of specific regulatory proteins. In parallel to the main degradative pathways, it appears that the function of certain proteins may also be modulated by a process called limited proteolysis. We have recently shown that the CDP/Cux transcription factor is proteolytically processed at the G(1)/S transition by the cathepsin L protease. Two aspects of these findings are discussed in the context of the cell cycle. Firstly, together with the cohesin subunit Scc1 and the HCF-1 factor, CDP/Cux represents a third example whereby the process of "limited proteolysis" plays a role in the control of cell cycle progression. Secondly, our findings provides compelling evidence that the cathepsin L protease, which was believed to be obligatorily targeted through the endoplasmic reticulum to the lysosomes or the extra-cellular milieu, could also be present in the nucleus and modulate the function of transcription factors. PMID:15254406

  16. Conditions for diffusion-limited and reaction-limited recombination in nanostructured solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Ansari-Rad, Mehdi, E-mail: ansari.rad@ut.ac.ir [Department of Physics, University of Tehran, 1439955961 Tehran (Iran, Islamic Republic of); Department of Physics, University of Shahrood, Shahrood (Iran, Islamic Republic of); Anta, Juan A., E-mail: anta@upo.es [Departamento de Sistemas Físicos, Químicos y Naturales, Universidad Pablo de Olavide, 41013 Sevilla (Spain); Arzi, Ezatollah [Department of Physics, University of Tehran, 1439955961 Tehran (Iran, Islamic Republic of)

    2014-04-07

    The performance of Dye-sensitized solar cells (DSC) and related devices made of nanostructured semiconductors relies on a good charge separation, which in turn is achieved by favoring charge transport against recombination. Although both processes occur at very different time scales, hence ensuring good charge separation, in certain cases the kinetics of transport and recombination can be connected, either in a direct or an indirect way. In this work, the connection between electron transport and recombination in nanostructured solar cells is studied both theoretically and by Monte Carlo simulation. Calculations using the Multiple-Trapping model and a realistic trap distribution for nanostructured TiO{sub 2} show that for attempt-to-jump frequencies higher than 10{sup 11}–10{sup 13} Hz, the system adopts a reaction limited (RL) regime, with a lifetime which is effectively independent from the speed of the electrons in the transport level. For frequencies lower than those, and depending on the concentration of recombination centers in the material, the system enters a diffusion-limited regime (DL), where the lifetime increases if the speed of free electrons decreases. In general, the conditions for RL or DL recombination depend critically on the time scale difference between recombination kinetics and free-electron transport. Hence, if the former is too rapid with respect to the latter, the system is in the DL regime and total thermalization of carriers is not possible. In the opposite situation, a RL regime arises. Numerical data available in the literature, and the behavior of the lifetime with respect to (1) density of recombination centers and (2) probability of recombination at a given center, suggest that a typical DSC in operation stays in the RL regime with complete thermalization, although a transition to the DL regime may occur for electrolytes or hole conductors where recombination is especially rapid or where there is a larger dispersion of energies of

  17. Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells

    OpenAIRE

    Fernando, R. N.; Eleuteri, B.; Abdelhady, S.; Nussenzweig, A; Andang, M; Ernfors, P.

    2011-01-01

    Adult neural stem cell proliferation is dynamic and has the potential for massive self-renewal yet undergoes limited cell division in vivo. Here, we report an epigenetic mechanism regulating proliferation and self-renewal. The recruitment of the PI3K-related kinase signaling pathway and histone H2AX phosphorylation following GABAA receptor activation limits subventricular zone proliferation. As a result, NSC self-renewal and niche size is dynamic and can be directly modulated in both directio...

  18. Thermodynamic limit of bifacial double-junction tandem solar cells

    Science.gov (United States)

    Ryyan Khan, M.; Alam, Muhammad A.

    2015-11-01

    A traditional single-junction solar panel cannot harness ground-scattered light (albedo reflectance, RA ), and also suffers from the fundamental sub-band-gap and the thermalization losses. In this paper, we explain how a "bifacial tandem" panel would dramatically reduce these losses, with corresponding improvement in thermodynamic performance. Our study predicts (i) the optimum combination of the band-gaps, empirically given by Eg(t ) o p t≈Eg(b ) o p t(2 +RA)/3 +(1 -RA) and the (ii) corresponding optimum normalized output power given by ηT(op t ) *≈RA (2 ηSJ (o p t ) ) +(1 -RA ) ηDJ (o p t ) . Empirically, ηT(op t ) * interpolates between the thermodynamic efficiency limit of classical double-junction tandem cell ( ηDJ ) and twice that of a single-junction cell ( ηSJ ). We conclude by explaining how the fundamental loss mechanisms evolve with RA in a bifacial tandem cell.

  19. Fundamental limitations of hot-carrier solar cells

    Science.gov (United States)

    Kirk, A. P.; Fischetti, M. V.

    2012-10-01

    Sunlight-generated hot-carrier transport in strongly absorbing direct band-gap GaAs—among the most optimal of semiconductors for high-efficiency solar cells—is simulated with an accurate full-band structure self-consistent Monte Carlo method, including short- and long-range Coulomb interaction, impact ionization, and optical and acoustic phonon scattering. We consider an ultrapure 100-nm-thick intrinsic GaAs absorber layer designed with quasiballistic carrier transport that achieves complete photon absorption down to the band edge by application of careful light trapping and that has a generous hot-carrier retention time of 10 ps prior to the onset of carrier relaxation. We find that hot-carrier solar cells can be severely limited in performance due to the substantially reduced current density caused by insufficient extraction of the widely distributed hot electrons (holes) through the requisite energy selective contacts.

  20. The Limits of Linked Suppression for Regulatory T cells

    Directory of Open Access Journals (Sweden)

    Toshiro eIto

    2016-03-01

    Full Text Available Background: We have previously found that CD4+CD25+ regulatory T cells (T regs can adoptively transfer tolerance after its induction with co-stimulatory blockade in a mouse model of murine cardiac allograft transplantation. In these experiments, we tested an hypothesis with three components: 1 the T regs that transfer tolerance have the capacity for linked suppression, 2 the determinants that stimulate the T regs are expressed by the indirect pathway, and 3 the donor peptides contributing to these indirect determinants are derived from donor MHC antigens. Methods: 1st heart transplants were performed from the indicated donor strain to B10.D2 recipients along with co-stimulatory blockade treatment (250μg i.p. injection of MR1 on day 0 and 250μg i.p. injection of CTLA-4 Ig on day 2. At least 8 weeks later a 2nd heart transplant was performed to a new B10.D2 recipient that had been irradiated with 450 cGy. This recipient was given 40 x 106 naïve B10.D2 spleen cells plus 40 x 106 B10.D2 spleen cells from the first (tolerant recipient. We performed 3 different types of heart transplants with using various donor.Results: 1. T regs suppress the graft rejection in an antigen-specific manner. 2. T regs generated in the face of MHC disparities suppress the rejection of grafts expressing third party MHC along with tolerant MHC. Conclusion:The limits of linkage appear to be quantitative and not universally determined by either the indirect pathway or by peptides of donor MHC antigens.

  1. Cell Reprogramming, IPS Limitations, and Overcoming Strategies in Dental Bioengineering

    OpenAIRE

    Gaskon Ibarretxe; Antonia Alvarez; Maria-Luz Cañavate; Enrique Hilario; Maitane Aurrekoetxea; Fernando Unda

    2012-01-01

    The procurement of induced pluripotent stem cells, or IPS cells, from adult differentiated animal cells has the potential to revolutionize future medicine, where reprogrammed IPS cells may be used to repair disease-affected tissues on demand. The potential of IPS cell technology is tremendous, but it will be essential to improve the methodologies for IPS cell generation and to precisely evaluate each clone and subclone of IPS cells for their safety and efficacy. Additionally, the current stat...

  2. Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

    OpenAIRE

    Nijagal, Amar; Wegorzewska, Marta; Jarvis, Erin; Le, Tom; Tang, Qizhi; MacKenzie, Tippi C.

    2011-01-01

    Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection. However, clinical use of IUHCTx has been hampered by poor engraftment, possibly due to a host immune response against the graft. Since the fetal immune system is relatively immature, we h...

  3. Prosthetic graft infection: limitations of indium white blood cell scanning

    International Nuclear Information System (INIS)

    The lack of a rapid, noninvasive, and accurate method to confirm or rule out prosthetic graft infection continues to constitute a compelling and vexing clinical problem. A host of adjunctive diagnostic techniques has been used in the past, but early promising results subsequently have usually not yielded acceptable sensitivity (reflecting false negatives) and specificity (reflecting false positive) data. White blood cell (WBC) indium 111 scanning has recently been added to this list. The utility and accuracy of 111In WBC scans were assessed by retrospective review of WBC scan results in 70 patients undergoing evaluation for possible prosthetic graft infection over a 7-year period. Operative and autopsy data (mean follow-up, 18 months for survivors with negative scans) were used to confirm the 22 positive, 45 negative, and three equivocal WBC scans. The false positive rate (+/- 70% confidence limits) was 36% +/- 6% (n = 8) among the 22 patients with positive scans (44% +/- 6% [11 of 25] if the three equivocal scans are included as false positive), yielding a specificity of 85% +/- 5% and an overall accuracy rate of 88% +/- 4% (80% +/- 5% and 84% +/- 5%, respectively, if the three equivocal cases are considered as false positive). All three patients with equivocal scans ultimately were judged not to have prosthetic graft infection. As implied by the high accuracy rate, the sensitivity of the test was absolute (100% [14 of 14]); there were no false negative results

  4. Association of mast cell-derived VEGF and proteases in Dengue shock syndrome.

    Directory of Open Access Journals (Sweden)

    Takahisa Furuta

    Full Text Available BACKGROUND: Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase and -related cytokines (IL-4, -9, and -17 between patients with differing severity of Dengue fever and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: The study was performed at Children's Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF, Dengue hemorrhagic fever (DHF, and Dengue shock syndrome (DSS, as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9. CONCLUSIONS: As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity.

  5. Potential and Limitation of HLA-Based Banking of Human Pluripotent Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Casimir de Rham

    2014-01-01

    Full Text Available Great hopes have been placed on human pluripotent stem (hPS cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well-characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA, the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues.

  6. Potential and limitation of HLA-based banking of human pluripotent stem cells for cell therapy.

    Science.gov (United States)

    de Rham, Casimir; Villard, Jean

    2014-01-01

    Great hopes have been placed on human pluripotent stem (hPS) cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well-characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA), the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS) cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues. PMID:25126584

  7. Proliferation of protease-enriched mast cells in sarcoptic skin lesions of raccoon dogs.

    Science.gov (United States)

    Noviana, D; W Harjanti, D; Otsuka, Y; Horii, Y

    2004-07-01

    Skin sites, tongue, lung, liver, jejunum and rectum from two raccoon dogs with Sarcoptes scabiei infestation and five normal (control) raccoon dogs were examined in terms of the distribution, proteoglycan properties and protease activity of mast cells. Infestation with S. scabiei caused a significant increase in the number of dermal mast cells. While the number of mast cells (average +/- standard deviation) in specimens of skin from the dorsum, dorsal neck, dorsal hind foot and dorsal fore foot was 40.0 +/- 19.8/mm2 in control animals, it was 236.1 +/- 58.9/mm2 in the skin of mange-infested animals. Histochemical analysis revealed the glycosaminoglycan, heparin, within the mast cells of all organs examined in both control and affected animals. Enzyme-histochemical detection of serine proteases demonstrated an increase in mast-cell-specific protease activity (i.e., chymase and tryptase) in the skin of infested animals. The percentage of mast cells demonstrating chymase activity was 53.0 +/- 27.4% in control animals and 73.8 +/- 19.4% in mite-infested animals. The corresponding results for tryptase activity were 53.5 +/- 25.2% and 89.4 +/- 9.8%. Increases in mast cell chymase or tryptase activity, or both, were also observed within other organs of the infected animals, but the total number of mast cells found at such sites (with the exception of liver and ventrolateral pinna) did not differ from those of control animals. PMID:15144797

  8. Two-dimensional diffusion limited system for cell growth

    International Nuclear Information System (INIS)

    A new cell system, the ''sandwich'' system, was developed to supplement multicellular spheroids as tumor analogues. Sandwiches allow new experimental approaches to questions of diffusion, cell cycle effects and radiation resistance in tumors. In this thesis the method for setting up sandwiches is described both theoretically and experimentally followed by its use in x-ray irradiation studies. In the sandwich system, cells are grown in a narrow gap between two glass slides. Where nutrients and waste products can move into or out of the local environment of the cells only by diffusing through the narrow gap between the slides. Due to the competition between cells, self-created gradients of nutrients and metabolic products are set up resulting in a layer of cells which resembles a living spheroid cross section. Unlike the cells of the spheroid, however, cells in all regions of the sandwich are visible. Therefore, the relative sizes of the regions and their time-dependent growth can be monitored visually without fixation or sectioning. The oxygen and nutrient gradients can be ''turned off'' at any time without disrupting the spatial arrangement of the cells by removing the top slide of the assembly and subsequently turned back on if desired. Removal of the top slide also provides access to all the cells, including those near the necrotic center, of the sandwich. The cells can then be removed for analysis outside the sandwich system. 61 refs., 17 figs

  9. Two-dimensional diffusion limited system for cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Hlatky, L.

    1985-11-01

    A new cell system, the ''sandwich'' system, was developed to supplement multicellular spheroids as tumor analogues. Sandwiches allow new experimental approaches to questions of diffusion, cell cycle effects and radiation resistance in tumors. In this thesis the method for setting up sandwiches is described both theoretically and experimentally followed by its use in x-ray irradiation studies. In the sandwich system, cells are grown in a narrow gap between two glass slides. Where nutrients and waste products can move into or out of the local environment of the cells only by diffusing through the narrow gap between the slides. Due to the competition between cells, self-created gradients of nutrients and metabolic products are set up resulting in a layer of cells which resembles a living spheroid cross section. Unlike the cells of the spheroid, however, cells in all regions of the sandwich are visible. Therefore, the relative sizes of the regions and their time-dependent growth can be monitored visually without fixation or sectioning. The oxygen and nutrient gradients can be ''turned off'' at any time without disrupting the spatial arrangement of the cells by removing the top slide of the assembly and subsequently turned back on if desired. Removal of the top slide also provides access to all the cells, including those near the necrotic center, of the sandwich. The cells can then be removed for analysis outside the sandwich system. 61 refs., 17 figs.

  10. Overcoming the Efficiency-Limiting Mechanisms in Commercial Si Solar Cells

    International Nuclear Information System (INIS)

    A brief review of performance-limiting processes in a commercial solar cell fabricated on low-cost substrate is given. Higher efficiencies require effective gettering of precipitated impurities present at the defect clusters, and improved cell and process designs. Overcoming these limitations is expected to lead to 18%-20 % cell efficiencies

  11. Modulation of histamine release from human colon mast cells by protease inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of protease inhibitors to modulate histamine release from human colon mast cells.METHODS: Enzymatically dispersed cells from human colon were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of tryptase and chymase inhibitors, and histamine release was determined.RESULTS: IgE dependent histamine release from colon mast cells was inhibited by up to approximately 37%, 26% and 36.8% by chymase inhibitors Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPFM), N-Tosyl-L-phenylalanyl-chloromethyl ketone (TPCK), and α1-antitrypsin, respectively. Similarly, inhibitors of tryptase leupeptin, N-tosyl-L-lysine chloromethyl ketone (TLCK), lactoferrin and protamine were also able to inhibit anti-IgE induced histamine release by a maximum of some 48%, 37%, 40% and 34%, respectively. Preincubation of these inhibitors with cells for 20 min before challenged with anti-IgE had small effect on the inhibitory actions of these inhibitors on colon mast cells. A specific inhibitor of aminopeptidase amastatin had no effect on anti-IgE induced histamine release. The significant inhibition of calcium ionophore induced histamine release was also observed with the inhibitors of tryptase and chymase examined. Apart from leupeptin and protamine, the inhibitors tested by themselves did not stimulate colon mast cells.CONCLUSION: It was demonstrated that both tryptase and chymase inhibitors could inhibit IgE dependent and calcium ionophore induced histamine release from dispersed colon mast cells in a concentration dependent of manner, which suggest that they are likely to be developed as a novel class of anti-inflammatory drugs to treat chronic of colitis in man.

  12. Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1±2.9 x 106/kg (n=10) and 3.1±1.5 x 105/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

  13. Legislating Limits on Human Embryonic Stem Cell Research

    Directory of Open Access Journals (Sweden)

    Sïna A. Muscati

    2003-04-01

    Full Text Available  Research on embryonic stem cells has generated great intrigue in the scientific community. Many medical researchers consider stem cell-based therapies to have the potential of treating a host of human ailments and yielding a number of medical benefits. They are motivated by the possibility of treating incurable diseases or facilitating effective treatment methods. Their enthusiasm is shared by many of those who are afflicted with these debilitating diseases.

  14. Band tailing and efficiency limitation in kesterite solar cells

    Science.gov (United States)

    Gokmen, Tayfun; Gunawan, Oki; Todorov, Teodor K.; Mitzi, David B.

    2013-09-01

    We demonstrate that a fundamental performance bottleneck for hydrazine processed kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells with efficiencies reaching above 11% can be the formation of band-edge tail states, which quantum efficiency and photoluminescence data indicate is roughly twice as severe as in higher-performing Cu(In,Ga)(S,Se)2 devices. Low temperature time-resolved photoluminescence data suggest that the enhanced tailing arises primarily from electrostatic potential fluctuations induced by strong compensation and facilitated by a lower CZTSSe dielectric constant. We discuss the implications of the band tails for the voltage deficit in these devices.

  15. Legal Limitations of Researching and Using the Stem Cells

    Directory of Open Access Journals (Sweden)

    Rustin-Petru CIASC

    2013-11-01

    Full Text Available The importance of research in view of using stem cells for scientific and medical purposes must be regulated in a clear and, to the degree possible, single manner, at European and world level. Beginning with this obvious necessity, this article attempts to review the relevant provisions in the domestic legislation, while supplying the required appreciations and criticism. In the end, it reaches the idea, also upon replying on some compared law elements, that not only some legislative modifications or adaptations are imposed, in connection to the normative acts in force, but particularly the creation of a complete and complex legislative framework. It must cover the existence of all practical situations and regulate the scientific research activity in this domain, without ignoring at any time the inviolability of human dignity and acknowledging the right of integrity of the person’s body and mind.

  16. On the Efficiency Limit of Conjugated Polymer:Fullerene-Based Bulk Heterojunction Solar Cells.

    Science.gov (United States)

    Scharber, Markus C

    2016-03-01

    The power conversion efficiency potential of eight high-performance polymer-fullerene blends is investigated. All studied absorbers show the typical organic solar cell losses limiting their performance to ≈13%. PMID:26757236

  17. Silicon solar cells reaching the efficiency limits: from simple to complex modelling

    Science.gov (United States)

    Kowalczewski, Piotr; Redorici, Lisa; Bozzola, Angelo; Andreani, Lucio Claudio

    2016-05-01

    Numerical modelling is pivotal in the development of high efficiency solar cells. In this contribution we present different approaches to model the solar cell performance: the diode equation, a generalization of the well-known Hovel model, and a complete device modelling. In all three approaches we implement a Lambertian light trapping, which is often considered as a benchmark for the optical design of solar cells. We quantify the range of parameters for which all three approaches give the same results, and highlight the advantages and limitations of different models. Using these methods we calculate the efficiency limits of single-junction crystalline silicon solar cells in a wide range of cell thickness. We find that silicon solar cells close to the efficiency limits operate in the high-injection (rather than in the low-injection) regime. In such a regime, surface recombination can have an unexpectedly large effect on cells with the absorber thickness lower than a few tens of microns. Finally, we calculate the limiting efficiency of tandem silicon-perovskite solar cells, and we determine the optimal thickness of the bottom silicon cell for different band gaps of the perovskite material.

  18. Silicon solar cells reaching the efficiency limits: from simple to complex modelling

    International Nuclear Information System (INIS)

    Numerical modelling is pivotal in the development of high efficiency solar cells. In this contribution we present different approaches to model the solar cell performance: the diode equation, a generalization of the well-known Hovel model, and a complete device modelling. In all three approaches we implement a Lambertian light trapping, which is often considered as a benchmark for the optical design of solar cells. We quantify the range of parameters for which all three approaches give the same results, and highlight the advantages and limitations of different models. Using these methods we calculate the efficiency limits of single-junction crystalline silicon solar cells in a wide range of cell thickness. We find that silicon solar cells close to the efficiency limits operate in the high-injection (rather than in the low-injection) regime. In such a regime, surface recombination can have an unexpectedly large effect on cells with the absorber thickness lower than a few tens of microns. Finally, we calculate the limiting efficiency of tandem silicon–perovskite solar cells, and we determine the optimal thickness of the bottom silicon cell for different band gaps of the perovskite material. (paper)

  19. All-silicon tandem solar cells: Practical limits for energy conversion and possible routes for improvement

    Science.gov (United States)

    Jia, Xuguang; Puthen-Veettil, Binesh; Xia, Hongze; Yang, Terry Chien-Jen; Lin, Ziyun; Zhang, Tian; Wu, Lingfeng; Nomoto, Keita; Conibeer, Gavin; Perez-Wurfl, Ivan

    2016-06-01

    Silicon nanocrystals (Si NCs) embedded in a dielectric matrix is regarded as one of the most promising materials for the third generation photovoltaics, owing to their tunable bandgap that allows fabrication of optimized tandem devices. Previous work has demonstrated fabrication of Si NCs based tandem solar cells by sputter-annealing of thin multi-layers of silicon rich oxide and SiO2. However, these device efficiencies were much lower than expected given that their theoretical values are much higher. Thus, it is necessary to understand the practical conversion efficiency limits for these devices. In this article, practical efficiency limits of Si NC based double junction tandem cells determined by fundamental material properties such as minority carrier, mobility, and lifetime are investigated. The practical conversion efficiency limits for these devices are significantly different from the reported efficiency limits which use Shockley-Queisser assumptions. Results show that the practical efficiency limit of a double junction cell (1.6 eV Si NC top cell and a 25% efficient c-Si PERL cell as the bottom cell) is 32%. Based on these results suggestions for improvement to the performance of Si nanocrystal based tandem solar cells in terms of the different parameters that were simulated are presented.

  20. Reduktion der posttraumatischen Entzündungsreaktion des zentralen Nervensystems durch die mastzell-spezifische Chymase murine Mastzellprotease-4

    OpenAIRE

    Kramer, Peter

    2014-01-01

    Mast cells (MC) can be detected in the central nervous system (CNS) of many vertebrates where they are mostly located in the dura mater and the leptomeninges, but they are also found within the parenchyma, for example in the thalamus. Data from experimental models of several neuroinflammatory pathologies such as multiple sclerosis or secondary damage after stroke indicate a fundamental role of MC in the exacerbation of the inflammation. Thus, a potentially detrimental role of MC in these proc...

  1. Dynamics inside the cancer cell attractor reveal cell heterogeneity, limits of stability, and escape.

    Science.gov (United States)

    Li, Qin; Wennborg, Anders; Aurell, Erik; Dekel, Erez; Zou, Jie-Zhi; Xu, Yuting; Huang, Sui; Ernberg, Ingemar

    2016-03-01

    The observed intercellular heterogeneity within a clonal cell population can be mapped as dynamical states clustered around an attractor point in gene expression space, owing to a balance between homeostatic forces and stochastic fluctuations. These dynamics have led to the cancer cell attractor conceptual model, with implications for both carcinogenesis and new therapeutic concepts. Immortalized and malignant EBV-carrying B-cell lines were used to explore this model and characterize the detailed structure of cell attractors. Any subpopulation selected from a population of cells repopulated the whole original basin of attraction within days to weeks. Cells at the basin edges were unstable and prone to apoptosis. Cells continuously changed states within their own attractor, thus driving the repopulation, as shown by fluorescent dye tracing. Perturbations of key regulatory genes induced a jump to a nearby attractor. Using the Fokker-Planck equation, this cell population behavior could be described as two virtual, opposing influences on the cells: one attracting toward the center and the other promoting diffusion in state space (noise). Transcriptome analysis suggests that these forces result from high-dimensional dynamics of the gene regulatory network. We propose that they can be generalized to all cancer cell populations and represent intrinsic behaviors of tumors, offering a previously unidentified characteristic for studying cancer. PMID:26929366

  2. Design of coated standing nanowire array solar cell performing beyond the planar efficiency limits

    Science.gov (United States)

    Zeng, Yang; Ye, Qinghao; Shen, Wenzhong

    2016-05-01

    The single standing nanowire (SNW) solar cells have been proven to perform beyond the planar efficiency limits in both open-circuit voltage and internal quantum efficiency due to the built-in concentration and the shifting of the absorption front. However, the expandability of these nano-scale units to a macro-scale photovoltaic device remains unsolved. The main difficulty lies in the simultaneous preservation of an effective built-in concentration in each unit cell and a broadband high absorption capability of their array. Here, we have provided a detailed theoretical guideline for realizing a macro-scale solar cell that performs furthest beyond the planar limits. The key lies in a complementary design between the light-trapping of the single SNWs and that of the photonic crystal slab formed by the array. By tuning the hybrid HE modes of the SNWs through the thickness of a coaxial dielectric coating, the optimized coated SNW array can sustain an absorption rate over 97.5% for a period as large as 425 nm, which, together with the inherited carrier extraction advantage, leads to a cell efficiency increment of 30% over the planar limit. This work has demonstrated the viability of a large-size solar cell that performs beyond the planar limits.

  3. The efficiency limit of CH3NH3PbI3 perovskite solar cells

    Science.gov (United States)

    Sha, Wei E. I.; Ren, Xingang; Chen, Luzhou; Choy, Wallace C. H.

    2015-06-01

    With the consideration of photon recycling effect, the efficiency limit of methylammonium lead iodide (CH3NH3PbI3) perovskite solar cells is predicted by a detailed balance model. To obtain convincing predictions, both AM 1.5 spectrum of Sun and experimentally measured complex refractive index of perovskite material are employed in the detailed balance model. The roles of light trapping and angular restriction in improving the maximal output power of thin-film perovskite solar cells are also clarified. The efficiency limit of perovskite cells (without the angular restriction) is about 31%, which approaches to Shockley-Queisser limit (33%) achievable by gallium arsenide (GaAs) cells. Moreover, the Shockley-Queisser limit could be reached with a 200 nm-thick perovskite solar cell, through integrating a wavelength-dependent angular-restriction design with a textured light-trapping structure. Additionally, the influence of the trap-assisted nonradiative recombination on the device efficiency is investigated. The work is fundamentally important to high-performance perovskite photovoltaics.

  4. The efficiency limit of CH3NH3PbI3 perovskite solar cells

    International Nuclear Information System (INIS)

    With the consideration of photon recycling effect, the efficiency limit of methylammonium lead iodide (CH3NH3PbI3) perovskite solar cells is predicted by a detailed balance model. To obtain convincing predictions, both AM 1.5 spectrum of Sun and experimentally measured complex refractive index of perovskite material are employed in the detailed balance model. The roles of light trapping and angular restriction in improving the maximal output power of thin-film perovskite solar cells are also clarified. The efficiency limit of perovskite cells (without the angular restriction) is about 31%, which approaches to Shockley-Queisser limit (33%) achievable by gallium arsenide (GaAs) cells. Moreover, the Shockley-Queisser limit could be reached with a 200 nm-thick perovskite solar cell, through integrating a wavelength-dependent angular-restriction design with a textured light-trapping structure. Additionally, the influence of the trap-assisted nonradiative recombination on the device efficiency is investigated. The work is fundamentally important to high-performance perovskite photovoltaics

  5. The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment.

    Science.gov (United States)

    Cebrian, Cristina; Asai, Naoya; D'Agati, Vivette; Costantini, Frank

    2014-04-10

    Nephrons, the functional units of the kidney, develop from progenitor cells (cap mesenchyme [CM]) surrounding the epithelial ureteric bud (UB) tips. Reciprocal signaling between UB and CM induces nephrogenesis and UB branching. Although low nephron number is implicated in hypertension and renal disease, the mechanisms that determine nephron number are obscure. To test the importance of nephron progenitor cell number, we genetically ablated 40% of these cells, asking whether this would limit kidney size and nephron number or whether compensatory mechanisms would allow the developing organ to recover. The reduction in CM cell number decreased the rate of branching, which in turn allowed the number of CM cells per UB tip to normalize, revealing a self-correction mechanism. However, the retarded UB branching impaired kidney growth, leaving a permanent nephron deficit. Thus, the number of fetal nephron progenitor cells is an important determinant of nephron endowment, largely via its effect on UB branching. PMID:24656820

  6. The Efficiency Limit of CH3NH3PbI3 Perovskite Solar Cells

    OpenAIRE

    Sha, Wei; Ren, X.; Chen, L.; Choy, WCH

    2015-01-01

    With the consideration of photon recycling effect, the efficiency limit of methylammonium lead iodide (CH3NH3PbI3) perovskite solar cells is predicted by a detailed balance model. To obtain convincing predictions, both AM 1.5 spectrum of Sun and experimentally measured complex refractive index of perovskite material are employed in the detailed balance model. The roles of light trapping and angular restriction in improving the maximal output power of thin-film perovskite solar cells are also ...

  7. Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium

    OpenAIRE

    Alunni, A.; Krecsmarik, M.; A Bosco; Galant, S.; Pan, L.; Moens, C.B.; Bally-Cuif, L.

    2013-01-01

    Maintaining the homeostasis of germinal zones in adult organs is a fundamental but mechanistically poorly understood process. In particular, what controls stem cell activation remains unclear. We have previously shown that Notch signaling limits neural stem cell (NSC) proliferation in the adult zebrafish pallium. Combining pharmacological and genetic manipulations, we demonstrate here that long-term Notch invalidation primarily induces NSC amplification through their activation from quiescenc...

  8. Degradation of C3a anaphylatoxins by rat mast cells

    International Nuclear Information System (INIS)

    Incubation of 125I-human C3a with rat peritoneal mast cells (RMC) causes extensive degradation of the ligand. Both cell-bound and free 125I-C3a (hu) was degraded by RMC, even at 00C, based on SDS-PAGE analysis. The authors examined several protease inhibitors for their ability to prevent degradation of 125I-C3a (hu). Degradation of 125I-C3a (hu) by RMC was not inhibited by leupeptin, antipain, elastatinal, pepstatin, α1-antitrypsin or EDTA. TPCK and TLCK were only partially effective. PMSF, chymostatin and SBTI were most effective in preventing 125I-C3a (hu) degradation. These latter compounds are effective inhibitors of the chymotrypsin-like enzyme chymase extracted from RMC, as is TPCK, based on hydrolysis of the substrate BTEE. Degradation of cell-bound ligand is totally prevented only by PMSF (or DFP). Therefore, 125I-C3a (hu) bound to the RMC appears to be degraded predominantly by chymase; however the cell-bound ligand is attacked by other surface proteases. Degradation of rat C3a by RMC was examined. After incubation with RMC, cell-bound and free 125I-C3a (rat) showed no evidence of degradation with or without inhibitors present. From these results, the authors conclude that chymase may not play a significant role in regulating anaphylatoxin activity. Furthermore, the authors propose that rat C3a is a preferred ligand for identifying receptors on mast cells because of its resistance to proteolysis

  9. Levels of Ycg1 Limit Condensin Function during the Cell Cycle

    Science.gov (United States)

    Arsenault, Heather E.; Benanti, Jennifer A.

    2016-01-01

    During mitosis chromosomes are condensed to facilitate their segregation, through a process mediated by the condensin complex. Although several factors that promote maximal condensin activity during mitosis have been identified, the mechanisms that downregulate condensin activity during interphase are largely unknown. Here, we demonstrate that Ycg1, the Cap-G subunit of budding yeast condensin, is cell cycle-regulated with levels peaking in mitosis and decreasing as cells enter G1 phase. This cyclical expression pattern is established by a combination of cell cycle-regulated transcription and constitutive degradation. Interestingly, overexpression of YCG1 and mutations that stabilize Ycg1 each result in delayed cell-cycle entry and an overall proliferation defect. Overexpression of no other condensin subunit impacts the cell cycle, suggesting that Ycg1 is limiting for condensin complex formation. Consistent with this possibility, we find that levels of intact condensin complex are reduced in G1 phase compared to mitosis, and that increased Ycg1 expression leads to increases in both levels of condensin complex and binding to chromatin in G1. Together, these results demonstrate that Ycg1 levels limit condensin function in interphase cells, and suggest that the association of condensin with chromosomes must be reduced following mitosis to enable efficient progression through the cell cycle. PMID:27463097

  10. Cryopreservation of Cell Sheets of Adipose Stem Cells: Limitations and Successes

    OpenAIRE

    Prata, F. P.; M.T. Cerqueira; Moreira-Silva, J.; Pirraco, Rogério P.; Reis, R. L.; Marques, A.P.

    2014-01-01

    Cell Sheets of hASCs (hASCs-CS) have been previously proposed for wound healing applications(1, 2) and despite the concern for production time reduction, the possibility of having these hASCs-CS off-the-shelf is appealing. The goal of this work was to define a cryopreservation methodology allowing to preserve cells viability and the properties CS matrix. hASCs-CS obtained from three different donors were created in UP-cell thermoresponsive dishes(Nunc, Germany) as previously reported(1,...

  11. The Utilization and Limitation of CD133 Epitopes in Lung Cancer Stem Cells Research

    Directory of Open Access Journals (Sweden)

    Yin CHEN

    2011-10-01

    Full Text Available Lung cancer is one of the most common tumor, which lacks of effective clinical treatment to lead to desirable prognosis. According to cancer stem cell hypothesis, lung cancer stem cells are considered to be responsible for carcinogenesis, development, metastasis, recurrence, invasion, resistance to chemotherapy and radiotherapy of lung cancer. In recent years, more and more institutes used glycosylated CD133 epitopes to define, isolate, purify lung cancer stem cells. However, along with deeply research, the application of CD133 epitopes in lung cancer stem cell research is questioned. The utilization and limitation of CD133 epitopes in lung cancer stem cells research for the past few years is summaried in this review.

  12. Radio-frequency Electrometry Using Rydberg Atoms in Vapor Cells: Towards the Shot Noise Limit

    Science.gov (United States)

    Kumar, Santosh; Fan, Haoquan; Jahangiri, Akbar; Kuebler, Harald; Shaffer, James P.; 5. Physikalisches Institut, Universitat Stuttgart, Germany Collaboration

    2016-05-01

    Rydberg atoms are a promising candidate for radio frequency (RF) electric field sensing. Our method uses electromagnetically induced transparency with Rydberg atoms in vapor cells to read out the effect that the RF electric field has on the Rydberg atoms. The method has the potential for high sensitivity (pV cm-1 Hz- 1 / 2) and can be self-calibrated. Some of the main factors limiting the sensitivity of RF electric field sensing from reaching the shot noise limit are the residual Doppler effect and the sensitivity of the optical read-out using the probe laser. We present progress on overcoming the residual Doppler effect by using a new multi-photon scheme and reaching the shot noise detection limit using frequency modulated spectroscopy. Our experiments also show promise for studying quantum optical effects such as superradiance in vapor cells using Rydberg atoms. This work is supported by DARPA, ARO, and NRO.

  13. Limitations of mRNA amplification from small-size cell samples

    Directory of Open Access Journals (Sweden)

    Myklebost Ola

    2005-10-01

    Full Text Available Abstract Background Global mRNA amplification has become a widely used approach to obtain gene expression profiles from limited material. An important concern is the reliable reflection of the starting material in the results obtained. This is especially important with extremely low quantities of input RNA where stochastic effects due to template dilution may be present. This aspect remains under-documented in the literature, as quantitative measures of data reliability are most often lacking. To address this issue, we examined the sensitivity levels of each transcript in 3 different cell sample sizes. ANOVA analysis was used to estimate the overall effects of reduced input RNA in our experimental design. In order to estimate the validity of decreasing sample sizes, we examined the sensitivity levels of each transcript by applying a novel model-based method, TransCount. Results From expression data, TransCount provided estimates of absolute transcript concentrations in each examined sample. The results from TransCount were used to calculate the Pearson correlation coefficient between transcript concentrations for different sample sizes. The correlations were clearly transcript copy number dependent. A critical level was observed where stochastic fluctuations became significant. The analysis allowed us to pinpoint the gene specific number of transcript templates that defined the limit of reliability with respect to number of cells from that particular source. In the sample amplifying from 1000 cells, transcripts expressed with at least 121 transcripts/cell were statistically reliable and for 250 cells, the limit was 1806 transcripts/cell. Above these thresholds, correlation between our data sets was at acceptable values for reliable interpretation. Conclusion These results imply that the reliability of any amplification experiment must be validated empirically to justify that any gene exists in sufficient quantity in the input material. This

  14. Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells

    OpenAIRE

    Ruiz, Sergio; Lopez Contreras, Andres J.; Gabut, Mathieu; Marion, Rosa M.; Guti??rrez Mart??nez, Paula; Bua, Sabela; Ram??rez, Oscar; Olalde, I??igo; Rodrigo Perez, Sara; Li, Han; Marqu??s i Bonet, Tom??s, 1975-; Serrano, Manuel; Blasco, Maria A; Batada, Nizar N; Fern??ndez Capetillo, Oscar

    2015-01-01

    The generation of induced pluripotent stem cells (iPSC) from adult somatic cells is one of the most remarkable discoveries in recent decades. However, several works have reported evidence of genomic instability in iPSC, raising concerns on their biomedical use. The reasons behind the genomic instability observed in iPSC remain mostly unknown. Here we show that, similar to the phenomenon of oncogene-induced replication stress, the expression of reprogramming factors induces replication stress....

  15. Fusion Pore Size Limits 5-HT Release From Single Enterochromaffin Cell Vesicles.

    Science.gov (United States)

    Raghupathi, Ravinarayan; Jessup, Claire F; Lumsden, Amanda L; Keating, Damien J

    2016-07-01

    Enterochromaffin cells are the major site of serotonin (5-HT) synthesis and secretion providing ∼95% of the body's total 5-HT. 5-HT can act as a neurotransmitter or hormone and has several important endocrine and paracrine roles. We have previously demonstrated that EC cells release small amounts of 5-HT per exocytosis event compared to other endocrine cells. We utilized a recently developed method to purify EC cells to demonstrate the mechanisms underlying 5-HT packaging and release. Using the fluorescent probe FFN511, we demonstrate that EC cells express VMAT and that VMAT plays a functional role in 5-HT loading into vesicles. Carbon fiber amperometry studies illustrate that the amount of 5-HT released per exocytosis event from EC cells is dependent on both VMAT and the H(+)-ATPase pump, as demonstrated with reserpine or bafilomycin, respectively. We also demonstrate that increasing the amount of 5-HT loaded into EC cell vesicles does not result in an increase in quantal release. As this indicates that fusion pore size may be a limiting factor involved, we compared pore diameter in EC and chromaffin cells by assessing the vesicle capture of different-sized fluorescent probes to measure the extent of fusion pore dilation. This identified that EC cells have a reduced fusion pore expansion that does not exceed 9 nm in diameter. These results demonstrate that the small amounts of 5-HT released per fusion event in EC cells can be explained by a smaller fusion pore that limits 5-HT release capacity from individual vesicles. PMID:26574734

  16. Photosynthetic efficiency, cell volume, and elemental stoichiometric ratios in Thalassirosira weissflogii under phosphorus limitation

    Institute of Scientific and Technical Information of China (English)

    LIU Sheng; GUO Zhiling; LI Tao; HUANGHui; LIN Senjie

    2011-01-01

    Nutrient limitation is known to inhibit growth and metabolism and to alter elemental stoichiometric ratios in phytoplankton.In this study,physiological changes in Thalassirosira weissflogii were measured under different dissolved inorganic phosphate (DIP) regimes in semi-continuous cultures to revisit the utility of the Redfield ratio for assessing nutrient limitation.The results showed that cell size increased with decreasing DIP availability.In the P-depleted treatment (f/2-P) the cell size was 1.48 times larger than that in the P-limited (f/100) treatment and 2.67 times larger than that in the P-saturated treatment (f/2 and f/10).The fucoxanthin to chlorophyll a ratio (Fuco/chl a) was relatively stable (about 0.3) in P-saturated cultures and was 10 times higher than that in P-limited and P-depleted cultures.During the experimental period,the photosynthetic efficiency index,△F/Fm',was relatively stable at ~0.50 in the P-saturated cultures,but quickly declined with decreasing DIP availability.Although cellular P content showed a significant difference between the P-saturated culture (1.6 pg/cell) and the P-limited culture (0.7 pg/cell),the N/P ratio in T.weissflogii did not show a trend with DIP availability and fluctuated slightly around 25.Our results suggest that cell division in T.weissflogii is not strictly size-gated but is probably regulated by a biochemical,and hence,an elemental stoichiometric ratio threshold,and that deviation of the cellular N/P ratio from the Redfield ratio is not a reliable indicator of algal nutrient stress.

  17. Asymptotic diffusion limit of cell temperature discretisation schemes for thermal radiation transport

    International Nuclear Information System (INIS)

    This paper attempts to unify the asymptotic diffusion limit analysis of thermal radiation transport schemes, for a linear-discontinuous representation of the material temperature reconstructed from cell centred temperature unknowns, in a process known as ‘source tilting’. The asymptotic limits of both Monte Carlo (continuous in space) and deterministic approaches (based on linear-discontinuous finite elements) for solving the transport equation are investigated in slab geometry. The resulting discrete diffusion equations are found to have nonphysical terms that are proportional to any cell-edge discontinuity in the temperature representation. Based on this analysis it is possible to design accurate schemes for representing the material temperature, for coupling thermal radiation transport codes to a cell centred representation of internal energy favoured by ALE (arbitrary Lagrange–Eulerian) hydrodynamics schemes

  18. Electric response of an electrolytic cell to a periodic excitation in the dc limit

    Energy Technology Data Exchange (ETDEWEB)

    Alexe-Ionescu, A.L. [Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca degli Abruzzo 24, 10129 Torino (Italy); University Politehnica of Bucharest, Faculty of Applied Sciences, Splaiul Independentei 313, 060042 Bucharest (Romania); Barbero, G. [Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca degli Abruzzo 24, 10129 Torino (Italy); Duarte, A.R. [Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca degli Abruzzo 24, 10129 Torino (Italy); Instituto de Física, Universidade de São Paulo, P.O. Box 66318, São Paulo 05314-970 (Brazil); Saracco, G. [Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca degli Abruzzo 24, 10129 Torino (Italy)

    2014-05-01

    We evaluate the electrical impedance of an electrolytic cell submitted to a low frequency external voltage. We show that in the limit where the circular frequency of the applied voltage, ω, is small with respect to Debye relaxation circular frequency, ω{sub D}, the response of the cell can be evaluated by means of a perturbational calculation, where the expansion parameter is x=ω/ω{sub D}. Simple expressions for the reactance and resistance in the dc limit of the electrolytic cell are obtained in the case where the electrodes are blocking and the diffusion coefficients of the negative and positive ions are equal. The case where the diffusion coefficients are different is also considered. In this framework, our analysis indicates that in the considered frequency range the effective diffusion coefficient coincides with the ambipolar diffusion coefficient. A possible extension of our approach to the case where the electrodes are not blocking is discussed too.

  19. Systematic single-cell analysis of Pichia pastoris reveals secretory capacity limits productivity.

    Directory of Open Access Journals (Sweden)

    Kerry Routenberg Love

    Full Text Available Biopharmaceuticals represent the fastest growing sector of the global pharmaceutical industry. Cost-efficient production of these biologic drugs requires a robust host organism for generating high titers of protein during fermentation. Understanding key cellular processes that limit protein production and secretion is, therefore, essential for rational strain engineering. Here, with single-cell resolution, we systematically analysed the productivity of a series of Pichia pastoris strains that produce different proteins both constitutively and inducibly. We characterized each strain by qPCR, RT-qPCR, microengraving, and imaging cytometry. We then developed a simple mathematical model describing the flux of folded protein through the ER. This combination of single-cell measurements and computational modelling shows that protein trafficking through the secretory machinery is often the rate-limiting step in single-cell production, and strategies to enhance the overall capacity of protein secretion within hosts for the production of heterologous proteins may improve productivity.

  20. Limits to anaerobic energy and cytosolic concentration in the living cell

    Science.gov (United States)

    Paglietti, A.

    2015-11-01

    For many physical systems at any given temperature, the set of all states where the system's free energy reaches its largest value can be determined from the system's constitutive equations of internal energy and entropy, once a state of that set is known. Such an approach is fraught with complications when applied to a living cell, because the cell's cytosol contains thousands of solutes, and thus thousands of state variables, which makes determination of its state impractical. We show here that, when looking for the maximum energy that the cytosol can store and release, detailed information on cytosol composition is redundant. Compatibility with cell's life requires that a single variable that represents the overall concentration of cytosol solutes must fall between defined limits, which can be determined by dehydrating and overhydrating the cell to its maximum capacity. The same limits are shown to determine, in particular, the maximum amount of free energy that a cell can supply in fast anaerobic processes, starting from any given initial state. For a typical skeletal muscle in normal physiological conditions this energy, i.e., the maximum anaerobic capacity to do work, is calculated to be about 960 J per kg of muscular mass. Such energy decreases as the overall concentration of solutes in the cytosol is increased. Similar results apply to any kind of cell. They provide an essential tool to understand and control the macroscopic response of single cells and multicellular cellular tissues alike. The applications include sport physiology, cell aging, disease produced cell damage, drug absorption capacity, to mention the most obvious ones.

  1. ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death.

    Science.gov (United States)

    Raab, M; Gentili, M; de Belly, H; Thiam, H R; Vargas, P; Jimenez, A J; Lautenschlaeger, F; Voituriez, Raphaël; Lennon-Duménil, A M; Manel, N; Piel, M

    2016-04-15

    In eukaryotic cells, the nuclear envelope separates the genomic DNA from the cytoplasmic space and regulates protein trafficking between the two compartments. This barrier is only transiently dissolved during mitosis. Here, we found that it also opened at high frequency in migrating mammalian cells during interphase, which allowed nuclear proteins to leak out and cytoplasmic proteins to leak in. This transient opening was caused by nuclear deformation and was rapidly repaired in an ESCRT (endosomal sorting complexes required for transport)-dependent manner. DNA double-strand breaks coincided with nuclear envelope opening events. As a consequence, survival of cells migrating through confining environments depended on efficient nuclear envelope and DNA repair machineries. Nuclear envelope opening in migrating leukocytes could have potentially important consequences for normal and pathological immune responses. PMID:27013426

  2. An improved model for nucleation-limited ice formation in living cells during freezing.

    Directory of Open Access Journals (Sweden)

    Jingru Yi

    Full Text Available Ice formation in living cells is a lethal event during freezing and its characterization is important to the development of optimal protocols for not only cryopreservation but also cryotherapy applications. Although the model for probability of ice formation (PIF in cells developed by Toner et al. has been widely used to predict nucleation-limited intracellular ice formation (IIF, our data of freezing Hela cells suggest that this model could give misleading prediction of PIF when the maximum PIF in cells during freezing is less than 1 (PIF ranges from 0 to 1. We introduce a new model to overcome this problem by incorporating a critical cell volume to modify the Toner's original model. We further reveal that this critical cell volume is dependent on the mechanisms of ice nucleation in cells during freezing, i.e., surface-catalyzed nucleation (SCN and volume-catalyzed nucleation (VCN. Taken together, the improved PIF model may be valuable for better understanding of the mechanisms of ice nucleation in cells during freezing and more accurate prediction of PIF for cryopreservation and cryotherapy applications.

  3. Recent advances on enzymatic glucose/oxygen and hydrogen/oxygen biofuel cells: Achievements and limitations

    Science.gov (United States)

    Cosnier, Serge; J. Gross, Andrew; Le Goff, Alan; Holzinger, Michael

    2016-09-01

    The possibility of producing electrical power from chemical energy with biological catalysts has induced the development of biofuel cells as viable energy sources for powering portable and implanted electronic devices. These power sources employ biocatalysts, called enzymes, which are highly specific and catalytic towards the oxidation of a biofuel and the reduction of oxygen or hydrogen peroxide. Enzymes, on one hand, are promising candidates to replace expensive noble metal-based catalysts in fuel cell research. On the other hand, they offer the exciting prospect of a new generation of fuel cells which harvest energy from body fluids. Biofuel cells which use glucose as a fuel are particularly interesting for generating electricity to power electronic devices inside a living body. Hydrogen consuming biofuel cells represent an emerging alternative to platinum catalysts due to comparable efficiencies and the capability to operate at lower temperatures. Currently, these technologies are not competitive with existing commercialised fuel cell devices due to limitations including insufficient power outputs and lifetimes. The advantages and challenges facing glucose biofuel cells for implantation and hydrogen biofuel cells will be summarised along with recent promising advances and the future prospects of these exotic energy-harvesting devices.

  4. Theoretical efficiency limit for a two-terminal multi-junction "step-cell" using detailed balance method

    Science.gov (United States)

    Abdul Hadi, Sabina; Fitzgerald, Eugene A.; Nayfeh, Ammar

    2016-02-01

    Here we present detailed balance efficiency limit for a novel two-terminal dual and triple junction "step-cell" under AM 1.5G and AM 0 incident spectrums. The step-cell is a multi-junction (MJ) solar cell in which part of the top cell is removed, exposing some of the bottom cell area to unfiltered incident light, thus increasing bottom cell's photogenerated current. Optical generation of the bottom cell is modeled in two parts: step part, limited by the bottom cell bandgap, and conventional part, additionally limited by the top cell absorption. Our results show that conventionally designed MJ cell with optimized bandgap combination of 1.64 eV/0.96 eV for dual junction and 1.91 eV/1.37 eV/0.93 eV for triple junction has the highest theoretical efficiency limit. However, the step-cell design provides significant efficiency improvement for cells with non-optimum bandgap values. For example, for 1.41 eV ( ˜GaAs)/Si dual junction under AM 1.5G, efficiency limit increases from ˜21% in a conventional design to 38.7% for optimized step-cell. Similar benefits are observed for three-junction step-cell and for AM 0 spectrum studied here. Step-cell relaxes bandgap requirements for efficient MJ solar cells, providing an opportunity for a wider selection of materials and cost reduction.

  5. Identification and Characterization of Performance Limiting Regions in Poly-Si Wafers for PV Cells

    International Nuclear Information System (INIS)

    As demand for silicon photovoltaic (PV) material increases, so does the need for cost-effective feedstock and production methods that will allow enhanced penetration of silicon PV into the total energy market. The focus on cost minimization for production of polycrystalline silicon (poly-Si) PV has led to relaxed feedstock purity requirements, which has also introduced undesirable characteristics into cast poly-Si PV wafers. To produce cells with the highest possible conversion efficiencies, it is crucial to understand how reduced purity requirements and defects that are introduced through the casting process can impair minority carrier properties in poly-Si PV cells. This is only possible by using multiple characterization techniques that give macro-scale information (such as the spatial distribution of performance-limiting regions), as well as micro and nano-scale information about the structural and chemical nature of such performance-limiting regions. This study demonstrates the usefulness of combining multiple techniques to analyze performance-limiting regions in the poly-Si wafers that are used for PV cells. This is done by first identifying performance-limiting regions using macro-scale techniques including photoluminescence (PL) imaging, microwave photoconductive decay (μPCD), and reflectometry), then using smaller-scale techniques such as scanning electron microscopy (SEM), electron backscattered diffraction (EBSD), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), cathodoluminescence (CL), and transmission electron microscopy (TEM) to understand the nature of such regions. This analysis shows that structural defects as well as metallic impurities are present in performance-limiting regions, which together act to decrease conversion efficiencies in poly-Si PV cells.

  6. Continuous macroscopic limit of a discrete stochastic model for interaction of living cells

    CERN Document Server

    Alber, M; Lushnikov, P M; Newman, S A; Alber, Mark; Chen, Nan; Lushnikov, Pavel M.; Newman, Stuart A.

    2007-01-01

    In the development of multiscale biological models it is crucial to establish a connection between discrete microscopic or mesoscopic stochastic models and macroscopic continuous descriptions based on cellular density. In this paper a continuous limit of a two-dimensional Cellular Potts Model (CPM) with excluded volume is derived, describing cells moving in a medium and reacting to each other through both direct contact and long range chemotaxis. The continuous macroscopic model is obtained as a Fokker-Planck equation describing evolution of the cell probability density function. All coefficients of the general macroscopic model are derived from parameters of the CPM and a very good agreement is demonstrated between CPM Monte Carlo simulations and numerical solution of the macroscopic model. It is also shown that in the absence of contact cell-cell interactions, the obtained model reduces to the classical macroscopic Keller-Segel model. General multiscale approach is demonstrated by simulating spongy bone for...

  7. Stability of limit cycles in a pluripotent stem cell dynamics model

    International Nuclear Information System (INIS)

    This paper is devoted to the study of the stability of limit cycles of a nonlinear delay differential equation with a distributed delay. The equation arises from a model of population dynamics describing the evolution of a pluripotent stem cells population. We study the local asymptotic stability of the unique nontrivial equilibrium of the delay equation and we show that its stability can be lost through a Hopf bifurcation. We then investigate the stability of the limit cycles yielded by the bifurcation using the normal form theory and the center manifold theorem. We illustrate our results with some numerics

  8. Multimodality Therapy for Limited-Stage Small-Cell Lung Cancer.

    Science.gov (United States)

    Almquist, Daniel; Mosalpuria, Kailash; Ganti, Apar Kishor

    2016-02-01

    Limited-stage small-cell lung cancer (SCLC) occurs in only one third of patients with SCLC, but it is potentially curable. Combined-modality therapy (chemotherapy and radiotherapy) has long been the mainstay of therapy for this condition, but more recent data suggest a role for surgery in early-stage disease. Prophylactic cranial irradiation seems to improve outcomes in patients who have responded to initial therapy. This review addresses the practical aspects of staging and treatment of patients with limited-stage SCLC. PMID:26869647

  9. Challenges and limitations of targeting cancer stem cells and/or the tumour microenvironment

    Directory of Open Access Journals (Sweden)

    Juan Sebastian Yakisich

    2012-05-01

    Full Text Available The existence of cancer cells with stem cell properties (Cancer Stem Cells, CSCs and their association with tumor resistance and relapse has led to the search for active compounds to eliminate these cells or modulate their stemness in the hope of curing cancer. So far, three classes of drugs that target cancer stemness (Stemness Modulator Drugs have been identified: i drugs that selectively eliminate CSCs (stem cell targeting drugs; ii drugs that decrease stemness (stemness inhibitor drugs; and iii drugs that promote stemness (stemness promoting drugs. In addition, microenvironment modulating drugs aimed at selectively targeting the stem cell niche are being investigated and may represent an important class of drug for cancer therapy. This article will briefly review the current use of these substances and discuss the potential outcomes, challenges and limitations of treatment modalities using these classes of drugs for cancer treatment. Finally, a modular tumor model will be proposed as a guide to integrate our knowledge on the biology of cancer stem cell with that of the tumor microenvironment to promote a more rational development of anticancer therapy.

  10. Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells

    Science.gov (United States)

    O'Leary, Claire E.; Riling, Christopher R.; Spruce, Lynn A.; Ding, Hua; Kumar, Suresh; Deng, Guoping; Liu, Yuhong; Seeholzer, Steven H.; Oliver, Paula M.

    2016-01-01

    Nedd4 family E3 ubiquitin ligases have been shown to restrict T-cell function and impact T-cell differentiation. We show here that Ndfip1 and Ndfip2, activators of Nedd4 family ligases, together limit accumulation and function of effector CD4+ T cells. Using a three-part proteomics approach in primary T cells, we identify stabilization of Jak1 in Ndfip1/2-deficient T cells stimulated through the TCR. Jak1 degradation is aborted in activated T cells that lack Ndfips. In wild-type cells, Jak1 degradation lessens CD4+ cell sensitivity to cytokines during TCR stimulation, while in Ndfip-deficient cells cytokine responsiveness persists, promoting increased expansion and survival of pathogenic effector T cells. Thus, Ndfip1/Ndfip2 regulate the cross talk between the T-cell receptor and cytokine signalling pathways to limit inappropriate T-cell responses. PMID:27088444

  11. Limitations of Data on Cell Phone Involvement in Collisions: A Case Study of California

    OpenAIRE

    Griswold, Julia B. Corresponding author; Grembek, Offer

    2014-01-01

    With the increasing prevalence of mobile technology and high-profile crashes bringing attention to distracted driving, data on cell phone involvement in collisions is critical for understanding the extent of the problem, examining the effectiveness of policies, and developing interventions to improve safety. Some limitations of existing data have been previously identified, but this paper examines the specific case of California’s collision data. Temporal, geographic, and jurisdictional tre...

  12. Solving cell infiltration limitations of electrospun nanofiber meshes for tissue engineering applications

    OpenAIRE

    Guimarães, Ana; Martins, Albino; Pinho, Elisabete D.; Faria, Susana; Reis, R. L.; Neves, N. M.

    2010-01-01

    AIM: Utilize the dual composition strategy to increase the pore size and solve the low cell infiltration capacity on random nanofiber meshes, an intrinsic limitation of electrospun scaffolds for tissue engineering applications. MATERIALS & METHODS: Polycaprolactone and poly(ethylene oxide) solutions were electrospun simultaneously to obtain a dual composition nanofiber mesh. Selective dissolution of the poly(ethylene oxide) nanofiber fraction was performed. The biologic performance of these e...

  13. Effects of Photovoltaic and Fuel Cell Hybrid System on Distribution Network Considering the Voltage Limits

    OpenAIRE

    ABYANEH, H. A.; B. Vahidi; RENANI, Y. K.

    2010-01-01

    Development of distribution network and power consumption growth, increase voltage drop on the line impedance and therefore voltage drop in system buses. In some cases consumption is so high that voltage in some buses exceed from standard. In this paper, effect of the fuel cell and photovoltaic hybrid system on distribution network for solving expressed problem is studied. For determining the capacity of each distributed generation source, voltage limitation on the bus voltages under diffe...

  14. Limited transplantation of antigen-expressing hematopoietic stem cells induces long-lasting cytotoxic T cell responses.

    Directory of Open Access Journals (Sweden)

    Warren L Denning

    Full Text Available Harnessing the ability of cytotoxic T lymphocytes (CTLs to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4-6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS.

  15. Poisson-Boltzmann theory of charged colloids: limits of the cell model for salty suspensions

    International Nuclear Information System (INIS)

    Thermodynamic properties of charge-stabilized colloidal suspensions and polyelectrolyte solutions are commonly modelled by implementing the mean-field Poisson-Boltzmann (PB) theory within a cell model. This approach models a bulk system by a single macroion, together with counterions and salt ions, confined to a symmetrically shaped, electroneutral cell. While easing numerical solution of the nonlinear PB equation, the cell model neglects microion-induced interactions and correlations between macroions, precluding modelling of macroion ordering phenomena. An alternative approach, which avoids the artificial constraints of cell geometry, exploits the mapping of a macroion-microion mixture onto a one-component model of pseudo-macroions governed by effective interparticle interactions. In practice, effective-interaction models are usually based on linear-screening approximations, which can accurately describe strong nonlinear screening only by incorporating an effective (renormalized) macroion charge. Combining charge renormalization and linearized PB theories, in both the cell model and an effective-interaction (cell-free) model, we compute osmotic pressures of highly charged colloids and monovalent microions, in Donnan equilibrium with a salt reservoir, over a range of concentrations. By comparing predictions with primitive model simulation data for salt-free suspensions, and with predictions from nonlinear PB theory for salty suspensions, we chart the limits of both the cell model and linear-screening approximations in modelling bulk thermodynamic properties. Up to moderately strong electrostatic couplings, the cell model proves accurate for predicting osmotic pressures of deionized (counterion-dominated) suspensions. With increasing salt concentration, however, the relative contribution of macroion interactions to the osmotic pressure grows, leading predictions from the cell and effective-interaction models to deviate. No evidence is found for a liquid

  16. Towards the efficiency limits of silicon solar cells: how thin is too thin?

    CERN Document Server

    Kowalczewski, Piotr

    2015-01-01

    It is currently possible to fabricate crystalline silicon solar cells with the absorber thickness ranging from a few hundreds of micrometers (conventional wafer-based cells) to devices as thin as $1\\,\\mu\\mathrm{m}$. In this work, we use a model single-junction solar cell to calculate the limits of energy conversion efficiency and estimate the optimal absorber thickness. The limiting efficiency for cells in the thickness range between 40 and $500\\,\\mu\\mathrm{m}$ is very similar and close to 29%. In this regard, we argue that decreasing the thickness below around $40\\,\\mu\\mathrm{m}$ is counter-productive, as it significantly reduces the maximum achievable efficiency, even when optimal light trapping is implemented. We analyse the roles of incomplete light trapping and extrinsic (bulk and surface) recombination mechanisms. For a reasonably high material quality, consistent with present-day fabrication techniques, the optimal thickness is always higher than a few tens of micrometers. We identify incomplete light ...

  17. Identification of performance limiting electrode using asymmetric cell configuration in vanadium redox flow batteries

    Science.gov (United States)

    Agar, Ertan; Dennison, C. R.; Knehr, K. W.; Kumbur, E. C.

    2013-03-01

    In this study, the performance of a vanadium redox flow battery (VRFB) is investigated using asymmetric electrode configurations with raw and functionalized (i.e., acid-treated and heat-treated) electrodes. The use of heat-treated electrodes in both half-cells is chosen as the baseline case for comparison, as this configuration shows the best performance. When the positive electrode in the baseline case is replaced with a raw or acid-treated electrode, the voltage efficiency is found to be comparable to that of the baseline case. However, in the case where the negative electrode in the baseline case is replaced with a raw or acid-treated electrode, a significantly lower efficiency is observed, suggesting that the negative half-cell reactions limit the performance of a VRFB. To further investigate this observation, an additional analysis is performed using cyclic voltammetry. The reaction kinetics data suggests that the poor performance of the negative half-cell is not due to the slow kinetics, but rather stems from the fact that the reduction reaction in the negative half-cell occurs at a potential that is very close to the onset of hydrogen evolution. The formation of hydrogen gas bubbles blocks the reaction sites and suppresses the favorable effects of functionalization in the negative half-cell.

  18. DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells

    Directory of Open Access Journals (Sweden)

    Hsu-Hsin Chen

    2014-11-01

    Full Text Available The scarcity of primordial germ cells (PGCs in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.

  19. Thymic regulatory T cell niche size is dictated by limiting interleukin 2 from antigen-bearing dendritic cells and feedback competition

    OpenAIRE

    Weist, Brian M.; Kurd, Nadia; Boussier, Jeremy; Chan, Shiao Wei; Robey, Ellen A.

    2015-01-01

    Thymic regulatory T (Treg) cell production requires interleukin 2 (IL-2) and agonist TCR ligands, and is controlled by competition for a limited developmental niche, but the thymic sources of IL-2 and the factors that limit access to the niche are poorly understood. Here we show that IL-2 produced by antigen-bearing dendritic cells plays a key role in Treg cell development, and that existing Treg cells limit new Treg cell development by competing for IL-2. . Our data suggest that antigen-pres...

  20. Fill factor in organic solar cells can exceed the Shockley-Queisser limit

    Science.gov (United States)

    Trukhanov, Vasily A.; Bruevich, Vladimir V.; Paraschuk, Dmitry Yu.

    2015-06-01

    The ultimate efficiency of organic solar cells (OSC) is under active debate. The solar cell efficiency is calculated from the current-voltage characteristic as a product of the open-circuit voltage (VOC), short-circuit current (JSC), and the fill factor (FF). While the factors limiting VOC and JSC for OSC were extensively studied, the ultimate FF for OSC is scarcely explored. Using numerical drift-diffusion modeling, we have found that the FF in OSC can exceed the Shockley-Queisser limit (SQL) established for inorganic p-n junction solar cells. Comparing charge generation and recombination in organic donor-acceptor bilayer heterojunction and inorganic p-n junction, we show that such distinctive properties of OSC as interface charge generation and heterojunction facilitate high FF, but the necessary condition for FF exceeding the SQL in OSC is field-dependence of charge recombination at the donor-acceptor interface. These findings can serve as a guideline for further improvement of OSC.

  1. Finite mobility effects on the radiative efficiency limit of pn -junction solar cells

    Science.gov (United States)

    Mattheis, Julian; Werner, Jürgen H.; Rau, Uwe

    2008-02-01

    The maximum power conversion efficiency of a solar cell as defined by the Shockley-Queisser (SQ) radiative recombination limit relies on the assumption that the collection probability for all photogenerated electron/hole pairs is unity. This assumption implies a virtually infinite mobility μn of the photogenerated charge carriers. In order to compute the radiative efficiency limit with finite mobilities, we solve the continuity equation for minority carrier transport including an additional photon recycling term that accounts for emission of photons by radiative recombination and their subsequent reabsorption. This approach quantitatively connects the SQ approach with the classical diode theory. Even when assuming radiative recombination as the only loss mechanism, the maximum efficiency achievable within our model is reduced drastically when μn drops below a critical value. This critical value depends on the absorption coefficient, the doping density of the absorber material, as well as on the thickness and the light trapping scheme of the solar cell. Thus, these material and device parameters gain a fundamental importance as soon as finite carrier mobility is considered. Our theory yields a criterion that has to be fulfilled by any photovoltaic material in order to guarantee charge separation even in an otherwise most ideal case. Exemplary application of our model to three real photovoltaic materials, crystalline silicon (c-Si) , amorphous silicon (a-Si:H) , as well as Cu(In,Ga)Se2 (CIGS), shows that mobilities of c-Si and CIGS are three, respectively, 1 order of magnitude above this critical limit whereas the effective hole mobilities in a-Si:H are scattered around the critical value. A comparison between solar cells and light-emitting diodes with finite mobility and finite nonradiative lifetime reveals that materials for these complementary devices have to fulfill different requirements.

  2. Understanding the Limitations of Circulating Cell Free Fetal DNA: An Example of Two Unique Cases.

    Science.gov (United States)

    Clark-Ganheart, Cecily A; Iqbal, Sara N; Brown, Donna L; Black, Susan; Fries, Melissa H

    2014-05-01

    Circulating cell free fetal DNA (cffDNA) is an effective screening modality for fetal aneuploidy. We report two cases of false positive results. The first case involves a female, with self-reported Down syndrome. CffDNA returned positive for trisomy 18 leading to a maternal diagnosis of mosaicism chromosome 18 with normal fetal karyotype. The second case involves a patient with an anomalous fetal ultrasound and cffDNA positive for trisomy 13. Amniocentesis demonstrated a chromosome 8p duplication/deletion. False positive cffDNA may arise in clinical scenarios where diagnostic testing is clearly indicated. Practitioners should recognize the limitations of cffDNA. PMID:25298847

  3. Speeding Up Simulations By Slowing Down Particles: Speed-Limited Particle-In-Cell Simulation

    CERN Document Server

    Werner, Gregory R

    2015-01-01

    Particle-in-cell (PIC) simulation is often impractical for the same reason that it is powerful: it includes too much physics. Sometimes the mere ability to simulate physics on small length or time scales requires those scales to be resolved (by the cell size and timestep) to avoid instability, even when the effects at those scales contribute negligibly to the phenomenon motivating the simulation. For example, a timestep larger than the inverse plasma frequency will often result in unphysical growth of plasma oscillations, even in simulations where plasma oscillations should not arise at all. Larger timesteps are possible in simulations based on reduced physics models, such as MHD or gyrokinetics, or in simulations with implicit time-advances. A new method, speed-limited PIC (SLPIC) simulation, allows larger timesteps without reduced physics and with an explicit time-advance. The SLPIC method slows down fast particles while still accurately representing the particle distribution. SLPIC is valid when fields and...

  4. An Electrochemical Impedance Study of the Capacity Limitations in Na–O2 Cells

    DEFF Research Database (Denmark)

    Knudsen, Kristian Bastholm; Nichols, Jessica E.; Vegge, Tejs;

    2016-01-01

    equivalent circuit model was used that takes into account the porous nature of the positive electrode and is able to distinguish between the electrolyte resistance in the pores and the charge-transfer resistance of the pore walls. The results obtained indicate that sudden death on discharge is caused by......Electrochemical impedance spectroscopy, pressure change measurements, and scanning electron microscopy were used to investigate the nonaqueous Na–O2 cell potential decrease and rise (sudden deaths) on discharge and charge, respectively. To fit the impedance spectra from operating cells, an......, depending on the current density, either accumulation of large NaO2 crystals that eventually block the electrode surface and/or a thin film of NaO2 forming on the cathode surface at the end of discharge, which limits charge-transfer. The commonly observed sudden rise in potential toward the end of charge...

  5. Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation.

    Science.gov (United States)

    Han, Jingjia; Wu, Qingling; Xia, Younan; Wagner, Mary B; Xu, Chunhui

    2016-05-01

    Enhancing the maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) will facilitate their applications in disease modeling and drug discovery. Previous studies suggest that cell alignment could enhance hPSC-CM maturation; however, the robustness of this approach has not been well investigated. To this end, we examined if the anisotropic orientation of hPSC-CMs imposed by the underlying aligned fibers within a 3D microenvironment could improve the maturation of hPSC-CMs. Enriched hPSC-CMs were cultured for two weeks on Matrigel-coated anisotropic (aligned) and isotropic (random) polycaprolactone (PCL) fibrous scaffolds, as well as tissue culture polystyrenes (TCPs) as a control. As expected, hPSC-CMs grown on the two types of fibrous scaffolds exhibited anisotropic and isotropic orientations, respectively. Similar to cells on TCPs, hPSC-CMs cultured on these scaffolds expressed CM-associated proteins and were pharmacologically responsive to adrenergic receptor agonists, a muscarinic agonist, and a gap junction uncoupler in a dose-dependent manner. Although hPSC-CMs grown on anisotropic fibrous scaffolds displayed the highest expression of genes encoding a number of sarcomere proteins, calcium handling proteins and ion channels, their calcium transient kinetics were slower than cells grown on TCPs. These results suggest that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. PMID:27131761

  6. Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

    Directory of Open Access Journals (Sweden)

    Jingjia Han

    2016-05-01

    Full Text Available Enhancing the maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs will facilitate their applications in disease modeling and drug discovery. Previous studies suggest that cell alignment could enhance hPSC-CM maturation; however, the robustness of this approach has not been well investigated. To this end, we examined if the anisotropic orientation of hPSC-CMs imposed by the underlying aligned fibers within a 3D microenvironment could improve the maturation of hPSC-CMs. Enriched hPSC-CMs were cultured for two weeks on Matrigel-coated anisotropic (aligned and isotropic (random polycaprolactone (PCL fibrous scaffolds, as well as tissue culture polystyrenes (TCPs as a control. As expected, hPSC-CMs grown on the two types of fibrous scaffolds exhibited anisotropic and isotropic orientations, respectively. Similar to cells on TCPs, hPSC-CMs cultured on these scaffolds expressed CM-associated proteins and were pharmacologically responsive to adrenergic receptor agonists, a muscarinic agonist, and a gap junction uncoupler in a dose-dependent manner. Although hPSC-CMs grown on anisotropic fibrous scaffolds displayed the highest expression of genes encoding a number of sarcomere proteins, calcium handling proteins and ion channels, their calcium transient kinetics were slower than cells grown on TCPs. These results suggest that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs.

  7. Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

    Science.gov (United States)

    Han, Jingjia; Wu, Qingling; Xia, Younan; Wagner, Mary B; Xu, Chunhui

    2016-01-01

    Enhancing the maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) will facilitate their applications in disease modeling and drug discovery. Previous studies suggest that cell alignment could enhance hPSC-CM maturation; however, the robustness of this approach has not been well investigated. To this end, we examined if the anisotropic orientation of hPSC-CMs imposed by the underlying aligned fibers within a 3D microenvironment could improve the maturation of hPSC-CMs. Enriched hPSC-CMs were cultured for two weeks on Matrigel-coated anisotropic (aligned) and isotropic (random) polycaprolactone (PCL) fibrous scaffolds, as well as tissue culture polystyrenes (TCPs) as a control. As expected, hPSC-CMs grown on the two types of fibrous scaffolds exhibited anisotropic and isotropic orientations, respectively. Similar to cells on TCPs, hPSC-CMs cultured on these scaffolds expressed CM-associated proteins and were pharmacologically responsive to adrenergic receptor agonists, a muscarinic agonist, and a gap junction uncoupler in a dose-dependent manner. Although hPSC-CMs grown on anisotropic fibrous scaffolds displayed the highest expression of genes encoding a number of sarcomere proteins, calcium handling proteins and ion channels, their calcium transient kinetics were slower than cells grown on TCPs. These results suggest that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. PMID:27131761

  8. Combined modality treatment of chemotherapy and thoracic radiotherapy for limited-stage small cell lung cancer

    International Nuclear Information System (INIS)

    Small cell lung cancer (SCLC) differs from other types of lung cancer in its more aggressive clinical course and superior responsiveness to chemo- and radiotherapy. Median survival of patients with unresectable limited disease was reported only 3 months by supportive care alone. SCLC was treated by surgery in 1950s, but results were disappointing. In a British study in the 1960s, radiotherapy proved superior to surgery in survival. However, most patients treated with thoracic radiotherapy alone died of instant metastases with median survival of 5-9 months, indicating a need for primary systemic treatment. In the 1970s, combined chemotherapy came to be the main treatment for SCLC; high response rate and improved survival led to the idea that thoracic radiotherapy added only toxicities with no therapeutic advantage in chemotherapy-treated patients. Considering the fact that 80% of patients treated with chemotherapy alone relapsed in primary sites, and that radio-therapy achieved response in 90% of limited disease patients, it is reasonable to attempt to combine systemic chemotherapy and thoracic radio-therapy to improve therapeutic results for this disease. In 1980s, several randomized trials comparing chemotherapy alone versus chemotherapy with thoracic radiotherapy were conducted to clarify the role of thoracic radio-therapy in combination with chemotherapy for limited SCLC. (author). 20 refs., 3 tabs

  9. Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways1

    OpenAIRE

    Jacobs, Sarah R.; Herman, Catherine E.; MacIver, Nancie J.; Wofford, Jessica A.; Wieman, Heather L.; Hammen, Jeremy J.; Rathmell, Jeffrey C.

    2008-01-01

    T cell activation potently stimulates cellular metabolism to support the elevated energetic and biosynthetic demands of growth, proliferation, and effector function. We show that glucose uptake is limiting in T cell activation and that CD28 costimulation is required to allow maximal glucose uptake following TCR stimulation by up-regulating expression and promoting the cell surface trafficking of the glucose transporter Glut1. Regulation of T cell glucose uptake and Glut1 was critical, as low ...

  10. Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer.

    Science.gov (United States)

    Stewart, David J

    2010-09-01

    While chemotherapy provides useful palliation, advanced lung cancer remains incurable since those tumors that are initially sensitive to therapy rapidly develop acquired resistance. Resistance may arise from impaired drug delivery, extracellular factors, decreased drug uptake into tumor cells, increased drug efflux, drug inactivation by detoxifying factors, decreased drug activation or binding to target, altered target, increased damage repair, tolerance of damage, decreased proapoptotic factors, increased antiapoptotic factors, or altered cell cycling or transcription factors. Factors for which there is now substantial clinical evidence of a link to small cell lung cancer (SCLC) resistance to chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P-gp (for non-platinum agents). SPECT MIBI and Tc-TF scanning appears to predict chemotherapy benefit in SCLC. In non-small cell lung cancer (NSCLC), the strongest clinical evidence is for taxane resistance with elevated expression or mutation of class III beta-tubulin (and possibly alpha tubulin), platinum resistance and expression of ERCC1 or BCRP, gemcitabine resistance and RRM1 expression, and resistance to several agents and COX-2 expression (although COX-2 inhibitors have had minimal impact on drug efficacy clinically). Tumors expressing high BRCA1 may have increased resistance to platinums but increased sensitivity to taxanes. Limited early clinical data suggest that chemotherapy resistance in NSCLC may also be increased with decreased expression of cyclin B1 or of Eg5, or with increased expression of ICAM, matrilysin, osteopontin, DDH, survivin, PCDGF, caveolin-1, p21WAF1/CIP1, or 14-3-3sigma, and that IGF-1R inhibitors may increase efficacy of chemotherapy, particularly in squamous cell carcinomas. Equivocal data (with some positive studies but other negative studies) suggest that NSCLC tumors with some EGFR mutations may have increased sensitivity to chemotherapy, while K-ras mutations

  11. Hydrogel limits stem cell dispersal in the deaf cochlea: implications for cochlear implants

    Science.gov (United States)

    Nayagam, Bryony A.; Backhouse, Steven S.; Cimenkaya, Cengiz; Shepherd, Robert K.

    2012-12-01

    Auditory neurons provide the critical link between a cochlear implant and the brain in deaf individuals, therefore their preservation and/or regeneration is important for optimal performance of this neural prosthesis. In cases where auditory neurons are significantly depleted, stem cells (SCs) may be used to replace the lost population of neurons, thereby re-establishing the critical link between the periphery (implant) and the brain. For such a therapy to be therapeutically viable, SCs must be differentiated into neurons, retained at their delivery site and damage caused to the residual auditory neurons minimized. Here we describe the transplantation of SC-derived neurons into the deaf cochlea, using a peptide hydrogel to limit their dispersal. The described approach illustrates that SCs can be delivered to and are retained within the basal turn of the cochlea, without a significant loss of endogenous auditory neurons. In addition, the tissue response elicited from this surgical approach was restricted to the surgical site and did not extend beyond the cochlear basal turn. Overall, this approach illustrates the feasibility of targeted cell delivery into the mammalian cochlea using hydrogel, which may be useful for future cell-based transplantation strategies, for combined treatment with a cochlear implant to restore function.

  12. IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease.

    Directory of Open Access Journals (Sweden)

    Christian Taube

    Full Text Available Interleukin (IL-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production of CCL17 (TARC, IL-5 and IL-13 in the lung. Mice treated with IL-22 before antigen challenge displayed reduced expression of CCL17 and IL-13 and significant amelioration of airway constriction and inflammation. We conclude that innate IL-22 limits airway inflammation, tissue damage and clinical decline in allergic lung disease.

  13. Stimulators of mineralization limit the invasive phenotype of human osteosarcoma cells by a mechanism involving impaired invadopodia formation.

    Directory of Open Access Journals (Sweden)

    Anna Cmoch

    Full Text Available BACKGROUND: Osteosarcoma (OS is a highly aggressive bone cancer affecting children and young adults. Growing evidence connects the invasive potential of OS cells with their ability to form invadopodia (structures specialized in extracellular matrix proteolysis. RESULTS: In this study, we tested the hypothesis that commonly used in vitro stimulators of mineralization limit the invadopodia formation in OS cells. Here we examined the invasive potential of human osteoblast-like cells (Saos-2 and osteolytic-like (143B OS cells treated with the stimulators of mineralization (ascorbic acid and B-glycerophosphate and observed a significant difference in response of the tested cells to the treatment. In contrast to 143B cells, osteoblast-like cells developed a mineralization phenotype that was accompanied by a decreased proliferation rate, prolongation of the cell cycle progression and apoptosis. On the other hand, stimulators of mineralization limited osteolytic-like OS cell invasiveness into collagen matrix. We are the first to evidence the ability of 143B cells to degrade extracellular matrix to be driven by invadopodia. Herein, we show that this ability of osteolytic-like cells in vitro is limited by stimulators of mineralization. CONCLUSIONS: Our study demonstrates that mineralization competency determines the invasive potential of cancer cells. A better understanding of the molecular mechanisms by which stimulators of mineralization regulate and execute invadopodia formation would reveal novel clinical targets for treating osteosarcoma.

  14. Cross-talk between human mast cells and bronchial epithelial cells in plasminogen activator inhibitor-1 production via transforming growth factor-β1.

    Science.gov (United States)

    Cho, Seong H; Lee, Sun H; Kato, Atsushi; Takabayashi, Tetsuji; Kulka, Marianna; Shin, Soon C; Schleimer, Robert P

    2015-01-01

    Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC-epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1-mediated activation pathway. PMID:24987792

  15. Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

    International Nuclear Information System (INIS)

    Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several

  16. Integration of filgrastim into chemoradiation for limited small cell lung cancer: a phase I study

    International Nuclear Information System (INIS)

    Purpose: Recent studies document the value of early combined modality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. Methods and Materials: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) ± filgrastim (5 μg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. Results: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1-3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete). Conclusions: Despite

  17. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    International Nuclear Information System (INIS)

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  18. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    1999-03-01

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  19. Exceeding the solar cell Shockley-Queisser limit via thermal up-conversion of low-energy photons

    CERN Document Server

    Boriskina, Svetlana V

    2013-01-01

    Maximum efficiency of ideal single-junction photovoltaic (PV) cells is limited to 33% (for one sun illumination) by intrinsic losses such as band edge thermalization, radiative recombination, and inability to absorb below-bandgap photons. This intrinsic thermodynamic limit, named after Shockley and Queisser (S-Q), can be exceeded by utilizing low-energy photons either via their electronic up-conversion or via thermophotovoltaic (TPV) conversion process. However, electronic up-conversion systems have extremely low efficiencies, and practical temperature considerations limit the operation of TPV converters to the narrow-gap PV cells. Here we develop a conceptual design of a hybrid TPV platform, which exploits thermal up-conversion of low-energy photons and is compatible with conventional silicon PV cells by using spectral and directional selectivity of the up-converter. The hybrid platform offers sunlight-to-electricity conversion efficiency exceeding that imposed by the S-Q limit on the corresponding PV cells ...

  20. JNK mitogen-activated protein kinase limits calcium-dependent chloride secretion across colonic epithelial cells.

    LENUS (Irish Health Repository)

    Donnellan, Fergal

    2010-01-01

    Neuroimmune agonists induce epithelial Cl(-) secretion through elevations in intracellular Ca2+ or cAMP. Previously, we demonstrated that epidermal growth factor receptor (EGFR) transactivation and subsequent ERK MAPK activation limits secretory responses to Ca2+-dependent, but not cAMP-dependent, agonists. Although JNK MAPKs are also expressed in epithelial cells, their role in regulating transport function is unknown. Here, we investigated the potential role for JNK in regulating Cl(-) secretion in T(84) colonic epithelial cells. Western blot analysis revealed that a prototypical Ca2+-dependent secretagogue, carbachol (CCh; 100 microM), induced phosphorylation of both the 46-kDa and 54-kDa isoforms of JNK. This effect was mimicked by thapsigargin (TG), which specifically elevates intracellular Ca2+, but not by forskolin (FSK; 10 microM), which elevates cAMP. CCh-induced JNK phosphorylation was attenuated by the EGFR inhibitor, tyrphostin-AG1478 (1 microM). Pretreatment of voltage-clamped T(84) cells with SP600125 (2 microM), a specific JNK inhibitor, potentiated secretory responses to both CCh and TG but not to FSK. The effects of SP600125 on CCh-induced secretion were not additive with those of the ERK inhibitor, PD98059. Finally, in apically permeabilized T(84) cell monolayers, SP600125 potentiated CCh-induced K+ conductances but not Na+\\/K+ATPase activity. These data demonstrate a novel role for JNK MAPK in regulating Ca2+ but not cAMP-dependent epithelial Cl(-) secretion. JNK activation is mediated by EGFR transactivation and exerts its antisecretory effects through inhibition of basolateral K+ channels. These data further our understanding of mechanisms regulating epithelial secretion and underscore the potential for exploitation of MAPK-dependent signaling in treatment of intestinal transport disorders.

  1. Simulation of limiting dilution technique in determination of immunocompetent cells frequency in irradiated cell cultures; Simulacao da tecnica de analise por limite de diluicao na determinacao da frequencia de celulas imunocompetentes em culturas contendo celulas irradiadas

    Energy Technology Data Exchange (ETDEWEB)

    Martini Filho, R.J.; Barlette, V.E.; Goes, E.G. [Centro Universitario Franciscano, Santa Maria, RS (Brazil); Covas, D.T.; Orellana, M. [Fundacao Hemocentro de Ribeirao Preto, SP (Brazil)

    2001-07-01

    Limiting dilution techniques (LDA) dose-response data have been used to detect immunocompetent T-Cells in microcultures. In this work, LDA frequencies estimates was obtained using {chi}2 minimization for irradiated cells in a range of 500 to 1,500 cGy. (author)

  2. Effects of Photovoltaic and Fuel Cell Hybrid System on Distribution Network Considering the Voltage Limits

    Directory of Open Access Journals (Sweden)

    ABYANEH, H. A.

    2010-11-01

    Full Text Available Development of distribution network and power consumption growth, increase voltage drop on the line impedance and therefore voltage drop in system buses. In some cases consumption is so high that voltage in some buses exceed from standard. In this paper, effect of the fuel cell and photovoltaic hybrid system on distribution network for solving expressed problem is studied. For determining the capacity of each distributed generation source, voltage limitation on the bus voltages under different conditions is considered. Simulation is done by using DIgSILENT software on the part of the 20 kV real life Sirjan distribution system. In this article, optimum location with regard to system and environmental conditions are studied in two different viewpoints.

  3. Operating limits of AL-alloyed high-low junctions for BSF solar cells

    Science.gov (United States)

    del Alamo, J.; Eguren, J.; Luque, A.

    1981-05-01

    Experimental estimations of the effective surface recombination velocity of the high-low junction and of the base diffusion length are carried out for Al-alloyed n(plus)pp(plus) bifacial cells and the results are presented in form of histograms. These results agree with calculated values of the effective surface recombination velocity when the characteristics of the recrystallized Si layer and heavy doping effects are taken into account. It is concluded that thick Al layers and high alloying temperatures (over 800 C) are necessary to obtain low values of the velocity. This conclusion agrees with experimental results of other authors. Recommendations to avoid diffusion length degradation are given and the operating limits of the Al alloying technology are discussed.

  4. Fundamental High-Speed Limits in Single-Molecule, Single-Cell, and Nanoscale Force Spectroscopies.

    Science.gov (United States)

    Amo, Carlos A; Garcia, Ricardo

    2016-07-26

    Force spectroscopy is enhancing our understanding of single-biomolecule, single-cell, and nanoscale mechanics. Force spectroscopy postulates the proportionality between the interaction force and the instantaneous probe deflection. By studying the probe dynamics, we demonstrate that the total force acting on the probe has three different components: the interaction, the hydrodynamic, and the inertial. The amplitudes of those components depend on the ratio between the resonant frequency and the frequency at which the data are measured. A force-distance curve provides a faithful measurement of the interaction force between two molecules when the inertial and hydrodynamic components are negligible. Otherwise, force spectroscopy measurements will underestimate the value of unbinding forces. Neglecting the above force components requires the use of frequency ratios in the 50-500 range. These ratios will limit the use of high-speed methods in force spectroscopy. The theory is supported by numerical simulations. PMID:27359243

  5. Subclassification of pulmonary non-small cell lung carcinoma in fine needle aspirates using a limited immunohistochemistry panel

    Directory of Open Access Journals (Sweden)

    Kusum Kapila

    2013-01-01

    Conclusion: Use of limited IHC panel helps categorize primary versus secondary tumors to the lung. The p63 is a useful marker for detecting squamous cell carcinoma. In countries where antibodies are not readily available, using a limited IHC panel of TTF-1, p63, and CK7 can help further type NSCLC lung tumors.

  6. The Result of Combined Modality Treatment for Limited Stage Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    From July 1984 to September 1988, 27 patients with limited stage small cell lung cancer were treated with combined modality(combination chemotherapy Plus radiotherapy) at the Department of Therapeutic Radiology in Kyungpook National University Hospital. Of the 27 patients, 19(70%) achieved a complete response, 6(22%) a partial response, and 2(8%) no response. Female, performance status HO, serum enolase level below 30ng/ml, radiation dose over 4500 cGy, and 4 or more cycles of chemotherapy had a favorable effect on the rates of complete response, although there were no statistical differences according to the variables. Median survival time was 10 Months and overall 1- and 2-year survival rates were 40.7% and 12.2%, respectively. Complete response(p<0.05), performance status HO(p<0.05), 4 or more cycles of chemotherapy(p<0.05), and radiation dose over 4500 cGy had a significantly favorable effect on 2-year survival rate. Prophylactic cranial irradiation or sex had no effect on survival. The results of this study suggest that radiation treatment should be combined with combination chemotherapy in the therapeutic strategy of SCLC of limited stage

  7. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg;

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT with a...... 2       years, 54% were without local or distant progression, and overall survival       was 47%. Within 6 months after treatment, one or more Grade >/=2 reactions       were observed in 48% of the patients. Conclusions: Stereotactic body       radiotherapy in patients with limited-stage NSCLC...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  8. Combined chemotherapy in the treatment of limited small cell lung carcinoma

    International Nuclear Information System (INIS)

    Between 1978 and 1983, 34 patients (32 evaluable) suffering from limited small cell lung carcinoma (SCLC-L) were treated following the protocol polychemotherapy (CAV) plus thoracic telecobaltotherapy and precaucional cranial irradiation (30 Gy in 2 weeks). Minimum follow-up was 30 months. After induction chemotherapy there was complete remission (CR) in 20% of cases whereas at the end of induction chemo-radiotherapy there was complete remission (CR) in 44% (p<0.05) of cases. Median duration of the responds was 12 months. Total median survival is 15 months, median NED survival 32 months (6-90 months). Seven out of 14 CR patients received consolidated thoracic radiotherapy (Rt); 6 of these survived disease-free for over 2 years. No salvage therapy carried out has proved useful. Only in one patient (3%) brain metastasis occurred. Iatric toxicity was also kept within limits of brain level. The role Rt plays in increasing the CR percentage, in drastically diminuishing the incidence of brain metastasis, in improving the quality of life by increasing the disease-free interval must be emphasized. Finally it should be noted that only CR patients have the possibility to become long survivors

  9. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

    Science.gov (United States)

    Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

    2016-05-01

    High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. PMID:27133169

  10. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients

    International Nuclear Information System (INIS)

    Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design. Blood samples from 40 metastatic melanoma patients and 10 normal blood donors were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification and copy number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear size, 1–250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5–371.5 CMCs ml−1). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this cell population may contribute to the design of effective personalized therapies in patients with melanoma. (paper)

  11. Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation

    Directory of Open Access Journals (Sweden)

    Madrid Marisa

    2013-02-01

    Full Text Available Abstract Background Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase. The cell integrity Pmk1 pathway is another MAPK cascade that regulates various processes in fission yeast, including cell wall construction, cytokinesis, and ionic homeostasis. Pmk1 pathway also becomes strongly activated in response to glucose deprivation but its role during glucose exhaustion and ensuing adaptation to respiratory metabolism is currently unknown. Results We found that Pmk1 activation in the absence of glucose takes place only after complete depletion of this carbon source and that such activation is not related to an endogenous oxidative stress. Notably, Pmk1 MAPK activation relies on de novo protein synthesis, is independent on known upstream activators of the pathway like Rho2 GTPase, and involves PKC ortholog Pck2. Also, the Glucose/cAMP pathway is required operative for full activation of the Pmk1 signaling cascade. Mutants lacking Pmk1 displayed a partial growth defect in respiratory media which was not observed in the presence of glucose. This phenotype was accompanied by a decreased and delayed expression of transcription factor Atf1 and target genes fbp1+ and pyp2+. Intriguingly, the kinetics of Sty1 activation in Pmk1-less cells was clearly altered during growth adaptation to non-fermentable carbon sources. Conclusions Unknown upstream elements

  12. Twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Seung Gu; Cho, Moon June; Kim, Sun Young; Kim, Ki Whan; Kim, Jun Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2006-06-15

    A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32 {approx} 75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45 {approx} 51 Gy). Concurrent chemotherapy consisted of CAV (cytoxan 1000 mg/m{sup 2}, adriamycin 40 mg/m{sup 2}, vincristine 1 mg/m{sup 2}) alternating with PE (cisplatin 60 mg/m{sup 2}, etoposide 100 mg/m{sup 2}) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1 {approx} 9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/ 10 fractions. Median follow up was 18 months (range, 1 {approx} 136 months). Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival ({rho} < 0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. Twice daily radiation therapy plus concurrent chemotherapy produced favorable

  13. Exceeding the solar cell Shockley-Queisser limit via thermal up-conversion of low-energy photons

    Science.gov (United States)

    Boriskina, Svetlana V.; Chen, Gang

    2014-03-01

    Maximum efficiency of ideal single-junction photovoltaic (PV) cells is limited to 33% (for 1 sun illumination) by intrinsic losses such as band edge thermalization, radiative recombination, and inability to absorb below-bandgap photons. This intrinsic thermodynamic limit, named after Shockley and Queisser (S-Q), can be exceeded by utilizing low-energy photons either via their electronic up-conversion or via the thermophotovoltaic (TPV) conversion process. However, electronic up-conversion systems have extremely low efficiencies, and practical temperature considerations limit the operation of TPV converters to the narrow-gap PV cells. Here we develop a conceptual design of a hybrid TPV platform, which exploits thermal up-conversion of low-energy photons and is compatible with conventional silicon PV cells by using spectral and directional selectivity of the up-converter. The hybrid platform offers sunlight-to-electricity conversion efficiency exceeding that imposed by the S-Q limit on the corresponding PV cells across a broad range of bandgap energies, under low optical concentration (1-300 suns), operating temperatures in the range 900-1700 K, and in simple flat panel designs. We demonstrate maximum conversion efficiency of 73% under illumination by non-concentrated sunlight. A detailed analysis of non-ideal hybrid platforms that allows for up to 15% of absorption/re-emission losses yields limiting efficiency value of 45% for Si PV cells.

  14. Limiting-dilution analysis for the determination of leukemic cell frequencies after bone marrow decontamination with mafosfamide or merocyanine 540

    Energy Technology Data Exchange (ETDEWEB)

    Porcellini, A.; Talevi, N.; Marchetti-Rossi, M.T.; Palazzi, M.; Manna, A.; Sparaventi, G.; Delfini, C.; Valentini, M.

    1987-11-01

    To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation.

  15. Limiting-dilution analysis for the determination of leukemic cell frequencies after bone marrow decontamination with mafosfamide or merocyanine 540

    International Nuclear Information System (INIS)

    To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation

  16. Conditioned medium from human amniotic mesenchymal stromal cells limits infarct size and enhances angiogenesis.

    Science.gov (United States)

    Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara; Cervio, Elisabetta; Calvillo, Laura; Copes, Francesco; Pisano, Federica; Mura, Manuela; Kleijn, Lennaert; de Boer, Rudolf A; Viarengo, Gianluca; Rosti, Vittorio; Spinillo, Arsenio; Roccio, Marianna; Gnecchi, Massimiliano

    2015-05-01

    The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC-CM by cytokine array. Our results strongly support the concept that the administration of hAMC-CM favors the repair process after acute myocardial infarction. PMID:25824141

  17. Comparison of dust charging between orbital-motion-limited theory and particle-in-cell simulations

    International Nuclear Information System (INIS)

    The Orbital-Motion-Limited (OML) theory has been modified to predict the dust charge and the results were contrasted with the Whipple approximation [X. Z. Tang and G. L. Delzanno, Phys. Plasmas 21, 123708 (2014)]. To further establish its regime of applicability, in this paper, the OML predictions (for a non-electron-emitting, spherical dust grain at rest in a collisionless, unmagnetized plasma) are compared with particle-in-cell simulations that retain the absorption radius effect. It is found that for large dust grain radius rd relative to the plasma Debye length λD, the revised OML theory remains a very good approximation as, for the parameters considered (rd/λD ≤ 10, equal electron and ion temperatures), it yields the dust charge to within 20% accuracy. This is a substantial improvement over the Whipple approximation. The dust collected currents and energy fluxes, which remain the same in the revised and standard OML theories, are accurate to within 15%–30%

  18. Oxidative damage to RPA limits the nucleotide excision repair capacity of human cells

    Science.gov (United States)

    Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

    2015-01-01

    Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin, interact with UVA radiation to generate reactive oxygen species (ROS) that diminish NER capacity by causing protein damage. The RPA DNA binding protein plays a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself is likely to be an important contributor to skin cancer risk. PMID:26134950

  19. Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma

    International Nuclear Information System (INIS)

    Purpose: To determine the patterns of loco-regional (LR) and distant failure in patients with limited-stage small cell lung carcinoma (LS-SCLC) treated with curative intent. Methods: From 1997 to 2008, 253 LS-SCLC patients were treated with curative intent chemo-radiation at our institution. A retrospective review identified sites of failure. The cumulative LR failure (LRF) rate was calculated. Distant failure-free survival (FFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Volumetric images of LR failures were delineated and registered with the original radiation treatment plans if available. Dosimetric parameters for the delineated failure volumes were calculated from the original treatment information. Results: The median follow-up was 19 months. The site of first failure was LR in 34, distant in 80 and simultaneous LR and distant in 31 patients. The cumulative LRF rate was 29% and 38% at 2 and 5 years. OS was 44% at 2 years. Seventy patients had electronically archived treatment plans of which there were 16 LR failures (7 local and 39 regional failure volumes). Of the local and regional failure volumes 29% and 31% were in-field, respectively. Conclusions: The predominant pattern of LR failure was marginal or out-of-field. LR failures may be preventable with improved radiotherapy target definition.

  20. Chest radiotherapy in limited-stage small cell lung cancer: facts, questions, prospects

    International Nuclear Information System (INIS)

    Limited-disease small cell lung cancer (LD-SCLC) is initially very sensitive to both radiotherapy and chemotherapy. However, the 5-year survival is generally only 10-15%, with most patients failing with therapy refractory relapses, both locally and in distant sites. The addition of chest irradiation to chemotherapy increases the absolute survival by approximately 5%. We reviewed the many controversies regarding optimal timing and irradiation technique. No strong data support total radiation doses over 50 Gy. According to one phase III trial and several retrospective studies, increasing the volume of the radiation fields to the pre-chemotherapy turnout volume instead of the post-chemotherapy volume does not improve local control. The total time in which the entire combined-modality treatment is delivered may be important. From seven randomized trials, it can be concluded that the timing of the radiotherapy as such is not very important. Some phase III trials support the use of accelerated chest radiation together with cisplatin-etoposide chemotherapy, delivered from the first day of treatment, although no firm conclusions can be drawn from the available data. The best results are reported in studies in which the time from the start of treatment to the end of the radiotherapy was less than 30 days. This has to be taken into consideration when treatment modalities incorporating new chemotherapeutic agents and radiotherapy are considered. (author)

  1. Comparison of dust charging between orbital-motion-limited theory and particle-in-cell simulations

    Energy Technology Data Exchange (ETDEWEB)

    Delzanno, Gian Luca, E-mail: delzanno@lanl.gov; Tang, Xian-Zhu, E-mail: xtang@lanl.gov [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2015-11-15

    The Orbital-Motion-Limited (OML) theory has been modified to predict the dust charge and the results were contrasted with the Whipple approximation [X. Z. Tang and G. L. Delzanno, Phys. Plasmas 21, 123708 (2014)]. To further establish its regime of applicability, in this paper, the OML predictions (for a non-electron-emitting, spherical dust grain at rest in a collisionless, unmagnetized plasma) are compared with particle-in-cell simulations that retain the absorption radius effect. It is found that for large dust grain radius r{sub d} relative to the plasma Debye length λ{sub D}, the revised OML theory remains a very good approximation as, for the parameters considered (r{sub d}/λ{sub D} ≤ 10, equal electron and ion temperatures), it yields the dust charge to within 20% accuracy. This is a substantial improvement over the Whipple approximation. The dust collected currents and energy fluxes, which remain the same in the revised and standard OML theories, are accurate to within 15%–30%.

  2. Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells.

    Science.gov (United States)

    Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

    2015-11-01

    Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin interact with UVA radiation to generate reactive oxygen species that diminish NER capacity by causing protein damage. The replication protein A (RPA) DNA-binding protein has a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation, and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage, and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself, is likely to be an important contributor to skin cancer risk. PMID:26134950

  3. Redirecting T-Cell Specificity to EGFR Using mRNA to Self-limit Expression of Chimeric Antigen Receptor.

    Science.gov (United States)

    Caruso, Hillary G; Torikai, Hiroki; Zhang, Ling; Maiti, Sourindra; Dai, Jianliang; Do, Kim-Anh; Singh, Harjeet; Huls, Helen; Lee, Dean A; Champlin, Richard E; Heimberger, Amy B; Cooper, Laurence J N

    2016-06-01

    Potential for on-target, but off-tissue toxicity limits therapeutic application of genetically modified T cells constitutively expressing chimeric antigen receptors (CARs) from tumor-associated antigens expressed in normal tissue, such as epidermal growth factor receptor (EGFR). Curtailing expression of CAR through modification of T cells by in vitro-transcribed mRNA species is one strategy to mitigate such toxicity. We evaluated expression of an EGFR-specific CAR coded from introduced mRNA in human T cells numerically expanded ex vivo to clinically significant numbers through coculture with activating and propagating cells (AaPC) derived from K562 preloaded with anti-CD3 antibody. The density of AaPC could be adjusted to affect phenotype of T cells such that reduced ratio of AaPC resulted in higher proportion of CD8 and central memory T cells that were more conducive to electrotransfer of mRNA than T cells expanded with high ratios of AaPC. RNA-modified CAR T cells produced less cytokine, but demonstrated similar cytolytic capacity as DNA-modified CAR T cells in response to EGFR-expressing glioblastoma cells. Expression of CAR by mRNA transfer was transient and accelerated by stimulation with cytokine and antigen. Loss of CAR abrogated T-cell function in response to tumor and normal cells expressing EGFR. We describe a clinically applicable method to propagate and modify T cells to transiently express EGFR-specific CAR to target EGFR-expressing tumor cells that may be used to limit on-target, off-tissue toxicity to normal tissue. PMID:27163741

  4. Inferring cell type innovations by phylogenetic methods-concepts, methods, and limitations.

    Science.gov (United States)

    Kin, Koryu

    2015-12-01

    Multicellular organisms are composed of distinct cell types that have specific roles in the body. Each cell type is a product of two kinds of historical processes-development and evolution. Although the concept of a cell type is difficult to define, the cell type concept based on the idea of the core regulatory network (CRN), a gene regulatory network that determines the identity of a cell type, illustrates the essential aspects of the cell type concept. The first step toward elucidating cell type evolution is to reconstruct the evolutionary relationships of cell types, or the cell type tree. The sister cell type model assumes that a new cell type evolves through divergence from a multifunctional ancestral cell type, creating tree-like evolutionary relationships between cell types. The process of generating a cell type tree can also be understood as the sequential addition of a new branching point on an ancestral cell differentiation hierarchy in evolution. A cell type tree thus represents an intertwined history of cell type evolution and development. Cell type trees can be reconstructed from high-throughput sequencing data, and the reconstruction of a cell type tree leads to the discovery of genes that are functionally important for a cell type. Although many issues including the lack of cross-species comparisons and the lack of a proper model for cell type evolution remain, the study of the origin of a new cell type using phylogenetic methods offers a promising new research avenue in developmental evolution. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 653-661, 2015. © 2015 Wiley Periodicals, Inc. PMID:26462996

  5. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells

    OpenAIRE

    Bidlingmaier, Scott; Zhu, Xiaodong; Liu, Bin

    2008-01-01

    Human CD133 (human prominin-1), a five transmembrane domain glycoprotein, was originally identified as a cell surface antigen present on CD34+ hematopoietic stem cells. Although the biological function of CD133 is not well understood, antibodies to CD133 epitopes have been widely used to purify hematopoietic stem and progenitor cells. The cancer stem cell (CSC) hypothesis postulates that a rare population of tumor cells possessing increased capacities for self-renewal and tumor initiation is ...

  6. Exceeding the solar cell Shockley-Queisser limit via thermal up-conversion of low-energy photons

    OpenAIRE

    Boriskina, Svetlana V.; Chen, Gang

    2013-01-01

    Maximum efficiency of ideal single-junction photovoltaic (PV) cells is limited to 33% (for one sun illumination) by intrinsic losses such as band edge thermalization, radiative recombination, and inability to absorb below-bandgap photons. This intrinsic thermodynamic limit, named after Shockley and Queisser (S-Q), can be exceeded by utilizing low-energy photons either via their electronic up-conversion or via thermophotovoltaic (TPV) conversion process. However, electronic up-conversion syste...

  7. The efficiency limit of CH{sub 3}NH{sub 3}PbI{sub 3} perovskite solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Sha, Wei E. I. [Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong (China); The University of Hong Kong Shenzhen Institute of Research and Innovation (HKU-SIRI), Shenzhen 518057 (China); Ren, Xingang; Chen, Luzhou; Choy, Wallace C. H., E-mail: chchoy@eee.hku.hk [Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong (China)

    2015-06-01

    With the consideration of photon recycling effect, the efficiency limit of methylammonium lead iodide (CH{sub 3}NH{sub 3}PbI{sub 3}) perovskite solar cells is predicted by a detailed balance model. To obtain convincing predictions, both AM 1.5 spectrum of Sun and experimentally measured complex refractive index of perovskite material are employed in the detailed balance model. The roles of light trapping and angular restriction in improving the maximal output power of thin-film perovskite solar cells are also clarified. The efficiency limit of perovskite cells (without the angular restriction) is about 31%, which approaches to Shockley-Queisser limit (33%) achievable by gallium arsenide (GaAs) cells. Moreover, the Shockley-Queisser limit could be reached with a 200 nm-thick perovskite solar cell, through integrating a wavelength-dependent angular-restriction design with a textured light-trapping structure. Additionally, the influence of the trap-assisted nonradiative recombination on the device efficiency is investigated. The work is fundamentally important to high-performance perovskite photovoltaics.

  8. Isolation and characterization of ubiquinol oxidase complexes from Paracoccus denitrificans cells cultured under various limiting growth conditions in the chemostat.

    Science.gov (United States)

    Bosma, G; Braster, M; Stouthamer, A H; van Verseveld, H W

    1987-06-15

    To obtain more information about the composition of the respiratory chain under different growth conditions and about the regulation of electron-transfer to several oxidases and reductases, ubiquinol oxidase complexes were partially purified from membranes of Paracoccus denitrificans cells grown in carbon-source-limited aerobic, nitrate-limited anaerobic and oxygen-limited chemostat cultures. The isolated enzymes consisted of cytochromes bc1, c552 and aa3. In comparison with the aerobic ubiquinol oxidase complex, the oxygen- and nitrate-limited ones contained, respectively, less and far less of the cytochrome aa3 subunits and the anaerobic complex also contained lower amounts of cytochrome c552. In addition, extra haem-containing polypeptides were present with apparent Mr of 14,000, 30,000 and 45,000, the former one only in the anaerobic and the latter two in both the anaerobic and oxygen-limited preparations. This is the first report describing four different membrane-bound c-type cytochromes. The potentiometric and spectral characteristics of the redox components in membrane particles and isolated ubiquinol oxidase fractions were determined by combined potentiometric analysis and spectrum deconvolution. Membranes of nitrate- and oxygen-limited cells contained extra high-potential cytochrome b in comparison with the membranes of aerobically grown cells. No difference was detected between the three isolated ubiquinol oxidase complexes. Aberrances with already published values of redox potentials are discussed. PMID:3036512

  9. T cell-mediated cytotoxicity against p53-protein derived peptides in bulk and limiting dilution cultures of healthy donors

    DEFF Research Database (Denmark)

    Röpke, M; Regner, M; Claesson, M H;

    1995-01-01

    -I restricted epitopes for T cell recognition and p53-derived peptides have been suggested as targets for tumour-specific cytotoxic T lymphocytes (CTL). Our primary aim was to estimate the frequencies of p53-peptide reactive CTL precursors (CTLp) in peripheral blood from healthy young individuals. We selected...... wild type and mutated peptides derived from the p53 sequence with a binding motif for HLA-A2.1 molecules. Peripheral blood mononuclear cells (PBMC) from healthy HLA-A2 donors were stimulated in vitro in bulk cultures as well as in limiting dilution cultures using autologous cells pulsed with p53...... peptides as stimulator cells. T cell reactivity was observed towards both wild type and mutated p53 peptide epitopes with CTL precursor frequencies varying from 1:2 x 10(4) to 1:1.5 x 10(5). These results might suggest the presence of an ongoing immune response in normal individuals against cells...

  10. Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

    International Nuclear Information System (INIS)

    We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

  11. Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ha, In Bong; Jeong, Bae Kwon; Jeong, Ho Jin; Choi, Hoon Sik; Chai, Gyu Young; Kang, Myoung Hee; Kim, Hoon Gu; Lee, Gyeong Won; Na, Jae Beom; Kang, Ki Mun [Gyeongsang National University School of Medicine, Jinju (Korea, Republic of)

    2013-12-15

    We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

  12. TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes

    OpenAIRE

    Leung, Monica W.L.; Shen, Shiqian; Lafaille, Juan J.

    2009-01-01

    Numerous studies have highlighted the importance of high-affinity interactions between T cell receptors (TCRs) and their ligands in the selection of Foxp3+ regulatory T cells (T reg cells). To determine the role of the TCR in directing T cells into the Foxp3+ lineage, we generated transgenic (Tg) mice expressing TCRs from Foxp3+ cells. Initial analyses of the TCR Tg mice crossed with RAG-deficient mice showed that the percentage of Foxp3+ cells was very low. However, intrathymic injection and...

  13. CD4+ CD25+ Foxp3+ T regulatory cells with limited T cell receptor diversity in control of autoimmunity1

    OpenAIRE

    Adeegbe, Dennis; Matsutani, Takaji; Yang, Jing; Altman, Norman H; Malek, Thomas R.

    2009-01-01

    The importance of high TCR diversity of Treg cells for self-tolerance is poorly understood. To address this issue, TCR diversity was measured for Treg cells after transfer into IL-2Rβ-/- mice, which develop lethal autoimmunity due to failed production of Treg cells. Here we show that high TCR diversity of pre-transferred Treg cells led to selection of therapeutic Treg cells with lower TCR diversity that prevented autoimmunity. Pre-transferred Treg cells with lower diversity led to selection o...

  14. Tim-3: An activation marker and activation limiter of innate immune cells

    Directory of Open Access Journals (Sweden)

    Gencheng eHan

    2013-12-01

    Full Text Available Tim-3 was initially identified on activated Th1, Th17, and Tc1 cells and induces T cell death or exhaustion after binding to its ligand, Gal-9. The observed relationship between dysregulated Tim-3 expression on T cells and the progression of many clinical diseases has identified this molecule as an important target for intervention in adaptive immunity. Recent data have shown that it also plays critical roles in regulating the activities of macrophages, monocytes, dendritic cells, mast cells, natural killer cells, and endothelial cells. Although the underlying mechanisms remain unclear, dysregulation of Tim-3 expression on these innate immune cells leads to an excessive or inhibited inflammatory response and subsequent autoimmune damage or viral or tumor evasion. In this review, we focus on the expression and function of Tim-3 on innate immune cells and discuss 1 how Tim-3 is expressed and regulated on different innate immune cells; 2 how it affects the activity of different innate immune cells; and 3 how dysregulated Tim-3 expression on innate immune cells affects adaptive immunity and disease progression. Tim-3 is involved in the optimal activation of innate immune cells through its varied expression. A better understanding of the physiopathological role of the Tim-3 pathway in innate immunity will shed new light on the pathogenesis of clinical diseases, such as autoimmune diseases, chronic viral infections, and cancer, and suggest new approaches to intervention.

  15. In vivo suppressive function of myeloid-derived suppressor cells is limited to the inflammatory site

    OpenAIRE

    Haverkamp, Jessica M.; Crist, Scott A.; Elzey, Bennett D.; Cimen, Cansu; Ratliff, Timothy L

    2011-01-01

    Current thinking suggests that despite the heterogeneity of myeloid-derived suppressor cells (MDSC), all Gr-1+CD11b+ cells can become suppressive when exposed to inflammatory stimuli. In vitro evaluation shows MDSC from multiple tissue sites have suppressive activity, and in vivo inhibition of MDSC function enhances T cell responses. However, the relative capacity of MDSC present at localized inflammatory sites or in peripheral tissues to suppress T cell responses in vivo has not been directl...

  16. Limited impact on glucose homeostasis of leptin receptor deletion from insulin- or proglucagon-expressing cells

    Directory of Open Access Journals (Sweden)

    Helen Soedling

    2015-09-01

    Conclusions/interpretation: The use here of a highly selective Cre recombinase indicates that leptin signalling plays a relatively minor, age- and sex-dependent role in the control of β cell function in the mouse. No in vivo role for leptin receptors on α cells, nor in other proglucagon-expressing cells, was detected in this study.

  17. Adult stem cells in neural repair: Current options,limitations and perspectives

    Institute of Scientific and Technical Information of China (English)

    Eric Domingos Mariano; Manoel Jacobsen Teixeira; Suely Kazue Nagahashi Marie; Guilherme Lepski

    2015-01-01

    Stem cells represent a promising step for the future ofregenerative medicine. As they are able to differentiateinto any cell type, tissue or organ, these cells are greatcandidates for treatments against the worst diseasesthat defy doctors and researchers around the world.Stem cells can be divided into three main groups (1)embryonic stem cells; (2) fetal stem cells; and (3) adultstem cells. In terms of their capacity for proliferation,stem cells are also classified as totipotent, pluripotentor multipotent. Adult stem cells, also known as somaticcells, are found in various regions of the adult organism,such as bone marrow, skin, eyes, viscera and brain.They can differentiate into unipotent cells of theresiding tissue, generally for the purpose of repair.These cells represent an excellent choice in regenerativemedicine, every patient can be a donor of adult stemcells to provide a more customized and efficient therapyagainst various diseases, in other words, they allow theopportunity of autologous transplantation. But in orderto start clinical trials and achieve great results, we needto understand how these cells interact with the hosttissue, how they can manipulate or be manipulated bythe microenvironment where they will be transplantedand for how long they can maintain their multipotentstate to provide a full regeneration.

  18. Limited energy supply in Müller cells alters glutamate uptake

    DEFF Research Database (Denmark)

    Toft-Kehler, Anne Katrine; Skytt, Dorte Marie; Poulsen, Kristian Arild;

    2014-01-01

    The viability of retinal ganglion cells (RGC) is essential for the maintenance of visual function. RGC homeostasis is maintained by the surrounding retinal glial cells, the Müller cells, which buffer the extracellular concentration of neurotransmitters and provide the RGCs with energy. This study...

  19. Kinetic energy discrimination in collision/reaction cell ICP-MS: Theoretical review of principles and limitations

    International Nuclear Information System (INIS)

    Kinetic energy discrimination (KED) is one of the means to control cell-formed interferences in collision/reaction cell ICP-MS, and also a technique to reduce polyatomic ion interferences derived from the plasma or vacuum interface in collision cell ICP-MS. The operation of KED is accurately described to explain how spectral interferences from polyatomic ions are reduced by this technique. The cell is operated under non-thermal conditions to implement KED, where the hard sphere collision model is aptly employed to portray the transmission of ions colliding with the cell gas that they don't chemically react with. It is theoretically explained that the analyte atomic ions surmount the energy barrier placed downstream of the cell and the interfering polyatomic ions do not due to their lower kinetic energy than the atomic ions, resulting in polyatomic interference reduction. The intrinsic limitations of this technique are shown to lie in the statistical nature of collision processes, which causes the broadening of ion kinetic energy distribution that hinders efficient KED. The reaction cell operation with KED, where plasma-derived interferences are reduced by the reactive cell gas while cell-formed interferences are suppressed by the energy barrier, is also described in a quantitative manner. This review paper provides an in-depth understanding of KED in cell-based ICP-MS for analysts to make better use of it. - Highlights: • Hard sphere collision model was employed to describe the polyatomic ion interference reduction by KED. • The intrinsic limitations of KED lies in the statistical nature of collision processes. • It was shown that lighter collision gas is more effective than heavier one for polyatomic ion reduction by KED. • In non-thermal H2 reaction cell ICP-MS, KED does not contribute to the reduction of plasma-based interfering ions

  20. Human umbilical cord blood mononuclear cells activate the survival protein Akt in cardiac myocytes and endothelial cells that limits apoptosis and necrosis during hypoxia.

    Science.gov (United States)

    Henning, Robert J; Dennis, Steve; Sawmiller, Darrell; Hunter, Lorynn; Sanberg, Paul; Miller, Leslie

    2012-06-01

    We have previously reported that human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic, mesenchymal, and endothelial stem cells, can significantly reduce acute myocardial infarction size. To determine the mechanism whereby HUCBC increase myocyte and vascular endothelial cell survival, we treated cardiac myocytes and coronary artery endothelial cells in separate experiments with HUCBC plus culture media or culture media alone and subjected the cells to 24 h of hypoxia or normoxia. We then determined in myocytes and endothelial cells activation of the cell survival protein Akt by Western blots. We also determined in these cells apoptosis by annexin V staining and necrosis by propidium iodide staining. Thereafter, we inhibited with API, a specific and sensitive Akt inhibitor, Akt activation in myocytes and endothelial cells cultured with HUCBC during hypoxia and determined cell apoptosis and necrosis. In cells cultured without HUCBC, hypoxia only slightly activated Akt. Moreover, hypoxia increased myocyte apoptosis by ≥ 226% and necrosis by 58% in comparison with myocytes in normoxia. Hypoxic treatment of endothelial cells without HUCBC increased apoptosis by 94% and necrosis by 59%. In contrast, hypoxia did not significantly affect HUCBC. Moreover, in myocyte + HUCBC cultures in hypoxia, HUCBC induced a ≥ 135% increase in myocyte phospho-Akt. Akt activation decreased myocyte apoptosis by 76% and necrosis by 35%. In endothelial cells, HUCBC increased phospho-Akt by 116%. HUCBC also decreased endothelial cell apoptosis by 58% and necrosis by 42%. Inhibition of Akt with API in myocytes and endothelial cells cultured with HUCBC during hypoxia nearly totally prevented the HUCBC-induced decrease in apoptosis and necrosis. We conclude that HUCBC can significantly decrease hypoxia-induced myocyte and endothelial cell apoptosis and necrosis by activating Akt in these cells and in this manner HUCBC can limit myocardial ischemia and injury. PMID

  1. Radiation induced mitochondrial biogenesis: limitations of metabolic viability based assays in measuring radiation induced cell death

    International Nuclear Information System (INIS)

    Many techniques based on metabolic viability of cells employing MTT and MTS assay are being widely used to measure the radiation and chemotherapeutics induced cell death, because of their high throughput capability. These assays are based on mitochondrial potential of cells to convert the substrate in to measurable products and remain dependent on this notion that all the cells untreated and treated will have equal mitochondrial content and metabolic potential. However, it is increasingly becoming clear that treatment induced changes in both mitochondrial content and metabolism can influence the metabolic viability of cells and radiation is a potential mitochondrial biogenesis inducer. Therefore, we tested if metabolic viability based assays are true measure of radiation induced cell death using the widely used cell lines like RAW264.7, HEK293, NIH3T3, J774.1, BMG-1, MDAMB231, MCF-7, A549 and HeLa. Cells were irradiated with gamma rays (60Co) and enumerated cell numbers (by hemocytometer) and metabolic viability using MTT assay at 24 and 48 hours after exposure. At all the absorbed doses (0-5 Gy), the extent of reduction in cell number was found to be larger than the decrease in formazan formation in all the cell lines tested. Further, this difference in the cell number and formazan formation varied significantly among the cell lines. To test if the increased formazan formation is due to increased mitochondrial content per cell, we analyzed the radiation induced mitochondrial biogenesis using mitochondria specific dye mitotracker red and found a 1.5 to 2 fold increase in mitochondrial content. These findings suggest that radiation induces mitochondrial biogenesis that enhances the metabolic potential leading to increased formazan formation. Therefore, conclusions drawn on radiation induced cytotoxicity based on metabolic viability assays are likely to be erroneous as it may not correlate with growth inhibition and/or loss of clonogenic survival. (author)

  2. Nitric Oxide Limits the Expansion of Antigen-Specific T Cells in Mice Infected with the Microfilariae of Brugia pahangi

    Science.gov (United States)

    O'Connor, Richard A.; Devaney, Eileen

    2002-01-01

    Infection of BALB/c mice with the microfilariae (Mf) of the filarial nematode Brugia pahangi results in an antigen-specific proliferative defect that is induced by high levels of NO. Using carboxyfluorescein diacetate succinimydl ester and cell surface labeling, it was possible to identify a population of antigen-specific T cells from Mf-infected BALB/c mice that expressed particularly high levels of CD4 (CD4hi). These cells proliferated in culture only when inducible NO synthase was inhibited and accounted for almost all of the antigen-specific proliferative response under those conditions. CD4hi cells also expressed high levels of CD44, consistent with their status as activated T cells. A similar population of CD4hi cells was observed in cultures from Mf-infected gamma interferon receptor knockout (IFN-γR−/−) mice. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining revealed that the CD4+ T cells from Mf-infected wild-type mice were preferentially susceptible to apoptosis compared to CD4+ T cells from IFN-γR−/− mice. These studies suggest that the expansion of antigen-specific T cells in Mf-infected mice is limited by NO. PMID:12379675

  3. Formaldehyde treatment of proteins can constrain presentation to T cells by limiting antigen processing.

    OpenAIRE

    Di Tommaso, A; De Magistris, M T; Bugnoli, M.; Marsili, I; Rappuoli, R; Abrignani, S.

    1994-01-01

    Proteins to be used as vaccines are frequently treated with formaldehyde, although little is known about the effects of this treatment on protein antigenicity. To investigate the effect of formaldehyde treatment on antigen recognition by T cells, we compared the in vitro T-cell response to proteins that have been formaldehyde treated with the response to untreated proteins. We found that peripheral blood mononuclear cells from individuals vaccinated with three formaldehyde-treated proteins (p...

  4. The Utilization and Limitation of CD133 Epitopes in Lung Cancer Stem Cells Research

    OpenAIRE

    Chen, Yin; Hong ZHONG

    2011-01-01

    Lung cancer is one of the most common tumor, which lacks of effective clinical treatment to lead to desirable prognosis. According to cancer stem cell hypothesis, lung cancer stem cells are considered to be responsible for carcinogenesis, development, metastasis, recurrence, invasion, resistance to chemotherapy and radiotherapy of lung cancer. In recent years, more and more institutes used glycosylated CD133 epitopes to define, isolate, purify lung cancer stem cells. However, along with deepl...

  5. Potential benefits and limitations of utilizing chondroprogenitors in cell-based cartilage therapy.

    Science.gov (United States)

    Jayasuriya, Chathuraka T; Chen, Qian

    2015-01-01

    Chondroprogenitor cells are a subpopulation of multipotent progenitors that are primed for chondrogenesis. They are believed to have the biological repertoire to be ideal for cell-based cartilage therapy. In addition to summarizing recent advances in chondroprogenitor cell characterization, this review discusses the projected pros and cons of utilizing chondroprogenitors in regenerative medicine and compares them with that of pre-existing methods, including autologous chondrocyte implantation (ACI) and the utilization of bone marrow derived mesenchymal stem cells (MSCs) for the purpose of cartilage tissue repair. PMID:26075411

  6. Once vs. twice daily thoracic irradiation in limited stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Sang; Kim, Jae Sung; Kim, Ju Ock; Kim, Sun Young; Cho, Moon June [College of Medicine, Chungnam National Univ., Taejon (Korea, Republic of)

    1998-09-01

    A retrospective study was conducted comparing single dally fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response, survival, pattern of failure, and acute toxicity. Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85%) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86%) ECOG performance score of less than 1 in BID TRT. By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGY BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/m{sup 2}, adriamycin 40 mg/m{sup 2}, vincristine 1 mg/m{sup 2}) alternating with VPP (cisplatin 60 mg/m{sup 2}, etoposide 100 mg/m{sup 2}) every 3 weeks in 25 (96%) of SDF TRT and in 40 (95%) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT. Follow-up ranged from 2 of 99 months (median, 14 months) in both groups. Of the 26 SDF TRT, 9 (35%) achieved a complete response

  7. Limited niche availability suppresses murine intrathymic dendritic-cell development from noncommitted progenitors.

    Science.gov (United States)

    Łyszkiewicz, Marcin; Ziętara, Natalia; Föhse, Lisa; Puchałka, Jacek; Diestelhorst, Jana; Witzlau, Katrin; Prinz, Immo; Schambach, Axel; Krueger, Andreas

    2015-01-15

    The origins of dendritic cells (DCs) and other myeloid cells in the thymus have remained controversial. In this study, we assessed developmental relationships between thymic dendritic cells and thymocytes, employing retrovirus-based cellular barcoding and reporter mice, as well as intrathymic transfers coupled with DC depletion. We demonstrated that a subset of early T-lineage progenitors expressed CX3CR1, a bona fide marker for DC progenitors. However, intrathymic transfers into nonmanipulated mice, as well as retroviral barcoding, indicated that thymic dendritic cells and thymocytes were largely of distinct developmental origin. In contrast, intrathymic transfers after in vivo depletion of DCs resulted in intrathymic development of non-T-lineage cells. In conclusion, our data support a model in which the adoption of T-lineage fate by noncommitted progenitors at steady state is enforced by signals from the thymic microenvironment unless niches promoting alternative lineage fates become available. PMID:25411428

  8. Cdc6 is a rate-limiting factor for proliferative capacity during HL60 cell differentiation

    International Nuclear Information System (INIS)

    The DNA replication (or origin) licensing pathway represents a critical step in cell proliferation control downstream of growth signalling pathways. Repression of origin licensing through down-regulation of the MCM licensing factors (Mcm2-7) is emerging as a ubiquitous route for lowering proliferative capacity as metazoan cells exit the cell division cycle into quiescent, terminally differentiated and senescent 'out-of-cycle' states. Using the HL60 monocyte/macrophage differentiation model system and a cell-free DNA replication assay, we have undertaken direct biochemical investigations of the coupling of origin licensing to the differentiation process. Our data show that down-regulation of the MCM loading factor Cdc6 acts as a molecular switch that triggers loss of proliferative capacity during early engagement of the somatic differentiation programme. Consequently, addition of recombinant Cdc6 protein to in vitro replication reactions restores DNA replication competence in nuclei prepared from differentiating cells. Differentiating HL60 cells over-expressing either wild-type Cdc6 or a CDK phosphorylation-resistant Cdc6 mutant protein (Cdc6A4) exhibit an extended period of cell proliferation compared to mock-infected cells. Notably, differentiating HL60 cells over-expressing the Cdc6A4 mutant fail to down-regulate Cdc6 protein levels, suggesting that CDK phosphorylation of Cdc6 is linked to its down-regulation during differentiation and the concomitant decrease in cell proliferation. In this experimental model, Cdc6 therefore plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme

  9. Identification and Characterization of Performance Limiting Regions in Poly-Si Wafers Used for PV Cells: Preprint

    International Nuclear Information System (INIS)

    As demand for silicon photovoltaic (PV) material increases, so does the need for cost-effective feedstock and production methods that will allow enhanced penetration of silicon PV into the total energy market. The focus on cost minimization for production of polycrystalline silicon (poly-Si) PV has led to relaxed feedstock purity requirements, which has also introduced undesirable characteristics into cast poly-Si PV wafers. To produce cells with the highest possible conversion efficiencies, it is crucial to understand how reduced purity requirements and defects that are introduced through the casting process can impair minority carrier properties in poly-Si PV cells. This is only possible by using multiple characterization techniques that give macro-scale information (such as the spatial distribution of performance-limiting regions), as well as micro and nano-scale information about the structural and chemical nature of such performance-limiting regions. This study demonstrates the usefulness of combining multiple techniques to analyze performance-limiting regions in the poly-Si wafers that are used for PV cells. This is done by first identifying performance-limiting regions using macro-scale techniques including photoluminescence (PL) imaging, microwave photoconductive decay (uPCD), and reflectometry, then using smaller-scale techniques such as scanning electron microscopy (SEM), electron backscattered diffraction (EBSD), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), cathodoluminescence (CL), and transmission electron microscopy (TEM) to understand the nature of such regions. This analysis shows that structural defects as well as metallic impurities are present in performance-limiting regions, which together act to decrease conversion efficiencies in poly-Si PV cells.

  10. Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits CD8+ T cell memory formation

    Science.gov (United States)

    Ji, Yun; Pos, Zoltan; Rao, Mahadev; Klebanoff, Christopher A.; Yu, Zhiya; Sukumar, Madhusudhanan; Reger, Robert N.; Palmer, Douglas C.; Borman, Zachary A.; Muranski, Pawel; Wang, Ena; Schrump, David S.; Marincola, Francesco M.; Restifo, Nicholas P.; Gattinoni, Luca

    2011-01-01

    Blimp-1 is a transcriptional repressor that promotes the differentiation of CD8+ T cells into short-lived KLRG-1+ effector cells (SLEC), but how it operates remains poorly defined. Here we show that Blimp-1 binds and represses the Id3 promoter in SLEC. Repression of Id3 by Blimp-1 was dispensable for SLEC development but limited their capacity to persist as memory cells. Enforced expression of Id3 was sufficient to rescue SLEC survival and enhanced recall responses. Id3 function was mediated in part through inhibition of E2a transcriptional activity and induction of genes regulating genome stability. These findings identify a Blimp-1-Id3-E2a axis as a key molecular switch that determines whether effector CD8+ T cells are programmed to die or enter the memory pool. PMID:22057288

  11. Long term observations in combined modality therapy for limited stage small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose/Objective: With the discovery that patients with small cell lung cancer (SCLC) exhibit a high level of sensitivity to both chemotherapy and radiotherapy, the treatment of SCLC became a model for the success of combined modality treatment. In this retrospective review, we analyze the outcomes and patterns of failure when patients are treated with chemotherapy and thoracic irradiation. The relative values of sequential and concurrent chemotherapy, in conjunction with chest irradiation, are assessed. The potential benefit of prophylactic cranial irradiation is explored. The impact of prognostic factors for long term survival of SCLC patients are examined to identify pretreatment patient characteristics and treatment parameters which might predict for a favorable outcome. Materials and Methods: We identified 190 patients treated at M.D. Anderson Cancer Center from January 1985 to December 1992 with curative intent for limited stage SCLC. Prognostic factors were determined using univariate and multivariate analysis. The significant covariates for each outcome endpoint were evaluated. Probabilities of local failure, overall survival, relapse-free survival, and distant metastasis-free survival were calculated from the time of treatment using actuarial life table analysis. Results: The median age was 61, with 51% males. There were 119 patients treated sequentially, and 71 concurrently. The Karnofsky Performance Status was >= 90 in 48% of patients in the concurrent cohort, vs. 35% of the sequential group. Prophylactic cranial irradiation (PCI) was delivered in 117 cases (62%). There were 51 long term survivors, defined as survival >=36 months. The median follow-up in surviving patients was 75 months. At the time of the analysis, 166 patients (87%) had expired. The crude 2 and 3 year survival rate for the entire group was 38.4% and 26.8%, respectively. The actuarial 2-year survival was 39.9%, and at 3 years the actuarial survival was 27.8%. The median actuarial

  12. IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease

    OpenAIRE

    Taube, C; Tertilt, C; Gyülveszi, G; Dehzad, N; Kreymborg, K; Schneeweiss, K; E. Michel; Reuter, S; Renauld, J C; Arnold-Schild, D; Schild, H; Buhl, R; Becher, B. (Bertram)

    2011-01-01

    Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-defi...

  13. IL-22 Is Produced by Innate Lymphoid Cells and Limits Inflammation in Allergic Airway Disease.

    OpenAIRE

    Taube, Christian; Tertilt, Christine; Gyülveszi, Gabor; Dehzad, Nina; Kreymborg, Katharina; Schneeweiss, Kristin; Michel, Erich; Reuter, Sebastian; Renauld, Jean-Christophe; Arnold-Schild, Danielle; Schild, Hansjörg; Buhl, Roland; Becher, Burkhard

    2011-01-01

    Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-defi...

  14. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

    Directory of Open Access Journals (Sweden)

    Yan-fei Liu

    Full Text Available Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2, which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.

  15. Overcoming the fill factor limit of double sided buried contact silicon solar cells

    Science.gov (United States)

    Ebong, A. U.; Lee, S. H.

    1997-11-01

    The double sided buried contact (DSBC) silicon solar cells have consistently demonstrated output parameters superior to those of its single sided counterparts. This is because the high surface recombination velocity of the single sided cells was reduced to minimum by the rear floating junction in conjunction with high quality silicon dioxide. However, the somewhat lower fill factor ( FF) exhibited by single sided illumination of the structure can disappear if the bifacial testing equipment is used to properly characterize the cells. A 2D simulation has shown that a rear illumination of only 0.2 sun in conjunction with 1 sun front illumination, is quite adequate to bias the rear junction to a high voltage required to maintain good fill factor. This article discusses the fill factor of double sided buried contact silicon solar cells under single and double sided illumination.

  16. Classifying general nonlinear force laws in cell-based models via the continuum limit

    OpenAIRE

    Murray, P.J.; Edwards, C M; Tindall, M.J.; Maini, P.K.

    2012-01-01

    Although discrete cell-based frameworks are now commonly used to simulate a whole range of biological phenomena, it is typically not obvious how the numerous different types of model are related to one another, nor which one is most appropriate in a given context. Here we demonstrate how individual cell movement on the discrete scale modeled using nonlinear force laws can be described by nonlinear diffusion coefficients on the continuum scale. A general relationship between nonlinear force la...

  17. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells

    Science.gov (United States)

    Bidlingmaier, Scott; Zhu, Xiaodong; Liu, Bin

    2008-01-01

    Human CD133 (human prominin-1), a five transmembrane domain glycoprotein, was originally identified as a cell surface antigen present on CD34+ hematopoietic stem cells. Although the biological function of CD133 is not well understood, antibodies to CD133 epitopes have been widely used to purify hematopoietic stem and progenitor cells. The cancer stem cell (CSC) hypothesis postulates that a rare population of tumor cells possessing increased capacities for self-renewal and tumor initiation is responsible for maintaining the growth of neoplastic tissue. The expression of the CD133 epitopes, AC133 and AC141, has been shown to define a subpopulation of brain tumor cells with significantly increased capacity for tumor initiation in xenograft models. Following the discovery of the AC133/AC141+ population of brain tumor stem cells, the AC133 and AC141 epitopes have been extensively used as markers for purifying CSCs in other solid tumors. There are, however, several issues associated with the use of the AC133 and AC141 CD133 epitopes as markers for CSCs. The antibodies routinely used for purification of AC133 and AC141-positive cells target poorly characterized glycosylated epitopes of uncertain specificity. Discordant expression of the AC133 and AC141 epitopes has been observed, and the epitopes can be absent despite the presence of CD133 protein. In addition, CD133 expression has recently been shown to be modulated by oxygen levels. These factors, in combination with the uncertain biological role of CD133, suggest that the use of CD133 expression as a marker for CSCs should be critically evaluated in each new experimental system and highlight the need for additional CSC surface markers that are directly involved in maintaining CSC properties. PMID:18535813

  18. Enhanced phosphorylation of caveolar PKC-α limits peptide internalization in lung endothelial cells

    OpenAIRE

    Hutchinson, Tarun E.; Zhang, Jianliang; Xia, Shen-Ling; Kuchibhotla, Sudeep; Block, Edward R.; Patel, Jawaharlal M.

    2011-01-01

    We previously reported that the vasoactive peptide 1 (P1, “SSWRRKRKESS”) modulates the tension of pulmonary artery vessels through caveolar endothelial nitric oxide synthase (eNOS) activation in intact lung endothelial cells (ECs). Since PKC-α is a caveolae resident protein and caveolae play a critical role in the peptide internalization process, we determined whether modulation of caveolae and/or caveolar PKC-α phosphorylation regulates internalization of P1 in lung ECs. Cell monolayers were...

  19. Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly

    OpenAIRE

    Campinho, Pedro; Behrndt, Martin; Ranft, Jonas; Risler, Thomas; Minc, Nicolas; Heisenberg, Carl-Philipp

    2015-01-01

    Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish ep...

  20. Asymptotic limit in a cell differentiation model with consideration of transcription

    Science.gov (United States)

    Friedman, Avner; Kao, Chiu-Yen; Shih, Chih-Wen

    T cells of the immune system, upon maturation, differentiate into either Th1 or Th2 cells that have different functions. The decision to which cell type to differentiate depends on the concentrations of transcription factors T-bet (x1) and GATA-3 (x2). These factors are translated by the mRNA whose levels of expression, y1 and y2, depend, respectively, on x1 and x2 in a nonlinear nonlocal way. The population density of T cells, ϕ(t,x1,x2,y1,y2), satisfies a hyperbolic conservation law with coefficients depending nonlinearly and nonlocally on (t,x1,x2,y1,y2), while the xi, yi satisfy a system of ordinary differential equations. We study the long time behavior of ϕ and show, under some conditions on the parameters of the system of differential equations, that the gene expressions in the T-cell population aggregate at one, two or four points, which connect to various cell differentiation scenarios.

  1. Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

    Science.gov (United States)

    Hansen, Juliana Frohnert; Brorson, Marianne Møller; Boas, Malene; Frederiksen, Hanne; Nielsen, Claus Henrik; Lindström, Emma Sofie; Hofman-Bang, Jacob; Hartoft-Nielsen, Marie-Louise; Frisch, Thomas; Main, Katharina M.; Bendtzen, Klaus; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla

    2016-01-01

    Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells. PMID:26985823

  2. Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro.

    Directory of Open Access Journals (Sweden)

    Juliana Frohnert Hansen

    Full Text Available Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP, di-(2-ethylhexyl phthalate (DEHP and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl phthalate (MEHP on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.

  3. Conditional knockdown of BCL2A1 reveals rate-limiting roles in BCR-dependent B-cell survival.

    Science.gov (United States)

    Sochalska, M; Ottina, E; Tuzlak, S; Herzog, S; Herold, M; Villunger, A

    2016-04-01

    Bcl2 family proteins control mitochondrial apoptosis and its members exert critical cell type and differentiation stage-specific functions, acting as barriers against autoimmunity or transformation. Anti-apoptotic Bcl2a1/Bfl1/A1 is frequently deregulated in different types of blood cancers in humans but its physiological role is poorly understood as quadruplication of the Bcl2a1 gene locus in mice hampers conventional gene targeting strategies. Transgenic overexpression of A1, deletion of the A1-a paralogue or constitutive knockdown in the hematopoietic compartment of mice by RNAi suggested rate-limiting roles in lymphocyte development, granulopoiesis and mast cell activation. Here we report on the consequences of conditional knockdown of A1 protein expression using a reverse transactivator (rtTA)-driven approach that highlights a critical role for this Bcl2 family member in the maintenance of mature B-cell homeostasis. Furthermore, we define the A1/Bim (Bcl-2 interacting mediator of cell death) axis as a target of key kinases mediating B-cell receptor (BCR)-dependent survival signals, such as, spleen tyrosine kinase (Syk) and Brutons tyrosine kinase (Btk). As such, A1 represents a putative target for the treatment of B-cell-related pathologies depending on hyperactivation of BCR-emanating survival signals and loss of A1 expression accounts, in part, for the pro-apoptotic effects of Syk- or Btk inhibitors that rely on the 'BH3-only' protein Bim for cell killing. PMID:26450454

  4. IRAK-M expression limits dendritic cell activation and proinflammatory cytokine production in response to Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Jessica Shiu

    Full Text Available Helicobacter pylori (H. pylori infects the gastric mucosa and persists for the life of the host. Bacterial persistence may be due to the induction of regulatory T cells (Tregs whichmay have protective effects against other diseases such as asthma. It has been shown that H. pylori modulates the T cell response through dendritic cell reprogramming but the molecular pathways involved are relatively unknown. The goal of this study was to identify critical elements of dendritic cell (DC activation and evaluate potential influence on immune activation. Microarray analysis was used to demonstrate limited gene expression changes in H. pylori stimulated bone marrow derived DCs (BMDCs compared to the BMDCs stimulated with E. coli. IRAK-M, a negative regulator of TLR signaling, was upregulated and we selectedit for investigation of its role in modulating the DC and T cell responses. IRAK-M(-/- and wild type BMDC were compared for their response to H. pylori. Cells lacking IRAK-M produced significantly greater amounts of proinflammatory MIP-2 and reduced amounts of immunomodulatory IL-10 than wild type BMDC. IRAK-M(-/- cells also demonstrated increased MHC II expression upon activation. However, IRAK-M(-/- BMDCs were comparable to wild type BMDCs in inducing T-helper 17 (TH17 and Treg responses as demonstrated in vitro using BMDC CD4+ T cells co-culture assays,and in vivo though the adoptive transfer of CD4(+ FoxP3-GFP T cells into H. pylori infected IRAK-M(-/- mice. These results suggest that H. pylori infection leads to the upregulation of anti-inflammatory molecules like IRAK-M and that IRAK-M has a direct impact on innate functions in DCs such as cytokine and costimulation molecule upregulation but may not affect T cell skewing.

  5. IRAK-M expression limits dendritic cell activation and proinflammatory cytokine production in response to Helicobacter pylori.

    Science.gov (United States)

    Shiu, Jessica; Czinn, Steven J; Kobayashi, Koichi S; Sun, Yezhou; Blanchard, Thomas G

    2013-01-01

    Helicobacter pylori (H. pylori) infects the gastric mucosa and persists for the life of the host. Bacterial persistence may be due to the induction of regulatory T cells (Tregs) whichmay have protective effects against other diseases such as asthma. It has been shown that H. pylori modulates the T cell response through dendritic cell reprogramming but the molecular pathways involved are relatively unknown. The goal of this study was to identify critical elements of dendritic cell (DC) activation and evaluate potential influence on immune activation. Microarray analysis was used to demonstrate limited gene expression changes in H. pylori stimulated bone marrow derived DCs (BMDCs) compared to the BMDCs stimulated with E. coli. IRAK-M, a negative regulator of TLR signaling, was upregulated and we selectedit for investigation of its role in modulating the DC and T cell responses. IRAK-M(-/-) and wild type BMDC were compared for their response to H. pylori. Cells lacking IRAK-M produced significantly greater amounts of proinflammatory MIP-2 and reduced amounts of immunomodulatory IL-10 than wild type BMDC. IRAK-M(-/-) cells also demonstrated increased MHC II expression upon activation. However, IRAK-M(-/-) BMDCs were comparable to wild type BMDCs in inducing T-helper 17 (TH17) and Treg responses as demonstrated in vitro using BMDC CD4+ T cells co-culture assays,and in vivo though the adoptive transfer of CD4(+) FoxP3-GFP T cells into H. pylori infected IRAK-M(-/-) mice. These results suggest that H. pylori infection leads to the upregulation of anti-inflammatory molecules like IRAK-M and that IRAK-M has a direct impact on innate functions in DCs such as cytokine and costimulation molecule upregulation but may not affect T cell skewing. PMID:23776703

  6. Limiting Current of Oxygen Reduction on Gas-Diffusion Electrodes for Phosphoric Acid Fuel Cells

    DEFF Research Database (Denmark)

    Li, Qingfeng; Gang, Xiao; Hjuler, Hans Aage;

    1994-01-01

    on polytetrafluorine-ethyl bonded gas-diffusion electordes in phosphoric acid with and without fluorinated additives. This provides an alternative to estimate the film thickness by combining it with the acid-adsorption measurements and the porosity analysis of the catalyst layer. It was noticed that the limiting...... expression for the limiting current density. The acid-film thickness estimated this way was found to be of 0.1 mum order of magnitude for the two types of electrodes used in phosphoric acid with and without fluorinated additives at 150-degrees-C....

  7. Lack of Protective Osmolytes Limits Final Cell Density and Volumetric Productivity of Ethanologenic Escherichia coli KO11 during Xylose Fermentation†

    OpenAIRE

    Underwood, S. A.; Buszko, M. L.; Shanmugam, K. T.; Ingram, L. O.

    2004-01-01

    Limited cell growth and the resulting low volumetric productivity of ethanologenic Escherichia coli KO11 in mineral salts medium containing xylose have been attributed to inadequate partitioning of carbon skeletons into the synthesis of glutamate and other products derived from the citrate arm of the anaerobic tricarboxylic acid pathway. The results of nuclear magnetic resonance investigations of intracellular osmolytes under different growth conditions coupled with those of studies using gen...

  8. Microbial nar-GFP cell sensors reveal oxygen limitations in highly agitated and aerated laboratory-scale fermentors

    Directory of Open Access Journals (Sweden)

    Rao Govind

    2009-01-01

    Full Text Available Abstract Background Small-scale microbial fermentations are often assumed to be homogeneous, and oxygen limitation due to inadequate micromixing is often overlooked as a potential problem. To assess the relative degree of micromixing, and hence propensity for oxygen limitation, a new cellular oxygen sensor has been developed. The oxygen responsive E. coli nitrate reductase (nar promoter was used to construct an oxygen reporter plasmid (pNar-GFPuv which allows cell-based reporting of oxygen limitation. Because there are greater than 109 cells in a fermentor, one can outfit a vessel with more than 109 sensors. Our concept was tested in high density, lab-scale (5 L, fed-batch, E. coli fermentations operated with varied mixing efficiency – one verses four impellers. Results In both cases, bioreactors were maintained identically at greater than 80% dissolved oxygen (DO during batch phase and at approximately 20% DO during fed-batch phase. Trends for glucose consumption, biomass and DO showed nearly identical behavior. However, fermentations with only one impeller showed significantly higher GFPuv expression than those with four, indicating a higher degree of fluid segregation sufficient for cellular oxygen deprivation. As the characteristic time for GFPuv expression (approx 90 min. is much larger than that for mixing (approx 10 s, increased specific fluorescence represents an averaged effect of oxygen limitation over time and by natural extension, over space. Conclusion Thus, the pNar-GFPuv plasmid enabled bioreactor-wide oxygen sensing in that bacterial cells served as individual recirculating sensors integrating their responses over space and time. We envision cell-based oxygen sensors may find utility in a wide variety of bioprocessing applications.

  9. On the performance limiting behavior of defect clusters in commercial silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B.L.; Chen, W.; Jones, K. [National Renewable Energy Lab., Golden, CO (United States); Gee, J. [Sandia National Labs., Albuquerque, NM (United States)

    1998-09-01

    The authors report the observation of defect clusters in high-quality, commercial silicon solar cell substrates. The nature of the defect clusters, their mechanism of formation, and precipitation of metallic impurities at the defect clusters are discussed. This defect configuration influences the device performance in a unique way--by primarily degrading the voltage-related parameters. Network modeling is used to show that, in an N/P junction device, these regions act as shunts that dissipate power generated within the cell.

  10. Space-time adaptive ADER discontinuous Galerkin finite element schemes with a posteriori sub-cell finite volume limiting

    CERN Document Server

    Zanotti, Olindo; Dumbser, Michael; Hidalgo, Arturo

    2015-01-01

    In this paper we present a novel arbitrary high order accurate discontinuous Galerkin (DG) finite element method on space-time adaptive Cartesian meshes (AMR) for hyperbolic conservation laws in multiple space dimensions, using a high order \\aposteriori sub-cell ADER-WENO finite volume \\emph{limiter}. Notoriously, the original DG method produces strong oscillations in the presence of discontinuous solutions and several types of limiters have been introduced over the years to cope with this problem. Following the innovative idea recently proposed in \\cite{Dumbser2014}, the discrete solution within the troubled cells is \\textit{recomputed} by scattering the DG polynomial at the previous time step onto a suitable number of sub-cells along each direction. Relying on the robustness of classical finite volume WENO schemes, the sub-cell averages are recomputed and then gathered back into the DG polynomials over the main grid. In this paper this approach is implemented for the first time within a space-time adaptive ...

  11. Xpg limits the expansion of haematopoietic stem and progenitor cells after ionising radiation.

    Science.gov (United States)

    Avila, Alush I; Illing, Anett; Becker, Friedrich; Maerz, Lars D; Morita, Yohei; Philipp, Melanie; Burkhalter, Martin D

    2016-07-27

    Reduced capacity of genome maintenance represents a problem for any organism, potentially causing premature death, carcinogenesis, or accelerated ageing. Strikingly though, loss of certain genome stability factors can be beneficial, especially for the maintenance of tissue stem cells of the intestine and the haematopoietic system. We therefore screened for genome stability factors negatively impacting maintenance of haematopoietic stem cells (HSC) in the context of ionising radiation (IR). We found that in vivo knock down of Xeroderma pigmentosum, complementation group G (Xpg) causes elevation of HSC numbers after IR treatment, while numbers of haematopoietic progenitors are elevated to a lesser extent. IR rapidly induces Xpg both on mRNA and on protein level. Prevention of this induction does not influence activation of the checkpoint cascade, yet attenuates late checkpoint steps such as induction of p21 and Noxa. This causes a leaky cell cycle arrest and lower levels of apoptosis, both contributing to increased colony formation and transformation rates. Xpg thus helps to adequately induce DNA damage responses after IR, thereby keeping the expansion of damaged cells under control. This represents a new function of Xpg in the response to IR, in addition to its well-characterized role in nucleotide excision repair. PMID:27137888

  12. Localization of type I interferon receptor limits interferon-induced TLR-3 in epithelial cells

    Science.gov (United States)

    This study aimed to expand on the role of type I IFNs in the influenza-induced upregulation of TLR3 and determine whether and how the localization of the IFN-alpha/beta receptor (IFNAR) in respiratory epithelial cells could modify IFN-induced responses. Using differentiated prima...

  13. Key factors limiting the open circuit voltage of n(+)pp(+) indium phosphide solar cells

    Science.gov (United States)

    Goradia, Chandra; Thesling, William; Weinberg, Irving

    1991-01-01

    Solar cells made from gallium arsenide (GaAs), with a room temperature bandgap of E(sub g) = 1.43 eV have exhibited the best measured open circuit voltage (V sub OC) of 1.05 V at 1 AMO, 25 C. The material InP is in many ways similar to GaAs. A simple calculation comparing InP to GaAs then shows that solar cells made from InP, with E(sub g) = 1.35 at 300 K, should exhibit the best measured (V sub OC) of approximately 950 mV at 1 AMO, 300 K. However, to date, the best measured V(sub OC) for InP solar cells made by any fabrication method is 899 mV at AM1.5, 25 C which would translate to 912 mV at 1 AMO, 25 C. The V(sub OC) of an n(+)pp(+) InP solar cell is governed by several factors. Of these, some factors, such as the thickness and doping of the emitter and base regions, are easily controlled and can be adjusted to desired values dictated by a good performance optimizing model. Such factors were not considered. There are other factors which also govern V(sub OC), and their values are not so easily controlled. The primary ones among these are (1) the indirect or Hall-Shockley-Read lifetimes in the various regions of the cell, (2) the low-doping intrinsic carrier concentration n(sub i) of the InP material, (3) the heavy doping factors in the emitter and BSF regions, and (4) the front surface recombination velocity S(sub F). The influence of these latter factors on the V(sub OC) of the n(+)pp(+) InP solar cell and the results were used to produce a near-optimum design of the n(+)pp(+) InP solar cell.

  14. Limitations of clonality analysis of B cell proliferations using CDR3 polymerase chain reaction

    OpenAIRE

    Hoeve, M A; Krol, A D G; Philippo, K; Derksen, P W B; Veenendaal, R. A.; Schuuring, E; Kluin, Ph M; Krieken, J.H.J.M. van

    2000-01-01

    Background/Aims—Detection of clonal immunoglobulin heavy chain (IgH) rearrangements by the polymerase chain reaction (PCR) is an attractive alternative to Southern blotting in lymphoma diagnostics. However, the advantages and limitations of PCR in clonality analysis are still not fully appreciated. In this study, clonality was analysed by means of PCR, focusing in particular on the sample size requirements when studying extremely small samples of polyclonal and monoclonal lesions.

  15. Low platinum, high limiting current density of the PEMFC (proton exchange membrane fuel cell) based on multilayer cathode catalyst approach

    International Nuclear Information System (INIS)

    Novel multilayer cathode electrodes structures for PEMFC (proton exchange membrane fuel cell) based on sputtering technique were developed to provide high performance with low loading Pt of 0.05 mg/cm² compared to the standard MEA (membrane electrode assembly) cathode (∼0.2–0.3 mg/cm²). Different configurations of cathode catalyst layer were made by altering Pt and CN (Carbon–Nafion) ink carefully prepared on gas diffusion layer containing MPL (micro porous layer). The performances of PEMFC containing the multilayer electrodes were compared based on their measured polarization curves. Higher limiting current densities were achieved compared to standard MEA with platinum loading of 0.2 mg/cm² both at the cathode and the anode sides. Limiting current densities over 1.1 A/cm2, 1.2 A/cm2 and 1.4 A/cm2 were reached whereas maximum powers were in the range of 500 mW/cm² at 600 mW/cm². The good performances obtained can be due to the structural improvement which has contributed to a better catalyst utilization compared to conventional methods. A CN loading inferior to 0.24 mg/cm² between each layer is preferred for multilayer electrode. - Highlights: • Multilayer cathode of PEM fuel cell. • Enhanced performances with carbon–Nafion layer of PEM fuel cell. • Effect of the number of Pt sputtered layers on cell performance. • Increased power densities achieved. • Increased limiting current densities achieved

  16. A New Figure of Merit for Organic Solar Cells with Transport-limited Photocurrents

    Science.gov (United States)

    Neher, Dieter; Kniepert, Juliane; Elimelech, Arik; Koster, L. Jan Anton

    2016-04-01

    Compared to their inorganic counterparts, organic semiconductors suffer from relatively low charge carrier mobilities. Therefore, expressions derived for inorganic solar cells to correlate characteristic performance parameters to material properties are prone to fail when applied to organic devices. This is especially true for the classical Shockley-equation commonly used to describe current-voltage (JV)-curves, as it assumes a high electrical conductivity of the charge transporting material. Here, an analytical expression for the JV-curves of organic solar cells is derived based on a previously published analytical model. This expression, bearing a similar functional dependence as the Shockley-equation, delivers a new figure of merit α to express the balance between free charge recombination and extraction in low mobility photoactive materials. This figure of merit is shown to determine critical device parameters such as the apparent series resistance and the fill factor.

  17. Fundamental High-Speed Limits in Single-Molecule, Single-Cell, and Nanoscale Force Spectroscopies

    OpenAIRE

    Amo, C. A.; Garcia, Ricardo

    2016-01-01

    Force spectroscopy is enhancing our understanding of single-biomolecule, single-cell, and nanoscale mechanics. Force spectroscopy postulates the proportionality between the interaction force and the instantaneous probe deflection. By studying the probe dynamics, we demonstrate that the total force acting on the probe has three different components: the interaction, the hydrodynamic, and the inertial. The amplitudes of those components depend on the ratio between the resonant frequency and the...

  18. Conditioned Medium From Human Amniotic Mesenchymal Stromal Cells Limits Infarct Size and Enhances Angiogenesis

    OpenAIRE

    Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara; Cervio, Elisabetta; Calvillo, Laura; Copes, Francesco; Pisano, Federica; Mura, Manuela; Kleijn, Lennaert; De Boer, Rudolf A.; Viarengo, Gianluca; Rosti, Vittorio; Spinillo, Arsenio; Roccio, Marianna; Gnecchi, Massimiliano

    2015-01-01

    The goal of this study was to elucidate whether human amniotic membrane-derived mesenchymal stromal cells (hAMCs) can exert beneficial paracrine effects on infarcted rat hearts. In particular, the administration of hAMC-conditioned medium repaired ischemic damage through cardioprotection and angiogenesis. Finally, several putative active paracrine mediators that might account for the effects observed were identified by gene and protein arrays.

  19. Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations

    Czech Academy of Sciences Publication Activity Database

    Lunov, Oleg; Zablotskyy, Vitaliy A.; Churpita, Olexandr; Chánová, Eliška; Syková, Eva; Dejneka, Alexandr; Kubinová, Šárka

    2014-01-01

    Roč. 4, NOV (2014), "7129-1"-"7129-11". ISSN 2045-2322 R&D Projects: GA MŠk LO1309 Grant ostatní: AV ČR(CZ) M100101219 Institutional support: RVO:68378271 ; RVO:61389013 ; RVO:68378041 Keywords : cell death * non-thermal plasma * therapeutic perspectives Subject RIV: BO - Biophysics; FH - Neurology (UEM-P); CD - Macromolecular Chemistry (UMCH-V) Impact factor: 5.578, year: 2014

  20. Nutrient Starvation Decreases Cx43 Levels and Limits Intercellular Communication in Primary Bovine Corneal Endothelial Cells.

    Science.gov (United States)

    D'hondt, Catheleyne; Iyyathurai, Jegan; Welkenhuyzen, Kirsten; Himpens, Bernard; Leybaert, Luc; Bultynck, Geert

    2016-06-01

    Connexin (Cx) proteins form large conductance channels which function as regulators of communication between neighboring cells via gap junctions and/or hemichannels. Intercellular communication is essential to coordinate cellular responses in tissues and organs, thereby fulfilling an essential role in the spreading of signaling, survival and death processes. Connexin 43 (Cx43), a major connexin isoform in brain and heart, is rapidly turned over. Recent studies implicated that autophagy, a lysosomal degradation pathway induced upon nutrient starvation, mediates connexins, including Cx43, degradation. Here, we examined the impact of nutrient starvation on endogenous Cx43-protein levels and endogenous Cx43-driven intercellular communication in primary bovine corneal endothelial cells (BCECs). Hank's Balanced Salt Solution (HBSS) was used as a starvation condition that induces autophagic flux without impacting the survival of the BCECs. Nutrient starvation of BCECs caused a rapid decline in Cx43-protein levels, both as gap junctions and as hemichannels. The time course of the decline in Cx43-protein levels coincided with the time course of the decline in intercellular communication, assessed as intercellular Ca(2+)-wave propagation in BCECs exposed to a single-cell mechanical stimulus. The decline in Cx43-protein levels, both as gap junctions and as hemichannels, could be prevented by the addition of bafilomycin A1, a lysosomal inhibitor, during the complete nutrient starvation period. Consistent with this, bafilomycin A1 significantly alleviated the decrease in intercellular Ca(2+)-wave propagation. This study further underpins the importance of autophagy as an important degradation pathway for Cx43 proteins during periods of nutrient deprivation, thereby impacting the ability of cells to perform intercellular communication. PMID:26873723

  1. Network Variability Limits Stimulus-Evoked Spike Timing Precision in Retinal Ganglion Cells

    OpenAIRE

    Murphy, Gabe J.; Rieke, Fred

    2006-01-01

    Visual, auditory, somatosensory, and olfactory stimuli generate temporally precise patterns of action potentials (spikes). It is unclear, however, how the pattern and variability of synaptic input elicited by physiological stimuli governs the precision of spike generation. We determined how synaptic conductances evoked by light stimuli that activate the rod bipolar pathway control spike generation in three identified types of mouse retinal ganglion cells (RGCs). The relative amplitude, timing...

  2. Understanding the cancer cell phenotype beyond the limitations of current omics analyses.

    Science.gov (United States)

    Moreno-Sánchez, Rafael; Saavedra, Emma; Gallardo-Pérez, Juan Carlos; Rumjanek, Franklin D; Rodríguez-Enríquez, Sara

    2016-01-01

    Efforts to understand the mechanistic principles driving cancer metabolism and proliferation have been lately governed by genomic, transcriptomic and proteomic studies. This paper analyzes the caveats of these approaches. As molecular biology's central dogma proposes a unidirectional flux of information from genes to mRNA to proteins, it has frequently been assumed that monitoring the changes in the gene sequences and in mRNA and protein contents is sufficient to explain complex cellular processes. Such a stance commonly disregards that post-translational modifications can alter the protein function/activity and also that regulatory mechanisms enter into action, to coordinate the protein activities of pathways/cellular processes, in order to keep the cellular homeostasis. Hence, the actual protein activities (as enzymes/transporters/receptors) and their regulatory mechanisms ultimately dictate the final outcomes of a pathway/cellular process. In this regard, it is here documented that the mRNA levels of many metabolic enzymes and transcriptional factors have no correlation with the respective protein contents and activities. The validity of current clinical mRNA-based tests and proposed metabolite biomarkers for cancer detection/prognosis is also discussed. Therefore, it is proposed that, to achieve a thorough understanding of the modifications undergone by proliferating cancer cells, it is mandatory to experimentally analyze the cellular processes at the functional level. This could be achieved (a) locally, by examining the actual protein activities in the cell and their kinetic properties (or at least kinetically characterize the most controlling steps of the pathway/cellular process); (b) systemically, by analyzing the main fluxes of the pathway/cellular process, and how they are modulated by metabolites, all which should contribute to comprehending the regulatory mechanisms that have been altered in cancer cells. By adopting a more holistic approach it may

  3. Upper limits on neutron bursts emitted from Ti pressurized D2 gas cells

    International Nuclear Information System (INIS)

    In a search for bursts of neutrons from Ti in pressurized D2 gas cells, no statistically significant deviations from the background were observed for events where five or more neutrons are detected over a ten day experiment, including 103 hours of counting with cells on, and 28 hours counting of various backgrounds. Up to four cells were used including some 60 grams of 662-Ti fillings in a pressurized cylinder with 40-60 atmosphere of D2 gas. Other Ti samples were used too. The samples were cooled to liquid nitrogen temperature and placed in front of the neutron detector while warming up to room temperature. Seven cooling cycles were used, for each sample. The neutron detector system included 12 liquid scintillator neutron detectors, arranged in a close packed geometry, with six detectors in the upper hemisphere and six in the lower hemisphere. A central detector placed 2 cm from the cells was used, in each hemisphere, as a scatterer for a time of flight coincidence measurement, yielding the total coincidence efficiency of ε=2±1%. The system was also used in singles mode to allow for counting with large efficiency. A neutron event is characterized by measuring its pulse heights, pulse shapes, and in some cases its time of flight. Special attention was given to reducing the background by using massive shielding, cosmic ray veto counters and geometrical arrangement that allowed to distinguish between a background event and expected data events. The so obtained background rate is 100 cph in the ''singles mode'' and in the upper hemisphere 0.4 cph in the ''coincidence mode.'' We are currently continuing our data analysis in search for random emission and a detailed study of background effects that may reveal the origin of conflicting results reported on neutron emission from ''cold fusion.'' 3 refs., 5 figs., 3 tabs

  4. Muscarinic acetylcholine receptor down-regulation limits the extent of inhibition of cell cycle progression in Chinese hamster ovary cells.

    OpenAIRE

    Detjen, K.; Yang, J; Logsdon, C D

    1995-01-01

    Cellular desensitization is believed to be important for growth control but direct evidence is lacking. In the current study we compared effects of wild-type and down-regulation-resistant mutant m3 muscarinic receptors on Chinese hamster ovary (CHO-K1) cell desensitization, proliferation, and transformation. We found that down-regulation of m3 muscarinic acetylcholine receptors was the principal mechanism of desensitization of receptor-activated inositol phosphate phospholipid hydrolysis in t...

  5. Particle-In-Cell Simulations of Shaped and Non-shaped Gaps in TEXTOR Test Limiter

    Czech Academy of Sciences Publication Activity Database

    Komm, M.; Pekarek, Z.; Pánek, Radomír; Matveev, D.; Kirschner, A.; Litnovsky, A.

    Vol. 2. Prague: MATFYZPRESS, Prague, 2009 - (Šafránková, J.; Pavlů, J.), s. 169-175 ISBN 978-80-7378-102-6. [Annual conference of doctoral students - WDS 2009 /18./. Prague (CZ), 02.06.2009-05.06.2009] Institutional research plan: CEZ:AV0Z20430508 Keywords : gap * divertor * limiter * PIC * deposition * SOL Subject RIV: BL - Plasma and Gas Discharge Physics http://www.mff.cuni.cz/veda/konference/wds/contents/pdf09/WDS09_229_f2_Komm.pdf

  6. Denaturation of DNA repair proteins as a possible rate limiting step in the thermal death of single cells

    International Nuclear Information System (INIS)

    The experiments to be described support the hypothesis that the denaturation of DNA repair proteins is a rate limiting step in the thermal death of cells grown in tissue culture. Mammalian fibroblasts were subjected to small changes in temperature before ultraviolet (uv) irradiation in order to detect changes in repair of uv induced damage. Repair of DNA was measured by several methods after uv treatment. In some experiments repair was measured by incorporating 3H-Thymidine at 370C for different lengths of time after uv irradiation. Autoradiography suggested that prior heat treatment impairs the repair in all of the cells rather than causes the thermal death of a large portion of the cells. Finally, an endonuclease specific assay was conducted to determine whether the effects were due to the thermal denaturation of the endonuclease repair enzyme or rather to some heat sensitive process. By using a dimer specific endonuclease from M. luteus, the number of dimers produced and repaired was measured directly. For both hamster ahd human fibroblasts, significantly less repair was observed in cells incubated at 410C prior to uv treatment than in cells incubated at 370C before uv treatment. This suggests that the endonuclease repair enzymes are denatured at the higher temperature

  7. Gold Nanoparticles Promote Proliferation of Human Periodontal Ligament Stem Cells and Have Limited Effects on Cells Differentiation

    Directory of Open Access Journals (Sweden)

    Chen Li

    2016-01-01

    Full Text Available Gold nanoparticles (AuNPs had been widely applied in the practice and advancement of chemistry, biology, and medicine due to facility of synthesis and versatility in surface functionalization. Recent studies had shown that AuNPs can be applied to cells, affecting cellular physiological processes such as proliferation and differentiation. In this study, four diameters of AuNPs (20, 40, 60, and 80 nm were cocultured with human periodontal ligament cells (hPDLCs at six different concentrations. The optimal size and concentration of AuNPs were selected to treat human periodontal ligament stem cells (hPDLSCs to evaluate proliferation. Moreover, the influence of AuNPs on multiple differentiation capacity of hPDLSCs was clarified. The results revealed that AuNPs (60 nm, 56 μM can effectively promote the proliferation of hPDLCs/hPDLSCs in vitro, slightly enhance osteoblastic differentiation, and have no effect on adipogenic differentiation. In addition, the expression of COL-1, Runx2, BSP, and OCN was upregulated in the presence of AuNPs (60 nm, 56 μM. These results indicated that AuNPs (60 nm, 56 μM can effectively promote the proliferation of hPDLCs/hPDLSCs and have no significant effect on the differentiation of hPDLSCs. These results provide an insight on the advantage of implementing of AuNPs on hPDLSCs culture and expose the influence of these materials on periodontal tissue engineering.

  8. Effect of iron limitation on cells of the diatom Cyclotella meneghiniana Kützing

    Directory of Open Access Journals (Sweden)

    Alicja Kosakowska

    2004-06-01

    Full Text Available The response of the Baltic diatom Cyclotella meneghiniana to iron deficiency was examined. The following growth parameters were measured: cell number, chlorophyll a and protein content. The results demonstrate the ability of this diatom to grow well with minimal iron availability; however, the rate of growth fell markedly at the lowest iron(III concentration. The results of spectrophotometric chlorophyll a measurements and protein assays using the Lowry and Bradford methods indicated a significant decrease in their quantities. Iron may therefore be an important regulatory factor controlling the growth of diatom C. meneghiniana in an aquatic ecosystem.

  9. Limited value of CT brain scans in the staging of small cell lung cancer

    International Nuclear Information System (INIS)

    Computed tomography of the brain was performed as part of the initial staging evaluation of 84 patients with small cell lung cancer. Brain scans indicative of metastatic disease were obtained in 12 (14%) patients, two of whom had no neurologic signs or symptoms. One of these had no other extrathoracic disease. Brainscans without evidence of metastatic disease were obtained in 72 patients, 58 (80.5%) of whom had no signs or symptoms suggestive of metastatic intracranial disease. In the 14 patients with neurologic symptoms but negative computed tomographic scans, other explanations than brain metastases were found. It was concluded that head scanning is a sensitive and accurate method of detecting central nervous system metastases in patients with small cell lung cancer. However, head computed tomography should not be included as part of the initial staging evaluation of the neurologically asymptomatic patients. In only one of 60 such patients did the brain scan change the initial clinical staging, which included chest films, liver and bone scans, and bone marrow biopsy

  10. Comparison of treatment outcomes between involved-field and elective nodal irradiation in limited-stage small cell lung cancer

    International Nuclear Information System (INIS)

    The present study was performed to assess the usefulness of involved-field irradiation and the impact of 18F-fluorodeoxyglucose-positron emission tomography-based staging on treatment outcomes in limited-stage small cell lung cancer. Eighty patients who received definitive chemoradiotherapy for limited-stage small cell lung cancer were retrospectively analyzed. Fifty patients were treated with involved-field irradiation, which means that the radiotherapy portal includes only clinically identifiable tumors. The other 30 patients were irradiated with a comprehensive portal, including uninvolved mediastinal and/or supraclavicular lymph nodes, so-called elective nodal irradiation. No significant difference was seen in clinical factors between the two groups. At a median follow-up of 27 months (range, 5-75 months), no significant differences were observed in 3 year overall survival (44.6 vs. 54.1%, P=0.220) and 3 year progression-free survival (24.4 vs. 42.8%, P=0.133) between the involved-field irradiation group and the elective nodal irradiation group, respectively. For patients who did not undergo positron emission tomography scans, 3 year overall survival (29.3 vs. 56.3%, P=0.022) and 3 year progression-free survival (11.0 vs. 50.0%, P=0.040) were significantly longer in the elective nodal irradiation group. Crude incidences of isolated nodal failure were 6.0% in the involved-field irradiation group and 0% in the elective nodal irradiation group, respectively. All isolated nodal failures were developed in patients who had not undergone positron emission tomography scans in their initial work-ups. If patients did not undergo positron emission tomography-based staging, the omission of elective nodal irradiation resulted in impaired survival outcomes and raised the risk of isolated nodal failure. Therefore, involved-field irradiation for limited-stage small cell lung cancer might be reasonable only with positron emission tomography scan implementation. (author)

  11. Limited value of technetium 99m-labeled red cell scintigraphy in localization of lower gastrointestinal bleeding

    International Nuclear Information System (INIS)

    The aim of this study was to assess the accuracy of technetium 99m-labeled red cell scintigraphy in localizing the site of lower gastrointestinal bleeding. The outcome of 203 patients undergoing technetium 99m-labeled red cell scintigraphy was reviewed, and the scan result was compared with the true site of bleeding. The true site of bleeding was determined by other methods including angiography and surgical pathology. Fifty-two scans (26%) were positive and indicated a specific site of bleeding. A definitive bleeding site was identified in 22 patients by other means and correlated with the technetium scan in only 9 cases. The nuclear scan was incorrect in the remaining 13 cases, implying a localization error of 25% (13 of 52). A subgroup of 19 patients with a positive scan underwent a surgical procedure directed by the nuclear scan. Eight of these 12 patients had incorrect surgical procedures based upon findings of more definitive tests, indicating a surgical error of 42% (8 of 19). We conclude that the technetium 99m-labeled red cell scan's ability to accurately localize the site of lower gastrointestinal bleeding is limited. Furthermore, performing a surgical procedure that relies exclusively on localization by red cell scintigraphy will produce an undesirable result in at least 42% of patients

  12. Limited value of technetium 99m-labeled red cell scintigraphy in localization of lower gastrointestinal bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Hunter, J.M.; Pezim, M.E. (Univ. of British Columbia, Vancouver (Canada))

    1990-05-01

    The aim of this study was to assess the accuracy of technetium 99m-labeled red cell scintigraphy in localizing the site of lower gastrointestinal bleeding. The outcome of 203 patients undergoing technetium 99m-labeled red cell scintigraphy was reviewed, and the scan result was compared with the true site of bleeding. The true site of bleeding was determined by other methods including angiography and surgical pathology. Fifty-two scans (26%) were positive and indicated a specific site of bleeding. A definitive bleeding site was identified in 22 patients by other means and correlated with the technetium scan in only 9 cases. The nuclear scan was incorrect in the remaining 13 cases, implying a localization error of 25% (13 of 52). A subgroup of 19 patients with a positive scan underwent a surgical procedure directed by the nuclear scan. Eight of these 12 patients had incorrect surgical procedures based upon findings of more definitive tests, indicating a surgical error of 42% (8 of 19). We conclude that the technetium 99m-labeled red cell scan's ability to accurately localize the site of lower gastrointestinal bleeding is limited. Furthermore, performing a surgical procedure that relies exclusively on localization by red cell scintigraphy will produce an undesirable result in at least 42% of patients.

  13. A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses.

    Science.gov (United States)

    Coria, Lorena M; Ibañez, Andrés E; Tkach, Mercedes; Sabbione, Florencia; Bruno, Laura; Carabajal, Marianela V; Berguer, Paula M; Barrionuevo, Paula; Schillaci, Roxana; Trevani, Analía S; Giambartolomei, Guillermo H; Pasquevich, Karina A; Cassataro, Juliana

    2016-05-15

    In this study, we demonstrate that the unlipidated (U) outer membrane protein (Omp) 19 from Brucella spp. is a competitive inhibitor of human cathepsin L. U-Omp19 inhibits lysosome cathepsins and APC-derived microsome activity in vitro and partially inhibits lysosomal cathepsin L activity within live APCs. Codelivery of U-Omp19 with the Ag can reduce intracellular Ag digestion and increases Ag half-life in dendritic cells (DCs). U-Omp19 retains the Ag in Lamp-2(+) compartments after its internalization and promotes a sustained expression of MHC class I/peptide complexes in the cell surface of DCs. Consequently, U-Omp19 enhances Ag cross-presentation by DCs to CD8(+) T cells. U-Omp19 s.c. delivery induces the recruitment of CD11c(+)CD8α(+) DCs and monocytes to lymph nodes whereas it partially limits in vivo Ag proteolysis inside DCs. Accordingly, this protein is able to induce CD8(+) T cell responses in vivo against codelivered Ag. Antitumor responses were elicited after U-Omp19 coadministration, increasing survival of mice in a murine melanoma challenge model. Collectively, these results indicate that a cysteine protease inhibitor from bacterial origin could be a suitable component of vaccine formulations against tumors. PMID:27084100

  14. Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease

    International Nuclear Information System (INIS)

    In a prospective controlled clinical trial, 102 patients with inoperable non-small lung cancer (NSCLC), limited disease, stage II and III were treated with combination chemotherapy, cisplatin 70 mg/m2 i.v. on day one and etoposide 100 mg/m2 i.v. on day one, and etoposide 200 mg/m2 orally on days 2 and 3, or radiotherapy given in 15 fractions of 2.8 Gy with two anterior/posterior fields during a period of three weeks. The patients completed a validated self-administered questionnaire before the start of treatment that assessed their psychosocial well-being, disease-related symptoms, personal functioning, and every day activity. These subjective varibles were evaluated together with treatment modality, WHO performance status, weight loss, and stage of disease, with regard to their value in predicting survival. Univariate survival analyses were undertaken for each individual factor, median survival was calculated according to life-table analyses. A step-wise multiple regression analysis was used to measure the prognostic value of the various factors. In the univariate analysis, general symptons (p=0.0006) psychosocial well-being (p=0.0002) and stage of disease (p=0.007) were the best predictive factors. In the multiple regression analyses the subjective variables, general symptons (p<0.01) and psychosocial well-being (p<0.05) were shown to have the best predictive value for the patients' survival. (author). 20 refs.; 4 figs.; 3 tabs

  15. Potential Uses, Limitations, and Basic Procedures of Micronuclei and Nuclear Abnormalities in Buccal Cells

    Directory of Open Access Journals (Sweden)

    Olivia Torres-Bugarín

    2014-01-01

    Full Text Available The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN and nuclear abnormalities (NA technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique.

  16. Pushing structural limits to reveal fundamental mechanisms of organic solar cell operation

    Science.gov (United States)

    Rand, Barry

    2015-03-01

    Organic-based solar cells are beginning to emerge with the potential to compete with other thin film photovoltaic technologies, with efficiencies of 12% recently demonstrated. Unique to the function of organic photovoltaics are the creation of tightly bound excitons that can only be efficiently separated at a donor/acceptor (D/A) interface capable of providing the necessary energetic driving force for dissociation. The consequences of this are the need for long exciton diffusion lengths and the presence of charge transfer (CT) states, ground state complexes that exist at the D/A interface. We have found that charge transfer states are more easily separated into free charge if they are delocalized; an aspect that becomes most feasible for highly ordered systems. I will discuss our recent efforts to template and control film morphology and molecular orientation. These studies allow us to understand the importance of molecular orientation, crystallite size, and crystal phase. We will show templated devices utilizing neat films as well as bulk heterojunctions, with crystallite dimensions spanning from the more standard nano-sized grains to those with highly ordered micron-sized crystalline domains revealing unprecedented thin film exciton diffusion lengths of 100s of nm. In these highly ordered films, owing to significant delocalization, we are able to directly measure photocurrent from multiple CT states, an aspect which has important consequences for the design of more efficient photocurrent generation. We acknowledge support from DOE BES Grant #11493344.

  17. Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability

    KAUST Repository

    Marcatili, P.

    2013-05-01

    Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated. Copyright © 2013 by The American Association of Immunologists, Inc.

  18. Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships.

    Science.gov (United States)

    Walker, Karen M; Okitsu, Shinji; Porter, David W; Duncan, Christopher; Amacker, Mario; Pluschke, Gerd; Cavanagh, David R; Hill, Adrian V S; Todryk, Stephen M

    2015-05-01

    This study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11-12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-119 , correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T-cell responses were detected in the form of interferon-γ and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-γ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-apical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related. PMID:25471322

  19. Study of quality and field limitation of superconducting 1.3 GHz 9-Cell RF-cavities at DESY

    International Nuclear Information System (INIS)

    The European XFEL and the International Linear Collider are based on superconducting rf cavities made of niobium. Their advantages are low ohmic losses which allow high duty cycles and the possibility to use a large beam aperture which is substantial to prevent wake fields at high current accelerators. To reach the theoretical limits of superconducting cavities, it is required to understand the present performance limitations. These are field emission, thermal breakdown (quench) and the ohmic losses dependent on the accelerating field, which are expressed in the quality factor. As the limiting mechanisms themselves are understood in general, the origin of the quench is often unclear. To determine the quench locations, a localisation tool for thermal breakdown using the second sound in superfluid helium has been installed at the cavity test facility at DESY and the results for a sample of about 30 cavities have been examined. The features of the distribution of the quench locations have been analysed and it has been found that the quench locations are in the area of the highest surface magnetic field and not necessarily at the equator of the cells. The data sample has been extended in an attempt to characterise the average behaviour of the quality factor related to the accelerating field. An analysis of the surface resistance of individual cavities shows that a recently developed model for the surface resistance of niobium is not able to describe the measurement in all detail, but the application of an additional mechanism showed promising results.

  20. Study of quality and field limitation of superconducting 1.3 GHz 9-Cell RF-cavities at DESY

    Energy Technology Data Exchange (ETDEWEB)

    Schlander, Felix

    2013-01-15

    The European XFEL and the International Linear Collider are based on superconducting rf cavities made of niobium. Their advantages are low ohmic losses which allow high duty cycles and the possibility to use a large beam aperture which is substantial to prevent wake fields at high current accelerators. To reach the theoretical limits of superconducting cavities, it is required to understand the present performance limitations. These are field emission, thermal breakdown (quench) and the ohmic losses dependent on the accelerating field, which are expressed in the quality factor. As the limiting mechanisms themselves are understood in general, the origin of the quench is often unclear. To determine the quench locations, a localisation tool for thermal breakdown using the second sound in superfluid helium has been installed at the cavity test facility at DESY and the results for a sample of about 30 cavities have been examined. The features of the distribution of the quench locations have been analysed and it has been found that the quench locations are in the area of the highest surface magnetic field and not necessarily at the equator of the cells. The data sample has been extended in an attempt to characterise the average behaviour of the quality factor related to the accelerating field. An analysis of the surface resistance of individual cavities shows that a recently developed model for the surface resistance of niobium is not able to describe the measurement in all detail, but the application of an additional mechanism showed promising results.

  1. Mast cell proteases as pharmacological targets.

    Science.gov (United States)

    Caughey, George H

    2016-05-01

    Mast cells are rich in proteases, which are the major proteins of intracellular granules and are released with histamine and heparin by activated cells. Most of these proteases are active in the granule as well as outside of the mast cell when secreted, and can cleave targets near degranulating mast cells and in adjoining tissue compartments. Some proteases released from mast cells reach the bloodstream and may have far-reaching actions. In terms of relative amounts, the major mast cell proteases include the tryptases, chymases, cathepsin G, carboxypeptidase A3, dipeptidylpeptidase I/cathepsin C, and cathepsins L and S. Some mast cells also produce granzyme B, plasminogen activators, and matrix metalloproteinases. Tryptases and chymases are almost entirely mast cell-specific, whereas other proteases, such as cathepsins G, C, and L are expressed by a variety of inflammatory cells. Carboxypeptidase A3 expression is a property shared by basophils and mast cells. Other proteases, such as mastins, are largely basophil-specific, although human basophils are protease-deficient compared with their murine counterparts. The major classes of mast cell proteases have been targeted for development of therapeutic inhibitors. Also, a human β-tryptase has been proposed as a potential drug itself, to inactivate of snake venins. Diseases linked to mast cell proteases include allergic diseases, such as asthma, eczema, and anaphylaxis, but also include non-allergic diseases such as inflammatory bowel disease, autoimmune arthritis, atherosclerosis, aortic aneurysms, hypertension, myocardial infarction, heart failure, pulmonary hypertension and scarring diseases of lungs and other organs. In some cases, studies performed in mouse models suggest protective or homeostatic roles for specific proteases (or groups of proteases) in infections by bacteria, worms and other parasites, and even in allergic inflammation. At the same time, a clearer picture has emerged of differences in the

  2. Cell Phone-Based and Adherence Device Technologies for HIV Care and Treatment in Resource-Limited Settings: Recent Advances.

    Science.gov (United States)

    Campbell, Jeffrey I; Haberer, Jessica E

    2015-12-01

    Numerous cell phone-based and adherence monitoring technologies have been developed to address barriers to effective HIV prevention, testing, and treatment. Because most people living with HIV and AIDS reside in resource-limited settings (RLS), it is important to understand the development and use of these technologies in RLS. Recent research on cell phone-based technologies has focused on HIV education, linkage to and retention in care, disease tracking, and antiretroviral therapy adherence reminders. Advances in adherence devices have focused on real-time adherence monitors, which have been used for both antiretroviral therapy and pre-exposure prophylaxis. Real-time monitoring has recently been combined with cell phone-based technologies to create real-time adherence interventions using short message service (SMS). New developments in adherence technologies are exploring ingestion monitoring and metabolite detection to confirm adherence. This article provides an overview of recent advances in these two families of technologies and includes research on their acceptability and cost-effectiveness when available. It additionally outlines key challenges and needed research as use of these technologies continues to expand and evolve. PMID:26439917

  3. Overcoming the Range Limitation of Medium-Duty Battery Electric Vehicles through the use of Hydrogen Fuel-Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wood, E.; Wang, L.; Gonder, J.; Ulsh, M.

    2013-10-01

    Battery electric vehicles possess great potential for decreasing lifecycle costs in medium-duty applications, a market segment currently dominated by internal combustion technology. Characterized by frequent repetition of similar routes and daily return to a central depot, medium-duty vocations are well positioned to leverage the low operating costs of battery electric vehicles. Unfortunately, the range limitation of commercially available battery electric vehicles acts as a barrier to widespread adoption. This paper describes the National Renewable Energy Laboratory's collaboration with the U.S. Department of Energy and industry partners to analyze the use of small hydrogen fuel-cell stacks to extend the range of battery electric vehicles as a means of improving utility, and presumably, increasing market adoption. This analysis employs real-world vocational data and near-term economic assumptions to (1) identify optimal component configurations for minimizing lifecycle costs, (2) benchmark economic performance relative to both battery electric and conventional powertrains, and (3) understand how the optimal design and its competitiveness change with respect to duty cycle and economic climate. It is found that small fuel-cell power units provide extended range at significantly lower capital and lifecycle costs than additional battery capacity alone. And while fuel-cell range-extended vehicles are not deemed economically competitive with conventional vehicles given present-day economic conditions, this paper identifies potential future scenarios where cost equivalency is achieved.

  4. Efficient Replication of Severe Acute Respiratory Syndrome Coronavirus in Mouse Cells Is Limited by Murine Angiotensin-Converting Enzyme 2

    Science.gov (United States)

    Li, Wenhui; Greenough, Thomas C.; Moore, Michael J.; Vasilieva, Natalya; Somasundaran, Mohan; Sullivan, John L.; Farzan, Michael; Choe, Hyeryun

    2004-01-01

    Replication of viruses in species other than their natural hosts is frequently limited by entry and postentry barriers. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2 molecules for their ability to serve as receptors for SARS-CoV. We found that, compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS-CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even less efficient, at near background levels for both activities. Murine 3T3 cells expressing human ACE2 supported SARS-CoV replication, whereas replication was less than 10% as efficient in the same cells expressing murine ACE2. These data imply that a mouse transgenically expressing human ACE2 may be a useful animal model of SARS. PMID:15452268

  5. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

    International Nuclear Information System (INIS)

    Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed

  6. Does Sex Influence the Impact That Smoking, Treatment Interruption and Impaired Pulmonary Function Have on Outcomes in Limited Stage Small Cell Lung Cancer Treatment?

    Directory of Open Access Journals (Sweden)

    Gregory MM Videtic

    2005-01-01

    Full Text Available PURPOSE: To look for survival differences between men and women with limited stage small cell lung cancer (LS-SCLC by examining stratified variables that impair treatment efficacy.

  7. Peptidoglycan metabolism is controlled by the WalRK (YycFG) and PhoPR two-component systems in phosphate-limited Bacillus subtilis cells.

    Science.gov (United States)

    Bisicchia, Paola; Lioliou, Efthimia; Noone, David; Salzberg, Letal I; Botella, Eric; Hübner, Sebastian; Devine, Kevin M

    2010-02-01

    In Bacillus subtilis, the WalRK (YycFG) two-component system controls peptidoglycan metabolism in exponentially growing cells while PhoPR controls the response to phosphate limitation. Here we examine the roles of WalRK and PhoPR in peptidoglycan metabolism in phosphate-limited cells. We show that B. subtilis cells remain viable in a phosphate-limited state for an extended period and resume growth rapidly upon phosphate addition, even in the absence of a PhoPR-mediated response. Peptidoglycan synthesis occurs in phosphate-limited wild-type cells at approximately 27% the rate of exponentially growing cells, and at approximately 18% the rate of exponentially growing cells in the absence of PhoPR. In phosphate-limited cells, the WalRK regulon genes yocH, cwlO(yvcE), lytE and ydjM are expressed in a manner that is dependent on the WalR recognition sequence and deleting these genes individually reduces the rate of peptidoglycan synthesis. We show that ydjM expression can be activated by PhoP approximately P in vitro and that PhoP occupies its promoter in phosphate-limited cells. However, iseA(yoeB) expression cannot be repressed by PhoP approximately P in vitro, but can be repressed by non-phosphorylated WalR in vitro. Therefore, we conclude that peptidoglycan metabolism is controlled by both WalRK and PhoPR in phosphate-limited B. subtilis cells. PMID:20487291

  8. Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

    Science.gov (United States)

    Nakagawa, Shunsuke; Shinkoda, Yuichi; Hazeki, Daisuke; Imamura, Mari; Okamoto, Yasuhiro; Kawakami, Kiyoshi; Kawano, Yoshifumi

    2016-07-01

    Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS. PMID:27089406

  9. A randomized trial of chest irradiation alone versus chest irradiation plus Lentinan in squamous cell lung cancer in limited stage

    International Nuclear Information System (INIS)

    In an attempt to evaluate the effect of Lentinan, polysaccharides from Lentinusedodes, in combination with chest irradiation for limited-stage squamous cell lung cancer, we conducted a randomized trial between January 1987 and July 1989. Patients were randomly allocated to receive either a definitive chest irradiation of 60 Gy alone (RT) or the chest irradiation plus Lentinan (RT+L). Patients allocated to the RT+L group received iv infusion of Lentinan, 1 mg twice a week or 2 mg once a week, as long as possible. Of 201 patients enrolled, 183 (94 for RT, and 89 for RT+L) were eligible for analysis of survival time, and 169 (86 for RT, and 83 for RT+L) were evaluated for tumor response, survival time and quality of life. The response rate to the treatments showed a trend favoring the RT+L group (65% vs. 51%, p=0.142). The median survival time was 455 days for the RT+L group and 371 days for the RT group. The difference was not statistically significant. In the subset of patients with cancer of hilar origin, however, RT+L group patients lived significantly longer than RT group patients: Progression-free interval from symptoms and quality of life were evaluated for the both groups based on manual records of an individual patient. RT+L group patients had a significantly longer progression-free interval from dyspneic feeling than the RT group patients. The RT+L group tended to have a feeling of well-being. We conclude that Lentinan in combination with chest irradiation is useful for patients with limited-stage squamous cell lung cancer in terms of prolongation of life and maintenance of a favorable quality of life as well. (author)

  10. Conversion efficiency limits and bandgap designs for multi-junction solar cells with internal radiative efficiencies below unity.

    Science.gov (United States)

    Zhu, Lin; Mochizuki, Toshimitsu; Yoshita, Masahiro; Chen, Shaoqiang; Kim, Changsu; Akiyama, Hidefumi; Kanemitsu, Yoshihiko

    2016-05-16

    We calculated the conversion-efficiency limit ηsc and the optimized subcell bandgap energies of 1 to 5 junction solar cells without and with intermediate reflectors under 1-sun AM1.5G and 1000-sun AM1.5D irradiations, particularly including the impact of internal radiative efficiency (ηint) below unity for realistic subcell materials on the basis of an extended detailed-balance theory. We found that the conversion-efficiency limit ηsc significantly drops when the geometric mean ηint* of all subcell ηint in the stack reduces from 1 to 0.1, and that ηsc degrades linearly to logηint* for ηint* below 0.1. For ηint*<0.1 differences in ηsc due to additional intermediate reflectors became very small if all subcells are optically thick for sun light. We obtained characteristic optimized bandgap energies, which reflect both ηint* decrease and AM1.5 spectral gaps. These results provide realistic efficiency targets and design principles. PMID:27409948

  11. Limits of light-trapping efficiency of prototypical lamellar 1-d metal gratings for amorphous silicon PV cells

    CERN Document Server

    Gablinger, David I

    2014-01-01

    One-dimensional lamellar gratings allow a particularly efficient way for solving Maxwell's equations by expanding the electromagnetic field in the basis of exact eigenmodes of the Helmholtz equation. Then, the solution can be expressed analytically as a superposition of these eigenmodes and the accuracy depends only on the number of modes $N$ included. On this basis, we compute ideal limits of light-trapping performance for prototypical lamellar metal surface relief gratings in amorphous silicon (a-Si) PV cells assuming that light absorption in the metal and front surface reflection can be suppressed. We show that geometric asymmetry can increase absorption. For large enough $N$, convergence of absorption spectra for E polarisation is reached. For H polarisation it is reached for wavelengths $\\lambda<$680-700 nm, while the integrated AM1.5-weighted absorption varies by less than 1\\% at large $N$. For an a-Si layer with height 200 nm and normal incidence, we obtain upper limits of the total absorption of 79...

  12. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation

    International Nuclear Information System (INIS)

    Purpose: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. Methods and Materials: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. Results: An unexpected 97% (29 out of 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. Conclusions: A high proportion of neurologically normal patients with limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration

  13. Adaptive interference-aware multichannel assignment for shared overloaded small-cell access points under limited feedback

    KAUST Repository

    Radaydeh, Redha Mahmoud

    2014-02-01

    This paper proposes a reduced-complexity multichannel assignment scheme for short-range cellular systems. It treats the scenario when a number of small-cell (e.g., femtocell) access points (APs) can be shared to serve active scheduled users. The APs employ isotropic antenna arrays and operate using an open-access control strategy. To improve the reuse ratio of physical resources, the APs are assumed to occupy a single physical channel, wherein coordination among them is infeasible. On the other hand, to improve the spatial coverage, a scheduled user can be served by a single transmit channel from an AP at a time. For the case of overloaded APs and when the feedback links are capacity limited, the scheme attempts to identify the suitable transmit channels from the deployed APs in an adaptive manner such that certain performance and/or processing load limits are satisfied. The effects of some system and design parameters on the outcomes of the scheme are thoroughly discussed. Novel results for the statistics of the resulting interference power are presented, from which results for some performance measures and processing loads are obtained. Numerical and simulations results are provided to clarify the achieved gains, as compared with related models under different operating conditions. © 2013 IEEE.

  14. A p53-dependent response limits epidermal stem cell functionality and organismal size in mice with short telomeres.

    Directory of Open Access Journals (Sweden)

    Ignacio Flores

    Full Text Available Telomere maintenance is essential to ensure proper size and function of organs with a high turnover. In particular, a dwarf phenotype as well as phenotypes associated to premature loss of tissue regeneration, including the skin (hair loss, hair graying, decreased wound healing, are found in mice deficient for telomerase, the enzyme responsible for maintaining telomere length. Coincidental with the appearance of these phenotypes, p53 is found activated in several tissues from these mice, where is thought to trigger cellular senescence and/or apoptotic responses. Here, we show that p53 abrogation rescues both the small size phenotype and restitutes the functionality of epidermal stem cells (ESC of telomerase-deficient mice with dysfunctional telomeres. In particular, p53 ablation restores hair growth, skin renewal and wound healing responses upon mitogenic induction, as well as rescues ESCmobilization defects in vivo and defective ESC clonogenic activity in vitro. This recovery of ESC functions is accompanied by a downregulation of senescence markers and an increased proliferation in the skin and kidney of telomerase-deficient mice with critically short telomeres without changes in apoptosis rates. Together, these findings indicate the existence of a p53-dependent senescence response acting on stem/progenitor cells with dysfunctional telomeres that is actively limiting their contribution to tissue regeneration, thereby impinging on tissue fitness.

  15. Lysosome-dependent p300/FOXP3 degradation and limits Treg cell functions and enhances targeted therapy against cancers.

    Science.gov (United States)

    Du, Taofeng; Nagai, Yasuhiro; Xiao, Yan; Greene, Mark I; Zhang, Hongtao

    2013-08-01

    p300 is one of several acetyltransferases that regulate FOXP3 acetylation and functions. Our recent studies have defined a complex set of histone acetyltransferase interactions which can lead to enhanced or repressed changes in FOXP3 function. We have explored the use of a natural p300 inhibitor, Garcinol, as a tool to understand mechanisms by which p300 regulates FOXP3 acetylation. In the presence of Garcinol, p300 appears to become disassociated from the FOXP3 complex and undergoes lysosome-dependent degradation. As a consequence of p300's physical absence, FOXP3 becomes less acetylated and eventually degraded, a process that cannot be rescued by the proteasome inhibitor MG132. p300 plays a complex role in FOXP3 acetylation, as it could also acetylate a subset of four Lys residues that repressively regulate total FOXP3 acetylation. Garcinol acts as a degradation device to reduce the suppressive activity of regulatory T cells (Treg) and to enhance the in vivo anti-tumor activity of a targeted therapeutic anti-p185(her2/neu) (ERBB2) antibody in MMTV-neu transgenics implanted with neu transformed breast tumor cells. Our studies provide the rationale for molecules that disrupt p300 stability to limit Treg functions in targeted therapies for cancers. PMID:23644046

  16. Limited disease of extra-pulmonary small cell carcinoma. Impact of local treatment and nodal status, role of cranial irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, A.C.; Gani, C.; Weinmann, M.; Bamberg, M.; Eckert, F. [Tuebingen Univ. (Germany). Dept. of Radiooncology; Mayer, F. [Tuebingen Univ. (Germany). Dept. of Medical Oncology; Sipos, B. [Tuebingen Univ. (Germany). Dept. of Pathology

    2012-03-15

    As extra-pulmonary small cell carcinoma (EPSCC) is a rare entity of tumors, the available treatment recommendations are mainly based on retrospective analyses and deduction from treatment of small cell lung cancer. The aim of this study was to provide a detailed analysis concerning prognostic factors and treatment modalities. A total of 20 patients with limited disease (LD) of EPSCC treated at our institution from 1999-2009 were retrospectively analyzed. Data were gathered from chart review. Localization, lymph node involvement, as well as local and systemic treatment were documented and their impact on pattern of failure and survival times statistically evaluated. With a median follow-up of 21 months, the estimated median overall- and disease-free survival were 59 and 25 months, respectively. Local control was excellent with 100% at 2 years. Nodal involvement was observed in 74% (n = 14/19) of evaluable patients. However, outcome was not altered by this parameter. Local treatment consisted of surgery in 10 cases, radiotherapy in 7 cases, and a combination of both in 3 cases. Only 3 patients (15%) developed hematogenous central nervous system metastases, while none of the patients received prophylactic cranial irradiation. Nodal involvement did not worsen prognosis. Local control was excellent irrespective of local treatment modality and the leading cause of failure was distant metastasis. Therefore, systemic treatment should not be omitted. Prophylactic cranial irradiation might be dispensable but discussed for head and neck malignancies.

  17. Inefficient assembly limits transport and cell surface expression of HLA-Cw4 molecules in C1R.

    Science.gov (United States)

    Zemmour, J

    1996-12-01

    HLA-C antigens are expressed to the cell surface at roughly 10% the level of HLA-B or -A, and their serological definition remains persistently difficult. To characterize the factors limiting surface expression, the processes of assembly and intracellular transport of HLA-Cw4 molecules were investigated in the C1R cell line. When appropriate peptides were added to cultured cells or in cell lysates significant amounts of conformed HLA-C molecules that associate with beta 2-microglobulin (beta 2 m) are detected, but are indeed not sufficient to restore expression to the level observed for HLA-A or -B molecules. Furthermore, a precursor/product relationship exists between the free class I heavy chain and the mature conformation of HLA-Cw4 molecules. Thus, HLA-C assembly promotes the conversion of HC-10-reactive molecules (weakly-beta 2m-associated non-ligand associated free HC form) into the beta 2m-associated class I molecules recognized by W6/32. To further investigate the factors that regulate cell surface expression, intracellular transport of HLA-Cw4 was studied in pulse chase analysis. In contrast to some HLA-A and B, maturation of HLA-Cw4 heavy chains and their export to the medial and trans-Golgi compartments are quite inefficient. After 4 h of chase period, roughly half of the pulse-labeled HLA-Cw4 molecules have transited to the medial-Golgi and acquired complex oligosaccharides characteristic of mature form. In addition, treatment with gamma-interferon does not appear to improve maturation of HLA-Cw4 heavy chains, suggesting that increased supply of peptides does not influence intracellular transport. Moreover, only a small fraction in the pool of HLA-Cw4 molecules was subsequently transported through the trans-Golgi network, as indicated by their acquisition of sialic acids. Taken together these studies show that HLA-Cw4 molecules are inefficiently transported through the Golgi apparatus and presumably retained in the endoplasmic reticulum or cis

  18. Correlations Between the Density of Tryptase Positive Mast Cells (DMCT) and that of New Blood Vessels (CD105+) in Patients with Gastric Cancer.

    Science.gov (United States)

    Micu, Gianina Viorica; Stăniceanu, Florica; Sticlaru, Liana Cătălina; Popp, Cristiana Gabriela; Bastian, Alexandra Eugenia; Gramada, Eliza; Pop, G; Mateescu, R B; Rimbaş, M; Archip, Bianca; Bleotu, Coralia

    2016-06-01

    Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells) and CD 105 (for new vessels). Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement. PMID:27352440

  19. Metabolic regulation of 'Ca. Methylacidiphilum fumariolicum' SolV cells grown under different nitrogen and oxygen limitations

    Directory of Open Access Journals (Sweden)

    Ahmad F. eKhadem

    2012-07-01

    Full Text Available Aerobic methanotrophic bacteria can use methane as their sole energy source. The discovery of ‘Ca. Methylacidiphilum fumariolicum’ strain SolV and other verrucomicrobial methanotrophs has revealed that the ability of bacteria to oxidize CH4 is much more diverse than has previously been assumed in terms of ecology, phylogeny and physiology. A remarkable characteristic of the methane-oxidizing Verrucomicrobia is their extremely acidophilic phenotype, growing even below pH 1. In this study we used RNA-Seq to analyze the metabolic regulation of ‘Ca. M. fumariolicum’ SolV cells growing at μmax in batch culture or under nitrogen fixing or oxygen limited conditions in chemostats, all at pH 2. The analysis showed that two of the three pmoCAB operons each encoding particulate methane monoxygenases were differentially expressed, probably regulated by the available oxygen. The hydrogen produced during N2 fixation is apparently recycled as demonstrated by the upregulation of the genes encoding a Ni/Fe-dependent hydrogenase. These hydrogenase genes were also upregulated under low oxygen conditions. Handling of nitrosative stress was shown by the expression of the nitric oxide reductase encoding genes norB and norC under all conditions tested, the upregulation of nitrite reductase nirK under oxygen limitation and of hydroxylamine oxidoreductase hao in the presence of ammonium. Unraveling the gene regulation of carbon and nitrogen metabolism helps to understand the underlying physiological adaptations of strain SolV in view of the harsh conditions of its natural ecosystem.

  20. Hyperosmosis and its combination with nutrient-limitation are novel environmental stressors for induction of triacylglycerol accumulation in cells of Chlorella kessleri.

    Science.gov (United States)

    Hirai, Kazuho; Hayashi, Taihei; Hasegawa, Yuri; Sato, Atsushi; Tsuzuki, Mikio; Sato, Norihiro

    2016-01-01

    Triacylglycerols of oleaginous algae are promising for production of food oils and biodiesel fuel. Air-drying of cells induces triacylglycerol accumulation in a freshwater green alga, Chlorella kessleri, therefore, it seems that dehydration, i.e., intracellular hyperosmosis, and/or nutrient-limitation are key stressors. We explored this possibility in liquid-culturing C. kessleri cells. Strong hyperosmosis with 0.9 M sorbitol or 0.45 M NaCl for two days caused cells to increase the triacylglycerol content in total lipids from 1.5 to 48.5 and 75.3 mol%, respectively, on a fatty acid basis, whereas nutrient-limitation caused its accumulation to 41.4 mol%. Even weak hyperosmosis with 0.3 M sorbitol or 0.15 M NaCl, when nutrient-limitation was simultaneously imposed, induced triacylglycerol accumulation to 61.9 and 65.7 mol%, respectively. Furthermore, culturing in three-fold diluted seawater, the chemical composition of which resembled that of the medium for the combinatory stress, enabled the cells to accumulate triacylglycerol up to 24.7 weight% of dry cells in only three days. Consequently, it was found that hyperosmosis is a novel stressor for triacylglycerol accumulation, and that weak hyperosmosis, together with nutrient-limitation, exerts a strong stimulating effect on triacylglycerol accumulation. A similar combinatory stress would contribute to the triacylglycerol accumulation in air-dried C. kessleri cells. PMID:27184595

  1. Patterns of failure in combined chemotherapy and radiotherapy for limited small cell lung cancer: Southeastern Cancer Study Group experience

    International Nuclear Information System (INIS)

    In this analysis, we compare the patterns of failure in the first 12 months for 660 eligible patients randomized to two Southeastern Cancer Study Group (SECSG) protocols for limited extent, small cell carcinoma of the lung between 1978 and 1985. In each protocol, a different schedule of radiotherapy was given in conjunction with combination chemotherapy and was compared with combination chemotherapy alone. In protocol 78 LUN 328, radiotherapy was given between courses of chemotherapy, and in protocol LUN 81343, it was given simultaneously. The rates of local failure, either as an initial or subsequent site, in the first 12 months were significantly lower when thoracic irradiation was given than when it was not (P less than .01). When the 2 radiotherapy arms were compared, there were no significant differences in the rates of local failure alone, but a smaller proportion of patients developed both local failure and distant metastases (P less than .01) when simultaneous radiotherapy was administered. Survival on all 4 arms was similar during the first 2 years of patient study. After 2 years, both radiotherapy regimens showed a trend toward improved survival compared with the combination drug alone (cyclophosphamide, doxorubicin, vincristine) arms. On both protocols, survival from 12 months was significantly longer for those with local control at 12 months than for those who did not show local control

  2. Limited-stage small cell lung cancer. Local failure after concurrent chemoradiotherapy with use of accelerated hyperfractionation

    International Nuclear Information System (INIS)

    The aim of this study was to update data of radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer, a retrospective study was conducted. Results of early concurrent chemoradiotherapy with accelerated hyperfractionation in 30 patients between 1998 and 2005 were retrospectively reviewed. The prescribed dose was 45 Gy in 30 fractions in all patients. All patients received a full dose of radiation therapy; however, interruptions for ≥5 days, mainly due to hematologic toxicity, were required in 18 patients (60%). The 5-year Kaplan-Meier survival rate and the median survival time were 26% and 26 months, respectively. The 4-year in-field control rate was 56%. Sites of relapse were local relapse in 9 patients (6 for in-field relapse, 3 for marginal relapse) and distant metastases in 16 patients (11 for distant metastases only, 5 for distant metastases with local relapse). The sites of marginal relapse were the upper margin in two patients and the peripheral margin in one patient. Grade 3 radiation esophagitis was observed in only three patients. Because in-field control was insufficient, a more effective approach should be sought to provide better local control. (author)

  3. Pancreatic GIST in a Patient with Limited Stage Small Cell Lung Cancer: A Case Report and Review of Published Cases.

    Science.gov (United States)

    Phan, Minh; Jones, Shari; Jenkins, Justin; Pant, Shubham; Khawandanah, Mohamad

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and usually occur in the stomach and the small intestine. The pancreas is an extremely rare primary site for GISTs and there are 25 reported cases of pancreatic GIST with most being treated with surgical resection. We describe a 52-year-old African-American female who was diagnosed with limited stage small cell carcinoma in November 2009 and treated with concurrent cisplatin/etoposide chemotherapy and radiation. She subsequently achieved complete remission. Two years later she was diagnosed with localized pancreatic GIST by endoscopic ultrasonography guided fine needle aspiration. We treated her with a tyrosine kinase inhibitor (TKI) imatinib 400 mg oral dose daily as she declined surgery. Her disease is stable based on computed tomography imaging scans 40 months after diagnosis without any metastasis. To the best of our knowledge, our case is the second case of localized pancreatic GIST treated with TKI monotherapy. PMID:27579203

  4. Limited external irradiation and interstitial 192iridium implant in the treatment of squamous cell carcinoma of the tonsillar region

    International Nuclear Information System (INIS)

    Between January 1976 and March 1982, 80 patients with histologically proven diagnosis of squamous cell carcinoma of the tonsillar region were treated with definitive radiotherapy. Sixty-five (81%) of these patients had locally advanced tumors (Stage III and IV); 49% of patients had clinically palpable cervical lymphadenopathy. All patients received a combined external megavoltage and interstitial irradiation. The dose of external irradiation was limited to 4500-5000 cGy over 41/2 to 51/2 weeks. This was followed by interstitial 192iridium implants to doses of 2000-2500 cGy in 50-60 hours for T1, T2 lesions and 3000-4000 cGy in 60-100 hours for T3, T4 lesions. The neck masses were also separately implanted to deliver additional doses of 2000-4000 cGy in 50-80 hours. Overall local tumor control was observed in 84% of patients with a minimum follow-up period of 2 years. An absolute 3-year disease free survival of the entire group was 72%. Treatment related complications such as soft tissue necrosis or osteoradionecrosis occurred in 6% (5/80) of patients. The salvage of neck failures and local failures was possible in 78 and 38% of patients, respectively, either by surgery or by re-irradiation employing interstitial 192iridium implants. Functional and esthetic integrity was well preserved in most cases

  5. CD4+ CD25+ FoxP3+ regulatory T cells suppress cytotoxicity of CD8+ effector T cells: implications for their capacity to limit inflammatory central nervous system damage at the parenchymal level

    Directory of Open Access Journals (Sweden)

    Göbel Kerstin

    2012-02-01

    Full Text Available Abstract Background CD4+ CD25+ forkhead box P3 (FoxP3+ regulatory T cells (T reg cells are known to suppress adaptive immune responses, key control tolerance and autoimmunity. Methods We challenged the role of CD4+ T reg cells in suppressing established CD8+ T effector cell responses by using the OT-I/II system in vitro and an OT-I-mediated, oligodendrocyte directed ex vivo model (ODC-OVA model. Results CD4+ T reg cells dampened cytotoxicity of an ongoing CD8+ T effector cell attack in vitro and within intact central nervous system tissue ex vivo. However, their suppressive effect was limited by the strength of the antigen signal delivered to the CD8+ T effector cells and the ratio of regulatory to effector T cells. CD8+ T effector cell suppression required T cell receptor-mediated activation together with costimulation of CD4+ T reg cells, but following activation, suppression did not require restimulation and was antigen non-specific. Conclusions Our results suggest that CD4+ T reg cells are capable of suppressing CD8+ T effector cell responses at the parenchymal site, that is, limiting parenchymal damage in autoimmune central nervous system inflammation.

  6. The Impact of Radiation Dose and Fractionation on Outcomes for Limited-Stage Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients and to compare the outcomes among three groups in which the total radiation doses were 45 Gy with accelerated hyperfractionation (AHF), <54 Gy with standard fractionation (SF), and ≥54 Gy with SF. Methods and Materials: LS-SCLC patients that had been treated with chemoradiotherapy between 1997 and 2007 at Aichi Cancer Center Hospital were reviewed in this study. Of the 127 eligible patients, there were 37 patients in the AHF group, 29 in the SF <54 Gy group, and 61 in the SF ≥54 Gy group. Results: Fifty-five patients (43%) were alive at the time of this analysis, and the median follow-up time of the surviving patients was 33 months. The median survival times were 30.0 months (95% confidence interval [CI] 16.3-43.7) for the AHF group, 14.0 months (CI 6.6-21.4) for the SF <54 Gy group, and 41.0 months (CI 33.9-48.1) for the SF ≥ 54 Gy group. As for the local control rates, and the overall and progression-free survival rates, all outcomes were significantly lower in the SF <54 Gy group than in the other two groups, although no significant difference was found between the AHF and SF ≥54 Gy groups. Conclusions: These results suggest the importance of a high dose of radiation when using once-daily regimen. This study will support future prospective studies to establish optimal radiation doses and fractionation.

  7. Role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae

    International Nuclear Information System (INIS)

    Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of posttreatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated

  8. Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration

    OpenAIRE

    Song, Minjung; Lavasani, Mitra; Thompson, Seth D.; Lu, Aiping; Ahani, Bahar; Huard, Johnny

    2013-01-01

    Introduction Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle. Methods We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24 -/-) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function. Results Our ...

  9. Optimal labeling dose, labeling time, and magnetic resonance imaging detection limits of ultrasmall superparamagnetic iron-oxide nanoparticle labeled mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Hansen, Louise; Friis, Tina;

    2013-01-01

    Background. Regenerative therapy is an emerging treatment modality. To determine migration and retention of implanted cells, it is crucial to develop noninvasive tracking methods. The aim was to determine ex vivo magnetic resonance imaging (MRI) detection limits of ultrasmall superparamagnetic iron...

  10. A meta-analysis of the Timing of Chest Radiotherapy in Patients with Limited-stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hui ZHAO

    2010-09-01

    Full Text Available Background and objective Although evidence for a significant survival benefit of chest radiotherapy has been proven, no conclusion could be drawn regarding the optimal timing of chest radiation. The aim of this study is to explore whether the timing of chest radiation may influence the survival of the patients with limited-stage small-cell lung cancer (LSSCLC by performing a literature-based meta-analysis. Methods By searching Medline, CENTRAL (the Cochrane central register of controlled trials, CBM, and CNKI, et al, we collected both domestic and overseas published documents about randomized trials comparing different timing chest radiotherapy in patients with LS-SCLC. Early chest radiation was regarded as beginning within 30 days after the start of chemotherapy. Random or fixed effect models were applied to conduct meta-analysis on the trials. The combined odds ratio (OR and the 95% confidence interval (CI were calculated to estimate the mortality in 2 or 3 years and toxicity of the two treatments. The statistical heterogeneity was determined by cochran’s Chi-square test (Q test. The Begg’ test was used to determine the publication bias. Results Six trials that included a total of 1 189 patients were analyzed in the meta-analysis 587 patients were in the early radiation group and 602 patients were in the late radiation group. Considering all 6 eligible trials, the overall survival at 2/3 years was not significantly different between early and late chest radiation (OR=0.78, 95%CI: 0.55-1.05, Z=1.68, P=0.093. For the toxicity, no obvious difference was observed for early chest radiotherapy compared with late irradiation in pneumonitis (OR=1.93, 95%CI: 0.97-3.86, P=0.797, esophagitis (OR=1.43, 95%CI: 0.95-2.13, P=0.572 and thrombocytopenia (OR=1.23, 95%CI: 0.88-1.77, P=0.746, respectively. Conclusion No statistical difference was observed in 2/3 years survival and toxicity, including pneumonitis, esophagitis and thrombocytopenia, between

  11. A Prospective Randomized Study of the Radiotherapy Volume for Limited-stage Small Cell Lung Cancer: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Xiao HU

    2010-07-01

    Full Text Available Background and objective Controversies exists with regard to target volumes as far as thoracic radiotherapy (TRT is concerned in the multimodality treatment for limited-stage small cell lung cancer (LSCLC. The aim of this study is to prospectively compare the local control rate, toxicity profiles, and overall survival (OS between patients received different target volumes irradiation after induction chemotherapy. Methods LSCLC patients received 2 cycles of etoposide and cisplatin (EP induction chemotherapy and were randomly assigned to receive TRT to either the post- or pre-chemotherapy tumor extent (GTV-T as study arm and control arm, CTV-N included the positive nodal drainage area for both arms. One to 2 weeks after induction chemotherapy, 45 Gy/30 Fx/19 d TRT was administered concurrently with the third cycle of EP regimen. After that, additional 3 cycles of EP consolidation were administered. Prophylactic cranial irradiation (PCI was administered to patients with a complete response. Results Thirty-seven and 40 patients were randomly assigned to study arm and control arm. The local recurrence rates were 32.4% and 28.2% respectively (P=0.80; the isolated nodal failure (INF rate were 3.0% and 2.6% respectively (P=0.91; all INF sites were in the ipsilateral supraclavicular fossa. Medastinal N3 disease was the risk factor for INF (P=0.02, OR=14.13, 95%CI: 1.47-136.13. During radiotherapy, grade I, II weight loss was observed in 29.4%, 5.9% and 56.4%, 7.7% patients respectively (P=0.04. Grade 0-I and II-III late pulmonary injury was developed in 97.1%, 2.9% and 86.4%, 15.4% patients respectively (P=0.07. Median survival time was 22.1 months and 26.9 months respectively. The 1 to 3-year OS were 77.9%, 44.4%, 37.3% and 75.8%, 56.3%, 41.7% respectively (P=0.79. Conclusion The preliminary results of this study indicate that irradiant the post-chemotherapy tumor extent (GTV-T and positive nodal drainage area did not decrease local control and overall

  12. Clinical outcomes of concurrent three-dimensional conformal radiotherapy and chemotherapy for limited-stage small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate therapeutic effects and complications of concurrent three-dimensional conformal radiotherapy (3DCRT) and chemotherapy in patients with limited-stage small cell lung cancer (LSCLC). Methods: From June 2000 to August 2005, 93 histologically proved LSCLC patients were randomized into two groups:3DCRT group (n =46) and conventional group (n =47). In both groups, patients received one cycle chemotherapy, followed by concurrent chemoradiotherapy and then received consolidate chemotherapy. Chemotherapy was four to six cycles of PE regimen. Conventional irradiation field was setup in conventional group, while in 3 DCRT group clinical target volume (CTV) only involved visible tumor and adjacent lymphatic region. Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week to a median total dose of 60 -64 Gy.Those who achieved a complete response were treated with prophylactic cranial irradiation (PCI) with 30 Gy in 10 fractions. Results: The follow-up rate was 100% in both groups. The number of patients completed 1-, 2-and 3-year follow-up were 36, 34 and 16 in 3DCRT group, 14, 7 and 8 in conventional group, respectively. The complete and overall response rate were 52% and 89% in 3DCRT group, while 47% and 85% in conventional group, respectively. The 1-, 2-and 3-year survival rates were 78%, 35% and 15% in 3DCRT group, 72%, 30% and 17% in conventional group, respectively. The median survival time was 23.2 and 22.8 months, respectively. There was no statistical difference in short-term (χ2 = 0.34, P = O.759) and long-term outcomes (χ2 = 0.18, P = 0.92). In 3DCRT group, the incidence of grade 1 + 2 acute radiation pneumonitis and esophagitis, grade 1 +2 and grade 3 chronic radiation pneumonitis were lower than those in conventional group. There was no grade 3 or 4 acute radiation pneumonitis or esophagitis, or grade 4 chronic radiation pneumonitis in both groups. There was no difference in grade 1 + 2, grade 3 or grade 4 acute

  13. The effect of dose fractionation on overall survival in patients with limited-stage small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To study the effect of different dose fractionation on overall survival in patients with limited-stage small cell lung cancer (LS-SCLC). Methods: LS-SCLC patients treated with radical combined chemotherapy and radiotherapy (RT) between January 2001 and Dec 2007 were analyzed retrospectively. According to the dose fractionation schemes, patients were divided into three groups: conventional fractionated RT (1. 8 -2.0 Gy, once daily), hyperfractionated RT (1.4 Gy, twice daily) and hypo fractionated RT (2. 5 Gy,once daily). Overall survival, disease free survival and pattern of failures of the three groups were compared. A total of 177 patients were enrolled, including 63 patients in conventional fractionated RT group, 79 in hyperfractionated RT group and 35 in hypo fractionated RT group. Results: The overall follow-up rate was 96. 6%. The patient numbers with follow-up of more than 2 and 5 years were 153 and 92, respectively. The median survival time of the entire group was 22. 4 months, and the 2-and 5-year survival rates were 43.4% and 23.5%, respectively. The 2-year survival rates for three groups were 31%, 46% and 59% (χ2 =7.94, P=0.019), respectively. The 2-year disease free survival for three groups were 20%, 31% and 40% (χ2 = 4.86, P = 0.088), respectively. In the pairwise comparisons, patients in hypo fractionated RT group have better survival than those in conventional fractionated RT group (χ2 = 7.81, P = 0.005), the effect of hyperfractionated RT group lies between the hypo-and the conventional fractionated RT groups, but no significant differences were detected (χ2 = 2.31, P = 0.128; χ2 = 2.95, P =0.086). The mildest side effect was found in the hypo fractionated RT group. No statistically significant differences were found in the patterns of first failure. Conclusion: The hypo fractionated RT scheme showed potential survival benefits for patients with LS-SCLC and should be considered in the setting of randomized clinical trials. (authors)

  14. Glucose oxidase as a biocatalytic enzyme-based bio-fuel cell using Nafion membrane limiting crossover

    Science.gov (United States)

    Naidoo, S.; Naidoo, Q.; Blottnitz, H.; Vaivars, G.

    2013-12-01

    A novel combination for an Enzyme-based Biofuel cell included a Nafion membrane as an ion transporter that maintained a working cell charge and inhibited membrane degradation. The prototype cell chamber used oxygen (O2) in the cathode cell and glucose in the anode. The Nafion membrane stability studied here was evidently in the region of 0% loss of conductivity as the charge was constant and increased after the addition of glucose. The prototype cell chamber used NaCl in the cathode cell and glucose oxidase (GOx) in the anodic chamber was successfully studied for membrane stability showed in this study no evidence of poisoning from membrane leakage in a controlled pH environment. There was no crossover at the anaerobic operating ambient temperatures and under physiological pH 5 - 7 conditions. In this research we have successfully used a Nafion membrane together with GOx and under controlled conditions produced respectable power densities.

  15. Glucose oxidase as a biocatalytic enzyme-based bio-fuel cell using Nafion membrane limiting crossover

    International Nuclear Information System (INIS)

    A novel combination for an Enzyme-based Biofuel cell included a Nafion membrane as an ion transporter that maintained a working cell charge and inhibited membrane degradation. The prototype cell chamber used oxygen (O2) in the cathode cell and glucose in the anode. The Nafion membrane stability studied here was evidently in the region of 0% loss of conductivity as the charge was constant and increased after the addition of glucose. The prototype cell chamber used NaCl in the cathode cell and glucose oxidase (GOx) in the anodic chamber was successfully studied for membrane stability showed in this study no evidence of poisoning from membrane leakage in a controlled pH environment. There was no crossover at the anaerobic operating ambient temperatures and under physiological pH 5 – 7 conditions. In this research we have successfully used a Nafion membrane together with GOx and under controlled conditions produced respectable power densities

  16. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells

    OpenAIRE

    Benoit, Marie E; Clarke, Elizabeth V.; Morgado, Pedro; Fraser, Deborah A.; Tenner, Andrea J.

    2012-01-01

    Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like auto-immune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. Here, we developed an autologous system using primary human lymphocytes and monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrop...

  17. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells.

    OpenAIRE

    Benoit, Marie E; Clarke, Elizabeth V.; Morgado, Pedro; Fraser, Deborah A.; Tenner, Andrea J.

    2012-01-01

    Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like autoimmune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. In this study, we developed an autologous system using primary human lymphocytes and human monocyte-derived macrophages (HMDMs) to characterize the effect of...

  18. Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169+ Macrophage Function during Viral Infection

    OpenAIRE

    Xu, Haifeng C.; Huang, Jun; Khairnar, Vishal; Duhan, Vikas; Pandyra, Aleksandra A; Grusdat, Melanie; Shinde, Prashant; McIlwain, David R.; Maney, Sathish Kumar; Gommerman, Jennifer; Löhning, Max; Ohashi, Pamela S.; Mak, Tak W; Pieper, Kathrin; Sic, Heiko

    2015-01-01

    The B cell-activating factor (BAFF) is critical for B cell development and humoral immunity in mice and humans. While the role of BAFF in B cells has been widely described, its role in innate immunity remains unknown. Using BAFF receptor (BAFFR)-deficient mice, we characterized BAFFR-related innate and adaptive immune functions following infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV). We identified a critical role for BAFFR signaling in the gener...

  19. The cotyledon cell wall and intracellular matrix are factors that limit iron bioavailability of the common bean (Phaseolus vulgaris).

    Science.gov (United States)

    Glahn, Raymond P; Tako, Elad; Cichy, Karen; Wiesinger, Jason

    2016-07-13

    Strategies that enhance the Fe bioavailability of the bean are of keen interest to nutritionists, bean breeders and growers. In beans, the cotyledons contain 75-80% of the total seed Fe, most of which appears to be located within the cotyledon cells. The cotyledon cell walls are known to be resistant to digestion in the stomach and the upper small intestine. Therefore, given the above and the general belief that the primary site for human Fe absorption is the upper small intestine, the present study was designed to determine if the cotyledon cell walls represent a barrier to Fe absorption from the bean. To do so, we utilized high pressure to rupture bean cotyledon cells. The iron bioavailability of cooked bean samples was assessed using an in vitro digestion/Caco-2 cell culture model. Microscopy analyses confirmed that the cotyledon cell walls are highly resistant to pepsin, the low pH of the stomach, and the pancreatic enzymes, indicating that the walls are a barrier to Fe absorption from the bean. Relatively high intracellular pressure (>4000 psi) was required to initiate cell wall rupture. Surprisingly, the lysis of cotyledon cells did not result in a consistent or strong enhancement of bioavailable Fe, suggesting that the liberated intracellular starch and protein influenced the Fe bioavailability by creating a matrix that inhibited the exchange of Fe with the cell transport mechanism. Such observations warrant further pursuit in vivo as the confirmation of these effects would reshape strategies to enhance Fe absorption from beans. PMID:27326892

  20. Production and cleavage specificity determination of serine proteases mMCP-4, mMCP-5, rMCP-2 and two platypus serine proteases of the chymase locus.

    OpenAIRE

    Sidibeh, Cherno Omar

    2013-01-01

    Serine proteases are a family of enzymes with a wide array of functions across both eukaryotes and prokaryotes. Here we have attempted to produce the serine proteases rat mast cell protease 2 and mouse mast cell protease 5 in a culture of HEK 293 cells; and mouse mast cell protease 4, platypus granzyme B-like protease and platypus hypothetical protease in a baculovirus expression system. Following production we wanted to analyse these serine proteases using a phage display assay and a battery...

  1. SF Treg cells transcribing high levels of Bcl-2 and microRNA-21 demonstrate limited apoptosis in RA

    NARCIS (Netherlands)

    van der Geest, Kornelis S. M.; Smigielska, Katarzyna; Park, Ji-Ah; Abdulahad, Wayel H.; Kim, Hye-Won; Kroesen, Bart-Jan; van den Berg, Anke; Boots, Annemieke M. H.; Lee, Eun-Bong; Brouwer, Elisabeth

    2015-01-01

    Objective. The aim of this study was to investigate the turnover of Treg cells in the SF of RA patients. Methods. Treg cells were enumerated in peripheral blood and SF of RA patients and analysed by flow cytometry for expression of the proliferation marker Ki-67 and binding of the apoptosis marker a

  2. Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota.

    Science.gov (United States)

    Sun, Jia; Furio, Laetitia; Mecheri, Ramine; van der Does, Anne M; Lundeberg, Erik; Saveanu, Loredana; Chen, Yongquan; van Endert, Peter; Agerberth, Birgitta; Diana, Julien

    2015-08-18

    Antimicrobial peptides (AMPs) expressed by epithelial and immune cells are largely described for the defense against invading microorganisms. Recently, their immunomodulatory functions have been highlighted in various contexts. However how AMPs expressed by non-immune cells might influence autoimmune responses in peripheral tissues, such as the pancreas, is unknown. Here, we found that insulin-secreting β-cells produced the cathelicidin related antimicrobial peptide (CRAMP) and that this production was defective in non-obese diabetic (NOD) mice. CRAMP administrated to prediabetic NOD mice induced regulatory immune cells in the pancreatic islets, dampening the incidence of autoimmune diabetes. Additional investigation revealed that the production of CRAMP by β-cells was controlled by short-chain fatty acids produced by the gut microbiota. Accordingly, gut microbiota manipulations in NOD mice modulated CRAMP production and inflammation in the pancreatic islets, revealing that the gut microbiota directly shape the pancreatic immune environment and autoimmune diabetes development. PMID:26253786

  3. Interference Alignment-based Precoding and User Selection with Limited Feedback in Two-cell Downlink Multi-user MIMO Systems

    Directory of Open Access Journals (Sweden)

    Yin Zhu

    2016-05-01

    Full Text Available Interference alignment (IA is a new approach to address interference in modern multiple-input multiple-out (MIMO cellular networks in which interference is an important factor that limits the system throughput. System throughput in most IA implementation schemes is significantly improved only with perfect channel state information and in a high signal-to-noise ratio (SNR region. Designing a simple IA scheme for the system with limited feedback and investigating system performance at a low-to-medium SNR region is important and practical. This paper proposed a precoding and user selection scheme based on partial interference alignment in two-cell downlink multi-user MIMO systems under limited feedback. This scheme aligned inter-cell interference to a predefined direction by designing user’s receive antenna combining vectors. A modified singular value decomposition (SVD-based beamforming method and a corresponding user-selection algorithm were proposed for the system with low rate limited feedback to improve sum rate performance. Simulation results show that the proposed scheme achieves a higher sum rate than traditional schemes without IA. The modified SVD-based beamforming scheme is also superior to the traditional zero-forcing beamforming scheme in low-rate limited feedback systems. The proposed partial IA scheme does not need to collaborate between transmitters and joint design between the transmitter and the users. The scheme can be implemented with low feedback overhead in current MIMO cellular networks.

  4. FOXP3 Inhibits Activation-Induced NFAT2 Expression in T Cells Thereby Limiting Effector Cytokine Expression

    OpenAIRE

    Torgerson, Troy R; Genin, Anna; Chen, Chunxia; Zhang, Mingce; Zhou, Bin; Añover-Sombke, Stephanie; Frank, M Barton; Dozmorov, Igor; Ocheltree, Elizabeth; Kulmala, Petri; Centola, Michael; Ochs, Hans D.; Wells, Andrew D.; Cron, Randy Q

    2009-01-01

    The forkhead DNA-binding protein FOXP3 is critical for the development and suppressive function of CD4+CD25+ regulatory T cells (TREG), which play a key role in maintaining self-tolerance. Functionally, FOXP3 is capable of repressing transcription of cytokine genes regulated by the Nuclear Factor of Activated T cells (NFAT). Various mechanisms have been proposed by which FOXP3 mediates these effects. Using novel cell lines that inducibly express either wild-type (WT) or mutant FOXP3, we have ...

  5. Keeping stem cells under control: New insights into the mechanisms that limit niche-stem cell signaling within the reproductive system.

    Science.gov (United States)

    Inaba, Mayu; Yamashita, Yukiko M; Buszczak, Michael

    2016-08-01

    Adult stem cells reside in specialized microenvironments, called niches, that maintain stem cells in an undifferentiated and self-renewing state. Defining and understanding the mechanisms that restrict niche signaling exclusively to stem cells is crucial to determine how stem cells undergo self-renewal while their progeny, often located just one cell diameter away from the niche, differentiate. Despite extensive studies on the signaling pathways that operate within stem cells and their niches, how this segregation occurs remains elusive. Here we review recent progress on the characterization of niche-stem cell interactions, with a focus on emerging mechanisms that spatially restrict niche signaling. Mol. Reprod. Dev. 83: 675-683, 2016 © 2016 Wiley Periodicals, Inc. PMID:27434704

  6. Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells.

    OpenAIRE

    Steinsbø, Øyvind; Dunand, Carole J. Henry; Huang, Min; Mesin, Luka; Salgado-Ferrer, Marlene; Lundin, Knut E. A; Jahnsen, Jørgen; Wilson, Patrick C.; Sollid, Ludvig M.

    2014-01-01

    Coeliac disease (CD), an enteropathy caused by cereal gluten ingestion, is characterized by CD4+ T cells recognizing deamidated gluten and by antibodies reactive to gluten or the self-antigen transglutaminase 2 (TG2). TG2-specific immunoglobulin A (IgA) of plasma cells (PCs) from CD lesions have limited somatic hypermutation (SHM). Here we report that gluten-specific IgA of lesion-resident PCs share this feature. Monoclonal antibodies were expression cloned from single PCs of patients either ...

  7. Experimental Investigation and Discussion on the Mechanical Endurance Limit of Nafion Membrane Used in Proton Exchange Membrane Fuel Cell

    OpenAIRE

    Yang Xiao; Chongdu Cho

    2014-01-01

    As a solution of high efficiency and clean energy, fuel cell technologies, especially proton exchange membrane fuel cell (PEMFC), have caught extensive attention. However, after decades of development, the performances of PEMFCs are far from achieving the target from the Department of Energy (DOE). Thus, further understanding of the degradation mechanism is needed to overcome this obstacle. Due to the importance of proton exchange membrane in a PEMFC, the degradation of the membrane, such as ...

  8. Smac/DIABLO release from mitochondria and XIAP inhibition are essential to limit clonogenicity of Type I tumor cells after TRAIL receptor stimulation.

    Science.gov (United States)

    Maas, C; Verbrugge, I; de Vries, E; Savich, G; van de Kooij, L W; Tait, S W G; Borst, J

    2010-10-01

    Death receptors, such as Fas/CD95 and TRAIL receptors, engage the extrinsic pathway for caspase activation, but also couple to the intrinsic mitochondrial route. In so-called Type II cells, death receptors require the mitochondrial pathway for apoptotic execution, whereas in Type I cells they reportedly do not. For established tumor cell lines, the Type I/Type II distinction is based on short-term apoptosis assays. We report here that the mitochondrial pathway is essential for apoptotic execution of Type I tumor cells by death receptors, when long-term clonogenicity is taken into account. A blockade of the mitochondrial pathway in Type I tumor cells - by RNA interference for Bid or Bcl-2 overexpression - reduced effector caspase activity and mediated significant clonogenic resistance to TRAIL. Downstream from the mitochondria, Caspase-9 did not contribute to clonogenic death of TRAIL-treated Type I cells. Rather, the release of Smac/DIABLO and the inhibition of XIAP activity proved to be crucial for full effector caspase activity and clonogenic execution. Thus, in Type I cells the intrinsic pathway downstream from death receptors is not redundant, but limits clonogenicity by virtue of Smac/DIABLO release and XIAP inhibition. This finding is relevant for cancer therapy using death receptor agonists. PMID:20395960

  9. Effects of atomic-bomb radiation on human immune responses. 12. Analysis of T cell function using the limiting dilution analysis

    International Nuclear Information System (INIS)

    The study was performed to see whether the exposure to the atomic-bomb radiation gave any influence on the T cell functions. The function of peripheral T cells was analyzed by the limiting dilution analysis in 159 highly exposed subjects (63 males and 96 females; 43-86 years old) whose exposure dose due to the atomic-bomb radiation had been estimated to exceed 1.5 Gy. The control was 251 subjects (102 males and 149 females; the same range of age as above) exposed at a long distance (<0.005 Gy). Subjects were those who visiting the authors' facility for the purpose of health examination and giving the consent. There was any significant difference neither between frequencies of T cells responsible to PHA for proliferation nor between those of CD4 T cells responsible to Con A. In highly exposed subjects, an increase of CD4 T cells incapable of producing IL-2 by Con A stimulation was detected, which suggested a shift of helper T cell to Th-2 cell. (K.H.)

  10. Estimation of the potential efficiency of a multijunction solar cell at a limit balance of photogenerated currents

    International Nuclear Information System (INIS)

    A method is proposed for estimating the potential efficiency which can be achieved in an initially unbalanced multijunction solar cell by the mutual convergence of photogenerated currents: to extract this current from a relatively narrow band-gap cell and to add it to a relatively wide-gap cell. It is already known that the properties facilitating relative convergence are inherent to such objects as bound excitons, quantum dots, donor-acceptor pairs, and others located in relatively wide-gap cells. In fact, the proposed method is reduced to the problem of obtaining such a required light current-voltage (I–V) characteristic which corresponds to the equality of all photogenerated short-circuit currents. Two methods for obtaining the required light I–V characteristic are used. The first one is selection of the spectral composition of the radiation incident on the multijunction solar cell from an illuminator. The second method is a double shift of the dark I–V characteristic: a current shift Jg (common set photogenerated current) and a voltage shift (−JgRs), where Rs is the series resistance. For the light and dark I–V characteristics, a general analytical expression is derived, which considers the effect of so-called luminescence coupling in multijunction solar cells. The experimental I–V characteristics are compared with the calculated ones for a three-junction InGaP/GaAs/Ge solar cell with Rs = 0.019 Ω cm2 and a maximum factual efficiency of 36.9%. Its maximum potential efficiency is estimated as 41.2%

  11. Improvement of the detection limit for determination of 129I in sediments by quadrupole inductively coupled plasma mass spectrometer with collision cell

    OpenAIRE

    Izmer, A. V.; Boulyga, S. F.; Zoriy, M. V.; Becker, J. S.

    2004-01-01

    The previously developed sample introduction device for the hot extraction of iodine from environmental samples (soils or sediments) and on-line introduction of analyte via the gas phase in quadrupole inductively coupled plasma mass spectrometry with hexapole collision cell (ICP-CC-QMS) was equipped with a cooling finger, which allowed intermediate iodine enrichment and improved the detection limits for I-129 down to 0.4 pg g(-1) without any additional sample preparation. A mixture of oxygen ...

  12. Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer

    OpenAIRE

    Ozawa, Yuichi; Omae, Minako; Fujii, Masato; Matsui, Takashi; KATO, Masato; Sagisaka, Shinya; Asada, Kazuhiro; Karayama, Masato; Shirai, Toshihiro; Yasuda, Kazumasa; Nakamura, Yutaro; Inui, Naoki; Yamada, Kazunari; Yokomura, Koshi; Suda, Takafumi

    2015-01-01

    Background Magnetic resonance imaging (MRI) enables a more sensitive detection of brain metastasis and stereotactic irradiation (SRI) efficiently controls brain metastasis. In limited-stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) in patients with good responses to initial treatment is recommended based on the survival benefit shown in previous clinical trials. However, none of these trials evaluated PCI effects using the management of brain metastasis with MRI...

  13. Reactive Oxygen Species Limit the Ability of Bone Marrow Stromal Cells to Support Hematopoietic Reconstitution in Aging Mice

    Science.gov (United States)

    Khatri, Rahul; Krishnan, Shyam; Roy, Sushmita; Chattopadhyay, Saborni; Kumar, Vikash

    2016-01-01

    Aging of organ and abnormal tissue regeneration are recurrent problems in physiological and pathophysiological conditions. This is most crucial in case of high-turnover tissues, like bone marrow (BM). Using reciprocal transplantation experiments in mouse, we have shown that self-renewal potential of hematopoietic stem and progenitor cells (HSPCs) and BM cellularity are markedly influenced with the age of the recipient mice rather than donor mice. Moreover, accumulation of excessive reactive oxygen species (ROS) in BM stromal cells compared to HSPC compartment, in time-dependent manner, suggests that oxidative stress is involved in suppression of BM cellularity by affecting microenvironment in aged mice. Treatment of these mice with a polyphenolic antioxidant curcumin is found to partially quench ROS, thereby rescues stromal cells from oxidative stress-dependent cellular injury. This rejuvenation of stromal cells significantly improves hematopoietic reconstitution in 18-month-old mice compared to age control mice. In conclusion, this study implicates the role of ROS in perturbation of stromal cell function upon aging, which in turn affects BM's reconstitution ability in aged mice. Thus, a rejuvenation therapy using curcumin, before HSPC transplantation, is found to be an efficient strategy for successful marrow reconstitution in older mice. PMID:27140293

  14. Therapeutic expansion of CD4+FoxP3+ regulatory T cells limits allergic airway inflammation during pulmonary fungal infection.

    Science.gov (United States)

    Schulze, Bianca; Piehler, Daniel; Eschke, Maria; Heyen, Laura; Protschka, Martina; Köhler, Gabriele; Alber, Gottfried

    2016-06-01

    Allergic asthma can be frequently caused and exacerbated by sensitization to ubiquitous fungal allergens associated with pulmonary mucus production, airway hyperresponsiveness and bronchial constriction, resulting in a complex disease that is often difficult to treat. Fungal infections are frequently complicated by the development of a type 2 immune response that prevents successful elimination of the fungal pathogen. Furthermore, production of type 2 cytokines triggers allergic airway inflammation. Following intranasal infection of BALB/c mice with the fungusCryptococcus neoformans, we recently described a more pronounced type 2 immune response in the absence of regulatory T (Treg) cells. To determine whether Treg cell expansion is able to suppress type 2-related fungal allergic inflammation, we increased Treg cell numbers during pulmonaryC. neoformansinfection by administration of an interleukin (IL)-2/anti-IL-2 complex. Expansion of Treg cells resulted in reduced immunoglobulin E production and decreased allergic airway inflammation including reduced production of pulmonary mucus and type 2 cytokines as well as production of immunosuppressive cytokines such as IL-10 and transforming growth factor-β1. From our data we conclude that Treg cells and/or their suppressive mediators represent potential targets for therapeutic intervention during allergic fungal airway disease. PMID:27001975

  15. A call to arms: a critical need for interventions to limit pulmonary toxicity in the stem cell transplantation patient population.

    Science.gov (United States)

    Radhakrishnan, Sabarinath Venniyil; Hildebrandt, Gerhard C

    2015-03-01

    Noninfectious pulmonary toxicity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) causes significant morbidity and mortality. Main presentations are idiopathic pneumonia syndrome (IPS) in the acute setting and bronchiolitis obliterans syndrome (BOS) and cryptogenic organizing pneumonia (COP) at later time point. While COP responds well to corticosteroids, IPS and BOS often are treatment refractory. IPS, in most cases, is rapidly fatal, whereas BOS progresses over time, resulting in chronic respiratory failure, impaired quality of life, and eventually, death. Standard second-line treatments are currently lacking, and current approaches, such as augmented T cell-directed immunosuppression, B cell depletion, TNF blockade, extracorporeal photopheresis, and tyroskine kinase inhibitor therapy, are unsatisfactory with responses in only a subset of patients. Better understanding of underlying pathophysiology hopefully results in the identification of future targets for preventive and therapeutic strategies along with an emphasis on currently underutilized rehabilitative and supportive measures. PMID:25662904

  16. A Markov Chain Approach for Defining the Fundamental Efficiency Limits of Classical and Bifacial Multi-junction Tandem Solar Cells

    CERN Document Server

    Alam, Muhammad A

    2016-01-01

    Bifacial tandem cells promise to reduce three fundamental losses (above-bandgap, below bandgap, and the uncollected light between panels) inherent in classical single junction PV systems. The successive filtering of light through the bandgap cascade, and requirement of current continuity make optimization of tandem cells difficult, accessible only to numerical solution through computer modeling. The challenge is even more complicated for bifacial design. In this paper, we use an elegantly simple Markov chain approach to show that the essential physics of optimization is intuitively obvious, and deeply insightful results can obtained analytically with a few lines of algebra. This powerful approach reproduces, as special cases, all the known results of traditional/bifacial tandem cells, and highlights the asymptotic efficiency gain of these technologies.

  17. Study on limiting efficiencies of a-Si:H/μc-Si:H-based single-nanowire solar cells under single and tandem junction configurations

    Science.gov (United States)

    Zhai, Xiongfei; Cao, Guoyang; Wu, Shaolong; Shang, Aixue; Li, Xiaofeng

    2015-11-01

    Detailed balance calculations are presented for a-Si:H/μc-Si:H-based single- and tandem-junction single-nanowire solar cells (S- and T-SNSCs). Our study is based on three-dimensional finite-element electromagnetic simulation and thermodynamic balanced analysis, which includes radiative and Auger recombinations simultaneously. We quantify and compare the limiting short-circuit current densities, open-circuit voltages, and light-conversion efficiencies of these highly compact photovoltaic cells, addressing especially the effect of Auger recombination on the open-circuit voltages of SNSCs. Results show that tandem design leads to much higher light-conversion capability than μc-Si:H S-SNSCs, but exhibits superior performance than a-Si:H S-SNSCs only for cells with large radii.

  18. Study on limiting efficiencies of a-Si:H/μc-Si:H-based single-nanowire solar cells under single and tandem junction configurations

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Xiongfei; Cao, Guoyang; Wu, Shaolong, E-mail: shaolong-wu@suda.edu.cn, E-mail: xfli@suda.edu.cn; Shang, Aixue; Li, Xiaofeng, E-mail: shaolong-wu@suda.edu.cn, E-mail: xfli@suda.edu.cn [College of Physics, Optoelectronics and Energy & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China); Key Lab of Advanced Optical Manufacturing Technologies of Jiangsu Province and Key Lab of Modern Optical Technologies of Education Ministry of China, Soochow University, Suzhou 215006 (China)

    2015-11-02

    Detailed balance calculations are presented for a-Si:H/μc-Si:H-based single- and tandem-junction single-nanowire solar cells (S- and T-SNSCs). Our study is based on three-dimensional finite-element electromagnetic simulation and thermodynamic balanced analysis, which includes radiative and Auger recombinations simultaneously. We quantify and compare the limiting short-circuit current densities, open-circuit voltages, and light-conversion efficiencies of these highly compact photovoltaic cells, addressing especially the effect of Auger recombination on the open-circuit voltages of SNSCs. Results show that tandem design leads to much higher light-conversion capability than μc-Si:H S-SNSCs, but exhibits superior performance than a-Si:H S-SNSCs only for cells with large radii.

  19. A limit to cell radiosensitivity modification under the consecutive actions of ionizing radiation and nonionizing physical factors

    International Nuclear Information System (INIS)

    The application of a mathematical model of synergism in describing the consecutive combined actions of ionizing radiation and other physical agents has been considered. Using various cell systems it has been shown that the model permits to predict the highest dose modifying factor and conditions in which it can be achieved

  20. Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf

    Science.gov (United States)

    Labi, Verena; Bertele, Daniela; Woess, Claudia; Tischner, Denise; Bock, Florian J; Schwemmers, Sven; Pahl, Heike L; Geley, Stephan; Kunze, Mirjam; Niemeyer, Charlotte M; Villunger, Andreas; Erlacher, Miriam

    2013-01-01

    Anti-apoptotic Bcl-2 family members are critical for the regulation of haematopoietic stem and progenitor cell (HSPC) survival. Little is known about the role of their pro-apoptotic antagonists, i.e. ‘BH3-only’ proteins, in this cell compartment. Based on the analysis of cytokine deprivation-induced changes in mRNA expression levels of Bcl-2 family proteins, we determined the consequences of BH3-only protein depletion on HSPC survival in culture and, for selected candidates, on engraftment in vivo. Thereby, we revealed a critical role for Bim and Bmf as regulators of HSPC dynamics both during early engraftment and long-term reconstitution. HSPCs derived from wild-type donors were readily displaced by Bim- or Bmf-deficient or Bcl-2-overexpressing HSPCs as early as 10 days after engraftment. Moreover, in the absence of Bim, significantly lower numbers of transplanted HSPCs were able to fully engraft radio-depleted recipients. Finally, we provide proof of principle that RNAi-based reduction of BIM or BMF, or overexpression of BCL-2 in human CD34+ cord blood cells may be an attractive therapeutic option to increase stem cell survival and transplantation efficacy. PMID:23180554

  1. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells

    Science.gov (United States)

    Benoit, Marie E.; Clarke, Elizabeth V.; Morgado, Pedro; Fraser, Deborah A.; Tenner, Andrea J.

    2012-01-01

    Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like auto-immune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. Here, we developed an autologous system using primary human lymphocytes and monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. C1q bound to autologous apoptotic lymphocytes modulated expression of genes associated with JAK/STAT signaling, chemotaxis, immunoregulation and NLRP3 inflammasome activation in LPS-stimulated HMDMs. Specifically, C1q sequentially induced type I interferons (IFNs), IL-27 and IL-10 in LPS-stimulated HMDMs and IL-27 in HMDMs when incubated with AL conditioned media. Co-incubation with C1q tails prevented the induction of type I IFNs and IL-27 in a dose dependent manner and neutralization of type I IFNs partially prevented IL-27 induction by C1q. Finally, C1q decreased procaspase-1 cleavage and caspase-1 dependent cleavage of IL-1β suggesting potent inhibitory effect of C1q on inflammasome activation. These results identify specific molecular pathways induced by C1q to suppress macrophage inflammation providing potential therapeutic targets to control macrophage polarization, and thus inflammation and autoimmunity. PMID:22523386

  2. USE OF LIMITED PROTOCOLS TO EVALUATE THE GENOTOXICITY OF HAZARDOUS WASTES IN MAMMALIAN CELL ASSAYS: COMPARISON TO 'SALMONELLA'

    Science.gov (United States)

    Dichloromethane extracts of four diverse hazardous wastes (coke plant, herbicide mfg., pulp and paper, and oil refining) were evaluated for mutagenicity in strains TA98 and TA100 of Salmonella. These extracts also were tested for biological activity in short-term mammalian cells ...

  3. Cytotoxicity testing of materials with limited in vivo exposure is affected by the duration of cell-material contact.

    Science.gov (United States)

    Ciapetti, G; Granchi, D; Stea, S; Savarino, L; Verri, E; Gori, A; Savioli, F; Montanaro, L

    1998-12-15

    Silicones for dental impression largely are used to record the geometry of hard and soft dental tissues. They are considered to be medical devices, and the assessment of cytotoxicity is a necessary step in the evaluation of their biocompatibility. Extracts of six addition-type and six condensation-type silicones have been tested with L929 cells according to the ISO 10993-Part 5 standard. The cytotoxicity was evaluated by three different methods: neutral red uptake, propidium iodide (PI) staining, and amido black staining. According to the selected specific assay, contact between cells and material extracts was maintained for 24 h in the first series of experiments; then, considering that in vivo application of these materials is restricted to a few minutes, additional experiments were performed after 1 h of cell/extract contact. Analysis of the results showed that the addition-type silicones are nontoxic even when tested after prolonged exposure of the cells to the materials while the condensation-type silicones were cytotoxic at 24 h of incubation. Nevertheless, harm to the patient actually could be negligible, considering its very short time of exposure in vivo. This is supported by our finding that most are not toxic after 1 h. We suggest that the experimental conditions of cytotoxicity testing have to be relevant to the in vivo situation; accordingly, the time of exposure should be designed carefully. PMID:9827670

  4. Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line

    International Nuclear Information System (INIS)

    Single-walled carbon nanotubes (SWCNT), fullerenes (C60), carbon black (CB), nC60, and quantum dots (QD) have been studied in vitro to determine their toxicity in a number of cell types. Here, we report that classical dye-based assays such as MTT and neutral red (NR) that determine cell viability produce invalid results with some NM (nanomaterials) due to NM/dye interactions and/or NM adsorption of the dye/dye products. In this study, human epidermal keratinocytes (HEK) were exposed in vitro to CB, SWCNT, C60, nC60, and QD to assess viability with calcein AM (CAM), Live/Dead (LD), NR, MTT, Celltiter 96 AQueous One (96 AQ), alamar Blue (aB), Celltiter-Blue (CTB), CytoTox OneTM (CTO), and flow cytometry. In addition, trypan blue (TB) was quantitated by light microscopy. Assay linearity (R2 value) was determined with HEK plated at concentrations from 0 to 25,000 cells per well in 96-well plates. HEK were treated with serial dilutions of each NM for 24 h and assessed with each of the viability assays. TB, CAM and LD assays, which depend on direct staining of living and/or dead cells, were difficult to interpret due to physical interference of the NM with cells. Results of the dye-based assays varied a great deal, depending on the interactions of the dye/dye product with the carbon nanomaterials (CNM). Results show the optimal high throughput assay for use with carbon and noncarbon NM was 96 AQ. This study shows that, unlike small molecules, CNM interact with assay markers to cause variable results with classical toxicology assays and may not be suitable for assessing nanoparticle cytotoxicity. Therefore, more than one assay may be required when determining nanoparticle toxicity for risk assessment

  5. A simple robust and accurate a posteriori sub-cell finite volume limiter for the discontinuous Galerkin method on unstructured meshes

    Science.gov (United States)

    Dumbser, Michael; Loubère, Raphaël

    2016-08-01

    In this paper we propose a simple, robust and accurate nonlinear a posteriori stabilization of the Discontinuous Galerkin (DG) finite element method for the solution of nonlinear hyperbolic PDE systems on unstructured triangular and tetrahedral meshes in two and three space dimensions. This novel a posteriori limiter, which has been recently proposed for the simple Cartesian grid case in [62], is able to resolve discontinuities at a sub-grid scale and is substantially extended here to general unstructured simplex meshes in 2D and 3D. It can be summarized as follows: At the beginning of each time step, an approximation of the local minimum and maximum of the discrete solution is computed for each cell, taking into account also the vertex neighbors of an element. Then, an unlimited discontinuous Galerkin scheme of approximation degree N is run for one time step to produce a so-called candidate solution. Subsequently, an a posteriori detection step checks the unlimited candidate solution at time t n + 1 for positivity, absence of floating point errors and whether the discrete solution has remained within or at least very close to the bounds given by the local minimum and maximum computed in the first step. Elements that do not satisfy all the previously mentioned detection criteria are flagged as troubled cells. For these troubled cells, the candidate solution is discarded as inappropriate and consequently needs to be recomputed. Within these troubled cells the old discrete solution at the previous time tn is scattered onto small sub-cells (Ns = 2 N + 1 sub-cells per element edge), in order to obtain a set of sub-cell averages at time tn. Then, a more robust second order TVD finite volume scheme is applied to update the sub-cell averages within the troubled DG cells from time tn to time t n + 1. The new sub-grid data at time t n + 1 are finally gathered back into a valid cell-centered DG polynomial of degree N by using a classical conservative and higher order

  6. Effects of Kapton Sample Cell Windows on the Detection Limit of Smectite: Implications for CheMin on the Mars Science Laboratory Mission

    Science.gov (United States)

    Achilles, C. N.; Ming, Douglas W.; Morris, R. V.; Blake, D. F.

    2012-01-01

    The CheMin instrument on the Mars Science Laboratory (MSL) rover Curiosity is an X-ray diffraction (XRD) and X-ray fluorescence (XRF) instrument capable of providing the mineralogical and chemical compositions of rocks and soils on the surface of Mars. CheMin uses a microfocus X-ray tube with a Co target, transmission geometry, and an energy-discriminating X-ray sensitive CCD to produce simultaneous 2-D XRD patterns and energy-dispersive X-ray histograms from powdered samples. CheMin has two different window materials used for sample cells -- Mylar and Kapton. Instrument details are provided elsewhere. Fe/Mg-smectite (e.g., nontronite) has been identified in Gale Crater, the MSL future landing site, by CRISM spectra. While large quantities of phyllosilicate minerals will be easily detected by CheMin, it is important to establish detection limits of such phases to understand capabilities and limitations of the instrument. A previous study indicated that the (001) peak of smectite at 15 Ang was detectable in a mixture of 1 wt.% smectite with olivine when Mylar is the window material for the sample cell. Complications arise when Kapton is the window material because Kapton itself also has a diffraction peak near 15 Ang (6.8 deg 2 Theta). This study presents results of mineral mixtures of smectite and olivine to determine smectite detection limits for Kapton sample cells. Because the intensity and position of the smectite (001) peak depends on the hydration state, we also analyzed mixtures with "hydrated" and "dehydrated"h smectite to examine the effects of hydration state on detection limits.

  7. A Limited Benefit of the Wicke-Kallenbach Cell for the Study of the Mass Transport Dynamics

    Czech Academy of Sciences Publication Activity Database

    Čapek, P.; Hejtmánek, Vladimír

    Bratislava: Slovak University of Technology, 2002 - (Markoš, J.; Štefuca, V.), s. 144 ISBN 80-227-1690-1. [International Conference of Slovak Society of Chemical Engineering /29./. Tatranské Matliare (SK), 27.05.2002-31.05.2002] Institutional research plan: CEZ:AV0Z4072921 Keywords : mass transport dynamics * Wicke-Kallenbach cell Subject RIV: CI - Industrial Chemistry, Chemical Engineering

  8. Limited influence of Si on the preservation of Fe mineral-encrusted microbial cells during experimental diagenesis.

    Science.gov (United States)

    Picard, A; Obst, M; Schmid, G; Zeitvogel, F; Kappler, A

    2016-05-01

    The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro-organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral-encrusted cells of the bacterium Acidovorax sp. BoFeN1 after long-term incubation under ambient conditions and after experimental diagenesis. We also evaluated the effects of Si on the preservation of microbial cells during the whole process. At ambient conditions, Si affected the morphology but not the identity (goethite) of Fe minerals that formed around cells. Fe-encrusted cells were morphologically well preserved after 1 week at 250 °C-140 MPa and after 16 weeks at 170 °C-120 MPa in the presence or in the absence of Si. Some goethite transformed to hematite and magnetite at 250 °C-140 MPa, but in the presence of Si more goethite was preserved. Proteins-the most abundant cellular components-were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. This study provides insights about the composition and potential preservation of microfossils that could have formed in Fe- and Si-rich Precambrian oceans. PMID:26695194

  9. Reduced Inflammation in the Tumor Microenvironment Delays the Accumulation of Myeloid-Derived Suppressor Cells and Limits Tumor Progression

    OpenAIRE

    Bunt, Stephanie K.; YANG, LINGLIN; Sinha, Pratima; Clements, Virginia K.; Leips, Jeff; Ostrand-Rosenberg, Suzanne

    2007-01-01

    Chronic inflammation is frequently associated with malignant growth and is thought to promote and enhance tumor progression, although the mechanisms which regulate this relationship remain elusive. We reported previously that interleukin (IL)-1β promoted tumor progression by enhancing the accumulation of myeloid-derived suppressor cells (MDSC), and hypothesized that inflammation leads to cancer through the production of MDSC which inhibit tumor immunity. If inflammation-induced MDSC promote t...

  10. Leptin contributes to long-term stabilization of HIF-1α in cancer cells subjected to oxygen limiting conditions.

    Science.gov (United States)

    Calgani, Alessia; Delle Monache, Simona; Cesare, Patrizia; Vicentini, Carlo; Bologna, Mauro; Angelucci, Adriano

    2016-06-28

    Leptin, a cytokine produced by the adipose tissue in response to food intake, is a key player in the regulation of energy balance and body weight control. Physiological action of leptin in modulating the metabolic adaptation of different peripheral tissues supports the hypothesis that it could also exert a direct effect on cancer cells. In vitro, treatment with leptin up-regulated HIF-1α and stimulated adhesion and invasion of prostate cancer cells cultured in hypoxia. Leptin action was effective in both low and high glycolytic cancer cell lines, and determined the up-regulation of lactate exporter MCT4 and its associated protein CD147. HIF-1α stabilization was oligomycin-independent and was associated with an important modulation of mitochondrial homeostasis. In fact, leptin treatment produced mitochondrial biogenesis, stabilization of mitochondrial membrane potential and increased uncoupled respiration through the up-regulation of UCP2. Furthermore, leptin counteracted the downmodulation of SIRT1 induced by hypoxia, and persistent high levels of SIRT1 were directly involved in HIF-1α stabilization. Leptin can sustain cancer progression in hypoxic environment and when mitochondrial respiration is impaired. Leptin signaling axis, including the new proposed intermediate SIRT1, could represent a new diagnostic and therapeutic target in prostate cancer. PMID:26996298

  11. Host-cell positive transcription elongation factor b kinase activity is essential and limiting for HIV type 1 replication

    OpenAIRE

    Flores, Osvaldo; Lee, Gary; Kessler, Joseph; Miller, Michael; Schlief, William; Tomassini, Joanne; Hazuda, Daria

    1999-01-01

    HIV-1 gene expression and viral replication require the viral transactivator protein Tat. The RNA polymerase II transcriptional elongation factor P-TEFb (cyclin-dependent kinase 9/cyclin T) is a cellular protein kinase that has recently been shown to be a key component of the Tat-transactivation process. For this report, we studied the requirement for P-TEFb in HIV-1 infection, and we now show that P-TEFb is both essential and limiting for HIV-1 replication. Attenuation of P-TEFb kinase activ...

  12. Peptidoglycan recognition protein 1 enhances experimental asthma by promoting Th2 and Th17 and limiting regulatory T cell and plasmacytoid dendritic cell responses.

    Science.gov (United States)

    Park, Shin Yong; Jing, Xuefang; Gupta, Dipika; Dziarski, Roman

    2013-04-01

    Asthma is a common inflammatory disease involving cross-talk between innate and adaptive immunity. We reveal that antibacterial innate immunity protein, peptidoglycan recognition protein (Pglyrp)1, is involved in the development of allergic asthma. Pglyrp1(-/-) mice developed less severe asthma than wild-type (WT) mice following sensitization with house dust mite (allergen) (HDM). HDM-sensitized Pglyrp1(-/-) mice, compared with WT mice, had diminished bronchial hyperresponsiveness (lung airway resistance); numbers of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and lungs; inflammatory cell infiltrates in the lungs around bronchi, bronchioles, and pulmonary arteries and veins; lung remodeling (mucin-producing goblet cell hyperplasia and metaplasia and smooth muscle hypertrophy and fibrosis); levels of IgE, eotaxins, IL-4, IL-5, and IL-17 in the lungs; and numbers of Th2 and Th17 cells and expression of their marker genes in the lungs. The mechanism underlying this decreased sensitivity of Pglyrp1(-/-) mice to asthma was increased generation and activation of CD8α(+)β(+) and CD8α(+)β(-) plasmacytoid dendritic cells (pDC) and increased recruitment and activity of regulatory T (Treg) cells in the lungs. In vivo depletion of pDC in HDM-sensitized Pglyrp1(-/-) mice reversed the low responsive asthma phenotype of Pglyrp1(-/-) mice to resemble the more severe WT phenotype. Thus, Pglyrp1(-/-) mice efficiently control allergic asthma by upregulating pDC and Treg cells in the lungs, whereas in WT mice, Pglyrp1 is proinflammatory and decreases pDC and Treg cells and increases proasthmatic Th2 and Th17 responses. Blocking Pglyrp1 or enhancing pDC in the lungs may be beneficial for prevention and treatment of asthma. PMID:23420883

  13. A case of limbic encephalitis presenting as a paraneoplastic manifestation of limited stage small cell lung cancer: a case report

    Directory of Open Access Journals (Sweden)

    Butt Mohammad

    2010-12-01

    Full Text Available Abstract Introduction The differential diagnosis of altered mental status and behavioral change is very extensive. Paraneoplastic limbic encephalitis is a rare cause of cognitive impairment, which should be considered in the differential diagnosis. Case presentation A 64-year-old British Caucasian woman presented to our hospital with a 12-week history of confusion and short-term memory loss. She was hyponatremic with a serum sodium level of 128mmol/L. Moreover, there was evidence of left hilar prominence on the chest radiograph. A thoracic computed tomography scan showed left hilar opacity with confluent lymphadenopathy. A percutaneous biopsy confirmed a diagnosis of small cell lung cancer. There was no radiological evidence of brain metastasis on the computed tomography scan. In view of continued cognitive impairment, which was felt to be disproportionate to hyponatremia, a magnetic resonance imaging scan of the brain was undertaken. It showed hyperintense signals from both hippocampi, highly suggestive of limbic encephalitis presenting as a paraneoplastic manifestation of small cell lung cancer. She had a significant radiological and clinical response following chemotherapy and radiotherapy. Conclusion This case highlights the importance of considering paraneoplastic syndromes in patients with neurological symptoms in the context of lung malignancy. If initial investigations fail to reveal the cause of cognitive impairment in a patient with malignancy, magnetic resonance imaging may be invaluable in the diagnosis of limbic encephalitis. The clinical presentation, diagnostic techniques and management of paraneoplastic limbic encephalitis are discussed in this case report.

  14. Experimental Investigation and Discussion on the Mechanical Endurance Limit of Nafion Membrane Used in Proton Exchange Membrane Fuel Cell

    Directory of Open Access Journals (Sweden)

    Yang Xiao

    2014-10-01

    Full Text Available As a solution of high efficiency and clean energy, fuel cell technologies, especially proton exchange membrane fuel cell (PEMFC, have caught extensive attention. However, after decades of development, the performances of PEMFCs are far from achieving the target from the Department of Energy (DOE. Thus, further understanding of the degradation mechanism is needed to overcome this obstacle. Due to the importance of proton exchange membrane in a PEMFC, the degradation of the membrane, such as hygrothermal aging effect on its properties, are particularly necessary. In this work, a thick membrane (Nafion N117, which is always used as an ionic polymer for the PEMFCs, has been analyzed. Experimental investigation is performed for understanding the mechanical endurance of the bare membranes under different loading conditions. Tensile tests are conducted to compare the mechanical property evolution of two kinds of bare-membrane specimens including the dog-bone and the deeply double edge notched (DDEN types. Both dog-bone and DDEN specimens were subjected to a series of degradation tests with different cycling times and wide humidity ranges. The tensile tests are repeated for both kinds of specimens to assess the strain-stress relations. Furthermore, Fourier transform infrared spectroscopy (FT-IR, X-ray diffraction (XRD and Scanning electron microscope (SEM observation and water absorption measurement were conducted to speculate the cause of this variation. The initial cracks along with the increasing of bound water content were speculated as the primary cause.

  15. On limit and limit setting.

    Science.gov (United States)

    Gorney, J E

    1994-01-01

    This article investigates the role of limit and limit setting within the psychoanalytic situation. Limit is understood to be a boundary between self and others, established as an interactional dimension of experience. Disorders of limit are here understood within the context of Winnicott's conception of the "anti-social tendency." Limit setting is proposed as a necessary and authentic response to the patient's acting out via holding and empathic responsiveness, viewed here as a form of boundary delineation. It is proposed that the patient attempts to repair his or her boundary problem through a seeking of secure limits within the analyst. The setting of secure and appropriate limits must arise from a working through of the analyst's own countertransference response to the patient. It is critical that this response be evoked by, and arise from, the immediate therapeutic interaction so that the patient can experience limit setting as simultaneously personal and authentic. PMID:7972580

  16. From invasion to latency: intracellular noise and cell motility as key controls of the competition between resource-limited cellular populations

    KAUST Repository

    Guerrero, Pilar

    2015-04-02

    © 2015, Springer-Verlag Berlin Heidelberg. In this paper we analyse stochastic models of the competition between two resource-limited cell populations which differ in their response to nutrient availability: the resident population exhibits a switch-like response behaviour while the invading population exhibits a bistable response. We investigate how noise in the intracellular regulatory pathways and cell motility influence the fate of the incumbent and invading populations. We focus initially on a spatially homogeneous system and study in detail the role of intracellular noise. We show that in such well-mixed systems, two distinct regimes exist: In the low (intracellular) noise limit, the invader has the ability to invade the resident population, whereas in the high noise regime competition between the two populations is found to be neutral and, in accordance with neutral evolution theory, invasion is a random event. Careful examination of the system dynamics leads us to conclude that (i) even if the invader is unable to invade, the distribution of survival times, PS(t), has a fat-tail behaviour (PS(t)∼t-1) which implies that small colonies of mutants can coexist with the resident population for arbitrarily long times, and (ii) the bistable structure of the invading population increases the stability of the latent population, thus increasing their long-term likelihood of survival, by decreasing the intensity of the noise at the population level. We also examine the effects of spatial inhomogeneity. In the low noise limit we find that cell motility is positively correlated with the aggressiveness of the invader as defined by the time the invader takes to invade the resident population: the faster the invasion, the more aggressive the invader.

  17. Feasibility and efficacy of simultaneous integrated boost intensity-modulated radiation therapy in patients with limited-disease small cell lung cancer

    OpenAIRE

    Han, Dan; QIN, Qin; Hao, Shaoyu; Huang, Wei; Wei, Yumei; Zhang, Zicheng; Wang, Zhongtang; LI, BAOSHENG

    2014-01-01

    Purpose To evaluate the feasibility and efficacy of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) in patients with limited-disease small-cell lung cancer (LD-SCLC). Methods Patients with LD-SCLC were treated with SIB-IMRT within 1 week after completion of 2 cycles of induction chemotherapy. Then 2-4 cycles of adjuvant chemotherapy were administered within 1 week after SIB-IMRT. Irradiation was given accelerated hyper-fractionated with the prescribed dose 57Gy ...

  18. Comparison of once daily radiotherapy to 60 Gy and twice daily radiotherapy to 45 Gy for limited stage small-cell lung cancer

    OpenAIRE

    Han, Dan; Hao, Shaoyu; Tao, Cheng; Zhao, Qian; Wei, Yumei; Song, Zhengzheng; LI, BAOSHENG

    2015-01-01

    Background This study was designed to compare toxicities, disease control, and survival outcomes for limited disease small-cell lung cancer (LD-SCLC) treated with once daily (QD) versus twice daily (BID) radiotherapy. Methods All of the patients received four to six cycles of platinum plus etoposide. In the QD group, irradiation was given via conventional radiotherapy with a dose of 60 Gy at 2 Gy per once-daily fraction. In the BID group, the dose was 45 Gy at 1.5 Gy per twice-daily fraction....

  19. Retrotransposition of limited deletion type of intracisternal A-particle elements in the myeloid leukemia cells of C3H/He mice

    International Nuclear Information System (INIS)

    The murine genome has about 1,000 copies of DNA elements for the intracisternal A-particle (IAP) that resembles a retrovirus. We previously reported that the genomic DNA of the cells from radiation-induced acute myeloid leukemia (AML) lines derived from C3H/He inbred mice was frequently rearranged by the integration of the IAP element. In this study, 8 IAP elements from the characteristic integration sites in 6 cell lines of radiation-induced AML from different mice were characterized and compared in structure with 114 IAP elements isolated from the normal C3H/He genome. One of the 8 elements was a full-length type I IAP, and 7 were of type-IΔ1 with a common deletion site. Although the type IΔ1 form is a minor population accounting for about 6% of total genomic IAP elements, it is predominantly retrotransposed in the AML cells from different C3H/He mice. This indicates that limited populations of the IAP elements contribute to the unique retrotransposition in AML cells. (author)

  20. Quench limits

    International Nuclear Information System (INIS)

    With thirteen beam induced quenches and numerous Machine Development tests, the current knowledge of LHC magnets quench limits still contains a lot of unknowns. Various approaches to determine the quench limits are reviewed and results of the tests are presented. Attempt to reconstruct a coherent picture emerging from these results is taken. The available methods of computation of the quench levels are presented together with dedicated particle shower simulations which are necessary to understand the tests. The future experiments, needed to reach better understanding of quench limits as well as limits for the machine operation are investigated. The possible strategies to set BLM (Beam Loss Monitor) thresholds are discussed. (author)

  1. Limited Neutrality

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2006-01-01

    Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."......Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."...

  2. Dose limits

    International Nuclear Information System (INIS)

    The dose limit is defined to be the level of harmfulness which must not be exceeded, so that an activity can be exercised in a regular manner without running a risk unacceptable to man and the society. The paper examines the effects of radiation categorised into stochastic and non-stochastic. Dose limits for workers and the public are discussed

  3. Use of age and CD4 cell count as criteria for identification of recent HIV infection in resource-limited countries

    Directory of Open Access Journals (Sweden)

    M Penazzato

    2012-11-01

    Full Text Available Background: Identification of recent HIV infection is crucial for estimating HIV incidence and transmitted drug resistance (TDR prevalence. Due to limited availability of diagnostic assays, WHO TDR surveys use age <25 yrs and/or CD4 >500 cells/mm3 at HIV diagnosis as epidemiological criteria to maximize inclusion of recently infected (within 3 yrs and ARV-naïve individuals. Accuracy of these criteria and variation by geographical region is unknown. Methods: A literature review of studies on HIV seroconverters (SC published through March 2012 was performed. Age at SC and CD4 decline in absence of treatment were abstracted. Accuracy of alternative TDR survey criteria was explored. Results: 11 studies provided age at SC: 7 in Africa, 2 in Latin America, 2 in Asia. Median age at SC ranged between 24 and 33 years in studies in Kenya and Zambia, respectively and was 29 [interquantile range (IQR 24, 34] in a large cohort study from Africa. Median age at SC was 29 years in studies on MSM in Brazil and China. 7 studies reported CD4 count decline: 5 in Africa, 1 in Latin America and 1 in Asia. Studies used ordinary least square regression or mixed models. None described median CD4 count 3 yrs after SC. The estimated mean CD4 count 3 yrs after SC ranged from 350–420 cells/mm3 in Africa and was 237 and 282 cells/mm3 in Asia and Latin America, respectively. Conclusion: HIV SC occurs at all ages (median 29 yrs in the assessed geographical regions. Enhancing feasibility of TDR survey implementation by including individuals >25 yrs decreases specificity, particularly in low HIV prevalence settings (Table.Use of age <25 yrs can maximized specificity to detect recent infection, but misses almost 75% of recent infections thus limiting feasibility of TDR survey implementation, particularly in low HIV prevalence settings. Lower mean CD4 count 3 yrs after SC was observed in Asia and Latin America compared to Africa. Regional differences may be explained by

  4. Upper limits on emission of neutrons from Ti in pressurized D2 gas cells: A test of evidence for ''cold fusion''

    International Nuclear Information System (INIS)

    We have used a low background detector with high efficiency for detection of bursts to search for emission of neutrons from Ti alloy in pressurized D2 gas cells (cooled to 77 K in liquid nitrogen). Each cell contained between 16 and 67 g of Ti alloy chips and was prepared by methods identical to those used in a recent Los Alamos-Brigham Young University collaboration of Menlove et al. Three to four cells were used in each experimental run, with a total counting time of 103 h, leading to an estimate (based on the early reports of Menlove et al.) of at least four bursts and as many as 12 bursts expected in our experiment. In a later report the burst rate of Menlove et al. is greatly reduced leading to only one or so burst(s) expected in our experiment. The data were analyzed in two modes. In the first mode (singles mode) all detectors were used to search for neutron bursts with an efficiency of 28% for neutron detection and a background of 100 counts per hour (cph). In the second mode (coincidence mode) the neutron time of flight was measured in a search for random emission with an efficiency of 2% and a background of 2 cph. No statistically significant deviations from the background were observed for correlated neutrons emitted in bursts or for neutrons emitted randomly. All events are shown (with 90% confidence) to be consistent with background. For bursts of neutrons we deduce (with 90% confidence) an upper limit on the bursts' size of 50 neutrons. Our upper limit on the random emission of neutrons, 0.008 n/sec (90% confidence), is a factor of 6 to 25 smaller than the range of rates for random emission above background reported by the Los Alamos--Brigham Young University collaboration

  5. Thermodynamic efficiency limit of molecular donor-acceptor solar cells and its application to diindenoperylene/C{sub 60}-based planar heterojunction devices

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, Mark; Wagner, Julia; Hoermann, Ulrich; Opitz, Andreas; Bruetting, Wolfgang [Institut fuer Physik, Universitaet Augsburg, Universitaetsstr.1, 86135 Augsburg (Germany); Klein, Konrad; Stutzmann, Martin [Walter Schottky Institut, Technische Universitaet Muenchen, Am Coulombwall 4, 85748 Garching (Germany)

    2012-09-15

    In organic photovoltaic (PV) cells, the well-established donor-acceptor (D/A) concept enabling photo-induced charge transfer between two partners with suitable energy level alignment has proven extremely successful. Nevertheless, the introduction of such a heterojunction is accompanied with additional energy losses as compared to an inorganic homojunction cell, owing to the presence of a charge-transfer (CT) state at the D/A interface. Based on the principle of detailed balance, a modified Shockley-Queisser theory is developed including the essential effects of interfacial CT states, that allows for a quantitative assessment of the thermodynamic efficiency limits of molecular D/A solar cells. Key parameters, apart from the optical gap of the absorber material, entering the model are the energy (E{sub CT}) and relative absorption strength ({alpha}{sub CT}) of the CT state. It is demonstrated how the open-circuit voltage (V{sub OC}) and thus the power conversion efficiency are affected by different parameter values. Furthermore, it is shown that temperature dependent device characteristics can serve to determine the CT energy, and thus the upper limit of V{sub OC} for a given D/A combination, as well as to quantify non-radiative recombination losses. The model is applied to diindenoperylene (DIP)-based photovoltaic devices, with open-circuit voltages between 0.9 and 1.4 V, depending on the partner, that have recently been reported. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Limiting Skepticism

    DEFF Research Database (Denmark)

    Hendricks, Vincent Fella; Symons, John

    2011-01-01

    Skeptics argue that the acquisition of knowledge is impossible given the standing possibility of error. We present the limiting convergence strategy for responding to skepticism and discuss the relationship between conceivable error and an agent’s knowledge in the limit. We argue that the skeptic...... must demonstrate that agents are operating with a bad method or are in an epistemically cursed world. Such demonstration involves a significant step beyond conceivability and commits the skeptic to potentially convergent inquiry...

  7. Mast cells and angiogenesis in primary and recurrent pterygia

    Directory of Open Access Journals (Sweden)

    Fatma Hüsniye DİLEK

    2007-09-01

    Full Text Available Pterygium is a common benign lesion of limbus but the pathogenesis are not completely understood. Pterygia have a chronic inflammatory cellular infiltrate and a rich vasculature. Mast cells are a heterogeneous group of multifunctional tissue-resident cells. It has been suggested that mast cells and their products may be responsible for the formation of new blood vessels. We investigated the number and phenotype of mast cells and neovascularization in pterygia specimens and compared with those in normal conjunctival specimensPterygia tissues were obtained during excisional surgery from 32 eyes of 32 consecutive patients. Seventeen of all cases were recurrent pterygia. Superior bulbar conjunctival tissue from the same eye was also sampled as control tissues. The tissue sections were stained with routine hematoxyline-eosin and toluidine blue stain for mast cells. For immunohistochemical studies anti-factor VIII-related antigen, monoclonal anti human mast cell tryptase and chymase were used as an endothelial and mast cell marker.The mean number of mast cells in pterygia was significantly higher than that in the normal conjunctival tissue and microvessel counts was significantly higher than the counts of the controls in both primary and recurrent pterygia. There was no correlation between microvessel numbers and mast cell numbers. There was no phenotypic difference between the mast cells in the ptergyia and those in the normal conjunctival tissues.This study confirms that mast cells are prominent in pterygia and our results suggest that mast cells and angiogenesis are independent factors in the genesis and progress of ptergyium.

  8. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Il Han, E-mail: ihkim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Byoung Hyuck [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Tae Min; Heo, Dae Seog [Department of Internal Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

  9. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level

  10. Regular exercise modulates cardiac mast cell activation in ovariectomized rats.

    Science.gov (United States)

    Phungphong, Sukanya; Kijtawornrat, Anusak; Wattanapermpool, Jonggonnee; Bupha-Intr, Tepmanas

    2016-03-01

    It is well accepted that regular exercise is a significant factor in the prevention of cardiac dysfunction; however, the cardioprotective mechanism is as yet not well defined. We have examined whether regular exercise can modulate the activity of cardiac mast cells (CMC) after deprivation of female sex hormones, as well as the density and percentage degranulation of mast cells, in ventricular tissue of ovariectomized (OVX) rats after an 11-week running program. A significant increase in CMC density with a greater percentage degranulation was induced after ovarian sex hormone deprivation. Increased CMC density was prevented by estrogen supplements, but not by regular training. To the contrary, increased CMC degranulation in the OVX rat heart was attenuated by exercise training, but not by estrogen supplement. These findings indicate a significant correlation between the degree of CMC degranulation and myocyte cross-section area. However, no change in the expression of inflammatory mediators, including chymase, interleukin-6, and interleukin-10, was detected. Taken together, these results clearly indicate one of the cardioprotective mechanisms of regular aerobic exercise is the modulation of CMC activation. PMID:26467449

  11. Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway

    International Nuclear Information System (INIS)

    Angiopoietin (Ang)-1 and Ang-2 interact in angiogenesis to activate the Tie-2 receptor, which may be involved in new vessel maturation and regression. Mast cells (MCs) are also involved in formation of new blood vessels and angiogenesis. The present study was designed to test whether MCs can mediate angiogenesis in myocardial microvascular endothelial cells (MMVECs). Using a rat MMVEC and MC co-culture system, we observed that Ang-1 protein levels were very low even though its mRNA levels were increased by MCs. Interestingly, MCs were able to enhance migration, proliferation, and capillary-like tube formation, which were associated with suppressed Ang-2 protein expression, but not Tie-2 expression levels. These MCs induced effects that could be reversed by either tryptase inhibitor [N-tosyl-L-lysine chloromethyl ketone (TLCK)] or chymase inhibitor (N-tosyl-L-phenylalanyl chloromethyl ketone), with TLCK showing greater effects. In conclusion, our data indicated that MCs can interrupt neovessel maturation via suppression of the Ang-2/Tie-2 signaling pathway

  12. Process of care and preliminary outcome in limited-stage small-cell lung cancer: results of the 1995-1997 patterns of care study in Japan

    International Nuclear Information System (INIS)

    Purpose: To evaluate the practice process using the national average (Na); to compare differences in the process of care by age group; and to provide a preliminary outcome data for limited-stage small-cell lung cancer in Japan. Methods and Materials: The Patterns of Care Study conducted a nationwide survey of the care process for Stage I-III small-cell lung cancer in Japan. Patients were divided into three age groups: <65 years (younger group, n = 73); between 65 and 74 years (intermediate group, n = 81); and ≥75 years (elderly group, n = 20). Results: The NA for the total dose was 49.0 Gy, and for use of photon energy ≥6 MV, chemotherapy, and prophylactic cranial irradiation was 77.3%, 93.2%, and 1.69%, respectively. Age stratification had no impact on the variables of radiotherapy (RT) such as total dose and field size. Only 37% of patients received chemotherapy and thoracic RT concurrently. The proportion of patients who received chemotherapy and RT concurrently was 44%, 27%, and 25% of the younger, intermediate, and elderly groups, respectively (p = 0.029). Etoposide and cisplatin were less frequently used in the elderly group (≥75 years old). Overall survival at 3 years for the entire group was 26%. The 3-year survival rate was 30% in the younger group, 28% in the intermediate group, and 9% in the elderly group. Variables found to have a significant impact on survival by multivariate analysis were the use of chemotherapy (p = 0.030), age (p 0.032), and T stage (p = 0.042). Conclusion: Calculated NAs showed that the results of clinical study had favorably penetrated into the practice process in Japan. The results demonstrated that patient age significantly influenced the process of chemotherapy such as the use of etoposide and cisplatin for limited-stage small-cell lung cancer in Japan. More concurrent chemotherapy and thoracic RT and the application of prophylactic cranial irradiation for complete responders need to be investigated in the future

  13. Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Colaco, Rovel J.; Huh, Soon; Nichols, Romaine; Morris, Christopher G.; Flampouri, Stella; Li, Zuofeng; Hoppe, Bradford S. [Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: bhoppe@floridaproton.org; D' Agostino, Harry [Dept. of Thoracic Surgery, Univ. of Florida Coll. of Medicine, Gainesville (United States); Pham, Dat C. [Dept. of Hematology and Medical Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Bajwa, Abubakr A. [Dept. of Medicine, Univ. of Florida Coll. of Medicine, Gainesville (United States)

    2013-04-15

    Background: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods: Six patients were treated; five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died; two of progressive disease and one after a fall. The latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further

  14. Involved-field radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer: disease control, patterns of failure and survival

    International Nuclear Information System (INIS)

    Full text: Introduction: Major randomised trials have employed elective nodal irradiation as part of combined modality therapy for limited-stage small-cell lung cancer (SCLC). The present investigation describes patterns of failure, disease control, and survival outcomes for involved-field radiotherapy with concurre chemotherapy, without elective irradiation of uninvolved mediastinal nodal regions. Methods: Retrospective analysis of SCLC patients treated with curative-in en accelerated, twice-daily radiotherapy and concurrent platinum-based chemotherapy at an academic institution. Treatment fields were reviewed, and patients who completed 242 Gy in 1.5 Gy twice-daily fractions to involved fields (without elective irradiation of uninvolved mediastinal lymphatic regions) were included in the present analysis. Initial patterns of failure, disease control and overall survival were recorded. Results: Fifty-two patients fulfilled study criteria and were included in the present analysis. All but one patient completed three to four cycles of chemotherapy, and 10 patients experienced grade 3 acute esophagitis. At a median survivor follow-up of 35 months (range 5.5-91.9), 22 patients were alive (15 without recurrence) and 30 had died (23 of/with disease, four of unknown cause, two of other cause and one of treatment toxicity). Initial site(s) of disease failure were loco-regional only (11 patients), distant only (14) and loco-regional plus distant (3). There were no cases of isolated out-of-field mediastinal recurrence in the absence of supraclavicular or more distant disease. The estimated 3-year disease-free and overall survivals were 36% and 44%, respectively. Conclusions: Involved-field radiotherapy did not appear to have an adverse impact on the anticipated patterns of failure, disease control, or overall survival in this population of limited-stage SCLC patients.

  15. Feasibility of omitting clinical target volume for limited-disease small cell lung cancer treated with chemotherapy and intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    To analyze the feasibility of omitting clinical target volume (CTV) for limited small cell lung cancer treated with chemotherapy and intensity modulated radiotherapy. 89 patients were treated from January 1, 2008 to August 31, 2011, 54 cases were irradiated with target volume without CTV, and 35 cases were irradiated with CTV. Both arms were irradiated post chemotherapy tumor extent and omitted elective nodal irradiation; dose prescription was 95% PTV56-63 Gy/28-35 F/5.6-7 weeks. In the arm without CTV and arm with CTV, the local relapse rates were 16.7% and 17.1% (p = 0.586) respectively. In the arm without CTV, of the 9 patients with local relapse, 6 recurred in-field, 2 recurred in margin, 1 recurred out of field. In the arm with CTV, of the 6 patients with local relapse, 4 recurred in-field, 1 recurred in margin, 1 recurred out of field. The distant metastases rates were 42.6% and 51.4% (p = 0.274) respectively. Grade 3-4 hematological toxicity and radiation esophagitis had no statistically significant, but grade 3-4 radiation pneumonia was observed in only 7.4% in the arm without CTV, compared 22.9% in the arm with CTV (p = 0.040). The median survival in the arm without CTV had not reached, compared with 38 months in the with CTV arm. The l- years, 2- years, 3- years survival rates of the arm without CTV and the arm with CTV were 81.0%, 66.2%, 61.5% and 88.6%, 61.7%, 56.6% (p = 0.517). The multivariate analysis indicated that the distant metastases (p = 0.000) and PCI factor (p = 0.004) were significantly related to overall survival. Target delineation omitting CTV for limited-disease small cell lung cancer received IMRT was feasible. The distant metastases and PCI factor were significantly related to overall survival

  16. Autoantibodies against G-Protein-Coupled Receptors Modulate Heart Mast Cells

    Institute of Scientific and Technical Information of China (English)

    Ludmila Okruhlicova; Rosemarie Morwinski; Wolfgang Schulze; Sabine Bartel; Peter Weismann; Narcisa Tribulova; Gerd Wallukat

    2007-01-01

    Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against α1-adrenoceptor and angiotensin Ⅱ AT1-receptor,agonist phenylephrine and angiotensin Ⅱ, and control IgG. The pretreated cultured cells were stained for selected mast cell markers tryptase, chymase and TNF-α. The cultured cells were also processed for observation with electron microscopy. The autoantibodies-treatment of the 3-day cultured cells caused both increased intensity of immunofluorescence (p<0.05) and their enlarged diameters of the mast cells when compared to age-matched ones.In contrast, the fluorescence of preincubated 10-day-old mast cells was decreased compared with controls (p<0.01).In control samples, the fluorescence of 10-day-old mast cells was significantly higher than that of 3-day-old ones (p<0.001). Results of electron microscopy examination demonstrated there was an increased granulation of treated 3-day-old mast cells, while a degranulation of mast cells at day 10 of application. The results suggest the modulation effect of the autoantibodies against G-protein-coupled receptors on mast cells, indicating a potential functional link between the autoantibodies against G-protein-coupled receptors and the mast cells in progression of heart disease.

  17. 局限期小细胞肺癌的胸部放射治疗%Thoracic radiotherapy in limited-stage small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    蓝柳

    2010-01-01

    局限期小细胞肺癌有效的治疗方式是放化疗联合治疗.放疗倾向于早期进行,而从治疗开始到放疗结束时间少于30 d能显著提高生存率.同期放化疗较序贯及交替疗法更能延长生存时间.放疗的总剂量尚无明确的定论.加速超分割照射较常规照射可能会提高疗效.%The effective therapy of limited stage-small cell lung cancer( LS-SCLC) is combined chemotherapy and thoracic radiotherapy(TRT). Early thoracic irradiation is better than later one. Start of any treatment and end of radiotherapy less than 30 days is associated with improved survival in LS-SCLC patients. Concurrent chemoradiotherapy results in longer survival time than sequential and alternating chemoradiotherapy. There are no clear answers on optimal irradiation dose. Hyperfractinated irradiation may have therapeutic benefit compared with conventional irradiation.

  18. Silicon photomultiplier (SPM) detection of low-level bioluminescence for the development of deployable whole-cell biosensors: possibilities and limitations.

    Science.gov (United States)

    Li, Huaqing; Lopes, Nicholas; Moser, Scott; Sayler, Gary; Ripp, Steven

    2012-03-15

    Whole-cell bacterial bioreporters await miniaturized photon counting modules with high sensitivity and robust compatible hardware to fulfill their promise of versatile, on-site biosensor functionality. In this study, we explore the photon counting readout properties of the silicon photomultiplier (SPM) with a thermoelectric cooler and the possibilities of detecting low-level bioluminescent signals. Detection performance was evaluated through a simulated LED light source and the bioluminescence produced by the genetically engineered Pseudomonas fluorescens bacterial bioreporter 5RL. Compared with the conventional photomultiplier tube (PMT), the results revealed that the cooled SPM exhibits a wider linear response to inducible substrate concentrations (salicylate) ranging from 250 to 5000 ppb. Although cooling of the SPM lowered dark count rates and improved the minimum detectable signal, and the application of a digital filter enhanced the signal-to-noise ratio, the detection of very low light signals is still limited and remains a challenge in the design of compact photon counting systems. PMID:22305444

  19. Gene transfer by cationic surfactants is essentially limited by the trapping of the surfactant/DNA complexes onto the cell membrane: a fluorescence investigation.

    Science.gov (United States)

    Clamme, J P; Bernacchi, S; Vuilleumier, C; Duportail, G; Mély, Y

    2000-08-25

    The interaction between complexes of plasmid DNA with cetyltrimethylammonium bromide (CTAB) and L929 fibroblasts was first examined using confocal microscopy. The complexes labeled with the DNA intercalator, YOYO-1, were found to be trapped onto the external face of the plasma membrane; a feature that may constitute a major limiting step in transfection. Moreover, since no cytotoxic effect appeared in these conditions, we further inferred that the CTAB molecules remained bound to the DNA. The interaction of the complexes with the membranes was best modeled with neutral vesicles. From anisotropy thermotropic curves of DPHpPC-labeled vesicles and fluorescence resonance energy transfer measurements between these vesicles and YOYO-labeled complexes, we evidenced that the binding of the complexes to the vesicle surface opened the micelle-like domains and unwound DNA. However, DNA was not released but remained stably bound via electrostatic interactions to the CTAB molecules incorporated in the external liposome leaflet. Consequently, the large diameter of the unwound plasmid DNA is likely the major factor that precludes its internalization into the cells by endocytosis. In contrast, anionic vesicles that mimic the cytoplasmic facing monolayer of the plasma membrane rapidly released DNA from the complex. This may explain the previously reported high transfection efficiency of DNA complexed with liposomes composed of neutral lipids and cationic surfactants, since the latter may destabilize the endosomal membrane and induce the release of DNA in the cytoplasm. PMID:11030593

  20. MicroRNA-related polymorphisms in apoptosis pathway genes are predictive of clinical outcome in patients with limited disease small cell lung cancer

    Science.gov (United States)

    Jiang, Wei; Bi, Nan; Zhang, Wen-Jue; Wu, Li-Hong; Liu, Li-Pin; Men, Yu; Wang, Jing-Bo; Liang, Jun; Hui, Zhou-Guang; Zhou, Zong-Mei; Wang, Lu-Hua

    2016-01-01

    We examined the impact of single nucleotide polymorphisms (SNPs) at miRNA binding sites in the 3′-UTRs of genes in the apoptosis pathway on the prognosis of patients with limited disease-small cell lung cancer (LD-SCLC). Twelve tagSNPs in seven genes were genotyped using blood samples from 146 LD-SCLC patients treated with chemoradiotherapy. Cox proportional hazard regression models and recursive partitioning analysis were performed to identify SNPs significantly associated with overall survival. Three SNPs, CASP8: rs1045494 (C > T), PIK3R1: rs3756668 (A > G) and CASP7: rs4353229 (T > C), were associated with longer overall survival in LD-SCLC patients after chemoradiotherapy. The adjusted hazard ratios (95% confidence intervals) were 0.480 (0.258–0.894), 0.405 (0.173–0.947) and 0.446 (0.247–0.802), respectively, and remained significant after multiple comparison correction. Moreover, subset analysis showed these SNPs were still predictive of overall survival in stage III patients. Recursive partitioning analysis enabled patients to be classified into three risk subgroups based on unfavorable genotype combinations of the rs1045494 and rs4353229 SNPs. These findings suggest miRNA-related polymorphisms in the apoptosis pathway may be useful biomarkers for selection of LD-SCLC patients likely to benefit from chemoradiotherapy. PMID:26988918

  1. Limits of ZnO Electrodeposition in Mesoporous Tin Doped Indium Oxide Films in View of Application in Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Christian Dunkel

    2014-04-01

    Full Text Available Well-ordered 3D mesoporous indium tin oxide (ITO films obtained by a templated sol-gel route are discussed as conductive porous current collectors. This paper explores the use of such films modified by electrochemical deposition of zinc oxide (ZnO on the pore walls to improve the electron transport in dye-sensitized solar cells (DSSCs. Mesoporous ITO film were dip-coated with pore sizes of 20–25 nm and 40–45 nm employing novel poly(isobutylene-b-poly(ethylene oxide block copolymers as structure-directors. After electrochemical deposition of ZnO and sensitization with the indoline dye D149 the films were tested as photoanodes in DSSCs. Short ZnO deposition times led to strong back reaction of photogenerated electrons from non-covered ITO to the electrolyte. ITO films with larger pores enabled longer ZnO deposition times before pore blocking occurred, resulting in higher efficiencies, which could be further increased by using thicker ITO films consisting of five layers, but were still lower compared to nanoporous ZnO films electrodeposited on flat ITO. The major factors that currently limit the application are the still low thickness of the mesoporous ITO films, too small pore sizes and non-ideal geometries that do not allow obtaining full coverage of the ITO surface with ZnO before pore blocking occurs.

  2. therapeutic effect of three-dimensional conformal involved-field radiotherapy combined with chemotherapy on limited disease stage small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To analyze the therapeutic effect of three-dimensional conformal involved-field radiotherapy (3D-CRT) combined with chemotherapy on limited disease stage small cell lung cancer (LD-SCLC). Methods: The clinical data of 85 patients of LD-SCLC treated with 3D-CRT at the dose of 2 Gy/fraction, 5 fractions per week for 5-7 weeks, with the median dose of 50 Gy (46-66 Gy), combined with 4-8 cycles chemotherapy, 64 males and 21 females, aged 29-76, were collected and analyzed. Results: The complete remission rate, partial remission rate, stability rate, and total effective rate were 36.5%, 52.9%, 10.6%, and 89.4%, respectively. The median survival time was 18 months, with the 1-, 2-, and 3-year overall survival rates of 65.9%, 33.8%, and 15.9%, respectively. The local recurrence rate, distant metastasis rate, and local recurrence + distant metastasis rate were 15.2% (9/85), 49.2% (29/85), and 35.6% (21/85), respectively. Body weight,response to therapy, cycles for chemotherapy, and concurrent chemo-radiotherapy were all independent prognostic factors for LD-SCLC. Cox multivariable regression was used to analyze the prognostic factors. Conclusions: Involved-field radiotherapy is effective for LD-SCLC. Distance metastasis is the main cause of treatment failure. (authors)

  3. Increased Biological Effective Dose of Radiation Correlates with Prolonged Survival of Patients with Limited-Stage Small Cell Lung Cancer: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Lucheng Zhu

    Full Text Available Thoracic radiotherapy (TRT is a critical component of the treatment of limited-stage small cell lung cancer (LS-SCLC. However, the optimal radiation dose/fractionation remains elusive. This study reviewed current evidence and explored the dose-response relationship in patients with LS-SCLC who were treated with radiochemotherapy.A quantitative analysis was performed through a systematic search of PubMed, Web of Science, and the Cochrane Library. The correlations between the biological effective dose (BED and median overall survival (mOS, median progression-free survival (mPFS, 1-, 3-, and 5-year overall survival (OS as well as local relapse (LR were evaluated.In all, 2389 patients in 19 trials were included in this study. Among these 19 trials, seven were conducted in Europe, eight were conducted in Asia and four were conducted in the United States. The 19 trials that were included consisted of 29 arms with 24 concurrent and 5 sequential TRT arms. For all included studies, the results showed that a higher BED prolonged the mOS (R2 = 0.198, p<0.001 and the mPFS (R2 = 0.045, p<0.001. The results also showed that increased BED improved the 1-, 3-, and 5-year OS. A 10-Gy increment added a 6.3%, a 5.1% and a 3.7% benefit for the 1-, 3-, and 5-year OS, respectively. Additionally, BED was negatively correlated with LR (R2 = 0.09, p<0.001. A subgroup analysis of concurrent TRT showed that a high BED prolonged the mOS (p<0.001 and the mPFS (p<0.001, improved the 1-, 3-, and 5-year OS (p<0.001 and decreased the rate of LR (p<0.001.This study showed that an increased BED was associated with improved OS, PFS and decreased LR in patients with LS-SCLC who were treated with combined chemoradiotherapy, which indicates that the strategy of radiation dose escalation over a limited time frame is worth exploring in a prospective clinical trial.

  4. Physical limits to biochemical signaling

    CERN Document Server

    Bialek, W

    2003-01-01

    Many crucial biological processes operate with surprisingly small numbers of molecules, and there is renewed interest in analyzing the impact of noise associated with these small numbers. Twenty--five years ago, Berg and Purcell showed that bacterial chemotaxis, where a single celled organism must respond to small changes in concentration of chemicals outside the cell, is limited directly by molecule counting noise, and that aspects of the bacteria's behavioral and computational strategies must be chosen to minimize the effects of this noise. Here we revisit and generalize their arguments to estimate the physical limits to signaling processes within the cell, and argue that recent experiments are consistent with performance approaching these limits.

  5. Positron Emission Tomography/Computed Tomography-Guided Intensity-Modulated Radiotherapy for Limited-Stage Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shirvani, Shervin M.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Heymach, John V.; Fossella, Frank V. [Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)

    2012-01-01

    Purpose: Omitting elective nodal irradiation from planning target volumes does not compromise outcomes in patients with non-small-cell lung cancer, but whether the same is true for those with limited-stage small-cell lung cancer (LS-SCLC) is unknown. Therefore, in the present study, we sought to determine the clinical outcomes and the frequency of elective nodal failure in patients with LS-SCLC staged using positron emission tomography/computed tomography and treated with involved-field intensity-modulated radiotherapy. Methods and Materials: Between 2005 and 2008, 60 patients with LS-SCLC at our institution underwent disease staging using positron emission tomography/computed tomography before treatment using an intensity-modulated radiotherapy plan in which elective nodal irradiation was intentionally omitted from the planning target volume (mode and median dose, 45 Gy in 30 fractions; range, 40.5 Gy in 27 fractions to 63.8 Gy in 35 fractions). In most cases, concurrent platinum-based chemotherapy was administered. We retrospectively reviewed the clinical outcomes to determine the overall survival, relapse-free survival, and failure patterns. Elective nodal failure was defined as recurrence in initially uninvolved hilar, mediastinal, or supraclavicular nodes. Survival was assessed using the Kaplan-Meier method. Results: The median age of the study patients at diagnosis was 63 years (range, 39-86). The median follow-up duration was 21 months (range, 4-58) in all patients and 26 months (range, 4-58) in the survivors. The 2-year actuarial overall survival and relapse-free survival rate were 58% and 43%, respectively. Of the 30 patients with recurrence, 23 had metastatic disease and 7 had locoregional failure. We observed only one isolated elective nodal failure. Conclusions: To our knowledge, this is the first study to examine the outcomes in patients with LS-SCLC staged with positron emission tomography/computed tomography and treated with definitive intensity

  6. Positron Emission Tomography/Computed Tomography-Guided Intensity-Modulated Radiotherapy for Limited-Stage Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: Omitting elective nodal irradiation from planning target volumes does not compromise outcomes in patients with non–small-cell lung cancer, but whether the same is true for those with limited-stage small-cell lung cancer (LS-SCLC) is unknown. Therefore, in the present study, we sought to determine the clinical outcomes and the frequency of elective nodal failure in patients with LS-SCLC staged using positron emission tomography/computed tomography and treated with involved-field intensity-modulated radiotherapy. Methods and Materials: Between 2005 and 2008, 60 patients with LS-SCLC at our institution underwent disease staging using positron emission tomography/computed tomography before treatment using an intensity-modulated radiotherapy plan in which elective nodal irradiation was intentionally omitted from the planning target volume (mode and median dose, 45 Gy in 30 fractions; range, 40.5 Gy in 27 fractions to 63.8 Gy in 35 fractions). In most cases, concurrent platinum-based chemotherapy was administered. We retrospectively reviewed the clinical outcomes to determine the overall survival, relapse-free survival, and failure patterns. Elective nodal failure was defined as recurrence in initially uninvolved hilar, mediastinal, or supraclavicular nodes. Survival was assessed using the Kaplan-Meier method. Results: The median age of the study patients at diagnosis was 63 years (range, 39–86). The median follow-up duration was 21 months (range, 4–58) in all patients and 26 months (range, 4–58) in the survivors. The 2-year actuarial overall survival and relapse-free survival rate were 58% and 43%, respectively. Of the 30 patients with recurrence, 23 had metastatic disease and 7 had locoregional failure. We observed only one isolated elective nodal failure. Conclusions: To our knowledge, this is the first study to examine the outcomes in patients with LS-SCLC staged with positron emission tomography/computed tomography and treated with definitive

  7. Local transplantation of osteogenic pre-differentiated autologous adipose-derived mesenchymal stem cells may accelerate non-union fracture healing with limited pro-metastatic potency.

    Science.gov (United States)

    Han, Duanyang; Han, Na; Zhang, Peixun; Jiang, Baoguo

    2015-01-01

    Fracture non-union is a serious complication in orthopedic clinical practice. Mesenchymal stem cells are believed to play a vital role in fracture healing process. Among various origins of mesenchymal stem cell, adipose derived stem cells hold great promise especially in clinical milieu. However, the wide spread application of mesenchymal stem cell based therapy is impeded by the pro-metastasis nature of the mesenchymal stem cell itself. Based on the findings from previous studies, we hypothesize that local transplanted osteogenic pre-differentiatiated adipose stem cell may promote the non-union fracture healing. Moreover, the pre-differnetiation stem cells by down-regulating the expression of CCL5 and CCL2. This novel osteogenic pre-differnetiation technique may help clinical orthopedists to resolve the refractory non-union cases and shed new light on other stem cell based therapies to counteract to avoid the pro-metastasis nature of the mesenchymal stem cells. PMID:25785146

  8. The yeast three-hybrid system as an experimental platform to identify proteins interacting with small signaling molecules in plant cells: Potential and limitations

    Directory of Open Access Journals (Sweden)

    Stéphanie eCottier

    2011-12-01

    Full Text Available Chemical genetics is a powerful scientific strategy that utilizes small bioactive molecules as experimental tools to unravel biological processes. Bioactive compounds occurring in nature represent an enormous diversity of structures that can be used to dissect functions of biological systems. Once the bioactivity of a natural or synthetic compound has been critically evaluated the challenge remains to identify its molecular target and mode of action, which usually is a time consuming and labor-intensive process. To facilitate this task, we decided to implement the yeast three-hybrid (Y3H technology as a general experimental platform to scan the whole Arabidopsis proteome for targets of small signaling molecules. The Y3H technology is based on the yeast two-hybrid system and allows direct cloning of proteins that interact in vivo with a synthetic hybrid ligand, which comprises the biologically active molecule of interest covalently linked to methotrexate (Mtx. In yeast nucleus the hybrid ligand connects two fusion proteins: the Mtx part binding to dihydrofolate reductase fused to a DNA binding domain (encoded in the yeast strain, and the bioactive molecule part binding to its potential protein target fused to a DNA activating domain (encoded on a cDNA expression vector. During cDNA library screening, the formation of this ternary, transcriptional activator complex leads to reporter gene activation in yeast cells, and thereby allows selection of the putative targets of small bioactive molecules of interest. Here we present the strategy and experimental details for construction and application of a Y3H platform, including chemical synthesis of different hybrid ligands, construction of suitable cDNA libraries, the choice of yeast strains, and appropriate screening conditions. Based on the results obtained and the current literature we discussed the perspectives and limitations of the Y3H approach for identifying targets of small bioactive molecules.

  9. Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer

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    Lee, Joo Hwan; Lee, Jeong Shin; Lee, Chang Geol; Cho, Jae Ho [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Jin Hyun; Kim, Jun Won [Dept. of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.

  10. Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer

    International Nuclear Information System (INIS)

    To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT

  11. Radiotherapy quality assurance review in a multi-center randomized trial of limited-disease small cell lung cancer: the Japan Clinical Oncology Group (JCOG) trial 0202

    International Nuclear Information System (INIS)

    The purpose of this study was to analyze the radiotherapy (RT) quality assurance (QA) assessment in Japan Clinical Oncology Group (JCOG) 0202, which was the first trial that required on-going RT QA review in the JCOG. JCOG 0202 was a multi-center phase III trial comparing two types of consolidation chemotherapy after concurrent chemoradiotherapy for limited-disease small cell lung cancer. RT requirements included a total dose of 45 Gy/30 fx (bis in die, BID/twice a day) without heterogeneity correction; elective nodal irradiation (ENI) of 30 Gy; at least 1 cm margin around the clinical target volume (CTV); and interfraction interval of 6 hours or longer. Dose constraints were defined in regards to the spinal cord and the lung. The QA assessment was classed as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable (I/NE). A total of 283 cases were accrued, of which 204 were fully evaluable, excluding 79 I/NE cases. There were 18 VU in gross tumor volume (GTV) coverage (8% of 238 evaluated); 4 VU and 23 DA in elective nodal irradiation (ENI) (2% and 9% of 243 evaluated, respectively). Some VU were observed in organs at risk (1 VU in the lung and 5 VU in the spinal cord). Overall RT compliance (PP + DA) was 92% (187 of 204 fully evaluable). Comparison between the former and latter halves of the accrued cases revealed that the number of VU and DA had decreased. The results of the RT QA assessment in JCOG 0202 seemed to be acceptable, providing reliable results

  12. Selective Nodal Irradiation on Basis of 18FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the results of selective nodal irradiation on basis of 18F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. Methods and Materials: A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. Results: A difference was seen in the involved nodal stations between the pretreatment 18F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. Conclusion: PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

  13. A retrospective analysis of survival outcomes for two different radiotherapy fractionation schedules given in the same overall time for limited stage small cell lung cancer

    International Nuclear Information System (INIS)

    To compare survival outcomes for two fractionation schedules of thoracic radiotherapy, both given over 3 weeks, in patients with limited stage small cell lung cancer (LS-SCLC). At Radiation Oncology Mater Centre (ROMC) and the Royal Brisbane and Women's Hospital (RBWH), patients with LS-SCLC treated with curative intent are given radiotherapy (with concurrent chemotherapy) to a dose of either 40Gy in 15 fractions ('the 40Gy/15⧣group') or 45Gy in 30 fractions ('the 45Gy/30⧣group'). The choice largely depends on institutional preference. Both these schedules are given over 3 weeks, using daily and twice-daily fractionation respectively. The records of all such patients treated from January 2000 to July 2009 were retrospectively reviewed and survival outcomes between the two groups compared. Of 118 eligible patients, there were 38 patients in the 40Gy/15⧣ group and 41 patients in the 45Gy/30⧣ group. The median relapse-free survival time was 12 months in both groups. Median overall survival was 21 months (95% CI 2–37 months) in the 40Gy/15⧣ group and 26 months (95% CI 1–48 months) in the 45Gy/30⧣ group. The 5-year overall survival rates were 20% and 25%, respectively (P=0.24). On multivariate analysis, factors influencing overall survival were: whether prophylactic cranial irradiation (PCI) was given (P=0.01) and whether salvage chemotherapy was given at the time of relapse (P=0.057). Given the small sample size, the potential for selection bias and the retrospective nature of our study it is not possible to draw firm conclusions regarding the efficacy of hypofractionated thoracic radiotherapy compared with hyperfractionated accelerated thoracic radiotherapy however hypofractionated radiotherapy may result in equivalent relapse-free survival.

  14. Limitations to the development of recombinant human embryonic kidney 293E cells using glutamine synthetase-mediated gene amplification: Methionine sulfoximine resistance.

    Science.gov (United States)

    Yu, Da Young; Noh, Soo Min; Lee, Gyun Min

    2016-08-10

    To investigate the feasibility of glutamine synthetase (GS)-mediated gene amplification in HEK293 cells for the high-level stable production of therapeutic proteins, HEK293E cells were transfected by the GS expression vector containing antibody genes and were selected at various methionine sulfoximine (MSX) concentrations in 96-well plates. For a comparison, CHOK1 cells were transfected by the same GS expression vector and selected at various MSX concentrations. Unlike CHOK1 cells, HEK293E cells producing high levels of antibodies were not selected at all. For HEK293E cells, the number of wells with the cell pool did not decrease with an increase in the concentration of MSX up to 500μM MSX. A q-RT-PCR analysis confirmed that the antibody genes in the HEK293E cells, unlike the CHOK1 cells, were not amplified after increasing the MSX concentration. It was found that the GS activity in HEK293E cells was much higher than that in CHOK1 cells (P<0.05). In a glutamine-free medium, the GS activity of HEK293E cells was approximately 4.8 times higher than that in CHOK1 cells. Accordingly, it is inferred that high GS activity of HEK293E cells results in elevated resistance to MSX and therefore hampers GS-mediated gene amplification by MSX. Thus, in order to apply the GS-mediated gene amplification system to HEK293 cells, the endogenous GS expression level in HEK293 cells needs to be minimized by knock-out or down-regulation methods. PMID:27288593

  15. The importance of glucose transport activity as the rate-limiting step of 2-deoxyglucose uptake in tumor cells in vitro

    International Nuclear Information System (INIS)

    Glucose transporter (GLUT) expression and hexokinase activity are thought to be related to high [18F]-fluorodeoxyglucose (FDG) uptake in tumor cells, but their relative importance is still unknown. To determine which is the predominant factor in FDG uptake in tumor cells, cultured tumor cell lines and a normal cell line were studied in vitro with respect to 2-deoxyglucose (DG) uptake, hexokinase activity, and the initial uptake rate of 3-O-methylglucose (3-O-MG) transport, which is generally accepted as indicating the amount of GLUT expressed on the plasma membrane. In 16 types of tumor cells and one fibroblast cell line, DG uptake was assessed for 60 min, the initial uptake rate of 3-O-MG transport was measured for 1 min, and total hexokinase activity, including that in the mitochondrial fraction, was determined. Across all 16 tumor cell lines, there was a significant correlation between DG uptake and 3-O-MG transport (p=0.0012, F test), but not between DG uptake and hexokinase activity. Hexokinase activity of the tumor cells was comparable to that of the human fibroblast cells in the exponential growth phase. Most tumor cells showed higher DG uptake and 3-O-MG transport than the human fibroblast cells. The results suggest that DG uptake of cultured tumor cells is governed by GLUT expression, which may be a distinct characteristic of the neoplastic process

  16. Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo

    Directory of Open Access Journals (Sweden)

    Littman Dan R

    2009-01-01

    Full Text Available Abstract Background Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1. Results Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains ex vivo, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown. Conclusion Thus, hCycT1 expression is beneficial to de novo HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.

  17. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    International Nuclear Information System (INIS)

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m2 IV) was given on day 1 and etoposide (120 mg/m2 IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538/Cancer and

  18. Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC

  19. Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer

    International Nuclear Information System (INIS)

    The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn’t been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC. Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed. The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273). Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment

  20. Feasibility and efficacy of simultaneous integrated boost intensity-modulated radiation therapy in patients with limited-disease small cell lung cancer

    International Nuclear Information System (INIS)

    To evaluate the feasibility and efficacy of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) in patients with limited-disease small-cell lung cancer (LD-SCLC). Patients with LD-SCLC were treated with SIB-IMRT within 1 week after completion of 2 cycles of induction chemotherapy. Then 2-4 cycles of adjuvant chemotherapy were administered within 1 week after SIB-IMRT. Irradiation was given accelerated hyper-fractionated with the prescribed dose 57Gy at 1.9Gy twice daily to the gross tumor volume (GTV) , 51Gy at 1.7Gy twice daily to the clinical tumor volume (CTV) and 45Gy at 1.5Gy twice daily to the planning target volume (PTV). The chemotherapy regimen consisted of platinum plus etoposide. Prophylactic cranial radiation (25Gy in 10 fractions) was administered to patients who got complete response (CR) or near complete response (nCR). The primary endpoint of this study was the frequency of grade 3 or higher acute non-hematologic treatment-related toxicities. Secondary end points included objective response, overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS). A cohort of 35 patients were enrolled in the study, the biological equivalent dose (BED) of the GTV in the SIB-IMRT was 59.16Gy. Grade 1, 2, and 3 esophagitis were observed in 11 (31%), 12 (34%), and 6 (17%) patients, respectively; Grade 1 and 2 pneumonitis were observed in 8 (23%) and 4 (11%) patients, respectively. The median OS and PFS of the whole group were 37.7 months and 29.3 months, respectively. The 1- and 2-year OS was 94.1% and 68.5%, respectively. The 1- and 2-year PFS was 76.8% and 40.7%, respectively. The 1- and 2-year LRFS was 87.7% and 73.8%, respectively. SIB-IMRT was feasible and well-tolerated in patients with LD-SCLC, and worth further evaluating in a large prospective clinical trial

  1. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Paulus, Rebecca [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Ettinger, David S. [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (United States); Videtic, Gregory M.M. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Glisson, Bonnie S. [Department of Thoracic/Head and Neck Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Langer, Corey J. [Thoracic Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Sause, William T. [Radiation Center, LDS Hospital, Salt Lake City, Utah (United States); Curran, Walter J. [Department of Radiation Oncology, Jefferson Medical College, Philadelphia, Pennsylvania (United States); Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (United States)

    2012-07-15

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m{sup 2} IV) was given on day 1 and etoposide (120 mg/m{sup 2} IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538

  2. Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Bing [Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai (China); Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou (China); Hong, Ling-Zhi [Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing (China); Cai, Xu-Wei; Zhu, Zheng-Fei; Liu, Qi; Zhao, Kuai-Le; Fan, Min; Mao, Jing-Fang; Yang, Huan-Jun; Wu, Kai-Liang [Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai (China); Fu, Xiao-Long, E-mail: xlfu1964@hotmail.com [Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (China)

    2015-03-01

    Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.

  3. Adult Human Pancreatic Islet Beta-Cells Display Limited Turnover and Long Lifespan as Determined by In-Vivo Thymidine Analog Incorporation and Radiocarbon Dating

    International Nuclear Information System (INIS)

    Diabetes mellitus results from an absolute or relative deficiency of insulin producing pancreatic beta-cells. The adult human beta-cell's turnover rate remains unknown. We employed novel techniques to examine adult human islet beta-cell turnover and longevity in vivo. Subjects enrolled in NIH clinical trials received thymidine analogues [iododeoxyuridine (IdU) or bromodeoxyuridine (BrdU)] 8-days to 4-years prior to death. Archival autopsy samples from ten patients (aged 17-74 years) were employed to assess beta-cell turnover by scoring nuclear analog labeling within insulin staining cells. Human adult beta-cell longevity was determined by estimating the cells genomic DNA integration of atmospheric carbon-14 (14C). DNA was purified from pancreatic islets isolated from cadaveric donors; whole islet prep DNA was obtained from a 15 year old donor, and purified beta-cell DNA was obtained from two donors (age 48 and 80 years). 14C levels were then determined using accelerator mass spectrometry (AMS). Cellular 'birth date' was determined by comparing the subject's DNA 14C content relative to a well-established 14C atmospheric prevalence curve. In the two subjects less than age 20 years, 1-2% of the beta-cell nuclei co-stained for BrdU/IdU. No beta-cell nuclei co-stained in the eight patients more than 30 years old. Consistent with the BrdU/IdU turnover data, beta-cell DNA 14C content indicated the cells 'birth date' occurred within the subject's first 30 years of life. Under typical circumstances, adult human beta-cells and their cellular precursors are established by young adulthood.

  4. Adult Human Pancreatic Islet Beta-Cells Display Limited Turnover and Long Lifespan as Determined by In-Vivo Thymidine Analog Incorporation and Radiocarbon Dating

    Energy Technology Data Exchange (ETDEWEB)

    Perl, S; Kushner, J A; Buchholz, B A; Meeker, A K; Stein, G M; Hsieh, M; Kirby, M; Pechhold, S; Liu, E H; Harlan, D M; Tisdale, J F

    2010-03-15

    Diabetes mellitus results from an absolute or relative deficiency of insulin producing pancreatic beta-cells. The adult human beta-cell's turnover rate remains unknown. We employed novel techniques to examine adult human islet beta-cell turnover and longevity in vivo. Subjects enrolled in NIH clinical trials received thymidine analogues [iododeoxyuridine (IdU) or bromodeoxyuridine (BrdU)] 8-days to 4-years prior to death. Archival autopsy samples from ten patients (aged 17-74 years) were employed to assess beta-cell turnover by scoring nuclear analog labeling within insulin staining cells. Human adult beta-cell longevity was determined by estimating the cells genomic DNA integration of atmospheric carbon-14 ({sup 14}C). DNA was purified from pancreatic islets isolated from cadaveric donors; whole islet prep DNA was obtained from a 15 year old donor, and purified beta-cell DNA was obtained from two donors (age 48 and 80 years). {sup 14}C levels were then determined using accelerator mass spectrometry (AMS). Cellular 'birth date' was determined by comparing the subject's DNA {sup 14}C content relative to a well-established {sup 14}C atmospheric prevalence curve. In the two subjects less than age 20 years, 1-2% of the beta-cell nuclei co-stained for BrdU/IdU. No beta-cell nuclei co-stained in the eight patients more than 30 years old. Consistent with the BrdU/IdU turnover data, beta-cell DNA {sup 14}C content indicated the cells 'birth date' occurred within the subject's first 30 years of life. Under typical circumstances, adult human beta-cells and their cellular precursors are established by young adulthood.

  5. Neonatal human retinal pigment epithelial cells secrete limited trophic factors in vitro and in vivo following striatal implantation in parkinsonian rats

    DEFF Research Database (Denmark)

    Russ, Kaspar; Flores, Joseph; Brudek, Tomasz; Doudet, Doris

    2015-01-01

    Human retinal pigment epithelial (hRPE) cell implants into the striatum have been investigated as a potential cell-based treatment for Parkinson's disease in a Phase II clinical trial that recently failed. We hypothesize that the trophic factor potential of the hRPE cells could potentially...... influence the function and/or survival of the implants and may be involved in an alternative mechanism of action. However, it is unclear if hRPE cells secreted trophic factors when handled in the manner used in the clinical Phase II trial. To address these questions, we investigated two neonatal hRPE cell...... lots, cultured in a similar manner to hRPE cells used in a Phase II clinical study, and longitudinally determined brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and pigment epithelium-derived factor concentrations in vitro and following striatal implantation into 6...

  6. Intrathecal application of neuroectodermally converted stem cells into a mouse model of ALS: limited intraparenchymal migration and survival narrows therapeutic effects.

    Science.gov (United States)

    Habisch, H-J; Janowski, M; Binder, D; Kuzma-Kozakiewicz, M; Widmann, A; Habich, A; Schwalenstöcker, B; Hermann, A; Brenner, R; Lukomska, B; Domanska-Janik, K; Ludolph, A C; Storch, A

    2007-01-01

    Stem and progenitor cells provide a promising therapeutic strategy for amyotrophic lateral sclerosis (ALS). To comparatively evaluate the therapeutic potentials of human bone marrow-derived mesodermal stromal cells (hMSCs) and umbilical cord blood cells (hUBCs) in ALS, we transplanted hMSCs and hUBCs and their neuroectodermal derivatives (hMSC-NSCs and hUBC-NSCs) into the ALS mouse model over-expressing the G93A mutant of the human SOD1 gene. We used a standardized protocol similar to clinical studies by performing a power calculation to estimate sample size prior to transplantation, matching the treatment groups for gender and hSOD-G93A gene content, and applying a novel method for directly injecting 100,000 cells into the CSF (the cisterna magna). Ten days after transplantation we found many cells within the subarachnoidal space ranging from frontal basal cisterns back to the cisterna magna, but only a few cells around the spinal cord. hMSCs and hMSC-NSCs were also located within the Purkinje cell layer. Intrathecal cell application did not affect survival times of mice compared to controls. Consistently, time of disease onset and first pareses, death weight, and motor neuron count in lumbar spinal cord did not vary between treatment groups. Interestingly, transplantation of hMSCs led to an increase of pre-symptomatic motor performance compared to controls in female animals. The negative outcome of the present study is most likely due to insufficient cell numbers within the affected brain regions (mainly the spinal cord). Further experiments defining the optimal cell dose, time point and route of application and particularly strategies to improve the homing of transplanted cells towards the CNS region of interest are warranted to define the therapeutic potential of mesodermal stem cells for the treatment of ALS. PMID:17510731

  7. Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules.

    OpenAIRE

    Yamazaki, T; Seko, Y; Tamatani, T; Miyasaka, M.; Yagita, H; Okumura, K.; R. Nagai; Yazaki, Y

    1993-01-01

    To elucidate the mechanism(s) of myocardial reperfusion injury, we investigated the roles of cell adhesion molecules on both leukocytes and vascular endothelial cells in the reperfused myocardia. We found that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia and clarified, for the first time, that the expression of intercellular adhesion molecule-1 was enhanced on the capillary and venous endothelial cells from 8 to 96 ...

  8. Smac/DIABLO release from mitochondria and XIAP inhibition are essential to limit clonogenicity of Type I tumor cells after TRAIL receptor stimulation

    OpenAIRE

    Borst, Jannie; Maas, Chiel; Verbrugge, Inge; de Vries, Evert; Savich, Gleb; Van De Kooij, Lambertus W; Tait, Stephen W.

    2010-01-01

    Abstract Death receptors such as Fas/CD95 and TRAIL receptors engage the extrinsic pathway for caspase activation, but also couple to the intrinsic mitochondrial route. In so-called Type II cells, death receptors require the mitochondrial pathway for apoptotic execution, whereas in Type I cells they reportedly do not. For established tumor cell lines, the Type I/Type II distinction is based on short-term apoptosis assays. We report here that the mitochondrial pathway is essential f...

  9. 长期服用苯那普利的高血压患者左室肥厚逆转与血管紧张素转换酶基因和Chymase基因多态性的相关性研究%Association between angiotensin converting enzyme gene, chymase gene and regression of left ventricular hypertrophy in patients treated with angiotensin converting enzyme inhibitors

    Institute of Scientific and Technical Information of China (English)

    和红; 李立明; 曹卫华; 刘美贞; 孙宁玲; 吕筠; 胡永华

    2004-01-01

    目的探讨长期服用苯那普利的原发性高血压患者左室肥厚逆转与血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性和Chymase(CMA)基因A/B多态性的关系.方法收集157例原发性高血压伴左室肥厚患者24个月的随访资料;应用聚合酶链反应和限制性片段长度多态性方法检测ACE基因I/D多态性以及CMA基因A/B多态性;超声心动测量左室舒张末期内径(LVDd)、舒张期室间隔厚度(IVST)及左室后壁厚度(LVPWT).结果 (1)治疗后血压明显下降而心率改变不明显;(2)能明显逆转LVH;(3)ACE基因型间除左室质量(LVM)下降值及左室质量指数(LVMI)下降值在DD基因型明显大于II型和ID型以外,其余各临床指标下降值在ACE基因型间的差异均无统计学意义;(4)CMA基因型间各临床指标下降值的差异均无统计学意义;(5)ACE基因中各基因型与CMA基因中各基因型间不存在交互作用;(6)多元线性逐步回归分析表明,仅ACE基因型与LVMI下降值有关.结论长期服用苯那普利可以明显降低血压、逆转LVH;其中ACE基因为DD型的患者较其他基因型患者更易于LVH逆转,而CMA基因多态性与LVH逆转不相关;两种基因间不存在交互作用.

  10. NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells.

    Science.gov (United States)

    de Valle, Elisha; Grigoriadis, George; O'Reilly, Lorraine A; Willis, Simon N; Maxwell, Mhairi J; Corcoran, Lynn M; Tsantikos, Evelyn; Cornish, Jasper K S; Fairfax, Kirsten A; Vasanthakumar, Ajithkumar; Febbraio, Mark A; Hibbs, Margaret L; Pellegrini, Marc; Banerjee, Ashish; Hodgkin, Philip D; Kallies, Axel; Mackay, Fabienne; Strasser, Andreas; Gerondakis, Steve; Gugasyan, Raffi

    2016-04-01

    We examined the role of NFκB1 in the homeostasis and function of peripheral follicular (Fo) B cells. Aging mice lacking NFκB1 (Nfκb1(-/-)) develop lymphoproliferative and multiorgan autoimmune disease attributed in large part to the deregulated activity of Nfκb1(-/-)Fo B cells that produce excessive levels of the proinflammatory cytokine interleukin 6 (IL-6). Despite enhanced germinal center (GC) B cell differentiation, the formation of GC structures was severely disrupted in the Nfκb1(-/-)mice. Bone marrow chimeric mice revealed that the Fo B cell-intrinsic loss of NFκB1 led to the spontaneous generation of GC B cells. This was primarily the result of an increase in IL-6 levels, which promotes the differentiation of Fo helper CD4(+)T cells and acts in an autocrine manner to reduce antigen receptor and toll-like receptor activation thresholds in a population of proliferating IgM(+)Nfκb1(-/-)Fo B cells. We demonstrate that p50-NFκB1 represses Il-6 transcription in Fo B cells, with the loss of NFκB1 also resulting in the uncontrolled RELA-driven transcription of Il-6.Collectively, our findings identify a previously unrecognized role for NFκB1 in preventing multiorgan autoimmunity through its negative regulation of Il-6 gene expression in Fo B cells. PMID:27022143

  11. Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Johansen, L E; Nielsen, O;

    2006-01-01

    , and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct...

  12. Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma.

    Science.gov (United States)

    Wang, Gang; Baines, Katherine J; Fu, Juan Juan; Wood, Lisa G; Simpson, Jodie L; McDonald, Vanessa M; Cowan, Douglas C; Taylor, D Robin; Cowan, Jan O; Gibson, Peter G

    2016-04-01

    Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT(n=18) and MCT/CPA3(mRNA expression ofTPSAB1andCPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identifiedCPA3(OR 1.21, p=0.004) rather thanTPSAB1(OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness. PMID:26699720

  13. Imaging of VSOP labeled stem cells in agarose phantoms with susceptibility weighted and T2* weighted MR Imaging at 3T: determination of the detection limit.

    Directory of Open Access Journals (Sweden)

    Donald Lobsien

    Full Text Available OBJECTIVES: This study aimed to evaluate the detectability of stem cells labeled with very small iron oxide particles (VSOP at 3T with susceptibility weighted (SWI and T2* weighted imaging as a methodological basis for subsequent examinations in a large animal stroke model (sheep. MATERIALS AND METHODS: We examined ovine mesenchymal stem cells labeled with VSOP in agarose layer phantoms. The experiments were performed in 2 different groups, with quantities of 0-100,000 labeled cells per layer. 15 different SWI- and T2*-weighted sequences and 3 RF coils were used. All measurements were carried out on a clinical 3T MRI. Images of Group A were analyzed by four radiologists blinded for the number of cells, and rated for detectability according to a four-step scale. Images of Group B were subject to a ROI-based analysis of signal intensities. Signal deviations of more than the 0.95 confidence interval in cell containing layers as compared to the mean of the signal intensity of non cell bearing layers were considered significant. RESULTS: GROUP A: 500 or more labeled cells were judged as confidently visible when examined with a SWI-sequence with 0.15 mm slice thickness. Group B: 500 or more labeled cells showed a significant signal reduction in SWI sequences with a slice thickness of 0.25 mm. Slice thickness and cell number per layer had a significant influence on the amount of detected signal reduction. CONCLUSION: 500 VSOP labeled stem cells could be detected with SWI imaging at 3 Tesla using an experimental design suitable for large animal models.

  14. Interferon Regulator Factor 8 (IRF8) Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells

    Science.gov (United States)

    Yu, Cheng-Rong; He, Chang; Mahdi, Rashid M.; Chan, Chi-Chao; Wang, Hongsheng; Morse, Herbert C.; Egwuagu, Charles E.

    2016-01-01

    Interferon Regulatory Factor-8 (IRF8) is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO) to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1) infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG) and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC) in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye. PMID:27171004

  15. Interferon Regulator Factor 8 (IRF8 Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells.

    Directory of Open Access Journals (Sweden)

    Lin Sun

    Full Text Available Interferon Regulatory Factor-8 (IRF8 is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1 infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye.

  16. Increased survival and decreased metastasis rates with early thoracic radiotherapy and prophylactic cranial irradiation in combined-modality treatment of limited-stage small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose/Objective: To evaluate the relative efficacy of concurrent vs. sequential timing of thoracic radiotherapy (RT) and chemotherapy consisting of cisplatin and etoposide (VP-16) with respect to absolute survival, freedom from relapse, control of thoracic disease, and frequency and distribution of distant metastases. The role of prophylactic cranial irradiation (PCI) in preventing CNS metastasis was also assessed. Materials and Methods: Forty-eight patients with limited-stage small cell lung cancer were treated either concurrently (29 patients) or sequentially (19 patients) with thoracic RT and chemotherapy consisting of cisplatin and etoposide. Thirty-four patients (71%) received thoracic irradiation to a dose of 45 Gy in 25 fractions (range, 30-55 Gy). Number of chemotherapy cycles ranged from 3 to 8; either 4 or 6 cycles were given to 36 patients (75%). Of 27 patients with a complete response at the completion of chemotherapy, 21 patients received PCI. Median follow-up was 29.3 months (range, 12-98 months). No patients were lost to follow-up. Potential prognostic variables were evaluated by both univariate and multivariate analysis. Results: The absolute survival rate for all patients was 42% at 2 years and 32% at 5 years. The relapse-free survival rate was 35% at 2 years and 31% at 5 years. Thirty-six sites of failure were observed in 27 patients. Thoracic recurrence occurred in 9 patients (all within the RT field). The CNS was the most common site of relapse (15 patients). Multivariate analysis revealed that (1) concurrent RT and chemotherapy vs. sequential chemotherapy followed by RT and (2) disease volume were variables significantly predictive for survival. Absolute survival was 41% for patients who had early concurrent RT, beginning with either cycle 1 or 2 of chemotherapy, vs. 25% for those who had sequential treatment (p=.036). Patients having a disease volume less than one third of the thoracic width had a survival rate of 41% vs. 23% for those with

  17. Tumor Progression Locus 2 (Tpl2) Activates the Mammalian Target of Rapamycin (mTOR) Pathway, Inhibits Forkhead Box P3 (FoxP3) Expression, and Limits Regulatory T Cell (Treg) Immunosuppressive Functions.

    Science.gov (United States)

    Li, Xin; Acuff, Nicole V; Peeks, Angela R; Kirkland, Rebecca; Wyatt, Kara D; Nagy, Tamas; Watford, Wendy T

    2016-08-01

    The serine/threonine kinase tumor progression locus 2 (Tpl2, also known as Map3k8/Cot) is a potent inflammatory mediator that drives the production of TNFα, IL-1β, and IFNγ. We previously demonstrated that Tpl2 regulates T cell receptor (TCR) signaling and modulates T helper cell differentiation. However, very little is known about how Tpl2 modulates the development of regulatory T cells (Tregs). Tregs are a specialized subset of T cells that express FoxP3 and possess immunosuppressive properties to limit excess inflammation. Because of the documented role of Tpl2 in promoting inflammation, we hypothesized that Tpl2 antagonizes Treg development and immunosuppressive function. Here we demonstrate that Tpl2 constrains the development of inducible Tregs. Tpl2(-/-) naïve CD4(+) T cells preferentially develop into FoxP3(+) inducible Tregs in vitro as well as in vivo in a murine model of ovalbumin (OVA)-induced systemic tolerance. Treg biasing of Tpl2(-/-) T cells depended on TCR signal strength and corresponded with reduced activation of the mammalian target of rapamycin (mTOR) pathway. Importantly, Tpl2(-/-) Tregs have basally increased expression of FoxP3 and immunosuppressive molecules, IL-10 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Furthermore, they were more immunosuppressive in vivo in a T cell transfer model of colitis, as evidenced by reduced effector T cell accumulation, systemic production of inflammatory cytokines, and colonic inflammation. These results demonstrate that Tpl2 promotes inflammation in part by constraining FoxP3 expression and Treg immunosuppressive functions. Overall, these findings suggest that Tpl2 inhibition could be used to preferentially drive Treg induction and thereby limit inflammation in a variety of autoimmune diseases. PMID:27261457

  18. Intestinal Cell Tight Junctions Limit Invasion of Candida albicans through Active Penetration and Endocytosis in the Early Stages of the Interaction of the Fungus with the Intestinal Barrier.

    Directory of Open Access Journals (Sweden)

    Marianne Goyer

    Full Text Available C. albicans is a commensal yeast of the mucous membranes in healthy humans that can also cause disseminated candidiasis, mainly originating from the digestive tract, in vulnerable patients. It is necessary to understand the cellular and molecular mechanisms of the interaction of C. albicans with enterocytes to better understand the basis of commensalism and pathogenicity of the yeast and to improve the management of disseminated candidiasis. In this study, we investigated the kinetics of tight junction (TJ formation in parallel with the invasion of C. albicans into the Caco-2 intestinal cell line. Using invasiveness assays on Caco-2 cells displaying pharmacologically altered TJ (i.e. differentiated epithelial cells treated with EGTA or patulin, we were able to demonstrate that TJ protect enterocytes against invasion of C. albicans. Moreover, treatment with a pharmacological inhibitor of endocytosis decreased invasion of the fungus into Caco-2 cells displaying altered TJ, suggesting that facilitating access of the yeast to the basolateral side of intestinal cells promotes endocytosis of C. albicans in its hyphal form. These data were supported by SEM observations of differentiated Caco-2 cells displaying altered TJ, which highlighted membrane protrusions engulfing C. albicans hyphae. We furthermore demonstrated that Als3, a hypha-specific C. albicans invasin, facilitates internalization of the fungus by active penetration and induced endocytosis by differentiated Caco-2 cells displaying altered TJ. However, our observations failed to demonstrate binding of Als3 to E-cadherin as the trigger mechanism of endocytosis of C. albicans into differentiated Caco-2 cells displaying altered TJ.

  19. A new loss-of-function allele 28y reveals a role of ARGONAUTE1 in limiting asymmetric division of stomatal lineage ground cell

    Institute of Scientific and Technical Information of China (English)

    Kezhen Yangy; Min Jiangy; Jie Le

    2014-01-01

    In Arabidopsis thaliana L., stomata are produced through a series of divisions including asymmetric and symmetric divisions. Asymmetric entry division of meristemoid mother cellproduces two daughter cells, the smal er meristemoid and the larger sister cell, a stomatal lineage ground cell(SLGC). Stomatal lineage ground cells can differentiate into epidermal pavement cells but have the potential to divide asymmetrical y, spacing divisions, to create satel ite meristemoids. Peptide ligands and TOO MANY MOUTHS (TMM) and ERECTA family receptors regulate the initiation of stomatal lineages, activity, and orientation of spacing divisions. Here, we reported that a natural mutant 28y displayed an increased stomatal density and index. Using map-based cloning, we identified mutation in ARGONAUTE1 (AGO1) as the cause of 28y phenotypes. Time-lapse tracing of stomatal lineage cells reveals that stomatal overproduction in 28y is caused by the excessive asymmetric spacing division of SLGCs.Further genetic results demonstrated that AGO1 acts down-stream of TMM and negatively regulates the SPCH transcripts, but in a brassinosteroid-independent manner. Upregulation of AGAMOUS-LIKE16 (AGL16) in 28y mutants suggests that AGO1 is required to restrict AGL16-mediated stomatal spacing divisions, an miRNA pathway in addition to ligand-receptor signaling modules.

  20. c-Kit Expression is Rate-Limiting for Stem Cell Factor-Mediated Disease Progression in Adenoid Cystic Carcinoma of the Salivary Glands

    Directory of Open Access Journals (Sweden)

    Janyaporn Phuchareon

    2014-10-01

    Full Text Available Adenoid cystic carcinoma (ACC is an aggressive malignant neoplasm of the salivary glands in which c-Kit is overexpressed and activated, although the mechanism for this is as yet unclear. We analyzed 27 sporadic ACC tumor specimens to examine the biologic and clinical significance of c-Kit activation. Mutational analysis revealed expression of wild-type c-Kit in all, eliminating gene mutation as a cause of activation. Because stem cell factor (SCF is c-Kit's sole ligand, we analyzed its expression in the tumor cells and their environment. Immunohistochemistry revealed its presence in c-Kit–positive tumor cells, suggesting an activation of autocrine signaling. We observed a significant induction of ERK1/2 in the cells. SCF staining was also found in other types of non-cancerous cells adjacent to tumors within salivary glands, including stromal fibroblasts, neutrophils, peripheral nerve, skeletal muscle, vascular endothelial cells, mucous acinar cells, and intercalated ducts. Quantitative PCR showed that the top quartile of c-Kit mRNA expression distinguished ACCs from normal salivary tissues and was cross-correlated with short-term poor prognosis. Expression levels of SCF and c-Kit were highly correlated in the cases with perineural invasion. These observations suggest that c-Kit is potentially activated by receptor dimerization upon stimulation by SCF in ACC, and that the highest quartile of c-Kit mRNA expression could be a predictor of poor prognosis. Our findings may support an avenue for c-Kit-targeted therapy to improve disease control in ACC patients harboring the top quartile of c-Kit mRNA expression.

  1. Opportunities and limits of the one gene approach: the ability of Atoh1 to differentiate and maintain hair cells depends on the molecular context.

    Directory of Open Access Journals (Sweden)

    Bernd Fritzsch

    2015-02-01

    Full Text Available Atoh1 (Math1 was the first gene discovered in ear development that showed no hair cell (HC differentiation when absent and could induce HC differentiation when misexpressed. These data implied that Atoh1 was both necessary and sufficient for hair cell development. However, other gene mutations also result in loss of initially forming HCs, notably null mutants for Pou4f3, Barhl1 and Gfi1. HC development and maintenance also depend on the expression of other genes (Sox2, Eya1, Gata3, Pax2 and several genes have been identified that can induce HCs when misexpressed (Jag1 or knocked out (Lmo4. In the ear Atoh1 is not only expressed in HCs but also in some supporting cells and neurons that do not differentiate into HCs. Simple removal of one gene, Neurod1, can de-repress Atoh1 and turns those neurons into HCs suggesting that Neurod1 blocks Atoh1 function in neurons. Atoh1 expression in inner pillar cells may also be blocked by too many Hes/Hey factors but conversion into HCs has only partially been achieved through Hes/Hey removal. Detailed analysis of cell cycle exit confirmed an apex to base cell cycle exit progression of HCs of the organ of Corti. In contrast, Atoh1 expression progresses from the base towards the apex with a variable delay relative to the cell cycle exit. Most HCs exit the cell cycle and are thus defined as precursors before Atoh1 is expressed. Atoh1 is a potent differentiation factor but can differentiate and maintain HCs only in the ear and when other factors are co-expressed. Upstream factors are essential to regulate Atoh1 level of expression duration while downstream, co-activated by other factors, will define the context of Atoh1 action. We suggest that these insights need to be taken into consideration and approaches beyond the simple Atoh1 expression need to be designed able to generate the radial and longitudinal variations in hair cell types for normal function of the organ of Corti.

  2. Kinetics of /sup 13/N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Rauch, B.; Helus, F.; Grunze, M.; Braunwell, E.; Mall, G.; Hasselbach, W.; Kuebler, W.

    1985-02-01

    To study kinetics and principles of cellular uptake of /sup 13/N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of /sup 13/N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 37 degrees C). Total extraction, 80 sec after the reaction start, was 786 +/- 159 mumol/ml cell volume. Cells destroyed by calcium overload were unable to extract /sup 13/N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. /sup 13/N-Ammonia uptake could also be reduced by 50 muM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 micrograms/ml 1-methionine sulfoximine, and by preincubation with 5 muM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of /sup 13/N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of /sup 13/N-ammonia may not always provide a valid measurement of myocardial perfusion.

  3. Production of proteolytic enzymes in mast cells, fibroblasts, vascular smooth muscle and endothelial cells cultivated under normoxic or hypoxic conditions

    Czech Academy of Sciences Publication Activity Database

    Maxová, H.; Bačáková, Lucie; Lisá, Věra; Novotná, J.; Tomášová, H.; Vízek, M.; Herget, J.

    2010-01-01

    Roč. 59, č. 5 (2010), s. 711-719. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/08/0108; GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : hypoxia * metalloproteinases * tryptase * chymase * immunofluorescence Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.646, year: 2010

  4. Exploring the limits of optical microscopy: live cell and superresolution fluorescence microscopy of HIV-1 Transfer Between T lymphocytes Across the Virological Synapse

    Science.gov (United States)

    McNerney, Gregory Paul

    Human immunodeficiency virus 1 (HIV-1) is a human retrovirus that efficiently, albeit gradually, overruns the immune system. An already infected T lymphocyte can latch onto another T lymphocyte whereby creating a virological synapse (VS); this junction drives viral assembly and transfer to the target cell in batches in an efficient, protective manor. My Ph.D. doctoral thesis focused on studying this transmission mechanism using advanced optical imaging modalities and the fully infectious fluorescent clone HIV Gag-iGFP. T lymphocytes are non-adherent cells (˜10 um thick) and the viral transmission process is fairly dynamic, hence we employed a custom spinning disk confocal microscope that revealed many interesting characteristics of this cooperative event. This methodology has low throughput as cell contact and transfer is at random. Optical tweezers was then added to the microscope to directly initiate cell contact at will. To assess when viral maturation occurs post-transfer, an optical assay based off of Forster resonance energy transfer was developed to monitor maturation. Structured illumination microscopy was further used to image the process at higher resolution and it showed that viral particles are not entering existing degradative compartments. Non-HIV-1 applications of the optical technologies are also reviewed.

  5. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Pillay, Deenan; Miners, Alec H;

    2008-01-01

    , the predicted proportion of potential life-years survived was 83% with viral load monitoring (switch when viral load >500 copies per mL), 82% with CD4 cell count monitoring (switch at 50% drop from peak), and 82% with clinical monitoring (switch when two new WHO stage 3 events or a WHO stage 4 event occur...

  6. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

    Science.gov (United States)

    Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

    2014-07-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

  7. Determination of thermodynamic properties and stability limit from fluorite phase of uranium and lanthanide mixed oxides, using galvanic cells with solid electrolytes

    International Nuclear Information System (INIS)

    A method for thermodynamic properties determination for oxygen solubility in oxide systems at temperature interval 973 ≤ T [K] ≤ 1773 is described. A galvanic cell using as solid electrolytes zircon dioxide doped with 15% of calcium oxide is presented. This method was used for determining the phase change, temperature dependent, of uranium-lanthanides-oxygen Ln U O4 stoichiometric system. (C.G.C.)

  8. Silicon photomultiplier (SPM) detection of low-level bioluminescence for the development of deployable whole-cell biosensors: Possibilities and limitations

    OpenAIRE

    Li, Huaqing; Lopes, Nicholas; Moser, Scott; Sayler, Gary; Ripp, Steven

    2012-01-01

    Whole-cell bacterial bioreporters await miniaturized photon counting modules with high sensitivity and robust compatible hardware to fulfill their promise of versatile, on-site biosensor functionality. In this study, we explore the photon counting readout properties of the silicon photomultiplier (SPM) with a thermoelectric cooler and the possibilities of detecting low-level bioluminescent signals. Detection performance was evaluated through a simulated LED light source and the bioluminescenc...

  9. The successes and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell-surface-targeted biological agents in patients

    OpenAIRE

    Polson, Andrew G; Fuji, Reina N

    2012-01-01

    To improve drug development outcomes, it is important to review when preclinical pharmacodynamic and safety models have successfully predicted human responses and when they have not. In a recent issue of the BJP, Bugelski and Martin examined the concordance between preclinical and human data for biopharmaceuticals targeted to cell-surface proteins. The cases are interesting and several trends emerge. The pharmacodynamics of biopharmaceuticals in non-human primates is largely predictive; the u...

  10. Reactive oxygen species and autophagy associated apoptosis and limitation of clonogenic survival induced by zoledronic acid in salivary adenoid cystic carcinoma cell line SACC-83.

    Directory of Open Access Journals (Sweden)

    Xi-Yuan Ge

    Full Text Available Salivary adenoid cystic carcinoma is an epithelial tumor in the head and neck region. Despite its slow growth, patients with salivary adenoid cystic carcinoma exhibit poor long term survival because of a high rate of distant metastasis. Lung and bone are common distant metastasis sites. Zoledronic acid, a third generation bisphosphonate, has been used for tumor-induced osteolysis due to bone metastasis and has direct antitumor activity in several human neoplasms. Here, we observed that zoledronic acid inhibited salivary adenoid cystic carcinoma cell line SACC-83 xenograft tumor growth in nude mice. In vitro, zoledronic acid induced apoptosis and reduced clonogenic survival in SACC-83. Flow cytometry and western blotting indicated that the cell cycle was arrested at G0/G1. Zoledronic acid treatment upregulated reactive oxygen species as well as the autophagy marker protein LC-3B. Reactive oxygen species scavenger N-acetylcysteine and autophagy antagonist 3-methyladenine decreased zoledronic acid-induced apoptosis and increased clonogenic survival. Silencing of the autophagy related gene Beclin-1 also decreased zoledronic acid-induced apoptosis and inhibition of clonogenic formation. In addition, isobolographic analysis revealed synergistic effects on apoptosis when zoledronic acid and paclitaxel/cisplatin were combined. Taken together, our results suggest that zoledronic acid induced apoptosis and reduced clonogenic survival via upregulation of reactive oxygen species and autophagy in the SACC-83 cell line. Thus, zoledronic acid should be considered a promising drug for the treatment of salivary adenoid cystic carcinoma.

  11. Human mast cell tryptase: Multiple cDNAs and genes reveal a multigene serine protease family

    International Nuclear Information System (INIS)

    Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the ∼1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5' regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family

  12. Key role of mast cells and their major secretory products in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He

    2004-01-01

    Hirtoncally, mast cells were known as a key cell type involved in type I hypersensitivity Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the iieum and colon of patients with IBD, which was accompanied by great changes of the content in mart cells such as dramatically increaed expression of TNFα, IL-16 and substance P.The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of petienta with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD.However, Iittle is known of the actions of histamine, tryptase,chymase and carboxypeptidase in IBD. Over the lart decade,heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the petienis showed good clinical and laberatory respense with no senous advere effectd. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast colls to amplify their own activationdegranulation signals in an autocrine or paracrine mannec.The hypethesis is that mast cell secretogogues induce mart cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H1 recepton.Whereas released tryptase acts similarly to hirtamine, but activates mart cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the

  13. HOME Income Limits

    Data.gov (United States)

    Department of Housing and Urban Development — HOME Income Limits are calculated using the same methodology that HUD uses for calculating the income limits for the Section 8 program. These limits are based on...

  14. The Utilization and Limitation of CD133 Epitopes in Lung Cancer Stem Cells Research%CD133作为肺癌干细胞标记物的应用及其局限性

    Institute of Scientific and Technical Information of China (English)

    陈寅

    2011-01-01

    Lung cancer is one of the most common tumor, which lacks of effective clinical treatment to lead to de-sirable prognosis. According to cancer stem cell hypothesis, lung cancer stem cells are considered to be responsible for carcino-genesis, development, metastasis, recurrence, invasion, resistance to chemotherapy and radiotherapy of lung cancer. In recent years, more and more institutes used glycosylated CD 133 epitopes to define, isolate, purify lung cancer stem cells. However, along with deeply research, the application of CD 133 epitopes in lung cancer stem cell research is questioned. The utilization and limitation of CD 133 epitopes in lung cancer stem cells research for the past few years is summaried in this review.%肺癌是临床上最常见的恶性肿瘤之一,尚缺乏预后较为理想的治疗方案.肿瘤干细胞学说认为肺癌干细胞是肺癌发生、发展、转移、复发、耐受放化疗以及肺癌细胞具有侵袭性的主要原因.近年来越来越多的机构利用CD133糖基化表位来鉴定、分离、提纯肺癌干细胞.然而,随着研究的深入,CD133作为肺癌干细胞标记物逐渐受到质疑.本文对近年来利用CD133作为肺癌干细胞表面标记物的应用及其局限性做一综述.

  15. 细致平衡理论计算CdS/CdTe异质结太阳电池的极限转换效率%DETAIL BALANCE LIMIT OF EFFICIENCY OF CdS/CdTe HETEROJUNCTION SOLAR CELLS

    Institute of Scientific and Technical Information of China (English)

    熊超; 陈磊; 袁洪春; 姚若河

    2013-01-01

    Based on detailed balance theory and considered the barriers at interface of heterojunction,which result from the band offset and block photon-generated carriers transport,a photoelectric conversion model for heterojunction solar cells was established.The problem of the limit efficiency of heterojunction solar cells was solved using the detailed balance theory.A method to realize the Ⅰ-Ⅴ characteristics of the CdS/CdTe heterojunction solar cells under the illumination and the limit conversion efficiency of CdS/CdTe solar cells was proposed in this article.Under the illumination,the Ⅰ-Ⅴ characteristics and maximum conversion efficiency are closely related to the built-in barrier of the CdS/CdTe solar cells.It is shown that a theoretical efficiency limit of 29% can be achieved for CdS/CdTe heterojunction solar cells under AM1.5 illumination.Considering the typical parameters of CdS and CdTe,the maximum conversion efficiency of 25% can be achieved.Analysis of the reality of the efficiency is not high and the feasibility of improving conversion efficiency of the CdS/CdTe heterojunction solar cells.%在细致平衡理论基础上,针对异质结电池在结处由于能带不连续而形成载流子运动势垒可能对光生载流子的运输存在阻碍作用,建立异质结太阳电池的光电转换模型,解决了细致平衡理论无法计算异质结太阳电池极限效率的问题,推导出CdS/CdTe异质结太阳电池光照下的Ⅰ-Ⅴ特性表达式以及最大光电转换效率的求法.指出电池的Ⅰ-Ⅴ特性以及最大转换效率与电池的内建势垒密切相关,并求出在理想情况AM1.5的光照下CdS/CdTe异质结太阳电池最大转换效率可达29%;考虑到CdS和CdTe的典型参数后,计算出其最大转换效率可达25%.分析了现实中电池效率不高的原因,并指出实现电池转换效率提高的可行性.

  16. Passive immitance limiters

    OpenAIRE

    Filinyuk N. A.; Lischinskaya L. B.; Chekhmestruk R. Yu.

    2015-01-01

    The paper presents quadripole R, L, C immittance limiters, in which output immittance to the certain value depends on the input immittance. A classification of immittance limiters is given. Basic parameters are considered: low and high levels of output immittance limiters; low and high values of input immittance, corresponding to low and high levels of limitation, accordingly; range of possible values of output immittance; steepness of immittance limiters; time of wearing-out (or delay); high...

  17. Tiling Spaces are Inverse Limits

    OpenAIRE

    Sadun, Lorenzo

    2002-01-01

    Let M be an arbitrary Riemannian homogeneous space, and let Omega be a space of tilings of M, with finite local complexity (relative to some symmetry group Gamma) and closed in the natural topology. Then Omega is the inverse limit of a sequence of compact finite-dimensional branched manifolds. The branched manifolds are (finite) unions of cells, constructed from the tiles themselves and the group Gamma. This result extends previous results of Anderson and Putnam, of Ormes, Radin and Sadun, of...

  18. Limits to adaptation

    Science.gov (United States)

    Dow, Kirstin; Berkhout, Frans; Preston, Benjamin L.; Klein, Richard J. T.; Midgley, Guy; Shaw, M. Rebecca

    2013-04-01

    An actor-centered, risk-based approach to defining limits to social adaptation provides a useful analytic framing for identifying and anticipating these limits and informing debates over society's responses to climate change.

  19. Purification and characterization of a fish granzymeA involved in cell-mediated immunity.

    Science.gov (United States)

    Matsuura, Yuta; Yabu, Takeshi; Shiba, Hajime; Moritomo, Tadaaki; Nakanishi, Teruyuki

    2016-07-01

    Granzymes are serine proteases involved in the induction of cell death against non-self cells. The enzymes differ in their primary substrate specificity and have one of four hydrolysis activities: tryptase, Asp-ase, Met-ase and chymase. Although granzyme genes have been isolated from several fishes, evidence for their involvement in cytotoxicity has not yet been reported. In the present study, we attempted to purify and characterize a fish granzyme involved in cytotoxicity using ginbuna crucian carp. The cytotoxicity of leukocytes was significantly inhibited by the serine protease inhibitor ''3, 4-dichloroisocoumarin''. In addition, we found that granzymeA-like activity (hydrolysis of Z-GPR-MCA) was inhibited by the same inhibitor and significantly enhanced by allo-antigen stimulation in vivo. Proteins from leukocyte extracts were subjected to two steps of chromatographic purification using benzamidine-Sepharose and SP-Sepharose. The molecular weight of the purified enzyme was estimated to be 26,900 Da by SDS-PAGE analysis. The purified enzyme displayed a Km of 220 μM, a Kcat of 21.7 sec(-1) and a Kcat/Km of 98,796 sec(-1) M(-1) with an optimal pH of 9.5 for the Z-GPR-MCA substrate. The protease was totally inhibited by serine protease inhibitors and showed granzymeA-like substrate specificity. Therefore, we conclude that the purified enzyme belongs to the mammalian granzymeA (EC 3.4.21.78) and appears to be involved in cytotoxicity in fish. PMID:26872543

  20. Interval graph limits

    CERN Document Server

    Diaconis, Persi; Janson, Svante

    2011-01-01

    We work out the graph limit theory for dense interval graphs. The theory developed departs from the usual description of a graph limit as a symmetric function $W(x,y)$ on the unit square, with $x$ and $y$ uniform on the interval $(0,1)$. Instead, we fix a $W$ and change the underlying distribution of the coordinates $x$ and $y$. We find choices such that our limits are continuous. Connections to random interval graphs are given, including some examples. We also show a continuity result for the chromatic number and clique number of interval graphs. Some results on uniqueness of the limit description are given for general graph limits.

  1. Passive immitance limiters

    Directory of Open Access Journals (Sweden)

    Filinyuk N. A.

    2015-06-01

    Full Text Available The paper presents quadripole R, L, C immittance limiters, in which output immittance to the certain value depends on the input immittance. A classification of immittance limiters is given. Basic parameters are considered: low and high levels of output immittance limiters; low and high values of input immittance, corresponding to low and high levels of limitation, accordingly; range of possible values of output immittance; steepness of immittance limiters; time of wearing-out (or delay; high and low cutoff frequencies; central working frequency; frequency band; relative range of working frequencies; non-linearity coefficient. The authors have designed passive R-, L-, C-limiters with possibility of limitation from above and from below. The influence of the input parasitic immittances on the immittance transfer characteristic is evaluated. In most cases parasite immittance does not influence the considered devices, including R-limiters «from above» with the input quality factor of QR(Linp=0,1…0,2 and L-limiters «from above» with high-quality input circuits with QL(Rinp>2. The analysis also shows that high-qualitiy circuits with QN(RinpN>3 should be used in C-limiters with input parasitic immittances, while at parasitic immittance of the limiting element low-quality circuits with QN(RiN>0,2 should be selected.

  2. The JET belt limiter

    International Nuclear Information System (INIS)

    A limiter with an effective area in contact with the plasma of about 16 m2 is presently being manufactured for installation in 1987. This belt limiter consists of two toroidal rings located above and below the equatorial plane of the vacuum vessel. Each of the two rings comprises a structure with water cooling pipes and fins welded to the pipes. The limiter material in contact with the plasma (graphite or beryllium) is inserted between fins in the form of tiles. The belt limiter is designed to handle up to 40 MW of total power at flux densities of 3 - 5 MW/m2 for 10 s and to permit rapid exchange of different limiter materials. The design and manufacture of the belt limiter and the results of thermomechanical analysis for different edge properties, power levels and shot repetition rates, are reported. (author)

  3. The jet belt limiter

    International Nuclear Information System (INIS)

    A limiter with an effective area in contact with the plasma of about 16 m/sup 2/ is presently being manufactured for installation in 1987. This belt limiter consists of two toroidal rings located above and below the equatorial plane of the vacuum vessel. Each of the two rings comprises a structure with water cooling pipes and fins welded to the pipes. The limiter material in contact with the plasma (graphite or beryllium) is inserted between fins in the form of tiles. The belt limiter is designed to handle up to 40 MW of total power at flux densities of 3 - 5 MW/m/sup 2/ for 10 s and to permit rapid exchange of different limiter materials. This paper describes the design and manufacture of the belt limiter and the results of thermomechanical analysis for different edge properties, power levels and shot repetition rates

  4. Limit loads in nozzles

    International Nuclear Information System (INIS)

    The static method for the evaluation of the limit loads of a perfectly elasto-plastic structure is presented. Using the static theorem of Limit Analysis and the Finite Element Method, a lower bound for the colapso load can be obtained through a linear programming problem. This formulation if then applied to symmetrically loaded shells of revolution and some numerical results of limit loads in nozzles are also presented. (Author)

  5. Reactor limit control system

    International Nuclear Information System (INIS)

    The very extensive use of limitations in the operational field between protection system and closed-loop controls is an important feature of German understanding of operational safety. The design of limitations is based on very large activities in the computational field but mostly on the high level of the plant-wide own commissioning experience of a turnkey contractor. Limitations combine intelligence features of closed-loop controls with the high availability of protection systems. (orig.)

  6. Limit analysis via creep

    International Nuclear Information System (INIS)

    In this paper it is presented a variational method for the limit analysis of an ideal plastic solid. This method has been denominated as Modified Secundary Creep and enables to find the collapse loads through a minimization of a functional and a limit process. Given an ideal plastic material it is shown how to determinate the associated secundary creep constitutive equation. Finally, as an application, it is found the limit load in an pressurized von Mises rigid plastic sphere. (Author)

  7. Friction Generated Limit Cycles

    OpenAIRE

    Ohlsson, Henrik; Åström, Karl Johan

    2001-01-01

    This paper treats limit cycles caused by friction. The goal has been to explain phenomena that have been observed experimentally in mechatronic systems. Experiments have shown that oscillations of qualitatively different types can be obtained simply by changing controller specifications. Stiction is important in some cases but not in others. Necessary conditions for limit cycle are given for the case where stiction is important. Conditions for local stability of the limit cycles are also pres...

  8. Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m2) Days 1 to 5 and paclitaxel (175 mg/m2) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard 'cohorts of 3' design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m2) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade ≥4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade ≥3 dyspnea, or Grade ≥2 pneumonitis. Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade ≥3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine

  9. The limits on trypanosomatid morphological diversity.

    Directory of Open Access Journals (Sweden)

    Richard John Wheeler

    Full Text Available Cell shape is one, often overlooked, way in which protozoan parasites have adapted to a variety of host and vector environments and directional transmissions between these environments. Consequently, different parasite life cycle stages have characteristic morphologies. Trypanosomatid parasites are an excellent example of this in which large morphological variations between species and life cycle stage occur, despite sharing well-conserved cytoskeletal and membranous structures. Here, using previously published reports in the literature of the morphology of 248 isolates of trypanosomatid species from different hosts, we perform a meta-analysis of the occurrence and limits on morphological diversity of different classes of trypanosomatid morphology (trypomastigote, promastigote, etc. in the vertebrate bloodstream and invertebrate gut environments. We identified several limits on cell body length, cell body width and flagellum length diversity which can be interpreted as biomechanical limits on the capacity of the cell to attain particular dimensions. These limits differed for morphologies with and without a laterally attached flagellum which we suggest represent two morphological superclasses, the 'juxtaform' and 'liberform' superclasses. Further limits were identified consistent with a selective pressure from the mechanical properties of the vertebrate bloodstream environment; trypanosomatid size showed limits relative to host erythrocyte dimensions. This is the first comprehensive analysis of the limits of morphological diversity in any protozoan parasite, revealing the morphogenetic constraints and extrinsic selection pressures associated with the full diversity of trypanosomatid morphology.

  10. Lactobacillus rhamnosus GR-1 Limits Escherichia coli-Induced Inflammatory Responses via Attenuating MyD88-Dependent and MyD88-Independent Pathway Activation in Bovine Endometrial Epithelial Cells.

    Science.gov (United States)

    Liu, Mingchao; Wu, Qiong; Wang, Mengling; Fu, Yunhe; Wang, Jiufeng

    2016-08-01

    Intrauterine Escherichia coli infection after calving reduces fertility and causes major economic losses in the dairy industry. We investigated the protective effect of the probiotic Lactobacillus rhamnosus GR-1 on E. coli-induced cell damage and inflammation in primary bovine endometrial epithelial cells (BEECs). L. rhamnosus GR-1 reduced ultrastructure alterations and the percentage of BEECs apoptosis after E. coli challenge. Increased messenger RNA (mRNA) expression of immune response indicators, including pattern recognition receptors (toll-like receptor [TLR]2, TLR4, nucleotide-binding oligomerization domain [NOD]1, and NOD2), inflammasome proteins (NOD-like receptor family member pyrin domain-containing protein 3, apoptosis-associated speck-like protein, and caspase-1), TLR4 downstream adaptor molecules (myeloid differentiation antigen 88 [MyD88], toll-like receptor adaptor molecule 2 [TICAM2]), nuclear transcription factor kB (NF-kB), and the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-18, and interferon (IFN)-β, was observed following E. coli challenge. However, these increases were attenuated by L. rhamnosus GR-1 pretreatment. Our data indicate that L. rhamnosus GR-1 ameliorates the E. coli-induced disruption of cellular ultrastructure, subsequently reducing the percentage of BEECs apoptosis and limiting inflammatory responses, partly via attenuation of MyD88-dependent and MyD88-independent pathway activation. Certain probiotics could potentially prevent postpartum uterine diseases in dairy cows, ultimately reducing the use of antibiotics. PMID:27236308

  11. Dose limits for astronauts

    Science.gov (United States)

    Sinclair, W. K.

    2000-01-01

    Radiation exposures to individuals in space can greatly exceed natural radiation exposure on Earth and possibly normal occupational radiation exposures as well. Consequently, procedures limiting exposures would be necessary. Limitations were proposed by the Radiobiological Advisory Panel of the National Academy of Sciences/National Research Council in 1970. This panel recommended short-term limits to avoid deterministic effects and a single career limit (of 4 Sv) based on a doubling of the cancer risk in men aged 35 to 55. Later, when risk estimates for cancer had increased and were recognized to be age and sex dependent, the NCRP, in Report No. 98 in 1989, recommended a range of career limits based on age and sex from 1 to 4 Sv. NCRP is again in the process of revising recommendations for astronaut exposure, partly because risk estimates have increased further and partly to recognize trends in limiting radiation exposure occupationally on the ground. The result of these considerations is likely to be similar short-term limits for deterministic effects but modified career limits.

  12. Numerical Limit Analysis:

    DEFF Research Database (Denmark)

    Damkilde, Lars

    2007-01-01

    Limit State analysis has a long history and many prominent researchers have contributed. The theoretical foundation is based on the upper- and lower-bound theorems which give a very comprehensive and elegant formulation on complicated physical problems. In the pre-computer age Limit State analysis...

  13. Limits to Inclusion

    Science.gov (United States)

    Hansen, Janne Hedegaard

    2012-01-01

    In this article, I will argue that a theoretical identification of the limit to inclusion is needed in the conceptual identification of inclusion. On the one hand, inclusion is formulated as a vision that is, in principle, limitless. On the other hand, there seems to be an agreement that inclusion has a limit in the pedagogical practice. However,…

  14. Universal Limits on Computation

    CERN Document Server

    Krauss, L M

    2004-01-01

    The physical limits to computation have been under active scrutiny over the past decade or two, as theoretical investigations of the possible impact of quantum mechanical processes on computing have begun to make contact with realizable experimental configurations. We demonstrate here that the observed acceleration of the Universe can produce a universal limit on the total amount of information that can be stored and processed in the future, putting an ultimate limit on future technology for any civilization, including a time-limit on Moore's Law. The limits we derive are stringent, and include the possibilities that the computing performed is either distributed or local. A careful consideration of the effect of horizons on information processing is necessary for this analysis, which suggests that the total amount of information that can be processed by any observer is significantly less than the Hawking-Beckenstein entropy associated with the existence of an event horizon in an accelerating universe.

  15. Modeling Complex Time Limits

    Directory of Open Access Journals (Sweden)

    Oleg Svatos

    2013-01-01

    Full Text Available In this paper we analyze complexity of time limits we can find especially in regulated processes of public administration. First we review the most popular process modeling languages. There is defined an example scenario based on the current Czech legislature which is then captured in discussed process modeling languages. Analysis shows that the contemporary process modeling languages support capturing of the time limit only partially. This causes troubles to analysts and unnecessary complexity of the models. Upon unsatisfying results of the contemporary process modeling languages we analyze the complexity of the time limits in greater detail and outline lifecycles of a time limit using the multiple dynamic generalizations pattern. As an alternative to the popular process modeling languages there is presented PSD process modeling language, which supports the defined lifecycles of a time limit natively and therefore allows keeping the models simple and easy to understand.

  16. Biological measurement beyond the quantum limit

    CERN Document Server

    Taylor, Michael A; Daria, Vincent; Knittel, Joachi; Hage, Boris; Bachor, Hans-A; Bowen, Warwick P

    2012-01-01

    Quantum noise places a fundamental limit on the per photon sensitivity attainable in optical measurements. This limit is of particular importance in biological measurements, where the optical power must be constrained to avoid damage to the specimen. By using non-classically correlated light, we demonstrated that the quantum limit can be surpassed in biological measurements. Quantum enhanced microrheology was performed within yeast cells by tracking naturally occurring lipid granules with sensitivity 2.4 dB beyond the quantum noise limit. The viscoelastic properties of the cytoplasm could thereby be determined with a 64% improved measurement rate. This demonstration paves the way to apply quantum resources broadly in a biological context.

  17. A quality-adjusted reanalysis of a Phase III trial comparing once-daily thoracic radiation vs. twice-daily thoracic radiation in patients with limited-stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: We undertook an analysis of quality-adjusted survival using the Q-TWiST (Quality Time Without Symptoms or Toxicity) methodology and developed a new graphic representation called a quality-adjusted life-years plot, which presents a complete and concise Q-TWiST analysis on a single plot. Methods and Materials: The Q-TWiST plot incorporates the time without symptoms or toxicity and several combinations of utility coefficients for toxicity and relapse days into the same plot. In addition, the plot includes threshold lines, to judge whether a particular combination of utility coefficients reaches a significance level. Results: The differential in toxicity incidence and severity between the two thoracic radiation treatment arms was inconsequential. Sensitivity analyses were run using Q-TWiST plots. For all combinations of the various toxicity definitions and utility coefficients, the median Q-TWiST was greater for the once-daily thoracic radiation treatment arm than for the twice-daily treatment arm, without achieved significance. Conclusion: This work refines the results previously reported for this Phase III clinical trial in patients with limited-stage small-cell cancer, and there was no significant difference in survival after adjusting for toxicity and progression. Furthermore, the new methods developed for this trial allow for a more detailed and parsimonious presentation of survival and toxicity data for all oncology clinical trials

  18. Tokamak pump limiters

    International Nuclear Information System (INIS)

    Recent experiments with a scoop limiter without active internal pumping have been carried out in the PDX tokamak with up to 6MW of auxiliary neutral beam heating. Experiments have also been done with a rotating head pump limiter in the PLT tokamak in conjunction with RF plasma heating. Extensive experiments have been done in the ISX-B tokamak and first experiments have been completed with the ALT-I limiter in TEXTOR. The pump limiter modules in these latter two machines have internal getter pumping. Experiments in ISX-B are with ohmic and auxiliary neutral beam heating. The results in ISX-B and TEXTOR show that active density control and particle removal is achieved with pump limiters. In ISX-B, the boundary layer (or scape-off layer) plasma partially screens the core plasma from gas injection. In both ISX-B and TEXTOR, the pressure internal to the module scales linearly with plasma density but in ISX-B, with neutral beam injection, a nonlinear increase is observed at the highest densities studied. Plasma plugging is the suspected cause. Results from PDX suggest that a region may exist in which core plasma energy confinement improves using a pump limiter during neutral beam injection. Asymmetric radial profiles and an increased edge electron temperature are observed in discharges with improved confinement. The injection of small amounts of neon into ISX-B has more clearly shown an improved electron core energy confinement during neutral beam injection. While carried out with a regular limiter, this Z-mode of operation is ideal for use with pump limiters and should be a way to achieve energy confinement times similar to values for H-mode tokamak plasmas. The implication of all these results for the design of a reactor pump limiter is described

  19. Interval Graph Limits

    OpenAIRE

    Diaconis, Persi; Holmes, Susan; Janson, Svante

    2012-01-01

    We work out the graph limit theory for dense interval graphs. The theory developed departs from the usual description of a graph limit as a symmetric function $W(x,y)$ on the unit square, with $x$ and $y$ uniform on the interval $(0,1)$. Instead, we fix a $W$ and change the underlying distribution of the coordinates $x$ and $y$. We find choices such that our limits are continuous. Connections to random interval graphs are given, including some examples. We also show a continuity result for th...

  20. Limit experiments of GARCH

    CERN Document Server

    Buchmann, Boris; 10.3150/10-BEJ328

    2012-01-01

    GARCH is one of the most prominent nonlinear time series models, both widely applied and thoroughly studied. Recently, it has been shown that the COGARCH model (which was introduced a few years ago by Kl\\"{u}ppelberg, Lindner and Maller) and Nelson's diffusion limit are the only functional continuous-time limits of GARCH in distribution. In contrast to Nelson's diffusion limit, COGARCH reproduces most of the stylized facts of financial time series. Since it has been proven that Nelson's diffusion is not asymptotically equivalent to GARCH in deficiency, in the present paper, we investigate the relation between GARCH and COGARCH in Le Cam's framework of statistical equivalence. We show that GARCH converges generically to COGARCH, even in deficiency, provided that the volatility processes are observed. Hence, from a theoretical point of view, COGARCH can indeed be considered as a continuous-time equivalent to GARCH. Otherwise, when the observations are incomplete, GARCH still has a limiting experiment, which we ...

  1. HUD Program Income Limits

    Data.gov (United States)

    Department of Housing and Urban Development — Income limits used to determine the income eligibility of applicants for assistance under three programs authorized by the National Housing Act. These programs are...

  2. Limited Income and Resources

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information for those with limited income and resources (those who may qualify for or already have the Low Income Subsidy to lower their prescription drug coverage...

  3. Limited Denial of Participation

    Data.gov (United States)

    Department of Housing and Urban Development — A Limited Denial of Participation (LDP) is an action taken by a HUD Field Office or the Deputy Assistant Secretary for Single Family (DASSF) or Multifamily (DASMF)...

  4. SIS - Annual Catch Limit

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Annual Catch Limit (ACL) dataset within the Species Information System (SIS) contains information and data related to management reference points and catch data.

  5. HOME Rent Limits

    Data.gov (United States)

    Department of Housing and Urban Development — In accordance with 24 CFR Part 92.252, HUD provides maximum HOME rent limits. The maximum HOME rents are the lesser of: The fair market rent for existing housing...

  6. Coagulation with limited aggregations

    CERN Document Server

    Bertoin, Jean

    2012-01-01

    Smoluchowski's coagulation equations can be used as elementary mathematical models for the formation of polymers. We review here some recent contributions on a variation of this model in which the number of aggregations for each atom is a priori limited. Macroscopic results in the deterministic setting can be explained at the microscopic level by considering a version of stochastic coalescence with limited aggregations, which can be related to the so-called random configuration model of random graph theory.

  7. Limits for Life

    Science.gov (United States)

    Marion, Giles M.; Kargel, Jeffrey S.

    The current mantra of astrobiology is “Follow the Water.” Where there is water, there may be life. The FREZCHEM model can determine the presence or absence of water down to the eutectic temperature, below which only solid phases are thermodynamically stable. Salinity, the desiccation potential, and acidity are other potentially life-limiting factors that are calculated by FREZCHEM. In Chapter 4, we discuss potential life-limiting factors such as temperature, salinity, acidity, desiccation, radiation, pressure, and time.

  8. Limited Liability Company

    OpenAIRE

    Jarolímková, Vendula

    2010-01-01

    Limited liability company is today the most common legal form of business entities. This is mainly due to its simple establishment together with a low capital requirements. Preconditions of a foundation of a limited liability company require an establishment of the company, optaining a business license, a pay off of capital to the extent specified by the founding documents and laws, the acting on behalf of the company before its birth, and filling for incorporation into the trade register. Th...

  9. The quantum geometric limit

    CERN Document Server

    Lloyd, Seth

    2012-01-01

    This letter analyzes the limits that quantum mechanics imposes on the accuracy to which spacetime geometry can be measured. By applying the fundamental physical bounds to measurement accuracy to ensembles of clocks and signals moving in curved spacetime -- e.g., the global positioning system -- I derive a covariant version of the quantum geometric limit: the total number of ticks of clocks and clicks of detectors that can be contained in a four volume of spacetime of radius r and temporal extent t is less than or equal to rt/\\pi x_P t_P, where x_P, t_P are the Planck length and time. The quantum geometric limit bounds the number of events or `ops' that can take place in a four-volume of spacetime: each event is associated with a Planck-scale area. Conversely, I show that if each quantum event is associated with such an area, then Einstein's equations must hold. The quantum geometric limit is consistent with and complementary to the holographic bound which limits the number of bits that can exist within a spat...

  10. Fundamental Limits of Cooperation

    CERN Document Server

    Lozano, Angel; Andrews, Jeffrey G

    2012-01-01

    Cooperation is viewed as a key ingredient for interference management in wireless systems. This paper shows that cooperation has fundamental limitations. The main result is that even full cooperation between transmitters cannot in general change an interference-limited network to a noise-limited network. The key idea is that there exists a spectral efficiency upper bound that is independent of the transmit power. First, a spectral efficiency upper bound is established for systems that rely on pilot-assisted channel estimation; in this framework, cooperation is shown to be possible only within clusters of limited size, which are subject to out-of-cluster interference whose power scales with that of the in-cluster signals. Second, an upper bound is also shown to exist when cooperation is through noncoherent communication; thus, the spectral efficiency limitation is not a by-product of the reliance on pilot-assisted channel estimation. Consequently, existing literature that routinely assumes the high-power spect...

  11. The International Atomic Energy Agency (IAEA) randomized trial of palliative treatment of incurable locally advanced non small cell lung cancer (NSCLC) using radiotherapy (RT) and chemotherapy (CHT) in limited resource setting

    International Nuclear Information System (INIS)

    Background: To optimize palliation in incurable locally advanced non-small cell lung cancer (NSCLC), the International Atomic Energy Agency conducted a prospective randomized study (NCT00864331) comparing protracted palliative radiotherapy (RT) course with chemotherapy (CHT) followed by short-course palliative RT. Methods and materials: Treatment-naive patients with histologically confirmed NSCLC, stage IIIA/IIIB, received either 39 Gy in 13 fractions as RT alone (arm A, n = 31) or 2–3 platinum-based CHT cycles followed by 10 Gy in a single fraction or 16 Gy in 2 fractions separated by one week (arm B, n = 34). Primary outcome was overall survival. Results: Treatment groups were balanced with respect to various variables. Median survival for all 65 patients was 8 months, while median survival was 7.1 and 8.1 months for the two arms, respectively (log-rank p = 0.4 by study arm, and p = 0.6 by Cox regression and stratified by country and sub-stage). One and three year survival rates for the two arms were 29%, and 9% and 41%, and 6%, respectively. There were no differences in any of the following endpoints: any failure, local failure, regional failure, contralateral thoracic failure, and distant failure between the two arms. High-grade (⩾3) toxicity was similar between the two arms. Symptoms, adverse events of any kind, KPS and body-mass index, were not different during treatment and during follow-up. There was no grade 5 toxicity. Conclusions: This incomplete and underpowered trial only hinted similar outcome between the treatment arms. Therefore, combined CHT-RT can perhaps be considered, in limited resource setting, where access to RT remains inadequate

  12. Force Limit System

    Science.gov (United States)

    Pawlik, Ralph; Krause, David; Bremenour, Frank

    2011-01-01

    The Force Limit System (FLS) was developed to protect test specimens from inadvertent overload. The load limit value is fully adjustable by the operator and works independently of the test system control as a mechanical (non-electrical) device. When a test specimen is loaded via an electromechanical or hydraulic test system, a chance of an overload condition exists. An overload applied to a specimen could result in irreparable damage to the specimen and/or fixturing. The FLS restricts the maximum load that an actuator can apply to a test specimen. When testing limited-run test articles or using very expensive fixtures, the use of such a device is highly recommended. Test setups typically use electronic peak protection, which can be the source of overload due to malfunctioning components or the inability to react quickly enough to load spikes. The FLS works independently of the electronic overload protection.

  13. Quantum-Limited Spectroscopy

    CERN Document Server

    Truong, Gar-Wing; May, Eric F; Stace, Thomas M; Luiten, Andre N

    2015-01-01

    Spectroscopy has an illustrious history delivering serendipitous discoveries and providing a stringent testbed for new physical predictions, including applications from trace materials detection, to understanding the atmospheres of stars and planets, and even constraining cosmological models. Reaching fundamental-noise limits permits optimal extraction of spectroscopic information from an absorption measurement. Here we demonstrate a quantum-limited spectrometer that delivers high-precision measurements of the absorption lineshape. These measurements yield a ten-fold improvement in the accuracy of the excited-state (6P$_{1/2}$) hyperfine splitting in Cs, and reveals a breakdown in the well-known Voigt spectral profile. We develop a theoretical model that accounts for this breakdown, explaining the observations to within the shot-noise limit. Our model enables us to infer the thermal velocity-dispersion of the Cs vapour with an uncertainty of 35ppm within an hour. This allows us to determine a value for Boltzm...

  14. Limits on nonlinear electrodynamics

    Science.gov (United States)

    Fouché, M.; Battesti, R.; Rizzo, C.

    2016-05-01

    In this paper we set a framework in which experiments whose goal is to test QED predictions can be used in a more general way to test nonlinear electrodynamics (NLED) which contains low-energy QED as a special case. We review some of these experiments and we establish limits on the different free parameters by generalizing QED predictions in the framework of NLED. We finally discuss the implications of these limits on bound systems and isolated charged particles for which QED has been widely and successfully tested.

  15. Limitation of Auditors' Liability

    DEFF Research Database (Denmark)

    Werlauff, Erik; Foged-Ladefoged, Lise Kolding

    2014-01-01

    The article examines the question of whether rules on the limitation of auditors’ liability within the perspective of EU law are needed, and if so, which rules can provide an appropriate balance between the potential injured party’s interests and those of the auditing sector, including with respect...

  16. The Limits of Laughter.

    Science.gov (United States)

    Mindess, Harvey

    1983-01-01

    Three incidents which elucidate the limits of laughter are described. Most persons enjoy humor as comic relief, but when humor strikes a blow at something they hold dear, they find it very hard to laugh. People are upset by an irreverent attitude toward things they hold in esteem. (RM)

  17. Occupational dose equivalent limits

    International Nuclear Information System (INIS)

    This paper considers methods of limiting individual radiation risks by recognizing the variation of risk with age at exposure, taking into account both somatic and genetic risks and proposes a simple formula for controlling individual cumulative exposure and hence risk. (Author)

  18. Limitations on blanket performance

    International Nuclear Information System (INIS)

    The limitations on the performance of breeding blankets in a fusion power plant are evaluated. The breeding blankets will be key components of a plant and their limitations with regard to power density, thermal efficiency and lifetime could determine to a large degree the attractiveness of a power plant. The performance of two rather well known blanket concepts under development in the frame of the European Blanket Programme is assessed and their limitations are compared with more advanced (and more speculative) concepts. An important issue is the question of which material (structure, breeder, multiplier, coatings) will limit the performance and what improvement would be possible with a 'better' structural material. This evaluation is based on the premise that the performance of the power plant will be limited by the blankets (including first wall) and not by other components, e.g. divertors, or the plasma itself. However, the justness of this premise remains to be seen. It is shown that the different blanket concepts cover a large range of allowable power densities and achievable thermal efficiencies, and it is concluded that there is a high incentive to go for better performance in spite of possibly higher blanket cost. However, such high performance blankets are usually based on materials and technologies not yet developed and there is a rather high risk that the development could fail. Therefore, it is explained that a part of the development effort should be devoted to concepts where the materials and technologies are more or less in hand in order to ensure that blankets for a DEMO reactor can be developed and tested in a given time frame. (orig.)

  19. Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01)

    NARCIS (Netherlands)

    Pechoux, C. Le; Laplanche, A.; Faivre-Finn, C.; Ciuleanu, T.; Wanders, R.; Lerouge, D.; Keus, R.; Hatton, M.; Videtic, G.M.; Senan, S.; Wolfson, A.; Jones, R.; Arriagada, R.; Quoix, E.; Dunant, A.; Bussink, J.

    2011-01-01

    BACKGROUND: We recently published the results of the PCI99 randomised trial comparing the effect of a prophylactic cranial irradiation (PCI) at 25 or 36 Gy on the incidence of brain metastases (BM) in 720 patients with limited small-cell lung cancer (SCLC). As concerns about neurotoxicity were a maj

  20. Auctions with Limited Commitment

    OpenAIRE

    Qingmin Liu; Konrad Mierendorff; Xianwen Shi

    2013-01-01

    We study auction design in the standard symmetric independent private values environment, where the seller lacks the commitment power to withhold an unsold object off the market. The seller has a single object and can conduct an infinite sequence of standard auctions with reserve prices to maximize her expected profit. In each period, the seller can commit to a reserve price for the current period but cannot commit to future reserve prices. We analyze the problem with limited commitment throu...

  1. Persuasion and Limited Communication

    OpenAIRE

    Itai Sher

    2008-01-01

    This paper studies optimal persuasion. A speaker must decide which arguments to present and a listener which arguments to accept. Communication is limited in that the arguments available to the speaker depend on her information. Optimality is assessed from the listener's perspective assuming that the listener can commit to a persuasion rule. I show that this seemingly simple scenario--introduced by Glazer and Rubinstein (2006)--is computationally intractable (formally, NP-hard). However under...

  2. Photovoltaic energy cost limit

    International Nuclear Information System (INIS)

    Referring to a photovoltaic system for grid connected applications, a parametric expression of kWh cost is derived. The limit of kWh cost is carried out extrapolating the values of cost components to their lowest figure. The reliability of the forecast is checked by disaggregating kWh cost in direct and indirect costs and by discussing the possible cost reduction of each component

  3. Limiting Similarity Revisited

    OpenAIRE

    Szabo, P; Meszena, G.

    2005-01-01

    We reinvestigate the validity of the limiting similarity principle via numerical simulations of the Lotka-Volterra model. A Gaussian competition kernel is employed to describe decreasing competition with increasing difference in a one-dimensional phenotype variable. The simulations are initiated by a large number of species, evenly distributed along the phenotype axis. Exceptionally, the Gaussian carrying capacity supports coexistence of all species, initially present. In case of any other, d...

  4. TFTR movable limiter installation

    International Nuclear Information System (INIS)

    The TFTR movable limiter is a poloidal limiter consisting of graphite tiles mounted on three blades with hinge connections supported by three independent actuators. The installed configuration is shown. The blades and actuators underwent mechanical, electrical and vacuum tests at the fabricator and at PPL prior to assembly with the TFTR vacuum vessel. During the preparation phase the installation crew removed the bus bar segments and air ducts that interfered with assembly and installed the support steel and the support table for the blade fixture. The actuators were assembled with the extension tubes and motor drives. The lower vertical actuator was rolled into the basement on carts, then pulled into position by a cable through the vacuum vessel. The upper vertical actuator was installed next by lowering into position from above. The three blades (with most of the graphite tiles installed), the cover plate, the horizontal actuator and water and instrumentation feed-throughs were mounted on an air cushion installation fixture, which was then lowered onto the support table. The assembly was floated into position with hand adjustment to engage the roller assemblies with the limiter bridges and the guide pins into the vacuum vessel. The cover plate was then bolted onto the vacuum vessel and the remaining graphite tiles are installed. The whole assembly underwent final adjustment and calibration after installation in the vacuum vessel

  5. 7 CFR 1400.204 - Limited partnerships, limited liability partnerships, limited liability companies, corporations...

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Limited partnerships, limited liability partnerships, limited liability companies, corporations, and other similar legal entities. 1400.204 Section 1400.204... entities. (a) A limited partnership, limited liability partnership, limited liability company,......

  6. Physical limits to magnetogenetics

    OpenAIRE

    Meister, Markus

    2016-01-01

    This is an analysis of how magnetic fields affect biological molecules and cells. It was prompted by a series of prominent reports regarding magnetism in biological systems. The first claims to have identified a protein complex that acts like a compass needle to guide magnetic orientation in animals (Qin et al., 2016). Two other articles report magnetic control of membrane conductance by attaching ferritin to an ion channel protein and then tugging the ferritin or heating it with a magnetic f...

  7. Mast cell in enterocolitis associated with Hirschsprung disease%肥大细胞检测在先天性巨结肠小肠结肠炎中的临床意义

    Institute of Scientific and Technical Information of China (English)

    沈涤华; 施诚仁; 周莹; 余世耀; 吴燕; 严文波; 孙莲萍

    2008-01-01

    目的 探讨肥大细胞在先天性巨结肠小肠结肠炎发病机制的作用,为临床治疗提供依据.方法 2004年5月~2006年5月在上海交通大学医学院附属新华医院行先天性巨结肠根治术中切除的狭窄段、移行段和扩张段肠管黏膜层标本,共30例.男23例,女7例,年龄1个月~7岁,平均1.2岁.短段型5例,普通型18例,长段型6例,全结肠型1例.根据术前有无小肠结肠炎临床症状将患儿分为巨结肠肠炎组(n=12)和非肠炎组(n=18).肥大细胞采用甲苯胺蓝染色和免疫组织化学染色(chymase)染色.结果 巨结肠肠炎组狭窄段、移行段和扩张段肥大细胞在黏膜,黏膜下及扩张的血管周围聚集,脱颗粒现象明显.非肠炎组结肠组织中肥大细胞在黏膜下,黏膜明显减少,脱颗粒现象轻微.结论 肥大细胞在肠炎的发生中起一定的作用,采用肥大细胞抑制剂是一种新的临床治疗先天性巨结肠小肠结肠炎途径.%Objective To assess the role of mast cell and Hirschsprung's disease(HD)associated enterocolitis.Methods We studied 30 patients(23 boys and 7 girls)with HD admitted into our hospital between May 2004 and May 2006.There were 5 short-segment,18 common type,6 long-segment type and 1 total colon type HD. The patients were divided into enterocolitis group(n=12)and non-enterocolitis group(n=18).The mast cells were irnmunostained with toluidine blue and chymase.Results The dilated vessels and the mast cells with degranulation were localized in mucosal and sub-mucosal layers in the enterocolitis group.In the non-enterocolitis group,the mast cells were mainly in submucosallayer and to less extent in the mucosal layer with minimal degranulation.Conclusions These results suggest that mast cells may be involved in the pathogenesis of Hischsprung's diseaseassociated enterocolitis.

  8. The inducible caspase-9 suicide gene system as a ‘safety switch’ to limit on-target, off-tumor toxicities of chimeric antigen receptor T-cells.

    Directory of Open Access Journals (Sweden)

    Tessa eGargett

    2014-10-01

    Full Text Available Immune modulation has become a central element in many cancer treatments, and T cells genetically engineered to express chimeric antigen receptors (CAR may provide a new approach to cancer immunotherapy. Autologous CAR T cells that have been re-directed towards tumor-associated antigens (TAA have shown promising results in phase 1 clinical trials, with some patients undergoing complete tumor regression. However this T-cell therapy must carefully balance effective T-cell activation, to ensure antitumor activity, with the potential for uncontrolled activation that may produce immunopathology. An inducible Caspase 9 (iCasp9 ‘safety switch’ offers a solution that allows for the removal of inappropriately activated CAR T cells. The induction of iCasp9 depends on the administration of the small molecule dimerizer drug AP1903 and dimerization results in rapid induction of apoptosis in transduced cells, preferentially killing activated cells expressing high levels of transgene. The iCasp9 gene has been incorporated into vectors for use in preclinical studies and demonstrates effective and reliable suicide gene activity in phase 1 clinical trials. A third-generation CAR incorporating iCasp9 re-directs T cells towards the GD2 TAA. GD2 is over-expressed in melanoma and other malignancies of neural crest origin and the safety and activity of these GD2-iCAR T cells will be investigated in CARPETS and other actively recruiting phase 1 trials.

  9. 胰酶限时消化在嗅鞘细胞培养中的运用%Application of pancreatic enzyme with limited digestion time for olfactory ensheathing cell culturing

    Institute of Scientific and Technical Information of China (English)

    徐朝伟; 李佳; 付裕; 周瑞瑞; 张旭

    2011-01-01

    目的 探索出一套高效、实用的大鼠嗅球嗅鞘细胞(OECs)的培养和纯化方案.方法 分离SD大鼠嗅球的外两层组织,剪切消化成细胞悬液进行接种.采用3种方法进行OECs的培养和纯化:(1)A组分别经6h、24 h两次差速贴壁去除杂质细胞,培养至12d左右消化重悬细胞进行爬片分析.(2)B组分别经6h、24 h两次差速贴壁去除杂质细胞,培养至12d左右经胰酶限时消化,留成纤维细胞于瓶壁,重悬的细胞进行爬片分析.(3)C组采用经典的Nash法(分别经18 h、36 h两次差速贴壁去除杂质细胞),培养至11d左右消化重悬细胞进行爬片分析.采用NGFRP75与碘化丙啶(PI)双染的方法进行OECs的鉴定和纯度分析.结果 在共聚焦显微镜下呈双染阳性的细胞为OECs,OECs多数突起细长,呈双极或三极,少量呈单极或多极.A、B、C组所纯化的OECs纯度分别为(67.3±6.2)%、(83.7±7.7)%和(74.6士9.5)%,3组间比较有统计学差异(F=13.633,P<0.01),B组所得OECs纯度均较另两组高(P<0.05).结论 经6h、24 h两次差速贴壁十胰酶限时消化可以获得较高纯度的OECs,能够满足动物实验的需要.%Objective To explore an efficient and practical method in culturing and purifing procedures of rat olfactory ensheathing cells (OECs). Methods The outer two layers of SD rat olfactory bulb were peel off, cut and digested into monoplast suspension for seeding. Three kinds of purification methods were taken for comparison: (1) In group A, the monoplast suspension was incubated twice for 6 h + 24 h subsequently according to different adherence, the purified OECs were cultured for about 12 days and then were analyzed on coverslip. (2) In group B, the monoplast suspension was incubated as group A and then pancreatic enzyme with limited digestion time was adopted to remain fibroblasts on the sidewall, the suspension was drawn off for analysis as group A. (3) In group C, the monoplast suspension was incubated by

  10. Orind Refractories Limited

    Institute of Scientific and Technical Information of China (English)

    Mr R. Mishra; Group Manging Director

    2005-01-01

    @@ "Sight can be acquired, Vision cannot". Orind Refractories Limited (ORIND), China was formed with this rare vision. At a time when the world was testing the tepid waters of China; Mr. Ravin Jhunjhunwala, Chairman of ORIND and the management of ORIND India had looked over the Great Wall to begin a journey of success. Incorported on 18th August 1994 with an initial investment of USD 5 million, ORL caters to the ever-demanding needs of the steel industry and beyond. Incidentally ORIND was the first wholly owned India company to set up base in China. Pesently, ORIND China has a 616 strong work force including 23 expatriates.

  11. (Limiting the greenhouse effect)

    Energy Technology Data Exchange (ETDEWEB)

    Rayner, S.

    1991-01-07

    Traveler attended the Dahlem Research Conference organized by the Freien Universitat, Berlin. The subject of the conference was Limiting the Greenhouse Effect: Options for Controlling Atmospheric CO{sub 2} Accumulation. Like all Dahlem workshops, this was a meeting of scientific experts, although the disciplines represented were broader than usual, ranging across anthropology, economics, international relations, forestry, engineering, and atmospheric chemistry. Participation by scientists from developing countries was limited. The conference was divided into four multidisciplinary working groups. Traveler acted as moderator for Group 3 which examined the question What knowledge is required to tackle the principal social and institutional barriers to reducing CO{sub 2} emissions'' The working rapporteur was Jesse Ausubel of Rockefeller University. Other working groups examined the economic costs, benefits, and technical feasibility of options to reduce emissions per unit of energy service; the options for reducing energy use per unit of GNP; and the significant of linkage between strategies to reduce CO{sub 2} emissions and other goals. Draft reports of the working groups are appended. Overall, the conference identified a number of important research needs in all four areas. It may prove particularly important in bringing the social and institutional research needs relevant to climate change closer to the forefront of the scientific and policy communities than hitherto.

  12. Smoothness of limit functors

    Indian Academy of Sciences (India)

    Benedictus Margaux

    2015-05-01

    Let be a scheme. Assume that we are given an action of the one dimensional split torus $\\mathbb{G}_{m,S}$ on a smooth affine -scheme $\\mathfrak{X}$. We consider the limit (also called attractor) subfunctor $\\mathfrak{X}_{}$ consisting of points whose orbit under the given action `admits a limit at 0’. We show that $\\mathfrak{X}_{}$ is representable by a smooth closed subscheme of $\\mathfrak{X}$. This result generalizes a theorem of Conrad et al. (Pseudo-reductive groups (2010) Cambridge Univ. Press) where the case when $\\mathfrak{X}$ is an affine smooth group and $\\mathbb{G}_{m,S}$ acts as a group automorphisms of $\\mathfrak{X}$ is considered. It also occurs as a special case of a recent result by Drinfeld on the action of $\\mathbb{G}_{m,S}$ on algebraic spaces (Proposition 1.4.20 of Drinfeld V, On algebraic spaces with an action of $\\mathfrak{G}_{m}$, preprint 2013) in case is of finite type over a field.

  13. Limits to biofuels

    Science.gov (United States)

    Johansson, S.

    2013-06-01

    Biofuel production is dependent upon agriculture and forestry systems, and the expectations of future biofuel potential are high. A study of the global food production and biofuel production from edible crops implies that biofuel produced from edible parts of crops lead to a global deficit of food. This is rather well known, which is why there is a strong urge to develop biofuel systems that make use of residues or products from forest to eliminate competition with food production. However, biofuel from agro-residues still depend upon the crop production system, and there are many parameters to deal with in order to investigate the sustainability of biofuel production. There is a theoretical limit to how much biofuel can be achieved globally from agro-residues and this amounts to approximately one third of todays' use of fossil fuels in the transport sector. In reality this theoretical potential may be eliminated by the energy use in the biomass-conversion technologies and production systems, depending on what type of assessment method is used. By surveying existing studies on biofuel conversion the theoretical limit of biofuels from 2010 years' agricultural production was found to be either non-existent due to energy consumption in the conversion process, or up to 2-6000TWh (biogas from residues and waste and ethanol from woody biomass) in the more optimistic cases.

  14. Limits to biofuels

    Directory of Open Access Journals (Sweden)

    Johansson S.

    2013-06-01

    Full Text Available Biofuel production is dependent upon agriculture and forestry systems, and the expectations of future biofuel potential are high. A study of the global food production and biofuel production from edible crops implies that biofuel produced from edible parts of crops lead to a global deficit of food. This is rather well known, which is why there is a strong urge to develop biofuel systems that make use of residues or products from forest to eliminate competition with food production. However, biofuel from agro-residues still depend upon the crop production system, and there are many parameters to deal with in order to investigate the sustainability of biofuel production. There is a theoretical limit to how much biofuel can be achieved globally from agro-residues and this amounts to approximately one third of todays’ use of fossil fuels in the transport sector. In reality this theoretical potential may be eliminated by the energy use in the biomass-conversion technologies and production systems, depending on what type of assessment method is used. By surveying existing studies on biofuel conversion the theoretical limit of biofuels from 2010 years’ agricultural production was found to be either non-existent due to energy consumption in the conversion process, or up to 2–6000TWh (biogas from residues and waste and ethanol from woody biomass in the more optimistic cases.

  15. Neurotoxic injury pathways in differentiated mouse motor neuron–neuroblastoma hybrid (NSC-34D) cells in vitro—Limited effect of riluzole on thapsigargin, but not staurosporine, hydrogen peroxide and homocysteine neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Hemendinger, Richelle A., E-mail: richelle.hemendinger@carolinashealthcare.org [ALS Translational Neuroscience Laboratory, Carolinas Medical Center, Charlotte, NC 28203 (United States); Carolinas Neuromuscular/ALS-MDA Center, Department of Neurology, Carolinas Medical Center, Charlotte, NC 28203 (United States); Armstrong, Edward J. [ALS Translational Neuroscience Laboratory, Carolinas Medical Center, Charlotte, NC 28203 (United States); Carolinas Neuromuscular/ALS-MDA Center, Department of Neurology, Carolinas Medical Center, Charlotte, NC 28203 (United States); Radio, Nick [ThermoScientific, Pittsburgh, PA (United States); Brooks, Benjamin Rix [ALS Translational Neuroscience Laboratory, Carolinas Medical Center, Charlotte, NC 28203 (United States); Carolinas Neuromuscular/ALS-MDA Center, Department of Neurology, Carolinas Medical Center, Charlotte, NC 28203 (United States); University of North Carolina School of Medicine-Charlotte Campus (United States)

    2012-01-15

    The neuroblastoma–spinal motor neuron fusion cell line, NSC-34, in its differentiated form, NSC-34D, permits examining the effects of riluzole, a proven treatment for amyotrophic lateral sclerosis (ALS) on cell death induction by staurosporine (STS), thapsigargin (Thaps), hydrogen peroxide (H{sub 2}O{sub 2}) and homocysteine (HCy). These neurotoxins, applied exogenously, have mechanisms of action related to the various proposed molecular pathogenetic pathways in ALS and are differentiated from endogenous cell death that is associated with cytoplasmic aggregate formation in motor neurons. Nuclear morphology, caspase-3/7 activation and high content imaging were used to assess toxicity of these neurotoxins with and without co-treatment with riluzole, a benzothiazole compound with multiple pharmacological actions. STS was the most potent neurotoxin at killing NSC-34D cells with a toxic concentration at which 50% of maximal cell death is achieved (TC{sub 50} = 0.01 μM), followed by Thaps (TC{sub 50} = 0.9 μM) and H{sub 2}O{sub 2} (TC{sub 50} = 15 μM) with HCy requiring higher concentrations to kill at the same level (TC{sub 50} = 2200 μM). Riluzole provided neurorescue with a 20% absolute reduction (47.6% relative reduction) in apoptotic cell death against Thaps-induced NSC-34D cell (p ≤ 0.05), but had no effect on STS-, H{sub 2}O{sub 2}- and HCy-induced NSC-34D cell death. This effect of riluzole on Thaps induction of cell death was independent of caspase-3/7 activation. Riluzole mitigated a toxin that can cause intracellular calcium dysregulation associated with endoplasmic reticulum (ER) stress but not toxins associated with other cell death mechanisms. -- Highlights: ► Calcium-dependent neurotoxins are potent cell death inducers in NSC-34D cells. ► Riluzole provides neurorescue against Thaps-induced NSC-34D cell death. ► Riluzole had no effect on neurotoxicity by STS, H{sub 2}O{sub 2} and Hcy. ► Riluzole reduces NSC-34D cell death independent of

  16. Neurotoxic injury pathways in differentiated mouse motor neuron–neuroblastoma hybrid (NSC-34D) cells in vitro—Limited effect of riluzole on thapsigargin, but not staurosporine, hydrogen peroxide and homocysteine neurotoxicity

    International Nuclear Information System (INIS)

    The neuroblastoma–spinal motor neuron fusion cell line, NSC-34, in its differentiated form, NSC-34D, permits examining the effects of riluzole, a proven treatment for amyotrophic lateral sclerosis (ALS) on cell death induction by staurosporine (STS), thapsigargin (Thaps), hydrogen peroxide (H2O2) and homocysteine (HCy). These neurotoxins, applied exogenously, have mechanisms of action related to the various proposed molecular pathogenetic pathways in ALS and are differentiated from endogenous cell death that is associated with cytoplasmic aggregate formation in motor neurons. Nuclear morphology, caspase-3/7 activation and high content imaging were used to assess toxicity of these neurotoxins with and without co-treatment with riluzole, a benzothiazole compound with multiple pharmacological actions. STS was the most potent neurotoxin at killing NSC-34D cells with a toxic concentration at which 50% of maximal cell death is achieved (TC50 = 0.01 μM), followed by Thaps (TC50 = 0.9 μM) and H2O2 (TC50 = 15 μM) with HCy requiring higher concentrations to kill at the same level (TC50 = 2200 μM). Riluzole provided neurorescue with a 20% absolute reduction (47.6% relative reduction) in apoptotic cell death against Thaps-induced NSC-34D cell (p ≤ 0.05), but had no effect on STS-, H2O2- and HCy-induced NSC-34D cell death. This effect of riluzole on Thaps induction of cell death was independent of caspase-3/7 activation. Riluzole mitigated a toxin that can cause intracellular calcium dysregulation associated with endoplasmic reticulum (ER) stress but not toxins associated with other cell death mechanisms. -- Highlights: ► Calcium-dependent neurotoxins are potent cell death inducers in NSC-34D cells. ► Riluzole provides neurorescue against Thaps-induced NSC-34D cell death. ► Riluzole had no effect on neurotoxicity by STS, H2O2 and Hcy. ► Riluzole reduces NSC-34D cell death independent of caspase-3/7 activation.

  17. Speed Limits for Entanglement

    CERN Document Server

    Hartman, Thomas

    2015-01-01

    We show that in any relativistic system, entanglement entropy obeys a speed limit set by the entanglement in thermal equilibrium. The bound is derived from inequalities on relative entropy with respect to a thermal reference state. Thus the thermal state constrains far-from-equilibrium entanglement dynamics whether or not the system actually equilibrates, in a manner reminiscent of fluctuation theorems in classical statistical mechanics. A similar shape-dependent bound constrains the full nonlinear time evolution, supporting a simple physical picture for entanglement propagation that has previously been motivated by holographic calculations in conformal field theory. We discuss general quantum field theories in any spacetime dimension, but also derive some results of independent interest for thermal relative entropy in 1+1d CFT.

  18. The Limits to Relevance

    Science.gov (United States)

    Averill, M.; Briggle, A.

    2006-12-01

    Science policy and knowledge production lately have taken a pragmatic turn. Funding agencies increasingly are requiring scientists to explain the relevance of their work to society. This stems in part from mounting critiques of the "linear model" of knowledge production in which scientists operating according to their own interests or disciplinary standards are presumed to automatically produce knowledge that is of relevance outside of their narrow communities. Many contend that funded scientific research should be linked more directly to societal goals, which implies a shift in the kind of research that will be funded. While both authors support the concept of useful science, we question the exact meaning of "relevance" and the wisdom of allowing it to control research agendas. We hope to contribute to the conversation by thinking more critically about the meaning and limits of the term "relevance" and the trade-offs implicit in a narrow utilitarian approach. The paper will consider which interests tend to be privileged by an emphasis on relevance and address issues such as whose goals ought to be pursued and why, and who gets to decide. We will consider how relevance, narrowly construed, may actually limit the ultimate utility of scientific research. The paper also will reflect on the worthiness of research goals themselves and their relationship to a broader view of what it means to be human and to live in society. Just as there is more to being human than the pragmatic demands of daily life, there is more at issue with knowledge production than finding the most efficient ways to satisfy consumer preferences or fix near-term policy problems. We will conclude by calling for a balanced approach to funding research that addresses society's most pressing needs but also supports innovative research with less immediately apparent application.

  19. Concurrent cisplatin, prolonged oral etoposide, and vincristine plus chest and brain irradiation for limited small cell lung cancer: A phase II study of the Southwest Oncology Group (SWOG-9229)

    International Nuclear Information System (INIS)

    Purpose: The primary objectives of the study were to evaluate the efficacy and safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy plus concurrent chest/brain irradiation induction, followed by CAV consolidation, in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD) within a cooperative group setting. Methods and Materials: Fifty-six eligible patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m2 i.v. (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m2 (days 1-14, 29-42, and 57-70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT) was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an AP:PA arrangement, to begin concomitantly with induction chemotherapy. Prophylactic cranial irradiation (PCI) was started on day 15 of induction therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21-day cycles of consolidation cyclophosphamide 750 mg/m2 i.v., doxorubicin 50 mg/m2 i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on day 106 or week 16, from the start of induction therapy. Results: Among 56 eligible patients, 93% had SWOG performance status 0-1. All had adequate organ function and had not received prior therapy. The overall confirmed response rate was 46%, including 16% complete responders and 30% partial responders. After a minimum follow-up duration of 17 months, the Kaplan-Meier median progression-free (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven patients (20%) discontinued secondary to toxicity and two patients died from treatment. The major toxicity was hematologic. The two deaths were secondary to infection. Of the

  20. LIMITED LIABILITY DALAM LIMITED LIABILITY PADA KONSTRUKSI PERUSAHAAN KELOMPOK PIRAMIDA

    Directory of Open Access Journals (Sweden)

    Ms. Sulistiowati

    2011-06-01

    Full Text Available Applicability of limited liability in corporate groups with pyramid construction creates a legal loophole in the form of a limited liability within a limited liability. To prevent moral hazard, it is necessary to stipulate new law that limits the number of levels in a corporate group. Berlakunya limited liability pada perusahaan kelompok dengan konstruksi piramida menciptakan celah hukum berupa limited liability dalam limited liability. Untuk mencegah munculnya moral hazard dari pemegang akhir atau induk perbuatan, perlu dilakukan terobosan hukum pembatasan jumlah lapisan anak perusahaan dalam konstruksi perusahaan kelompok.

  1. Capsulorhexis: Its safe limits

    Directory of Open Access Journals (Sweden)

    Vasavada Abhay

    1995-01-01

    Full Text Available We undertook this study to determine the safe limits of capsulorhexis during nucleus expression in 40 eyes of patients undergoing extracapsular cataract extraction (ECCE with a posterior chamber intraocular lens (PC IOL implantation and in 30 cadaver eyes. In group I (patient eyes, capsulorhexis of 4.5 to 7.5 mm was performed and the nucleus was expressed by hydrodissection. The nuclei measured 4.5 to 9.0 mm. One relaxing incision at 12 o′clock position had to be placed in 9 patients. In group II (cadaver eyes, continuous curvilinear capsulotomies of 4.0, 4.5, 5.0, 5.5, 6.0 and 6.5 mm were made in 5 eyes each. No relaxing incisions were placed. In both the groups, nuclei of all sizes could be safely delivered through intact capsulotomies measuring 5.5 mm or more. In two patient eyes, posterior capsule rupture occurred with rhexis measuring 4.5 and 5.0 mm, respectively. In the cadaver eyes, intracapsular extraction occurred in 4 eyes with rhexis measuring 5.0 mm or less. We conclude that a rhexis less than 5.5 mm is not safe for nucleus delivery during ECCE.

  2. GCFR core cladding temperature limits

    International Nuclear Information System (INIS)

    This paper reviews the phenomena that affect selection of the GCFR cladding faulted temperature limit. The limiting effects are determined to be clad melting, strength and oxidation rate. The selected temperature limit is 13000C (23700F). The limits for normal, upset and emergency events are also breifly reviewed, and some changes under consideration are discussed

  3. Protocol for the CONVERT trial—Concurrent ONce-daily VErsus twice-daily RadioTherapy: an international 2-arm randomised controlled trial of concurrent chemoradiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small cell lung cancer (LS-SCLC) and good performance status

    OpenAIRE

    Faivre-Finn, Corinne; Falk, Sally; Ashcroft, Linda; Bewley, Michelle; Lorigan, Paul; Wilson, Elena; Groom, Nicki; Snee, Michael; Fournel, Pierre; Cardenal, Felipe; Bezjak, Andrea; Blackhall, Fiona

    2016-01-01

    Introduction Concurrent ONce-daily VErsus twice-daily RadioTherapy (CONVERT) is the only multicentre, international, randomised, phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy (RT) in limited stage small cell lung cancer (LS-SCLC). Following on from the Turrisi trial of once-daily versus twice-daily (BD) concurrent chemoradiotherapy, there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily r...

  4. The limits of deterrence

    International Nuclear Information System (INIS)

    The objective of this contribution is to propose a better insight of the validity of the theory of deterrence, and of related doctrines in more complex and more various situations than in the past: emergence of powers like China and India, of new nuclear States like North Korea and Pakistan, of countries planning to acquire nuclear weapons like Iran, and possibility of a new wave of nuclear proliferation in Middle-East and north-eastern Asia. It also aims at providing arguments in the debates on the struggle against nuclear proliferation and on the future of deterrence. The author first presents and comments the principles of deterrence, and illustrates them by more or less recent historical situations (Iran during the war with Iraq, USA after Pearl Harbour, Arab-Israeli wars, Iraq, and so on). He notably outlines that the notion of deterrence is present in Islamic culture, and that Iran has well integrated it in its defence strategy. Examples of statements and behaviours of other Arab leaders are discussed. The author also briefly indicates how the deterrence strategy is present in the official doctrines of Russia, India, Pakistan, and North Korea. In a second part, based on various examples, the author analyses the practical limitations of deterrence by distinguishing the psychological dimension (bounded rationality, political leaders suffering from various psychological problems, importance of the ideological and spiritual dimension, values prevailing on interests, the case of Iran), and the strategic dimension (good understanding of the enemy, sensitivity of the threat of massive damages, existence of a single decision centre and of an efficient communication). The author finally proposes seven recommendations for better deterrence efficiency

  5. Limits to Tidal Power

    Science.gov (United States)

    Garrett, C.

    2008-12-01

    Ocean tides have been proposed as a source of renewable energy, though the maximum available power may be shown to be only a fraction of the present dissipation rate of 3.5 TW, which is small compared with global insolation (nearly 105 TW), wind dissipation (103 TW), and even human power usage of 15 TW. Nonetheless, tidal power could be a useful contributor in some locations. Traditional use of tidal power, involving the trapping of water behind a barrage at high tide, can produce an average power proportional to the area of the headpond and the square of the tidal range; the power density is approximately 6 W per square meter for a tidal range of 10 m. Capital costs and fears of environmental damage have put barrage schemes in disfavor, with interest turning to the exploitation of strong tidal currents, using turbines in a manner similar to wind turbines. There is a limit to the available power, however, as adding turbines reduces the flow, ultimately reducing the power. For sinusoidal forcing of flow in a channel connecting two large open basins, the maximum available power may be shown to be given approximately by 0.2ρ g a Q_max, where ρ is the water density, g gravity, a the amplitude of the tidal sea level difference along the channel, and Q_max is the maximum volume flux in the natural state. The same formula applies if the channel is the entrance to a semi-enclosed basin, with a now the amplitude of the external tide. A flow reduction of approximately 40% is typically associated with the maximum power extraction. The power would be reduced if only smaller environmental changes are acceptable, and reduced further by drag on supporting structures, dissipation in turbine wakes, and internal inefficiencies. It can be suggested that the best use of strong, cold, tidal currents is to provide cooling water for nuclear reactors.

  6. FED pumped limiter configuration issues

    International Nuclear Information System (INIS)

    Impurity control in the Fusion Engineering Device (FED) is provided by a toroidal belt pumped limiter. Limiter design issues addressed in this paper are (1) poloidal location of the limiter belt, (2) shape of the limiter surface facing the plasma, and (3) whether the belt is pumped from one or both sides. The criteria used for evaluation of limiter configuration features were sensitivity to plasma-edge conditions and ease of maintenance and fabrication. The evaluation resulted in the selection of a baseline FED limiter that is located at the bottom of the device and has a flat surface with a single leading edge

  7. Practical Roadmap and Limits to Nanostructured Photovoltaics

    OpenAIRE

    Lunt, Richard R.; Rowehl, Jill A.; Osedach, Timothy Paul; Brown, Patrick Richard; Bulovic, Vladimir

    2011-01-01

    The significant research interest in the engineering of photovoltaic (PV) structures at the nanoscale is directed toward enabling reductions in PV module fabrication and installation costs as well as improving cell power conversion efficiency (PCE). With the emergence of a multitude of nanostructured photovoltaic (nano-PV) device architectures, the question has arisen of where both the practical and the fundamental limits of performance reside in these new systems. Here, the former is address...

  8. Charter Halibut Limited Access Program

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This limited access system limits the number of charter vessels that may participate in the guided sport fishery for halibut in area 2C and 3A. NMFS issues a...

  9. Generalized current-voltage analysis and efficiency limitations in non-ideal solar cells: Case of Cu2ZnSn(SxSe1-x)4 and Cu2Zn(SnyGe1-y)(SxSe1-x)4

    Science.gov (United States)

    Hages, Charles J.; Carter, Nathaniel J.; Agrawal, Rakesh; Unold, Thomas

    2014-06-01

    Detailed electrical characterization of nanoparticle based Cu2ZnSn(SxSe1-x)4 (CZTSSe) and Cu2Zn(SnyGe1-y)(SxSe1-x)4 (CZTGeSSe) solar cells has been conducted to understand the origin of device limitations in this material system. Specifically, temperature dependent current-voltage analysis has been considered, with particular application to the characterization of solar cells with non-ideal device behavior. Due to the presence of such non-ideal device behavior, typical analysis techniques—commonly applied to kesterite-type solar cells—are found to be insufficient to understand performance limitations, and an analysis methodology is presented to account for the non-idealities. Here, the origin of non-ideal device behavior is chiefly considered in terms of electrostatic and band gap potential fluctuations, low minority carrier lifetimes, temperature dependent band edges, high surface/bulk recombination rates, and tunneling enhanced recombination. For CZTSSe and CZTGeSSe, the main limitations to improved device performance (voltage limitations) are found to be associated with significant EA deficits (EA-EG) at 300 K, large ideality factors, and voltage-dependent carrier collection, which we associate with the bulk material properties of the absorbers. The material origin of these non-ideal electrical properties is considered. Additionally, for CZTGeSSe, the effect of Ge-incorporation on the electrical properties of the solar cells is discussed, with improvements in the electrical properties characterized for the Ge-alloyed devices.

  10. Limitations of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays

    OpenAIRE

    van Tonder, Alet; Joubert, Annie M; Cromarty, A Duncan

    2015-01-01

    Background The tetrazolium-based MTT assay has long been regarded as the gold standard of cytotoxicity assays as it is highly sensitive and has been miniaturised for use as a high-throughput screening assay. However, various reports refer to interference by different test compounds, including the glycolysis inhibitor 3-bromopyruvate, with the conversion of the dye to coloured formazan crystals. This study assessed the linear range and reproducibility of three commonly used cell enumeration as...

  11. Mass transport limitation in implantable defibrillator batteries

    Science.gov (United States)

    Schmidt, C.; Tam, G.; Scott, E.; Norton, J.; Chen, K.

    Using cells with lithium reference electrodes, the power-limiting behavior in the lithium-SVO cell was shown to be due to a rapid voltage transition at the anode. A novel test cell was developed to explore the influence of current density, bulk LiAsF 6 concentration, separator type and separator proximity to the anode on the time to onset ( τ) of the anode polarization. The results were found to follow a relationship, iτ1/2∝ Cbulk, consistent with the Sand equation. This relationship also predicts that the critical concentration of LiAsF 6, at which onset of the anode polarization occurs, is near the solubility limit of LiAsF 6 in our system (around 3.5-4.0 M). This general phenomenon was found to be quantitatively similar for two dissimilar separator types, and the anode polarization could also be induced in the absence of separator at high concentration and current density. However, it appears that τ decreases with closer proximity of the separator to the anode surface (i.e. cell stack pressure), suggesting that the effect of separator is to inhibit convective transport to and from the Li surface.

  12. Limits to Chemically Guided Multicellular Migration

    Science.gov (United States)

    Varennes, Julien; Han, Bumsoo; Mugler, Andrew

    Collective cell migration in response to a chemical cue requires both multicellular sensing of chemical gradients and coordinated mechanical action. Examples from morphogenesis and cancer metastasis demonstrate that clusters of migratory cells are extremely sensitive, responding to gradients of less than 1% difference in chemical concentration across a cell body. While the limits to multicellular sensing are becoming known, the ensuing consequences for coherent migration remain poorly understood. We develop a model of multicellular sensing and migration based on the cellular Potts model. Multicellular sensing of noisy chemical gradients is modeled as a process of local excitation and global inhibition (LEGI) among communicating cells. The output of the sensing process is coupled to individual cells' polarization to model migratory behavior. We find that larger clusters of cells detect the gradient direction with higher precision and thus achieve stronger polarization bias. At the same time, larger clusters are also accompanied by less coherent collective motion. The trade-off between these two effects leads to an optimally efficient cluster size. We discuss how our results relate to cancer metastasis.

  13. Theoretical efficiency limits for thermoradiative energy conversion

    International Nuclear Information System (INIS)

    A new method to produce electricity from heat called thermoradiative energy conversion is analyzed. The method is based on sustaining a difference in the chemical potential for electron populations above and below an energy gap and let this difference drive a current through an electric circuit. The difference in chemical potential originates from an imbalance in the excitation and de-excitation of electrons across the energy gap. The method has similarities to thermophotovoltaics and conventional photovoltaics. While photovoltaic cells absorb thermal radiation from a body with higher temperature than the cell itself, thermoradiative cells are hot during operation and emit a net outflow of photons to colder surroundings. A thermoradiative cell with an energy gap of 0.25 eV at a temperature of 500 K in surroundings at 300 K is found to have a theoretical efficiency limit of 33.2%. For a high-temperature thermoradiative cell with an energy gap of 0.4 eV, a theoretical efficiency close to 50% is found while the cell produces 1000 W/m2 has a temperature of 1000 K and is placed in surroundings with a temperature of 300 K. Some aspects related to the practical implementation of the concept are discussed and some challenges are addressed. It is, for example, obvious that there is an upper boundary for the temperature under which solid state devices can work properly over time. No conclusions are drawn with regard to such practical boundaries, because the work is aimed at establishing upper limits for ideal thermoradiative devices

  14. Material Limitations on the Detection Limit in Refractometry

    Directory of Open Access Journals (Sweden)

    Niels Asger Mortensen

    2009-10-01

    Full Text Available We discuss the detection limit for refractometric sensors relying on high-Q optical cavities and show that the ultimate classical detection limit is given by min {Δn} ≳ η with n + iη being the complex refractive index of the material under refractometric investigation. Taking finite Q factors and filling fractions into account, the detection limit declines. As an example we discuss the fundamental limits of silicon-based high-Q resonators, such as photonic crystal resonators, for sensing in a bio-liquid environment, such as a water buffer. In the transparency window (λ ≳ 1100 nm of silicon the detection limit becomes almost independent on the filling fraction, while in the visible, the detection limit depends strongly on the filling fraction because the silicon absorbs strongly.

  15. Material Limitations on the Detection Limit in Refractometry

    CERN Document Server

    Skafte-Pedersen, Peder; Xiao, Sanshui; Mortensen, Niels Asger; 10.3390/s91108382

    2009-01-01

    We discuss the detection limit for refractometric sensors relying on high-Q optical cavities and show that the ultimate classical detection limit is given by min{Dn} > eta with n+i*eta being the complex refractive index of the material under refractometric investigation. Taking finite Q factors and filling fractions into account, the detection limit declines. As an example we discuss the fundamental limits of silicon-based high-Q resonators, such as photonic crystal resonators, for sensing in a bio-liquid environment, such as a water buffer. In the transparency window of silicon the detection limit becomes almost independent on the filling fraction, while in the visible, the detection limit depends strongly on the filling fraction because silicon absorbs strongly.

  16. Material Limitations on the Detection Limit in Refractometry

    OpenAIRE

    Niels Asger Mortensen; Sanshui Xiao; Peder Skafte-Pedersen; Pedro S. Nunes

    2009-01-01

    We discuss the detection limit for refractometric sensors relying on high-Q optical cavities and show that the ultimate classical detection limit is given by min {Δn} ≳ η with n + iη being the complex refractive index of the material under refractometric investigation. Taking finite Q factors and filling fractions into account, the detection limit declines. As an example we discuss the fundamental limits of silicon-based high-Q resonators, such as photonic crystal resonators, for sensing in a...

  17. Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27–restricted human immune response

    OpenAIRE

    Dazert, Eva; Neumann-Haefelin, Christoph; Bressanelli, Stéphane; Fitzmaurice, Karen; Kort, Julia; Timm, Jörg; McKiernan, Susan; Kelleher, Dermot; Gruener, Norbert; Tavis, John E.; Rosen, Hugo R.; Shaw, Jaqueline; Bowness, Paul; Blum, Hubert E.; Klenerman, Paul

    2009-01-01

    There is an association between expression of the MHC class I molecule HLA-B27 and protection following human infection with either HIV or HCV. In both cases, protection has been linked to HLA-B27 presentation of a single immunodominant viral peptide epitope to CD8+ T cells. If HIV mutates the HLA-B27–binding anchor of this epitope to escape the protective immune response, the result is a less-fit virus that requires additional compensatory clustered mutations. Here, we sought to determine wh...

  18. The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2

    DEFF Research Database (Denmark)

    Mølgaard, Anne; Arnau, Jose; Lauritzen, C.; Larsen, Sine; Petersen, Gitte; Pedersen, John

    2007-01-01

    hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease involved in zymogen activation of granule-associated proteases, including granzymes A and B from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil elastase, and mast cell tryptase and chymase. In the...

  19. Rate limits of sensorimotor synchronization

    Directory of Open Access Journals (Sweden)

    Bruno H. Repp

    2006-01-01

    Full Text Available Empirical evidence for upper and lower rate li-mits of sensorimotor synchronization (typically, finger tapping with anauditory or visual event sequence is reviewed. If biomechanical constraints are avoided, the upper rate limit can be as high as 8-10 Hz (sequence event inter-onset intervals of 100-125 ms with auditory stimuli, but has been found to be less than 2.5 Hz (> 400 ms with simple visual stimuli (flashesof light. The upper rate limit for auditory stimuli varies with task difficulty and musical experience; that for visual stimuli requires further investigation. The lower rate limit, according to one definition,tend stobe at about 0.56 Hz (1800 ms, regardless of modality. Attentional, perceptual, and sensorimotor explanations of these limits are considered. Rate limits of sensorimotor synchronization place important constraints on musical ensemble performance and other forms of rhythmic coordination.

  20. Material limitations on the detection limit in refractometry

    DEFF Research Database (Denmark)

    Skafte-Pedersen, Peder; Nunes, Pedro; Xiao, Sanshui;

    2009-01-01

    We discuss the detection limit for refractometric sensors relying on high-Q optical cavities and show that the ultimate classical detection limit is given by min {Δn} ≳ η with n + iη being the complex refractive index of the material under refractometric investigation. Taking finite Q factors and...

  1. Welfare Dynamics Under Time Limits

    OpenAIRE

    Jeff Grogger; Charles Michalopoulos

    1999-01-01

    Among the most important changes brought about by the Personal Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA) is the imposition of time limits. In this paper, we analyze a simple model in which a potential welfare recipient chooses how to allocate her time-limited endowment of benefits so as to maximize her expected lifetime utility. Not surprisingly, the model reveals that time limits provide an incentive for the consumer to conserve, or bank, her benefits. More inte...

  2. Thermodynamic Limit for Polydisperse Fluids

    OpenAIRE

    Banerjee, S.; Griffiths, R. B.; Widom, M.

    2000-01-01

    We examine the thermodynamic limit of fluids of hard core particles that are polydisperse in size and shape. In addition, particles may interact magnetically. Free energy of such systems is a random variable because it depends on the choice of particles. We prove that the thermodynamic limit exists with probability 1, and is independent of the choice of particles. Our proof applies to polydisperse hard-sphere fluids, colloids and ferrofluids. The existence of a thermodynamic limit implies sys...

  3. Tetrabromobisphenol A (TBBPA)-stimulated reactive oxygen species (ROS) production in cell-free model using the 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay-limitations of method.

    Science.gov (United States)

    Szychowski, Konrad A; Rybczyńska-Tkaczyk, Kamila; Leja, Marcin L; Wójtowicz, Anna K; Gmiński, Jan

    2016-06-01

    Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant, applied in a variety of commercial and household products, mainly electronic ones. Since the production of reactive oxygen species (ROS) is considered one of the principal cytotoxicity mechanisms, numerous studies undertake that aspect of TBBPA's mechanism of action. The present study verifies if the fluorogenic substrate 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) should be used to detect ROS production induced by TBBPA. To determine the ability of TBBPA alone to stimulate the conversion of H2DCFDA to its fluorescent product 2',7'-dichlorofluorescein (DCF), we used a cell-free model. In the experiments we check different cultured media also in combination with free radical scavenger N-acetyl-l-cysteine (NAC). Additionally, experiments with stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH·) have been made. The presented data showed that TBBPA in all tested concentrations interacts with H2DCFDA in phosphate-buffered saline (PBS) buffer while in micromolar concentrations in the DMEM/F12 medium with and without serum. The addition of NAC inhibited the interaction of TBBPA with H2DCFDA. Experiments with DPPH· showed that, in the presence of NAC, TBBPA acts like a free radical. TBBPA has similar properties to free radical and is susceptible to free radical scavenging properties of NAC. Our results indicated that H2DCFDA assay cannot be used to evaluate cellular ROS production in TBBPA studies. The study connected with TBBPA-stimulated ROS production in cell culture models using the H2DCFDA assay should be revised using a different method. However, due to the free radical-like nature of TBBPA, it can be very difficult. Therefore, further investigation of the nature of TBBPA as a compound with similar properties to free radical is required. PMID:26976009

  4. Sickle Cell Tests

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Sickle Cell Tests Share this page: Was this page helpful? ... else I should know? How is it used? Sickle cell tests are used to identify the presence of ...

  5. Limit cycles in quantum systems

    Energy Technology Data Exchange (ETDEWEB)

    Niemann, Patrick

    2015-04-27

    In this thesis we investigate Limit Cycles in Quantum Systems. Limit cycles are a renormalization group (RG) topology. When degrees of freedom are integrated out, the coupling constants flow periodically in a closed curve. The presence of limit cycles is restricted by the necessary condition of discrete scale invariance. A signature of discrete scale invariance and limit cycles is log-periodic behavior. The first part of this thesis is concerned with the study of limit cycles with the similarity renormalization group (SRG). Limit cycles are mainly investigated within conventional renormalization group frameworks, where degrees of freedom, which are larger than a given cutoff, are integrated out. In contrast, in the SRG potentials are unitarily transformed and thereby obtain a band-diagonal structure. The width of the band structure can be regarded as an effective cutoff. We investigate the appearance of limit cycles in the SRG evolution. Our aim is to extract signatures as well as the scaling factor of the limit cycle. We consider the 1/R{sup 2}-potential in a two-body system and a three-body system with large scattering lengths. Both systems display a limit cycle. Besides the frequently used kinetic energy generator we apply the exponential and the inverse generator. In the second part of this thesis, Limit Cycles at Finite Density, we examine the pole structure of the scattering amplitude for distinguishable fermions at zero temperature in the medium. Unequal masses and a filled Fermi sphere for each fermion species are considered. We focus on negative scattering lengths and the unitary limit. The properties of the three-body spectrum in the medium and implications for the phase structure of ultracold Fermi gases are discussed.

  6. Limit cycles in quantum systems

    International Nuclear Information System (INIS)

    In this thesis we investigate Limit Cycles in Quantum Systems. Limit cycles are a renormalization group (RG) topology. When degrees of freedom are integrated out, the coupling constants flow periodically in a closed curve. The presence of limit cycles is restricted by the necessary condition of discrete scale invariance. A signature of discrete scale invariance and limit cycles is log-periodic behavior. The first part of this thesis is concerned with the study of limit cycles with the similarity renormalization group (SRG). Limit cycles are mainly investigated within conventional renormalization group frameworks, where degrees of freedom, which are larger than a given cutoff, are integrated out. In contrast, in the SRG potentials are unitarily transformed and thereby obtain a band-diagonal structure. The width of the band structure can be regarded as an effective cutoff. We investigate the appearance of limit cycles in the SRG evolution. Our aim is to extract signatures as well as the scaling factor of the limit cycle. We consider the 1/R2-potential in a two-body system and a three-body system with large scattering lengths. Both systems display a limit cycle. Besides the frequently used kinetic energy generator we apply the exponential and the inverse generator. In the second part of this thesis, Limit Cycles at Finite Density, we examine the pole structure of the scattering amplitude for distinguishable fermions at zero temperature in the medium. Unequal masses and a filled Fermi sphere for each fermion species are considered. We focus on negative scattering lengths and the unitary limit. The properties of the three-body spectrum in the medium and implications for the phase structure of ultracold Fermi gases are discussed.

  7. Know the single-receptor sensing limit? Think again

    CERN Document Server

    Aquino, Gerardo; Endres, Robert G

    2015-01-01

    How cells reliably infer information about their environment is a fundamentally important question. While sensing and signaling generally start with cell-surface receptors, the degree of accuracy with which a cell can measure external ligand concentration with even the simplest device - a single receptor - is surprisingly hard to pin down. Recent studies provide conflicting results for the fundamental physical limits. Comparison is made difficult as different studies either suggest different readout mechanisms of the ligand-receptor occupancy, or differ on how ligand diffusion is implemented. Here we critically analyse these studies and present a unifying perspective on the limits of sensing, with wide-ranging biological implications.

  8. Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation in limited disease small cell lung cancer-a Danish Oncological Lung Cancer Group (DOLG) phase II trial

    DEFF Research Database (Denmark)

    Sorensen, Morten; Lassen, Ulrik; Palshof, Torben;

    2007-01-01

    topotecan with concurrent twice-daily radiochemotherapy in LD SCLC. PATIENT AND METHODS: Multicentre phase II study of three cycles of regimen A (topotecan i.v., 1.5mg/m(2), day 1-5; cisplatin 50mg/m(2), day 1) and three cycles of regimen B (etoposide i.v., 120mg/m(2), day 1-3; carboplatin, AUC=5, day 1......; vincristine, 1.3mg/m(2), day 1) given in the following sequence: A-B-B-A-B-A every 21 days. Twice-daily radiotherapy (1.5Gyx30, 10fr/wk, 45Gy) was delivered concurrently with the first cycle B. Prophylactic cranial irradiation was offered to patients (pts) in complete remission. Eligible were pts with LD SCLC...... with no prior treatment for SCLC, adequate organ functions, and WHO performance status (PS) two times the upper limit were excluded. RESULT: Fourty-five pts were included in four centres. Five patients did not meet the inclusion criteria. The median age of the eligible pts was 60 years, range 43-75. PS...

  9. Solubility limits on radionuclide dissolution

    Energy Technology Data Exchange (ETDEWEB)

    Kerrisk, J.F.

    1984-12-31

    This paper examines the effects of solubility in limiting dissolution rates of a number of important radionuclides from spent fuel and high-level waste. Two simple dissolution models were used for calculations that would be characteristics of a Yucca Mountain repository. A saturation-limited dissolution model, in which the water flowing through the repository is assumed to be saturated with each waste element, is very conservative in that it overestimates dissolution rates. A diffusion-limited dissolution model, in which element-dissolution rates are limited by diffusion of waste elements into water flowing past the waste, is more realistic, but it is subject to some uncertainty at this time. Dissolution rates of some elements (Pu, Am, Sn, Th, Zr, Sm) are always limited by solubility. Dissolution rates of other elements (Cs, Tc, Np, Sr, C, I) are never solubility limited; their release would be limited by dissolution of the bulk waste form. Still other elements (U, Cm, Ni, Ra) show solubility-limited dissolution under some conditions. 9 references, 3 tables.

  10. Time Limits and Welfare Use

    Science.gov (United States)

    Grogger, Jeffrey

    2004-01-01

    Time limits represent a substantial departure from previous welfare policy. Theory suggests that their effects should vary according to the age of the youngest child of the family. I test this prediction using data from the Current Population Survey and find that time limits indeed have larger effects on families with younger children. I further…

  11. Prediction of Limit Strains in Limiting Dome Height Formability Test

    Science.gov (United States)

    Zadpoor, Amir A.; Sinke, Jos; Benedictus, Rinze

    2007-04-01

    In this paper, the Marciniak-Kunczynski (MK) method is combined with the Storen-Rice analysis in order to improve accuracy of the predicted limit strains in Limiting Dome Height (LDH) test. FEM simulation is carried out by means of a commercial FEM code (ABAQUS) and FEM results are postprocessed by using an improved MK code. It has been shown that while original MK method considerably misspredicts the limit strains, a combination of MK method and Storen-Rice analysis can predict the dome height with a very good accuracy.

  12. Operator dependent choice of prostate cancer biopsy has limited impact on a gene signature analysis for the highly expressed genes IGFBP3 and F3 in prostate cancer epithelial cells.

    Directory of Open Access Journals (Sweden)

    Zhuochun Peng

    Full Text Available BACKGROUND: Predicting the prognosis of prostate cancer disease through gene expression analysis is receiving increasing interest. In many cases, such analyses are based on formalin-fixed, paraffin embedded (FFPE core needle biopsy material on which Gleason grading for diagnosis has been conducted. Since each patient typically has multiple biopsy samples, and since Gleason grading is an operator dependent procedure known to be difficult, the impact of the operator's choice of biopsy was evaluated. METHODS: Multiple biopsy samples from 43 patients were evaluated using a previously reported gene signature of IGFBP3, F3 and VGLL3 with potential prognostic value in estimating overall survival at diagnosis of prostate cancer. A four multiplex one-step qRT-PCR test kit, designed and optimized for measuring the signature in FFPE core needle biopsy samples was used. Concordance of gene expression levels between primary and secondary Gleason tumor patterns, as well as benign tissue specimens, was analyzed. RESULTS: The gene expression levels of IGFBP3 and F3 in prostate cancer epithelial cell-containing tissue representing the primary and secondary Gleason patterns were high and consistent, while the low expressed VGLL3 showed more variation in its expression levels. CONCLUSION: The assessment of IGFBP3 and F3 gene expression levels in prostate cancer tissue is independent of Gleason patterns, meaning that the impact of operator's choice of biopsy is low.

  13. Efficacy and limitations of an ATP-based monitoring system.

    Science.gov (United States)

    Turner, Danielle E; Daugherity, Erin K; Altier, Craig; Maurer, Kirk J

    2010-03-01

    Monitoring of sanitation is an essential function of laboratory animal facilities. The purpose of the current study was to assess the ability of an ATP-based system to detect microbes and organic contaminants. Serial dilutions of Escherichia coli, Staphylococcus aureus, Toxocara canis eggs, Toxoplasma gondii tachyzoites, epithelial cells, and rodent blood, urine, and feces were analyzed according to the manufacturer's recommendations. The limit of E. coli detection was 10(4) organisms; sonication of E. coli significantly improved detection, indicating incomplete bacterial lysis in the detection system. Detection of S. aureus was significantly greater than that of E. coli with a limit of detection of 10(2); sonication did not alter results. In contrast, detection of T. canis, T. gondii, RBC, and epithelial cells was robust and ranged from 2 T. canis eggs to 10 epithelial cells. Urine was weakly detected, with a limit of detection at 1:10 dilution. Detection of all cell types except epithelia had a strong linear correlation to total cell number. In addition, our data demonstrate that the efficacy of the detection system can be affected adversely by residual disinfectants and that sample-bearing swabs are stable for more than 7 h after swabbing. These data demonstrate that this ATP based system sensitively detects pure cells and organic contaminants with a strong degree of linear predictability. A limitation of the system is its inability to detect gram-negative bacteria efficiently because of incomplete cell lysis. PMID:20353694

  14. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

  15. Fundamental limit of light trapping in grating structures

    KAUST Repository

    Yu, Zongfu

    2010-08-11

    We use a rigorous electromagnetic approach to analyze the fundamental limit of light-trapping enhancement in grating structures. This limit can exceed the bulk limit of 4n 2, but has significant angular dependency. We explicitly show that 2D gratings provide more enhancement than 1D gratings. We also show the effects of the grating profile’s symmetry on the absorption enhancement limit. Numerical simulations are applied to support the theory. Our findings provide general guidance for the design of grating structures for light-trapping solar cells.

  16. Spatially limited growth of an epithelium

    Science.gov (United States)

    Deforet, Maxime; Cochet, Olivier; Buguin, Axel; Silberzan, Pascal

    2012-02-01

    We present a study dealing with the growth of an epithelium on a spatially limited adhesive substrate. Adhesive patterns (typical size: 50μm to 500μm) are created by micro-fabrication techniques: A protein repellent polymeric gel homogeneously grafted on a coverslip is selectively ablated by plasma treatment through a thin layer of photoresist. The technique achieves a high resolution of patterning (around 2μm). After seeding cells (MDCK) on circular adhesive patterns, we let the monolayer grow for 30 hours after reaching the confluence. We use physical descriptors to describe migration and compaction. Two days after the confluence, we observe and characterize by confocal microscopy, the appearance of a tridimensionnal assembly of cells in the peripherical zone of the adhesive pattern (a ``rim''). Moreover using other patterns, the existence of a tissue line tension and internal pressure is investigated.

  17. Tokamak plasma interaction with limiters

    International Nuclear Information System (INIS)

    The importance of plasma purity is first discussed in terms of the general requirements of controlled thermonuclear fusion. The tokamak approach to fusion and its inherent problem of plasma contamination are introduced. A main source of impurities is due to the bombardment of the limiter by energetic particles and thus the three main aspects of the plasma-limiter interaction are reviewed, boundary plasma conditions, fuelling/recycling and impurity production. The experiments, carried out on the DITE tokamak at Culham Laboratory, UK, investigated these three topics and the results are compared with predicted behaviour; new physical phenomena are presented in all three areas. Simple one-dimensional fluid equations are found to adequately describe the SOL plasma, except in regard to the pre-sheath electric field and ambipolarity; that is, the electric field adjacent to the limiter surface appears to be weak and the associated plasma flow can be non-ambipolar. Recycling of fuel particles from the limiter is observed to be near unity at all times. The break-up behaviour of recycled and gas puffed D2 molecules is dependent on the electron temperature, as expected. Impurity production at the limiter is chemical erosion of graphite being negligible. Deposition of limiter and wall-produced impurities is found on the limiter. The spatial distributions of impurities released from the limiter are observed and are in good agreement with a sputtered atom transport code. Finally, preliminary experiments on the transport of impurity ions along field lines away from the limiter have been performed and compared with simple analytic theory. The results suggest that the pre-sheath electric field in the SOL is much weaker than the simple fluid model would predict

  18. Fundamental Limits of Ultrathin Metasurfaces

    CERN Document Server

    Arbabi, Amir

    2014-01-01

    We present universal theoretical limits on the operation and performance of non-magnetic passive ultrathin metasurfaces. In particular, we prove that their local transmission, reflection, and polarization conversion coefficients are confined to limited regions of the complex plane. As a result, full control over the phase of the light transmitted through such metasurfaces cannot be achieved if the polarization of the light is not to be affected at the same time. We also establish fundamental limits on the maximum polarization conversion efficiency of these metasurfaces, and show that they cannot achieve more than 25% polarization conversion efficiency in transmission.

  19. The plastic limit of clays

    OpenAIRE

    Haigh, Stuart K.; Vardanega, Paul J.; Bolton, Malcolm D.

    2013-01-01

    The plastic limit of soils was first described by Atterberg in 1911. The thread-rolling test was standardised at the US Public Roads Bureau in the 1920s and 1930s, and has subsequently become one of the standard tests of soil mechanics. This paper reviews the original definitions of plastic limit as proposed by Atterberg, and proposes that the brittle failure observed in the plastic limit test is caused by either air entry or cavitation in the clay. Critical state soil mechanics is used to sh...

  20. Limit laws for Zipf's law

    International Nuclear Information System (INIS)

    In this communication we establish stochastic limit laws leading from Zipf's law to Pareto's and Heaps' laws. We consider finite ensembles governed by Zipf's law and study their asymptotic statistics as the ensemble size tends to infinity. A Lorenz-curve analysis establishes three types of limit laws for the ensembles' statistical structure: 'communist', 'monarchic', and Paretian. Further considering a dynamic setting in which the ensembles grow stochastically in time, a functional central limit theorem analysis establishes a Gaussian approximation for the ensembles' stochastic growth. The Gaussian approximation provides a generalized and corrected formulation of Heaps' law. (fast track communication)

  1. Nuclear Structure at the Limits

    International Nuclear Information System (INIS)

    One of the frontiers of today's nuclear science is the ''journey to the limits'': of atomic charge and nuclear mass, of neutron-to-proton ratio, and of angular momentum. The tour to the limits is not only a quest for new, exciting phenomena but the new data are expected, as well, to bring qualitatively new information about the fundamental properties of the nucleonic many-body system, the nature of the nuclear interaction, and nucleonic correlations at various energy-distance scales. In this talk, current developments in nuclear structure at the limits are discussed from a theoretical perspective

  2. Nuclear Structure at the Limits

    International Nuclear Information System (INIS)

    One of the frontiers of todays nuclear science is the journey to the limits of atomic charge and nuclear mass, of neutron-to-proton ratio, and of angular momentum. The tour to the limits is not only a quest for new, exciting phenomena, but the new data are expected, as well, to bring qualitatively new information about the fundamental properties of the nucleonic many-body system, the nature of the nuclear interaction, and nucleonic correlations at various energy-distance scales. In this series of lectures, current developments in nuclear structure at the limits are discussed from a theoretical perspective, mainly concentrating on medium-mass and heavy nuclei

  3. A cidade: limite do mundo

    OpenAIRE

    Borges Abel, António

    2010-01-01

    A cidade é hoje, por força do desenvolvimento das NTIC, uma cidade alargada ou, se se preferir, uma “aldeia global”. Porém, se sob o ponto de vista da comunicação, os limites da cidade se confundem com os limites do mundo, sob o ponto de vista da cidade física, geográfica, o “capitalismo cognitivo” força cada vez mais aquela a não conhecer limites, a transformar a hibridez num novo conceito e numa nova realidade espacial, pulverizando a anterior realidade: a cidade como contraponto do camp...

  4. Nuclear Structure at the Limits

    Energy Technology Data Exchange (ETDEWEB)

    Nazarewicz, Witold

    1997-12-31

    One of the frontiers of today`s nuclear science is the ``journey to the limits``: of atomic charge and nuclear mass, of neutron-to-proton ratio, and of angular momentum. The tour to the limits is not only a quest for new, exciting phenomena but the new data are expected, as well, to bring qualitatively new information about the fundamental properties of the nucleonic many-body system, the nature of the nuclear interaction, and nucleonic correlations at various energy-distance scales. In this talk, current developments in nuclear structure at the limits are discussed from a theoretical perspective.

  5. Quasi-Static Hydrodynamic Limits

    Science.gov (United States)

    De Masi, Anna; Olla, Stefano

    2015-12-01

    We consider hydrodynamic limits of interacting particles systems with open boundaries, where the exterior parameters change in a time scale slower than the typical relaxation time scale. The limit deterministic profiles evolve quasi-statically. These limits define rigorously the thermodynamic quasi static transformations also for transitions between non-equilibrium stationary states. We study first the case of the symmetric simple exclusion, where duality can be used, and then we use relative entropy methods to extend to other models like zero range systems. Finally we consider a chain of anharmonic oscillators in contact with a thermal Langevin bath with a temperature gradient and a slowly varying tension applied to one end.

  6. Brassicas limited in weed control

    OpenAIRE

    Kristiansen, Mr P

    2006-01-01

    This article discusses the limitations of using brassica cover crops for weed control. A brief overview of the role of cover crops is provided, followed by a short review of research looking at brassica cover crops.

  7. Multifamily Tax Subsidy Income Limits

    Data.gov (United States)

    Department of Housing and Urban Development — Multifamily Tax Subsidy Projects (MTSP) Income Limits were developed to meet the requirements established by the Housing and Economic Recovery Act of 2008 (Public...

  8. Limited-Access Heart Surgery

    Science.gov (United States)

    ... Heart tumor removal Atrial septal defect (ASD) repair Patent foramen ovale repair Catheter ablation for atrial fibrillation As with other kinds of limited-access surgery, robotic-assisted surgery can mean shorter hospital stays and ...

  9. Casimir Effect The Classical Limit

    CERN Document Server

    Feinberg, J; Revzen, M

    2001-01-01

    We analyze the high temperature limit of the Casimir effect. A simple physical argument suggests that the Casimir energy (as opposed to the Casimir free energy) should vanish in the classical limit. We check the validity of this argument for massless scalar field confined in a cavity with boundaries of arbitrary shape, using path integral formalism. We are able to verify this suggestion only when the boundaries consist of disjoint pieces. Moreover, we find in these cases that the contribution to the Casimir entropy by field modes that depend on that separation, tends, in the classical limit, to a finite asymptotic value which depends only on the geometry of the cavity. Thus the Casimir force between disjoint pieces of the boundary in the classical limit is entropy driven and is governed by a dimensionless number characterizing the arbitrary geometry of the cavity. Contributions to the Casimir thermodynamical quantities due to each individual connected component of the boundary exhibit logarithmic deviations i...

  10. Superconducting dc fault current limiter

    International Nuclear Information System (INIS)

    Within the framework of the electric power market liberalization, DC networks have many interests compared to alternative ones, but their protections need to use new systems. Superconducting fault current limiters enable by an overstepping of the critical current to limit the fault current to a preset value, lower than the theoretical short-circuit current. For these applications, coated conductors offer excellent opportunities. We worked on the implementation of these materials and built a test bench. We carried out limiting experiments to estimate the quench homogeneity at various short-circuit parameters. An important point is the temperature measurement by deposited sensors on the ribbon, results are in good correlation with the theoretical models. Improved quench behaviours for temperatures close to the critical temperature have been confirmed. Our results enable to better understand the limitation mechanisms of coated conductors. (author)

  11. Limits on the photon mass

    International Nuclear Information System (INIS)

    Is the photon mass strictly null as it is told in quantum electrodynamics. In fact, a coherent theory can be build with a massive photon. Experiences have been regularly led to try to make obvious an eventual non null photon mass. Superior limits more and more strict have been found. Here is given a general survey of the consequences of a non null photon mass, different methods to measure it and the achieved limits. (author). 30 refs., 1 fig

  12. Limit cycles of effective theories

    OpenAIRE

    Glazek, Stanislaw D.

    2006-01-01

    A simple example is used to show that renormalization group limit cycles of effective quantum theories can be studied in a new way. The method is based on the similarity renormalization group procedure for Hamiltonians. The example contains a logarithmic ultraviolet divergence that is generated by both real and imaginary parts of the Hamiltonian matrix elements. Discussion of the example includes a connection between asymptotic freedom with one scale of bound states and the limit cycle with a...

  13. Penrose limits and maximal supersymmetry

    International Nuclear Information System (INIS)

    We show that the maximally supersymmetric pp-wave of IIB superstring and M-theories can be obtained as a Penrose limit of the supersymmetric AdSxS solutions. In addition, we find that in a certain large tension limit, the geometry seen by a brane probe in an AdSxS background is either Minkowski space or a maximally supersymmetric pp-wave. (letter to the editor)

  14. Time Limits and Welfare Use

    OpenAIRE

    Jeff Grogger

    2000-01-01

    Time limits are a central component of recent welfare reforms and represent a substantial departure from previous policy. However, several recent studies suggest that they have had no effect on welfare use. In this paper I attempt to reconcile those findings with results from Grogger and Michalopoulos, who find time limits to have substantial effects that vary by the age of the youngest child in the family. Using data from the Current Population Survey, I obtain results similar to those of pr...

  15. Penrose Limits and Spacetime Singularities

    OpenAIRE

    Blau, Matthias; Borunda, Monica; O'Loughlin, Martin; Papadopoulos, George

    2003-01-01

    We give a covariant characterisation of the Penrose plane wave limit: the plane wave profile matrix $A(u)$ is the restriction of the null geodesic deviation matrix (curvature tensor) of the original spacetime metric to the null geodesic, evaluated in a comoving frame. We also consider the Penrose limits of spacetime singularities and show that for a large class of black hole, cosmological and null singularities (of Szekeres-Iyer ``power-law type''), including those of the FRW and Schwarzschil...

  16. Time Limits : Effects on Recall

    OpenAIRE

    Hirano, Kinue

    2000-01-01

    This study investigates the effects of differing time limits and the level of language proficiency on the written recalls of 66 Japanese EFL undergraduates. Results showed that different time limits affected total recall, but not main ideas recalled. Regardless of proficiency level, the 20-minute group (Group 2) recalled a greater number of idea units than the 8-minute group (Group 1). However, no significant difference was found between Groups 1 and 2 regarding the recall of main ideas, alth...

  17. Infusion of mesenchymal stem cells limits fibrogenesis in irradiated rat lung%间充质干细胞对延缓大鼠放射性肺纤维化进展的作用研究

    Institute of Scientific and Technical Information of China (English)

    常鹏宇; 夏诚诚; 侯雪; 石硙岩; 宋宇哲; 张玉宇; 赵钦; 马利新; 曲雅勤

    2015-01-01

    目的 评价人脂肪来源间充质干细胞对大鼠放射性肺纤维化进展的抑制作用.方法 选用雄性SD大鼠,共48只.采用随机数字表法从中选出36只大鼠,给予右侧全肺15 Gy X射线照射.造模结束后2h,随机数字表法将受照大鼠分为3组:PBS对照组、成纤维细胞治疗组和干细胞治疗组,每组12只,剩余12只未受照大鼠作为健康对照组.于照射后第24周分别对受照右肺进行影像学及病理学检测.后者包括HE染色,Masson染色,免疫组织化学染色(α-SMA及TGF-β1).分别获取受照大鼠的外周血及支气管-肺泡灌洗液样本,采用ELISA法检测样本中的肝细胞生长因子(HGF)和转化生长因子-β1(TGF-β1)的含量.采用实时荧光定量PCR法对受照肺组织内Ⅰ型胶原-α1(Collagen Ⅰ-α1)及Ⅲ型胶原-α1(CollagenⅢ-α1)基因的表达量进行检测.结果 影像学检查结果显示,受照肺在造模后第24周出现高密度影,病变以右下叶最为明显.PBS对照组及成纤维细胞治疗组的大鼠右肺下叶受损程度较干细胞治疗组重.病理结果提示,PBS对照组及成纤维细胞治疗组的大鼠右肺下叶结构被破坏,表现为肺泡塌陷及肺泡间隔增宽.两组大鼠右肺下叶细胞外基质沉积明显;组织内Collagen Ⅰ-α1及CollagenⅢ-α1的表达量较干细胞治疗组提高(F =4.39、7.73,P<0.05).PBS对照组及成纤维细胞治疗组的大鼠右肺下叶α-SMA及TGF-β1的表达明显.ELISA结果提示,干细胞治疗组的大鼠血清中及支气管-肺泡灌洗液中HGF的浓度显著高于其余两组(F=14.97、41.13,P<0.05);TGF-β1的浓度低于其余两组(F=172.49、62.82,P<0.05).结论 人脂肪来源间充质干细胞能够抑制放射性肺纤维化的进展,对受照肺组织具有一定的保护作用.%Objective To evaluate the inhibitory effect of human adipose tissue-derived mesenchymal stem cells on radiation-induced pulmonary fibrosis.Methods A total of 48 male Sprague

  18. Introduction to Stem Cell Therapy

    OpenAIRE

    Biehl, Jesse K.; Russell, Brenda

    2009-01-01

    Stem cells have the ability to differentiate into specific cell types. The two defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are two major classes of stem cells: pluripotent that can become any cell in the adult body, and multipotent that are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation and therapeutic applications are discussed. Stem cel...

  19. Statistical limitations on molecular evolution.

    Science.gov (United States)

    Perlovsky, Leonid I

    2002-06-01

    Complexity of functions evolving in an evolution process are expected to be limited by the time length of an evolution process among other factors. This paper outlines a general method of deriving function-complexity limitations based on mathematical statistics and independent from details of a biological or genetic mechanism of the evolution of the function. Limitations on the emergence of life are derived, these limitations indicate a possibility of a very fast evolution and are consistent with "RNA world" hypothesis. The discussed method is general and can be used to characterize evolution of more specific biological organism functions and relate functions to genetic structures. The derived general limitations indicate that a co-evolution of multiple functions and species could be a slow process, whereas an evolution of a specific function might proceed very fast, so that no trace of intermediate forms (species) is preserved in fossil records of phenotype or DNA structure; this is consistent with a picture of "punctuated equilibrium". PMID:12023805

  20. Fermi coordinates and Penrose limits

    Energy Technology Data Exchange (ETDEWEB)

    Blau, Matthias; Frank, Denis; Weiss, Sebastian [Institut de Physique, Universite de Neuchatel Rue Breguet 1, CH-2000 Neuchatel (Switzerland)

    2006-06-07

    We propose a formulation of the Penrose plane wave limit in terms of null Fermi coordinates. This provides a physically intuitive (Fermi coordinates are direct measures of geodesic distance in spacetime) and manifestly covariant description of the expansion around the plane wave metric in terms of components of the curvature tensor of the original metric, and generalizes the covariant description of the lowest order Penrose limit metric itself, obtained in Blau et al (2004 Class. Quantum Grav. 21 L43-9). We describe in some detail the construction of null Fermi coordinates and the corresponding expansion of the metric, and then study various aspects of the higher order corrections to the Penrose limit. In particular, we observe that in general the first-order corrected metric is such that it admits a light-cone gauge description in string theory. We also establish a formal analogue of the Weyl tensor peeling theorem for the Penrose limit expansion in any dimension, and we give a simple derivation of the leading (quadratic) corrections to the Penrose limit of AdS{sub 5} x S{sup 5}.