Sample records for bep protocol bleomycin

  1. Extensive deep vein thrombosis as a complication of testicular cancer treated with the BEP protocol (bleomycin, etoposide and cisplatin: case report

    Max Senna Mano

    Full Text Available CONTEXT: There are no reports in the literature of massive deep venous thrombosis (DVT associated with cisplatin, bleomycin and etoposide (BEP cancer treatment. CASE REPORT: The patient was a 18-year-old adolescent with a nonseminomatous germ cell tumor of the right testicle, with the presence of pulmonary, liver, and massive retroperitoneal metastases. Following radical orchiectomy, the patient started chemotherapy according to the BEP protocol (without routine prophylaxis for DVT. On day 4 of the first cycle, massive DVT was diagnosed, extending from both popliteal veins up to the thoracic segment of the inferior vena cava. Thrombolytic therapy with streptokinase was immediately started. On day 2 of thrombolytic therapy, the patient developed acute renal failure, due to extension of the thrombosis to the renal veins. Streptokinase was continued for six days and the outcome was remarkably favorable.

  2. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer

    de Wit, Ronald; Skoneczna, Iwona; Daugaard, Gedske


    To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).......To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC)....

  3. BEP Protocol for Ovarian Endodermal Sinus Tumor:Report of Five Cases%BEP方案治疗卵巢内胚窦瘤病例分析



    Objective Treatments and follow-up results of 5 patients with ovarian endodermal sinus tumors admitted to our hospital from 1996 to 2002 were analyzed retrospectively, to demonstrate the exact effect of etoposide + cisplatin + bleo-mycin ( BEP ) protocol. Methods Five patients underwent BEP protocol chemotherapy after operations. One course of treatment was 4 weeks, 4 times of medication in 1 course, altogether 4 courses. Results Four patients survived till now ( 7 ~ 14 years ); 1 had only 1 course of chemotherapy after whole hysterectomy and double oophorectomy and died 5 months after operation. Conclusion BEP, which can prolong survival time of patients and especially retain young women's fertility, should be used as first-line chemotherapeutic protocol.%目的 回顾性分析1996-2002年在本院收治的5例卵巢内胚窦瘤患者的治疗及随诊结果,论证足叶乙甙+顺铂+平阳霉素(BEP)方案对此病的确切疗效.方法 5例卵巢内胚窦瘤患者术后行BEP方案化疗,每4周为1个疗程,每疗程用药4 d,共治疗4个疗程,化疗后随访.结果 4例分别存活至今(7~14年);1例全子宫双附件切除术后只行1疗程化疗,术后5个月死亡.结论 BEP方案化疗疗效可延长患者的生存时间,特别是对于年轻妇女可保留其生育能力,应作为一线化疗方案.

  4. Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin

    Lauritsen, Jakob; Kier, Maria Gry Gundgaard; Bandak, Mikkel


    PURPOSE: For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring...... of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors. PATIENTS AND METHODS: All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured...... the diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1 second, and forced vital capacity were performed systematically before, during, and after treatment with BEP for 5 years of follow-up. According to local protocol, bleomycin was discontinued if hemoglobin...




    33 patients (median age 39 years) with advanced seminoma were treated with 4 courses of alternating cisplatin-containing chemotherapy PVB/BEP (cisplatin, vinblastine and bleomycin; bleomycin, etoposide and cisplatin). Patients were classified as stage IIC (n = 7), IID (n = 9), III (n = 13) and IV (n




    This study was performed to determine the changes in pulmonary function in patients randomised to receive treatment with four cycles of bleomycin, etoposide and cisplatin (BEP) (27 patients) or with four cycles of etoposide and cisplatin (EP) (27 patients) for disseminated non-seminomatous testicula

  7. Enhanced effects of bleomycin on pulmonary function disturbances in patients with decreased renal function due to cisplatin

    Sleijfer, S; vanderMark, TW; Mulder, NH; Schraffordt Koops, H.


    We examined whether cisplatin-induced nephrotoxicity augmented bleomycin-induced pulmonary toxicity in patients with testicular cancer treated with etoposide and cisplatin with (BEP) or without bleomycin (EP). Before and at 3-week intervals during chemotherapy, creatinine clearance and lung function

  8. BEPS Action Plan: Global Tax Cooperation

    Andrei Shelepov


    Full Text Available Given the dynamics of economic and financial globalization, national tax authorities often do not have adequate tools to effectively combat tax avoidance practices that exploit gaps in the existing tax rules. To address the global problem of tax base erosion and profit shifting (BEPS, the Organisation for Economic Co-operation and Development (OECD and the Group of 20 (G20 have consolidated their efforts on an equal footing. Their joint BEPS Action Plan allowed to involve more than 100 countries, both developing and advanced, in designing and implementing rules aimed at aligning the generation of profits and their taxation and increasing the predictability, transparency and flexibility of the international tax environment for business. This article examines the history of the BEPS project, emphasizing the mode of OECD-G20 engagement in global tax governance, describes the key recommendations made by international institutions to tackle BEPS and forecasts further developments in the area. The author pays special attention to the mechanisms designed to stimulate participation by non-OECD and non-G20 members in the BEPS project and the stance of business on the proposed reforms. He concludes that the work on BEPS is far from finished. Different interpretations of standards, risks of strengthening tax competition between countries and potentially excessive tax burdens on businesses should be addressed. In this regard, OECD and G20 should strengthen their efforts to ensure the participation of developing countries and the private sector, which would stimulate other reforms in international taxation to support global growth and development.

  9. Basic Education and Policy Support (BEPS) Activity.

    Creative Associates International, Inc., Washington, DC.

    The Basic Education and Policy Support (BEPS) Activity is a multi-year, worldwide, indefinite quantity contract by which the U.S. Agency for International Development (USAID) Global Bureau Center for Human Capacity (G/HCD) can work to achieve four objectives: (1) improve the quality, efficiency, access, and equity of education, particularly basic…

  10. Protective effects of a bacterially expressed NIF-KGF fusion protein against bleomycin-induced acute lung injury in mice.

    Li, Xinping; Li, Shengli; Zhang, Miaotao; Li, Xiukun; Zhang, Xiaoming; Zhang, Wenlong; Li, Chuanghong


    Current evidence suggests that the keratinocyte growth factor (KGF) and the polymorphonuclear leukocyte may play key roles in the development of lung fibrosis. Here we describe the construction, expression, purification, and identification of a novel NIF (neutrophil inhibitory factor)-KGF mutant fusion protein (NKM). The fusion gene was ligated via a flexible octapeptide hinge and expressed as an insoluble protein in Escherichia coli BL21 (DE3). The fusion protein retained the activities of KGF and NIF, as it inhibited both fibroblast proliferation and leukocyte adhesion. Next, the effects of NKM on bleomycin-induced lung fibrosis in mice were examined. The mice were divided into the following four groups: (i) saline group; (ii) bleomycin group (instilled with 5 mg/kg bleomycin intratracheally); (iii) bleomycin plus dexamethasone (Dex) group (Dex was given intraperitoneally (i.p.) at 1 mg/kg/day 2 days prior to bleomycin instillation and daily after bleomycin instillation until the end of the treatment); and (iv) bleomycin plus NKM group (NKM was given i.p. at 2 mg/kg/day using the same protocol as the Dex group). NKM significantly improved the survival rates of mice exposed to bleomycin. The marked morphological changes and increased hydroxyproline levels resulted from the instillation of bleomycin (on Day 17) in the lungs were significantly inhibited by NKM. These results revealed that NKM can attenuate bleomycin-induced lung fibrosis, suggesting that NKM could be used to prevent bleomycin-induced lung damage or other interstitial pulmonary fibrosis.

  11. Beamed-Energy Propulsion (BEP) Study

    George, Patrick; Beach, Raymond


    The scope of this study was to (1) review and analyze the state-of-art in beamed-energy propulsion (BEP) by identifying potential game-changing applications, (2) formulate a roadmap of technology development, and (3) identify key near-term technology demonstrations to rapidly advance elements of BEP technology to Technology Readiness Level (TRL) 6. The two major areas of interest were launching payloads and space propulsion. More generally, the study was requested and structured to address basic mission feasibility. The attraction of beamed-energy propulsion (BEP) is the potential for high specific impulse while removing the power-generation mass. The rapid advancements in high-energy beamed-power systems and optics over the past 20 years warranted a fresh look at the technology. For launching payloads, the study concluded that using BEP to propel vehicles into space is technically feasible if a commitment to develop new technologies and large investments can be made over long periods of time. From a commercial competitive standpoint, if an advantage of beamed energy for Earth-to-orbit (ETO) is to be found, it will rest with smaller, frequently launched payloads. For space propulsion, the study concluded that using beamed energy to propel vehicles from low Earth orbit to geosynchronous Earth orbit (LEO-GEO) and into deep space is definitely feasible and showed distinct advantages and greater potential over current propulsion technologies. However, this conclusion also assumes that upfront infrastructure investments and commitments to critical technologies will be made over long periods of time. The chief issue, similar to that for payloads, is high infrastructure costs.

  12. Bleomycin-induced flagellate dermatitis

    Guilherme Devidé Mota


    Full Text Available A 29-year-old woman with stage IVB Hodgkin's lymphoma was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine. Two weeks after the first cycle was completed, she developed pruritic, linear erythematous lesions in a flagellate-like pattern on the trunk, neck and arms. After oral prednisone therapy and cessation of bleomycin, the lesions started to recede.

  13. Death by bleomycin pulmonary toxicity in ovarian dysgerminoma with pathologic complete response to chemotherapy. A case report.

    Calzas Rodríguez, Julia; Carmen Juarez Morales, María Del; Casero, Miguel Angel Racionero


    With cisplatin-based chemotherapy, most patients with ovarian dysgerminoma will survive long-term. Bleomycin is an important part of ovarian germ cell tumors (OGCT) treatment, and its dose-limiting toxicity is the development of pulmonary toxicity and it is increased in patients older than 40 years. We report the case of an elderly patient with an unresectable ovarian dysgerminoma who received neoadjuvant chemotherapy and who developed fatal bleomycin pulmonary toxicity (BPT) after surgery. A monitoring of pulmonary function is not routinely recommended for detecting BPT, although together with carefully assessment for symptoms or signs suggestive of pulmonary toxicity is the best way to reduce the risk of BPT. The frequency of pulmonary events in older patients makes us to think about the possibility of either reduce the dose of bleomycin or removing it from the BEP in ovarian GCT.

  14. Bleomycin: A worthy alternative

    Gursev Sandlas


    Full Text Available Context : Lymphangiomas are developmental anomalies presenting mainly in the first two years of life. Surgical excision has been the mainstay of treatment; however a potentially disfiguring surgery along with presence of important structures in the vicinity and infiltration into surrounding structures makes the dissection difficult. Aims : To study the safety and efficacy of Bleomycin as a sclerosing agent for lymphatic malformations in children. Settings and Design : Prospective non comparative nonrandomized trial. Materials and Methods: The study was carried out in 15 children between Day 5 of life to 12 years of age who presented between May2008 to May 2009. Bleomycin aqueous solution was injected intralesionally at a dose not exceeding 0.6 to 0.8 mg. /kg Body wt. The response to therapy was monitored clinically by measuring the length, breadth and area as well as by measuring the two largest perpendicular dimensions. The response was graded as excellent [total disappearance], good [>50% reduction] and poor [50% reduction in the size of their swellings. 2 patients [13.33%] showed a poor response to therapy and achieved less than 50% reduction in the size of the swelling. Complications of the therapy were few and far between. 2 patients developed fever after injection, one patients reported a transient increase in size of swelling, 2 patients have developed discoloration of the overlying skin and are currently being followed up for final outcome. None of the patients developed leucopenia or leukocytosis. All of the complications were managed with conservatively. Patients are on long term follow up to evaluate long term effects, if any.

  15. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    Daugaard, G; Skoneczna, I; Aass, N


    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor......-prognosis germ-cell cancer (GCC). Patient and methods: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual....

  16. Energy consumption in commercial buildings: A comparison with BEPS budgets


    Metered energy consumption data were collected on existing commercial buildings to help establish the proposed building energy performance standards (BEPS). The search has identified 84 buildings whose metered energy consumption is equal to or less than that proposed for their BEPS budgets and another 7 buildings whose metered consumption is less than 20 percent above their BEPS budgets. The methodology used to identify the buildings and to collect their metered energy consumption data are described. The data are analyzed and summarized and conclusions are drawn.

  17. Bleomycin-Induced Lung Injury

    Tomás Reinert


    Full Text Available Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and Hodgkin’s lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. The mechanism of bleomycin-induced pneumonitis (BIP involves oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and the elaboration of inflammatory cytokines. Ultimately, BIP can progress to lung fibrosis. The diagnosis of BIP is established by the combination of systemic symptoms, radiological and histological findings, and respiratory function tests abnormalities, while other disorders should be excluded. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. In general, the clinical picture is extremely complex. A greater understanding of the BIP pathogenesis may lead to the development of new agents capable of preventing or even treating the injury already present. Physicians who prescribe bleomycin must be aware of the potential pulmonary toxicity, especially in the presence of risk factors. This review will focus on BIP, mainly regarding recent advances and perspectives in diagnosis and treatment.

  18. Bleomycin clinical pharmacology by radioimmunoassay

    Hall, S.W.; Strong, J.E.; Broughton, A.; Frazier, M.L.; Benjamin, R.S.


    Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m/sup 2/ and the volume of distribution was 13.2 l/m/sup 2/. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m/sup 2/ and the volume of distribution was 19.2 l/m/sup 2/. Bleomycin plasma clearance correlated well with serum creatinine (r/sup 2/=0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.

  19. Pockets of opportunity: multicultural marketing strategies for BEP growth.

    Schaefer, Kelly


    Ranked among the 50 largest food service corporations in America, the Randolph-Sheppard Business Enterprise Program (BEP) represents a challenging and rewarding career opportunity for Americans who are legally blind. In recent years, however, the number of facilities and facility managers has declined. Multicultural consumers represent a major emerging growth market. The multicultural market is one of the most overlooked retail markets in the United States--and the one with the most buying power and growth potential. Multicultural marketing is among the least understood strategies available to facility managers, vocational rehabilitation counselors and BEP directors. Four major minority markets are discussed and marketing strategies are offered to help BEPs target and serve these unique consumers.

  20. Bleomycin treatment of brain tumors: an evaluation

    Linnert, Mette; Gehl, Julie


    Bleomycin has been used in the treatment of brain tumors for over 30 years. Currently, we are evaluating electrochemotherapy (the use of electric pulses to enhance uptake of bleomycin) for patients with secondary brain tumors. We, therefore, reviewed the literature with specific reference...... to the tolerability and toxicity of bleomycin. Using the keywords 'brain' and 'bleomycin', a database search without date restriction was performed and over 500 articles were found. Twenty-five articles were used for this study based on relevance determined by: (i) clinical studies, (ii) use of bleomycin, and (iii......) direct injection into brain tissue or cysts. There were two main indications for the use of bleomycin directly into the brain: (i) cystic tumors in the form of craniopharyngiomas and (ii) solid brain tumors such as glioblastomas and astrocytomas. The most frequent adverse effects reported were transient...

  1. Effects of the "Behavior Education Program" (BEP) on Office Discipline Referrals of Elementary School Students

    Hawken, Leanne S.; Sandra MacLeod, K.; Rawlings, Linda


    The "Behavior Education Program" (BEP; Crone et al., 2004) is a modified check-in, check-out intervention implemented with students who are at risk for more severe problem behaviors. The purpose of this study was to evaluate the effects of the BEP on problem behavior with 12 elementary school students. Results indicated that the BEP was…

  2. Strategic Control of Transfer Pricing in a BEPS Context

    Rossing, Christian Plesner; Pearson, Thomas C.; Nesimi, Ardit


    In the context of the BEPS Final Reports released by the OECD on 5 October 2015, the need to develop and implement strategies for international transfer pricing has been further intensified. Currently, the quality of transfer pricing strategies across multinational enterprises (multinationals...

  3. Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG: toward integrated treatment of symptoms related to traumatic loss

    Geert E. Smid


    Full Text Available Background: Traumatic events such as disasters, accidents, war, or criminal violence are often accompanied by the loss of loved ones, and may then give rise to traumatic grief. Traumatic grief refers to a clinical diagnosis of persistent complex bereavement disorder (PCBD with comorbid (symptoms of posttraumatic stress disorder (PTSD and/or major depressive disorder (MDD following confrontation with a traumatic loss. Trauma survivors, who are frequently from different cultural backgrounds, have often experienced multiple losses and ambiguous loss (missing family members or friends. Current evidence-based treatments for PTSD do not focus on traumatic grief. Objective: To develop a treatment for traumatic grief combining treatment interventions for PTSD and PCBD that may accommodate cultural aspects of grief. Method: To provide a rationale for treatment, we propose a cognitive stress model of traumatic grief. Based on this model and on existing evidence-based treatments for PTSD and complicated grief, we developed Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG for the treatment of patients with traumatic grief. The treatment is presented along with a case vignette. Results: Processes contributing to traumatic grief include inadequately integrating the memory of the traumatic loss, negative appraisal of the traumatic loss, sensitivity to matching triggers and new stressors, and attempting to avoid distress. BEP-TG targets these processes. The BEP-TG protocol consists of five parts with proven effectiveness in the treatment of PCBD, PTSD, and MDD: information and motivation, grief-focused exposure, memorabilia and writing assignments, finding meaning and activation, and a farewell ritual. Conclusion: Tailored to fit the needs of trauma survivors, BEP-TG can be used to address traumatic grief symptoms related to multiple losses and ambiguous loss, as well as cultural aspects of bereavement through its different components.

  4. BEPS redesign of 168 commercial buildings: summary report

    Stoops, J.L.; Deringer, J.J.; Moreno, S.; Misuriello, H.P.


    The objective of this report is to present, in usable form, summary data from the Building Energy Performance Standards (BEPS) Phase II commercial buildings energy research conducted in 1978-1979. Summary data presented were obtained from two major research efforts: the BEPS Phase II Redesign experiment; and the related research on ASHRAE Standard 90-75R. The bulk of this report consists of data tabulations of key energy parameters for the 168 sample buildings, which were tabulated from computer-stored files of the 1978-1979 data. Two kinds of tabulations are included: numerical tabulations that extracted information from the computer-stored data base for the 168 sample buildings; and graphic presentations of the computer-generated data, plus data extracted from other sources. The intent is to provide a single data compendium of key energy-related factors from the 1978 redesign experiment and the associated 1978-1979 ASHRAE Standard 90-75R research. This report also supplements the information for which there was not space in the magazine articles. Thus, for some building types, additional analysis, comments, and data tabulations are included that could not be included in the articles because space was limited. These additional analysis items are not consistent across building types because both the energy conservation opportunities and the design strategies applied by the building designers varied considerably by building type. The chapters have been entered individually into EDB and ERA.

  5. BEPS Hybrid Entities Proposal: A slippery slope, especially for developing countries

    Sanghavi, Dhruv


    Article 1(2) has been proposed in the final report on G20/OECD's Base Erosion and Profit Shifting (BEPS) Action 2. Two principle purposes of the BEPS project can be identified: First, to combat against aggressive tax planning which results in less than single taxation, and secondly, to allocate taxi

  6. Bleomycin induced urethral stricture in Hodgkin′s disease

    Ritesh Tapkire


    Full Text Available Bleomycin is a glycoprotein that is extensively used in combination with other anti-cancer agents because of its relative lack of hematological and gastrointestinal toxicity. However, pulmonary toxicity is common with bleomycin and limits its therapeutic utility. Urethral stricture as a result of bleomycin toxicity has not been reported in literature. In this case report, a young male patient who developed urethral stricture after bleomycin-based chemotherapy is described and the possible effects of bleomycin on the urethra are discussed.

  7. Modeling Space Radiation with Radiomimetic Agent Bleomycin

    Lu, Tao


    Space radiation consists of proton and helium from solar particle events (SPE) and high energy heavy ions from galactic cosmic ray (GCR). This mixture of radiation with particles at different energy levels has different effects on biological systems. Currently, majority studies of radiation effects on human were based on single-source radiation due to the limitation of available method to model effects of space radiation on living organisms. While NASA Space Radiation Laboratory is working on advanced switches to make it possible to have a mixed field radiation with particles of different energies, the radiation source will be limited. Development of an easily available experimental model for studying effects of mixed field radiation could greatly speed up our progress in our understanding the molecular mechanisms of damage and responses from exposure to space radiation, and facilitate the discovery of protection and countermeasures against space radiation, which is critical for the mission to Mars. Bleomycin, a radiomimetic agent, has been widely used to study radiation induced DNA damage and cellular responses. Previously, bleomycin was often compared to low low Linear Energy Transfer (LET) gamma radiation without defined characteristics. Our recent work demonstrated that bleomycin could induce complex clustered DNA damage in human fibroblasts that is similar to DNA damage induced by high LET radiation. These type of DNA damage is difficult to repair and can be visualized by gamma-H2Ax staining weeks after the initial insult. The survival ratio between early and late plating of human fibroblasts after bleomycin treatment is between low LET and high LET radiation. Our results suggest that bleomycin induces DNA damage and other cellular stresses resembling those resulted from mixed field radiation with both low and high LET particles. We hypothesize that bleomycin could be used to mimic space radiation in biological systems. Potential advantages and limitations of

  8. Heterologous Matrix Metalloproteinase Gene Promoter Activity Allows In Vivo Real-time Imaging of Bleomycin-Induced Lung Fibrosis in Transiently Transgenized Mice

    Stellari, Fabio Franco; Ruscitti, Francesca; Pompilio, Daniela; Ravanetti, Francesca; Tebaldi, Giulia; Macchi, Francesca; Verna, Andrea Elizabeth; Villetti, Gino; Donofrio, Gaetano


    Idiopathic pulmonary fibrosis is a very common interstitial lung disease derived from chronic inflammatory insults, characterized by massive scar tissue deposition that causes the progressive loss of lung function and subsequent death for respiratory failure. Bleomycin is used as the standard agent to induce experimental pulmonary fibrosis in animal models for the study of its pathogenesis. However, to visualize the establishment of lung fibrosis after treatment, the animal sacrifice is necessary. Thus, the aim of this study was to avoid this limitation by using an innovative approach based on a double bleomycin treatment protocol, along with the in vivo images analysis of bleomycin-treated mice. A reporter gene construct, containing the luciferase open reading frame under the matrix metalloproteinase-1 promoter control region, was tested on double bleomycin-treated mice to investigate, in real time, the correlation between bleomycin treatment, inflammation, tissue remodeling and fibrosis. Bioluminescence emitted by the lungs of bleomycin-treated mice, corroborated by fluorescent molecular tomography, successfully allowed real time monitoring of fibrosis establishment. The reporter gene technology experienced in this work could represent an advanced functional approach for real time non-invasive assessment of disease evolution during therapy, in a reliable and translational living animal model. PMID:28298912

  9. Pressure loss tests for DR-BEP of fullsize 17 x 17 PWR fuel assembly

    Chung, Moon Ki; Chun, Se Young; Chang, Seok Kyu; Won, Soon Youn; Cho, Young Rho; Kim, Bok Deuk; Min, Kyoung Ho [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)


    This report describes the conditions, procedure and results in the pressure loss tests carried out for a double grid type debris resistance bottom end piece (DR-BEP) designed by KAERI. In this test, the pressure loss coefficients of the full size 17 x 17 PWR simulated fuel assembly with DR-BET and with standard-BEP were measured respectively, and the pressure loss coefficients of DR-BEP were compared with the coefficients of STD-BET. The test conditions fall within the ranges of loop pressure from 5.2 to 45 bar, loop temperature from 27 to 221 deg C and Reynolds number in fuel bundle from 2.17 x 10{sup 4} to 3.85 x 10{sup 5}. (Author) 5 refs., 18 figs., 5 tabs.

  10. Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice

    OU Xue-mei; FENG Yu-lin; WEN Fu-qiang; HUANG Xiang-yang; XIAO Jun; WANG Ke; WANG Tao


    Background Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.Methods Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days.We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.Results Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (Ⅰand Ⅲ) mRNA expression induced by bleomycin. Moreover,simvastatin down-regulated the increased expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-(] (TNF-a) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore,the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.Conclusions Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-βI and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

  11. An Investigation of the Impact of Function of Problem Behavior on Effectiveness of the Behavior Education Program (BEP)

    Hawken, Leanne S.; O'Neill, Robert E.; MacLeod, K. Sandra


    The Behavior Education Program (BEP) is a check-in, check-out intervention implemented with students who are at-risk for engaging in more severe problem behavior. Previous research with middle and elementary school students found that the BEP was more effective with students who had adult attention maintained problem behavior. The purposes of this…

  12. BID-F1 and BID-F2 domains of Bartonella henselae effector protein BepF trigger together with BepC the formation of invasome structures.

    Truttmann, Matthias C; Guye, Patrick; Dehio, Christoph


    The gram-negative, zoonotic pathogen Bartonella henselae (Bhe) translocates seven distinct Bartonella effector proteins (Beps) via the VirB/VirD4 type IV secretion system (T4SS) into human cells, thereby interfering with host cell signaling [1], [2]. In particular, the effector protein BepG alone or the combination of effector proteins BepC and BepF trigger massive F-actin rearrangements that lead to the establishment of invasome structures eventually resulting in the internalization of entire Bhe aggregates [2], [3]. In this report, we investigate the molecular function of the effector protein BepF in the eukaryotic host cell. We show that the N-terminal [E/T]PLYAT tyrosine phosphorylation motifs of BepF get phosphorylated upon translocation but do not contribute to invasome-mediated Bhe uptake. In contrast, we found that two of the three BID domains of BepF are capable to trigger invasome formation together with BepC, while a mutation of the WxxxE motif of the BID-F1 domain inhibited its ability to contribute to the formation of invasome structures. Next, we show that BepF function during invasome formation can be replaced by the over-expression of constitutive-active Rho GTPases Rac1 or Cdc42. Finally we demonstrate that BID-F1 and BID-F2 domains promote the formation of filopodia-like extensions in NIH 3T3 and HeLa cells as well as membrane protrusions in HeLa cells, suggesting a role for BepF in Rac1 and Cdc42 activation during the process of invasome formation.

  13. BID-F1 and BID-F2 domains of Bartonella henselae effector protein BepF trigger together with BepC the formation of invasome structures.

    Matthias C Truttmann

    Full Text Available The gram-negative, zoonotic pathogen Bartonella henselae (Bhe translocates seven distinct Bartonella effector proteins (Beps via the VirB/VirD4 type IV secretion system (T4SS into human cells, thereby interfering with host cell signaling [1], [2]. In particular, the effector protein BepG alone or the combination of effector proteins BepC and BepF trigger massive F-actin rearrangements that lead to the establishment of invasome structures eventually resulting in the internalization of entire Bhe aggregates [2], [3]. In this report, we investigate the molecular function of the effector protein BepF in the eukaryotic host cell. We show that the N-terminal [E/T]PLYAT tyrosine phosphorylation motifs of BepF get phosphorylated upon translocation but do not contribute to invasome-mediated Bhe uptake. In contrast, we found that two of the three BID domains of BepF are capable to trigger invasome formation together with BepC, while a mutation of the WxxxE motif of the BID-F1 domain inhibited its ability to contribute to the formation of invasome structures. Next, we show that BepF function during invasome formation can be replaced by the over-expression of constitutive-active Rho GTPases Rac1 or Cdc42. Finally we demonstrate that BID-F1 and BID-F2 domains promote the formation of filopodia-like extensions in NIH 3T3 and HeLa cells as well as membrane protrusions in HeLa cells, suggesting a role for BepF in Rac1 and Cdc42 activation during the process of invasome formation.

  14. The effects of Bleomycin A5 on infantile maxillofacial haemangioma

    Zhao Fu-yun


    Full Text Available Abstract Objective To examine the effects of bleomycin A5 on infantile maxillofacial haemangiomas. Methods Bleomycin A5 was given by multiple intralesinoal injections and the dosage was given according to the age of the patient and size of the lesion. Parts of patients were accompanied by prednisone treatment(2-5 mg/kg, po, QOD. Results All the haemangiomas involuted completely after treated with bloemycin A5 with better recovery of skin color and less scar forming in small haemangiomas. Conclusion Infantile haemangioma could be effectively treated with bleomycin A5 without serious side effects.


    范保星; 张开泰; 李刚; 谢玲; 马淑华; 葛世丽; 项小琼; 胡迎春; 王升启; 周平坤; 吴德昌


    Objective: To detect the expression difference of 60 lung cancer associated genes in human bronchial epithelial malignant transformation cell model (BEP2D) induced by alpha-particles. Methods: 60 lung cancer associated genes were collected and micro-arrayed onto the microscope slides using Cartesian PixSys5500 cDNA Microarray machine. Total RNA from BEP2D cells and passage 20 (Rl5H-20), passage 35 (R15H-35) cells derived from BEP2D following 1.5 Gy alpha-particles was extracted and labeled by fluorescent dye. The labeled probe was then hybridized with the cDNA. Results: 40, 47, 20 genes were detected in BEP2D, R15H-20 and R15H-35 respectively. The expression level of tumor suppressor genes decreased greatly in the transformed R15H-35. Most oncogenes decreased slightly in R15H-20. Most growth factors expressed only in R15H-20. Conclusion: In human bronchial epithelial malignant transformed cell model generated by alpha-particles, the loss-function of tumor suppressor genes at initiation stage was dominant, some related oncogenes and growth factors promoted the malignant transformation.

  16. Bleomycin lung toxicity: who are the patients with increased risk?

    Azambuja, E; Fleck, J F; Batista, R G; Menna Barreto, S S


    Bleomycin is an antibiotic drug with anticancer properties produced by Streptomyces verticillus [Cheson BD. Pharmacology of cancer chemotherapy: miscellaneous chemotherapeutic agents. In De Vita Jr. VT, Hellmann S, Rosenberg AS, editors. Cancer principles and practice of oncology. Lippincott Willians & Wilkins; 2001. p. 452-459]. It was isolated in 1966 by Umezawa et al. and its mechanism of action is breaking the DNA double helix by the production of free radicals, which is oxygen and iron dependent [Cheson BD. Pharmacology of cancer chemotherapy: miscellaneous chemotherapeutic agents. In De Vita Jr. VT, Hellmann S, Rosenberg AS, editors. Cancer principles and practice of oncology. Lippincott Willians & Wilkins; 2001. p. 452-459; Hay J, Shahzeidi S, Laurent G. Mechanisms of bleomycin-induced lung damage. Arch Toxicol 1991;65:81-94]. Bleomycin may be inactivated by bleomycin hidrolase presents in normal and tumoral cells [Cheson BD. Pharmacology of cancer chemotherapy: miscellaneous chemotherapeutic agents. In De Vita Jr. VT, Hellmann S, Rosenberg AS, editors. Cancer principles and practice of oncology. Lippincott Willians & Wilkins; 2001. p. 452-459; Hay J, Shahzeidi S, Laurent G. Mechanisms of bleomycin-induced lung damage. Arch Toxicol 1991;65:81-94; Jules-Elysee K, White DA. Bleomycin-induced pulmonary toxicity. Clinics Chest Med 1990;11:1-20]. The complex bleomycin-Fe has been the most studied because bleomycin joins the DNA and Fe at the same time, and release of free radicals happens in the presence of molecular oxygen [Hay J, Shahzeidi S, Laurent G. Mechanisms of bleomycin-induced lung damage. Arch Toxicol 1991;65:81-94]. Bleomycin has a renal metabolism with 50% of dose eliminated in 4h after its administration and 70% in the next 24h. Its half-life (T 1/2) is not altered, although the creatinine clearance drops to 25-35 ml/min [Cheson BD. Pharmacology of cancer chemotherapy: miscellaneous chemotherapeutic agents. In De Vita Jr. VT, Hellmann S, Rosenberg

  17. Serial Analysis of Gene Expression in Immortalized BEP2D Cells and Malignant Transformed BEP2D Cells Induced by α-particle%SAGE方法分析永生化BEP2D细胞及α粒子诱发恶性转化BEP2D细胞的基因表达

    葛世丽; 李刚; 陈伟; 楼铁柱; 吴德昌



  18. BEP-relations for N2 dissociation over stepped transition metal and alloy surfaces

    Fronczek-Munter, Ture Rønved; Bligaard, Thomas; Christensen, Claus H.


    We present density functional theory (DFT) calculations for N(2) dissociation on stepped face-centred cubic (211) surface slabs. By using the same crystal structure, the same adsorption site for atomic nitrogen, and the same transition-state bond length of N(2) over a range of pure metal surfaces...... is a general electronic structure effect, and that geometric effects are responsible for the scatter which is normally observed around the BEP line. The BEP relation is also shown to be valid for both surface and bulk alloys. The scatter is, however, larger than for the pure elements. This can be understood...... as a larger geometrical variance. To analyze the accuracy of the DFT calculations a detailed convergence study is performed for several adsorbates on stepped hexagonal close-packed and face-centred cubic Ru slabs....

  19. Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats.

    Sogut, Sadik; Ozyurt, Huseyin; Armutcu, Ferah; Kart, Levent; Iraz, Mustafa; Akyol, Omer; Ozen, Suleyman; Kaplan, Suleyman; Temel, Ismail; Yildirim, Zeki


    Oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Therefore, erdosteine, an antioxidant, is expected to have an inhibitor potential against the disease. Rats were given one dose of bleomycin in pulmonary fibrosis groups and saline in controls. The first dose of oral erdosteine (10 mg/kg/day) was given 2 days before the bleomycin injection to achieve the plateau level in blood and continued until killing. At day 14, fibrotic changes were evaluated, using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a fivefold increase in fibrosis score that was decreased by 87% by erdosteine (P>0.001) and almost twofold increases in hydroxyproline content which were completely prevented by erdosteine. Myeloperoxidase activities and MDA levels, which were significantly higher in the bleomycin group, were then significantly attenuated by erdosteine. These results revealed that oral erdosteine may prevent the development of acute pulmonary inflammation caused by bleomycin injection via the repression of neutrophil accumulation and lipid peroxidation, resulting in the inhibition of subsequent lung fibrosis.

  20. Bleomycin and radiation-induced lung damage in mice

    Collis, C.H.; Down, J.D.; Pearson, A.E.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)


    Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

  1. Detection of lung cancer with /sup 55/Co-bleomycin using a positron camera

    Nieweg, O.E.; Beekhuis, H.; Paans, A.M.J.; Piers, D.A.; Vaalburg, W.; Welleweerd, J.; Wiegman, T.; Woldring, M.G.


    /sup 57/Co-bleomycin is useful in the detection and staging of lung cancer, but the long half-life of /sup 57/Co(270 days) has discouraged its widespread acceptance. We investigated the shorter living positron emitting /sup 55/Co(half-life 18.2 h) as a label for bleomycin. In eleven patients with proven lung cancer scintigraphy with /sup 55/Co-bleomycin, using a positron camera, demonstrated the tumor in ten cases. Tumor to lung ratios were calculated. The results were superior to those obtained with /sup 55/Co-bleomycin single photon imaging but inferior to those obtained with /sup 57/Co-bleomycin scintigraphy.

  2. Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats.

    Yildirim, Zeki; Turkoz, Yusuf; Kotuk, Mahir; Armutcu, Ferah; Gurel, Ahmet; Iraz, Mustafa; Ozen, Suleyman; Aydogdu, Ismet; Akyol, Omer


    Reactive oxygen and nitrogen species have been implicated in the pathogenesis of bleomycin-induced lung fibrosis. The effects of aminoguanidine and erdosteine on the bleomycin-induced lung fibrosis were evaluated in rats. The animals were placed into five groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + aminoguanidine (200 mg/kg), bleomycin + erdosteine (10 mg/kg), and bleomycin + erdosteine + aminoguanidine. Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology, which is completely prevented by erdosteine and aminoguanidine. A strong staining for nitro tyrosine antibody in lung tissue and increased levels of lung NO were found in bleomycin group, that were significantly reduced by aminoguanidine and erdosteine. Aminoguanidine and erdosteine significantly prevented depletion of superoxide dismutase and glutathione peroxidase and elevated myeloperoxidase activities, malondialdehyde level in lung tissue produced by bleomycin. Data presented here indicate that aminoguanidine and erdosteine prevented bleomycin-induced lung fibrosis and that nitric oxide mediated tyrosine nitration of proteins plays a significant role in the pathogenesis of bleomycin-induced lung fibrosis. Also our data suggest that antifibrotic affect of antioxidants may be due to their inhibitory effect on nitric oxide generation in this model.

  3. Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice

    Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi


    The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

  4. [Bleomycin and pulmonary function changes in children with malignant lymphomas].

    Kuijten, R R; Voûte, P A; van Nierop, J C; van Leeuwen, E F; Griffioen, R W; Wagner-Soeters, R E


    In 25 patients under 18 years of age with Hodgkin's disease or non-Hodgkin lymphoma treated with bleomycin as part of the treatment with several cytostatics, the diffusion capacity of the lung for carbon monoxide (DLCO) was determined before, during and after this treatment to investigate the damaging effect of bleomycin on the lungs. The DLCO decreased in 18 of the 25 children; the degree of decrease depended both on the total dosage (max. 120 mg/sq.m body surface) and on the dose per administration (5 or 10 mg/sq.m). Eight of these 18 children were followed up for some time after discontinuation of bleomycin treatment. During the relatively brief follow-up period of one year on average, complete recovery of pulmonary function was seen in none of these children; in two, partial recovery occurred. It is necessary to study the changes of DLCO for a longer period after bleomycin treatment, as well as the factors that influence recovery of pulmonary function in children.

  5. Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin

    WANG Ping; TIAN Qing; LIANG Zhi-xin; YANG Zhen; XU Shu-feng; SUN Ji-ping; CHEN Liang-an


    Background Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated.However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction.This study investigated the effect of gefitinib on lung fibrosis in mice.Methods We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib.C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline.Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.Results The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells.In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR).Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens Ⅰ and Ⅲ.Conclusions These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.

  6. BEP-Ⅲ酶免分析仪使用过程中常见故障的排除

    丁卫平; 李拴林; 马瑶



  7. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948).

    Fossa, S.D.; Paluchowska, B.; Horwich, A.; Kaiser, G.; Mulder, P.H.M. de; Koriakine, O.; Oosterom, A.T. van; Prijck, L. de; Collette, L.; Wit, R. de


    New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of

  8. Effects of bleomycin and antioxidants on the fatty acid profile of testicular cancer cell membranes.

    Cort, A; Ozben, T; Melchiorre, M; Chatgilialoglu, C; Ferreri, C; Sansone, A


    Bleomycin is used in chemotherapy regimens for the treatment of patients having testicular germ-cell tumor (TGCT). There is no study in the literature investigating the effects of bleomycin on membrane lipid profile in testicular cancer cells. We investigated membrane fatty acid (FA) profiles isolated, derivatized and analyzed by gas chromatography of NTera-2 testicular cancer cells incubated with bleomycin (Bleo) for 24 h in the absence and presence of N-Acetyl-L-Cysteine (NAC) and curcumin (Cur) as commonly used antioxidant adjuvants. At the same time the MAPK pathway and EGFR levels were followed up. Bleomycin treatment increased significantly saturated fatty acids (SFA) of phospholipids at the expense of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Bleomycin also led to a significant increase in the trans lipid isomers of oleic and arachidonic acids due to its free radical producing effect. Incubation with bleomycin increased the p38 MAPK and JNK levels and downregulated EGFR pathway. Coincubation of bleomycin with NAC reversed effects caused by bleomycin. Our results highlight the important role of membrane fatty acid remodeling occurring during the use of bleomycin and its concurrent use with antioxidants which can adjuvate the cytotoxic effects of the chemotherapeutic agents.

  9. Cisplatin, vindesine, and bleomycin (DVB) combination chemotherapy for esophageal carcinoma.

    Kelsen, D P; Bains, M; Chapman, R; Golbey, R


    Forty-six patients with epidermoid carcinoma of the esophagus have been treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Of the 40 patients currently evaluable for response, 21 have had partial remissions (52%). At least four of these responses were almost complete, with only microscopic disease found on endoscopy or review of the resected specimen. Toxic effects have, in general, been manageable. The major toxic effects included nausea and vomiting, nephrotoxicity, and myelosuppression. There were two drug-related deaths: one due to renal failure and one due to sepsis. The three-drug combination appears to be substantially more effective than either the two-drug combination of cisplatin and bleomycin or vindesine alone. Effects on survival cannot yet be evaluated.

  10. The Rise and Attenuation of the Basic Education Programme (BEP) in Botswana: A Global-Local Dialectic Approach

    Tabulawa, Richard


    Using a global-local dialectic approach, this paper traces the rise of the basic education programme in the 1980s and 1990s in Botswana and its subsequent attenuation in the 2000s. Amongst the local forces that led to the rise of BEP were Botswana's political project of nation-building; the country's dire human resources situation in the decades…

  11. Bleomycin induced epithelial–mesenchymal transition (EMT) in pleural mesothelial cells

    Chen, Li-Jun [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Ye, Hong [Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China); Zhang, Qian; Li, Feng-Zhi; Song, Lin-Jie; Yang, Jie; Mu, Qing [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Rao, Shan-Shan [Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Cai, Peng-Cheng [Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Xiang, Fei; Zhang, Jian-Chu [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China); Su, Yunchao [Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, GA (United States); Xin, Jian-Bao, E-mail: [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China); Ma, Wan-Li, E-mail: [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China)


    Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial–mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis. - Highlights: • Bleomycin induces collagen-I synthesis in pleural mesothelial cells (PMCs). • Bleomycin induces increases in vimentin and α-SMA protein in PMCs. • Bleomycin induces decreases in cytokeratin-8 and E-cadherin protein in PMCs • TGF-β1-Smad2/3 signaling pathway is involved in the PMC EMT induced by bleomycin.

  12. Extensive pneumothorax, pneumomediastinum and surgical emphysema as a complication of bleomycin therapy

    Jain, Tarun P.; Thulkar, Sanjay; Saha, Sanchita [All India Institute of Medical Sciences, Department of Radiology, New Delhi (India); Bakhshi, Sameer; Dominic, Joseph [All India Institute of Medical Sciences, Department of Medical Oncology, New Delhi (India)


    Bleomycin is a commonly used chemotherapeutic agent and one of the commonest cytotoxic drugs leading to pulmonary parenchymal damage. It generally leads to interstitial pneumonitis and fibrosis, hypersensitivity reactions and acute respiratory distress syndrome. We describe an 8-year-old boy who, following prolonged bleomycin therapy, demonstrated extensive air dissection and extrapulmonary air, an unusual and fatal complication. (orig.)

  13. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor

    Stergios Boussios


    Full Text Available Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis.

  14. Evaluating the inhibitory potential of sulindac against the bleomycin-induced pulmonary fibrosis in wistar rats.

    Verma, Ramesh; Brahmankar, Mahesh; Kushwah, Lokendra; Suresh, Balakrishnan


    The present study examined the protective effect of sulindac on bleomycin-induced lung fibrosis in rats. Animals were divided into saline group, bleomycin group (single intra-tracheal instillation of bleomycin) and bleomycin+sulindac (orally from day 1 to day 20). Bleomycin administration reduced the body weight, altered antioxidant status (such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione) while it increased the lung weight, hydroxyproline content, collagen deposition and lipid peroxidation. However, simultaneous administration of sulindac improved the body weight, antioxidant status and decreased the collagen deposition in lungs. Moreover, the levels of inflammatory cytokine tumour necrosis factor-α increased in bleomycin-induced group, whereas, on treatment with sulindac the levels of tumour necrosis factor-α were found reduced. Finally, histological evidence also supported the ability of sulindac to inhibit bleomycin-induced lung fibrosis. The results of the present study indicate that sulindac can be used as an agent against bleomycin-induced pulmonary fibrosis.

  15. Metformin Reduces Bleomycin-induced Pulmonary Fibrosis in Mice

    Choi, Sun Mi; Jang, An-Hee; Kim, Hyojin; Lee, Kyu Hwa; Kim, Young Whan


    Metformin has anti-inflammatory and anti-fibrotic effects. We investigated whether metformin has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis in a murine model. A total of 62 mice were divided into 5 groups: control, metformin (100 mg/kg), BLM, and BLM with metformin (50 mg/kg or 100 mg/kg). Metformin was administered to the mice orally once a day from day 1. We sacrificed half of the mice on day 10 and collected the bronchoalveolar lavage fluid (BALF) from their left lu...

  16. Intralesional bleomycin for the treatment of periocular capillary hemangiomas

    Derrick P Smit


    Full Text Available Periocular infantile capillary hemangiomas do not always respond well to conventional treatment modalities such as systemic or intralesional corticosteroids, radiotherapy or debulking surgery. The authors describe the use of intralesional bleomycin injections (IBIs to treat potentially amblyogenic lesions in two cases where other modalities have failed. In both cases monthly IBIs successfully cleared the visual axis of the affected eye before the age of 1 year thus preventing permanent sensory deprivation amblyopia. A total of five and nine injections, respectively, were used and no significant side effects were noted. IBI appears to be a useful alternative in the treatment of periocular capillary hemangiomas refractory to more conventional modalities.

  17. BEP Enhancement for Semi-Femtocell MIMO Systems Employing SC-QICs and OSTBCs

    Ardavan Rahimian


    Full Text Available In mobile cellular networks, it is estimated that more than 60% of voice and data services occur indoors. Therefore, cellular network operators have shown an unprecedented interest in research on femtocell systems from various aspects to extend the indoor wireless coverage for providing high-quality and high data-rate wireless multimedia services contents. In an effort for reducing the bit-error probabilities (BEPs and also increasing bit/symbol capacity of bandwidth limited error-prone wireless channels in femtocell propagation areas, this paper presents the performance of a promising candidate technology designed based on the state-of-the-art techniques. The performance of powerful space-time turbo codes (STTCs based on serial concatenation of quadratic interleaved codes (SC-QICs with the optimal and also suboptimal decoding algorithms, in conjunction with orthogonal space-time block codes (OSTBCs have been presented in this contribution for wireless multiple-input single-output (MISO, and multiple-input multiple-output (MIMO semi-femtocells.

  18. Structure of 8B from elastic and inelastic 7Be+p scattering

    Mitchell, J P; Johnson, E D; Baby, L T; Kemper, K W; Moro, A M; Peplowski, P; Volya, A S; Wiedenhoever, I


    Motivation: Detailed experimental knowledge of the level structure of light weakly bound nuclei is necessary to guide the development of new theoretical approaches that combine nuclear structure with reaction dynamics. Purpose: The resonant structure of 8B is studied in this work. Method: Excitation functions for elastic and inelastic 7Be+p scattering were measured using a 7Be rare isotope beam. Excitation energies ranging between 1.6 and 3.4 MeV were investigated. An R-matrix analysis of the excitation functions was performed. Results: New low-lying resonances at 1.9, 2.5, and 3.3 MeV in 8B are reported with spin-parity assignment 0+, 2+, and 1+, respectively. Comparison to the Time Dependent Continuum Shell (TDCSM) model and ab initio no-core shell model/resonating-group method (NCSM/RGM) calculations is performed. This work is a more detailed analysis of the data first published as a Rapid Communication. [J.P. Mitchell, et al, Phys. Rev. C 82, 011601(R) (2010)] Conclusions: Identification of the 0+, 2+, 1+...

  19. Prostaglandin E₂ protects murine lungs from bleomycin-induced pulmonary fibrosis and lung dysfunction.

    Dackor, Ryan T; Cheng, Jennifer; Voltz, James W; Card, Jeffrey W; Ferguson, Catherine D; Garrett, Ryan C; Bradbury, J Alyce; DeGraff, Laura M; Lih, Fred B; Tomer, Kenneth B; Flake, Gordon P; Travlos, Gregory S; Ramsey, Randle W; Edin, Matthew L; Morgan, Daniel L; Zeldin, Darryl C


    Prostaglandin E(2) (PGE(2)) is a lipid mediator that is produced via the metabolism of arachidonic acid by cyclooxygenase enzymes. In the lung, PGE(2) acts as an anti-inflammatory factor and plays an important role in tissue repair processes. Although several studies have examined the role of PGE(2) in the pathogenesis of pulmonary fibrosis in rodents, results have generally been conflicting, and few studies have examined the therapeutic effects of PGE(2) on the accompanying lung dysfunction. In this study, an established model of pulmonary fibrosis was used in which 10-12-wk-old male C57BL/6 mice were administered a single dose (1.0 mg/kg) of bleomycin via oropharyngeal aspiration. To test the role of prostaglandins in this model, mice were dosed, via surgically implanted minipumps, with either vehicle, PGE(2) (1.32 μg/h), or the prostacyclin analog iloprost (0.33 μg/h) beginning 7 days before or 14 days after bleomycin administration. Endpoints assessed at 7 days after bleomycin administration included proinflammatory cytokine levels and measurement of cellular infiltration into the lung. Endpoints assessed at 21 days after bleomycin administration included lung function assessment via invasive (FlexiVent) analysis, cellular infiltration, lung collagen content, and semiquantitative histological analysis of the degree of lung fibrosis (Ashcroft method). Seven days after bleomycin administration, lymphocyte numbers and chemokine C-C motif ligand 2 expression were significantly lower in PGE(2)- and iloprost-treated animals compared with vehicle-treated controls (P fibrosis, and collagen production that is associated with 3 wk of bleomycin exposure. However, PGE(2) had no therapeutic effect on these parameters when administered 14 days after bleomycin challenge. In summary, PGE(2) prevented the decline in lung static compliance and protected against lung fibrosis when it was administered before bleomycin challenge but had no therapeutic effect when administered

  20. Synthesis of samarium binding bleomycin - a possible NCT radiosensitizer

    Mendes, B.M., E-mail: bmm@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Mendes, T.M.; Campos, T.P.R., E-mail: campos@nuclear.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)


    Bleomycin (BLM) is a drug that has attractive features for the development of a new radiopharmaceutical, particularly with regard to neutron capture therapy (NCT) sensitized by Sm-149. It has the ability to chelate many metal ions. In vitro studies have shown that up to 78% of BLM present in a cell is accumulated inside the nucleus or in the nuclear membrane. In addition, this drug has higher affinity for tumor tissues than for normal tissues. Radioactive isotopes carried by this antibiotic would be taken preferentially to one important cellular targets DNA. Besides, BLM displays intrinsic anti-tumor activity - it is a chemotherapic antibiotic clinically used against some cancers. This study aimed to obtain bleomycin molecules bound to samarium (BLM-Sm) for NCT studies in vitro and in vivo. The binding technique employed in this work has great simplicity and low cost. Thin layer chromatography, high performance liquid chromatography, fast protein liquid chromatography and analysis by ICP-AES were applied to verify the binding molecule. ICP-AES results showed the presence of samarium in the sample peaks related to BLM-Sm. However, efficiency and stability of this bond needs to be investigated. (author)

  1. Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway

    Yanli He


    Full Text Available Pingyangmycin is an anticancer drug known as bleomycin A5 (A5, discovered in the Pingyang County of Zhejiang Province of China. Bleomycin (BLM is a mixture of mainly two compounds (A2 and B2, which is on the World Health Organization’s list of essential medicines. Both BLM and A5 are hydrophilic molecules that depend on transporters or endocytosis receptors to get inside of cells. Once inside, the anticancer activities rely on their abilities to produce DNA breaks, thus leading to cell death. Interestingly, the half maximal inhibitory concentration (IC50 of BLMs in different cancer cell lines varies from nM to μM ranges. Different cellular uptake, DNA repair rate, and/or increased drug detoxification might be some of the reasons; however, the molecules and signaling pathways responsible for these processes are largely unknown. In the current study, we purified the A2 and B2 from the BLM and tested the cytotoxicities and the molecular mechanisms of each individual compound or in combination with six different cell lines, including a Chinese hamster ovary (CHO cell line defective in glycosaminoglycan biosynthesis. Our data suggested that glycosaminoglycans might be involved in the cellular uptake of BLMs. Moreover, both BLM and A5 shared similar signaling pathways and are involved in cell cycle and apoptosis in different cancer cell lines.

  2. Complete Resolution of Cystic Hygroma with Single Session of Intralesional Bleomycin

    Fadi Atwan


    Full Text Available Intralesional sclerotherapy as a primary modality of management for cystic hygroma is successfully described in literature. It has many benefits over surgical approach; recurrence being the concern of as much as 20% of patients in which apparent complete excision has been performed. Bleomycin is one of sclerosing agents used as intralesional therapy in cystic hygroma. Complete response usually occurs in multiple sessions of sclerotherapy. Rarely, complete resolution occurs with single session of bleomycin sclerotherapy. We share our experience of managing a case of cystic hygroma of neck that completely resolved with single session of bleomycin sclerotherapy.

  3. Assessment of a high resolution annual WRF-BEP/CMAQ simulation for the urban area of Madrid (Spain)

    de la Paz, David; Borge, Rafael; Martilli, Alberto


    Urban air quality has become one of the main environmental issues worldwide and there is an increasing need for modelling tools able to accurately reproduce the complex atmospheric phenomena that determine pollutant concentrations within cities. Eulerian 3D mesoscale models can consistently describe a wide range of spatial scales. However, urban areas present features that are usually missed by land-surface and PBL modules commonly implemented in such models. The Weather Research and Forecasting model (WRF) incorporates urban parameterizations to take into account changes in albedo, roughness length and thermal properties imposed by buildings. In this study, a model configuration based on the multi-layer Building Effect Parameterization (BEP) scheme is tested over the city of Madrid with the primarily aim of understanding the effect that the use of this urban canopy model may have on routinely (annual) air quality modelling activities in this urban area using the Community Multiscale Air Quality (CMAQ) model. To do so, the results for the main meteorological variables (temperature, planetary boundary layer height and wind fields) are compared with those from the WRF reference configuration (based on the BULK simple scheme) that has been used in the past for practical applications in this urban area. Both model outputs are compared with observations to assess changes in model performance. It was found that the BEP-based configuration improved significantly wind speed results over built areas, with an annual average bias of -0.3 m s-1 in comparison with the 1.6 m s-1 yielded by the reference WRF run. Meteorological outputs from the two alternative configurations were used to feed the CMAQ model to assess the influence of this urban parameterization on air quality predictions. The effect was a clear improvement of the model performance regarding the most relevant pollutants, reducing NO2 underestimation to only 1.6 μg m-3. Model skills to reproduce O3 and PM2

  4. The genome-wide DNA sequence specificity of the anti-tumour drug bleomycin in human cells.

    Murray, Vincent; Chen, Jon K; Tanaka, Mark M


    The cancer chemotherapeutic agent, bleomycin, cleaves DNA at specific sites. For the first time, the genome-wide DNA sequence specificity of bleomycin breakage was determined in human cells. Utilising Illumina next-generation DNA sequencing techniques, over 200 million bleomycin cleavage sites were examined to elucidate the bleomycin genome-wide DNA selectivity. The genome-wide bleomycin cleavage data were analysed by four different methods to determine the cellular DNA sequence specificity of bleomycin strand breakage. For the most highly cleaved DNA sequences, the preferred site of bleomycin breakage was at 5'-GT* dinucleotide sequences (where the asterisk indicates the bleomycin cleavage site), with lesser cleavage at 5'-GC* dinucleotides. This investigation also determined longer bleomycin cleavage sequences, with preferred cleavage at 5'-GT*A and 5'- TGT* trinucleotide sequences, and 5'-TGT*A tetranucleotides. For cellular DNA, the hexanucleotide DNA sequence 5'-RTGT*AY (where R is a purine and Y is a pyrimidine) was the most highly cleaved DNA sequence. It was striking that alternating purine-pyrimidine sequences were highly cleaved by bleomycin. The highest intensity cleavage sites in cellular and purified DNA were very similar although there were some minor differences. Statistical nucleotide frequency analysis indicated a G nucleotide was present at the -3 position (relative to the cleavage site) in cellular DNA but was absent in purified DNA.

  5. Bleomycin sensitivity in Escherichia coli is medium-dependent.

    Tao Xu

    Full Text Available Bleomycin (BLM is a glycopeptide antibiotic and anti-tumor agent that targets primarily the furanose rings of DNA and in the presence of ferrous ions produces oxidative damage and DNA strand breaks. Escherichia coli cells growing in broth medium and exposed to low concentrations of BLM contain double-strand breaks and require homologous recombination to survive. To a lesser extent, the cells also require the abasic (AP endonucleases associated with base excision repair, presumably to repair oxidative damage. As expected, there is strong induction of the SOS system in treated cells. In contrast, E. coli cells growing in glucose or glycerol minimal medium are resistant to the lethal action of BLM and do not require either homologous recombination functions or AP-endonucleases for survival. DNA ligase activity, however, is needed for cells growing in minimal medium to resist the lethal effects of BLM. There is weak SOS induction in such treated cells.

  6. Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy

    Dhar S


    Full Text Available Background: Though not in regular practice, intralesional (IL bleomycin has been used for the treatment of warts since the 1970s and on the other hand, till now cryotherapy is quite regularly used to treat warts. Aim: Our aim was to assess the evidence for the efficacy of IL bleomycin, in comparison with a control group of similar sample receiving cryotherapy, in the treatment of cutaneous warts. Methods: Patients were randomized using computer-generated codes to receive either cryotherapy (double freeze-thaw cycle or IL bleomycin (0.1% solution with concurrent anesthesia for a maximum of four treatments 3 weeks apart and a maximum of five warts treated in each visit for both groups. Patients had their warts measured at base-line and with each return visit including a post treatment follow-up that was 8 weeks apart from last treatment taken. Results: Of the 73 patients completing the study, 39 (53% were treated with IL bleomycin and 34 (47% were treated with cryotherapy. Out of 155 treated warts, 87 (56% were treated with IL beomycin and 68 (44% were treated with cryotherapy. The clearance rates in context of number of patients and number of warts were 94.9% and 97% for bleomycin and 76.5% and 82% for cryotherapy respectively ( P < 0.05 by x 2 analysis and RR = 7.67. Conclusion: IL bleomycin injection was significantly more effective than cryotherapy for treatment of cutaneous wart.

  7. Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats.

    Cortijo, J; Cerdá-Nicolás, M; Serrano, A; Bioque, G; Estrela, J M; Santangelo, F; Esteras, A; Llombart-Bosch, A; Morcillo, E J


    Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study examines the effect of N-acetylcysteine (NAC) on bleomycin-induced lung fibrosis in rats. NAC (3 mmol x kg(-1); oral) was given daily from 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) or saline, until 14 days postinstillation. NAC partially decreased the augmented collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,354+/-386 and 3,416+/-326 microg x lung(-1) in vehicle-treated and NAC-treated rats, respectively; p < 0.05). The histological assessment using a semiquantitative score showed less collagen deposition and inflammatory cells in NAC-treated rats compared to those receiving bleomycin alone. NAC failed to inhibit the bleomycin-induced increases in lung wet weight and in cell counts and protein levels of bronchoalveolar lavage fluid, but significantly increased total glutathione and taurine levels in bronchoalveolar lavage fluid. These results indicate that oral N-acetylcysteine improves the pulmonary antioxidant protection and may be useful in reducing lung damage produced by bleomycin.

  8. Genome-wide Screening Identifies Phosphotransferase System Permease BepA to Be Involved in Enterococcus faecium Endocarditis and Biofilm Formation.

    Paganelli, Fernanda L; Huebner, Johannes; Singh, Kavindra V; Zhang, Xinglin; van Schaik, Willem; Wobser, Dominique; Braat, Johanna C; Murray, Barbara E; Bonten, Marc J M; Willems, Rob J L; Leavis, Helen L


    Enterococcus faecium is a common cause of nosocomial infections, of which infective endocarditis is associated with substantial mortality. In this study, we used a microarray-based transposon mapping (M-TraM) approach to evaluate a rat endocarditis model and identified a gene, originally annotated as "fruA" and renamed "bepA," putatively encoding a carbohydrate phosphotransferase system (PTS) permease (biofilm and endocarditis-associated permease A [BepA]), as important in infective endocarditis. This gene is highly enriched in E. faecium clinical isolates and absent in commensal isolates that are not associated with infection. Confirmation of the phenotype was established in a competition experiment of wild-type and a markerless bepA mutant in a rat endocarditis model. In addition, deletion of bepA impaired biofilm formation in vitro in the presence of 100% human serum and metabolism of β-methyl-D-glucoside. β-glucoside metabolism has been linked to the metabolism of glycosaminoglycans that are exposed on injured heart valves, where bacteria attach and form vegetations. Therefore, we propose that the PTS permease BepA is directly implicated in E. faecium pathogenesis.

  9. Prognostic Factors and Treatment Results After Bleomycin, Etoposide, and Cisplatin in Germ Cell Cancer

    Kier, Maria G; Lauritsen, Jakob; Mortensen, Mette S


    a small proportion of the patients received BEP. OBJECTIVE: To estimate survival probabilities after BEP, evaluate the IGCCCG prognostic classification, and propose new prognostic factors for outcome. DESIGN, SETTING, AND PARTICIPANTS: Of a Danish population-based cohort of GCC patients (1984-2007), 1889...... received first-line BEP, with median follow-up of 15 yr. Covariates evaluated as prognostic factors were age, year of treatment, primary site, non-pulmonary visceral metastases, pulmonary metastases, and tumor markers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes measured were 5-yr progression......-free survival (PFS), 5-yr disease-specific survival (DSS), and 5-yr overall survival (OS) as calculated using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS AND LIMITATIONS: The 5-yr PFS, DSS, and OS were 87%, 95%, and 93%, respectively, for patients with seminomatous GCC (SGCC...

  10. Micronuclei frequency induced by bleomycin in human peripheral lymphocytes: correlating BLHX polymorphism with mutagen sensitivity.

    Maffei, Francesca; Carbone, Fabio; Angelini, Sabrina; Forti, Giorgio Cantelli; Norppa, Hannu; Hrelia, Patrizia


    Mutagen sensitivity assay, by measuring chromosome damage induced by an in vitro treatment of peripheral lymphocytes with bleomycin, has been proposed as a biomarker for assessing cancer susceptibility. Recently, a single nucleotide polymorphism (SNP A1450G) of the gene for bleomycin hydrolase (BLHX), a specific neutral cysteine protease able to metabolise bleomycin, was proposed as a plausible candidate to variation in mutagen sensitivity. To shed more light on the effect of BLHX genotype on the expression of chromosome damage induced in vitro by bleomycin, we determined mutagen sensitivity for 45 non-smoker healthy volunteers. The level of bleomycin-induced chromosome damage was assessed as frequencies of micronuclei (MN) in cytokinesis-blocked lymphocytes. The subjects were genotyped for the BLHX gene, to determine the possible effect of this polymorphism on mutagen sensitivity. No difference in the spontaneous value of MN was detected between the homozygotes wild-type (A/A) and the carriers of variant alleles A/G heterozygotes or G/G homozygotes (MN/1000 binucleated (BN) cells: 6.69+/-2.53 and 6.37+/-4.87, respectively). A substantial effect of BLHX polymorphism in predetermining individual mutagen sensitivity status was observed: subjects with the BLHX A/A genotype displayed significantly lower mean levels of bleomycin-induced MN frequency than the carriers of A/G or G/G variant alleles combined (12.00+/-3.76 MN/1000 BN vs. 16.37+/-8.86 MN/1000 BN, respectively; P=0.029). The multiple regression analysis, including BLHX genotype and age, confirmed the significant effect of BLHX variant alleles (A/G, G/G) on the chromosome damage induced by bleomycin (P=0.01), whereas age correlated only with the spontaneous MN frequency.

  11. BEP-Ⅲ全自动酶免分析系统一例特殊故障的排除

    柏亮; 丁卫平



  12. Static and dynamic mechanics of the murine lung after intratracheal bleomycin

    Papiris Spyridon


    Full Text Available Abstract Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods Single intratracheal injections of saline (50 μL or bleomycin (2 mg/Kg in 50 μL saline were administered to C57BL/6 (n = 40 and Balb/c (n = 32 mice. Injury/fibrosis score, tissue volume density (TVD, collagen content, airway resistance (RN, tissue damping (G and elastance coefficient (H, hysteresivity (η, and area of pressure-volume curve (PV-A were determined after 7 and 21 days (inflammation and fibrosis stage, respectively. Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. Results Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. Conclusions Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than

  13. A Highly Sensitive Spectrophotometric Assay of Bleomycins Based on the Fading Reaction of Some Halofluorescein Dyes

    LIU,Jiang-Tao; LIU,Zhong-Fang; HU,Xiao-Li; Kong,Ling; LIU,Shao-Pu


    In weak acidic medium, anticancer antibiotics bleomycin A5 (BLMA5) and bleomycin A2 (BLMA2) can react with halofluorescein dyes such as erythrosin (Ery), eosin Y (EY), eosin B (EB) and rose bengal (RB) by virtue of electrostatic attraction and hydrophobic force to form the ion-association complexes, which can result in the fading reactions of four halofluorescein dyes. The maximum fading wavelengths of these four dyes were located at 527 nm for Ery, 515 nm for EY, 517 nm for EB and 546 nm for RB, respectively. The decrements of absorbance (△A) were directly proportional to the concentrations of bleomycin in a certain range. A new method for the determination of bleomycins anticancer drugs based on fading reactions of halofluorescein dyes has been developed. The method was not only highly sensitive but also simple and rapid. The molar absorptivities (ε) ranged from 1.5 × 105 to 7.5 ×105 L·mol-1·cm-1. It was applied to determination of the bleomycins in human serum, urine and rabbit serum samples. In this work, the spectral properties and the optimum reaction conditions were investigated. The structure of ion-association complexes and the reaction mechanism were discussed.

  14. Rapamycin Regulates Bleomycin-Induced Lung Damage in SP-C-Deficient Mice

    Satish K. Madala


    Full Text Available Injury to the distal respiratory epithelium has been implicated as an underlying cause of idiopathic lung diseases. Mutations that result in SP-C deficiencies are linked to a small subset of spontaneous and familial cases of interstitial lung disease (ILD and interstitial pulmonary fibrosis (IPF. Gene-targeted mice that lack SP-C (−/− develop an irregular ILD-like disease with age and are a model of the human SP-C related disease. In the current study, we investigated whether rapamycin could ameliorate bleomycin-induced fibrosis in the lungs of −/− mice. +/+ and −/− mice were exposed to bleomycin with either preventative administration of rapamycin or therapeutic administration beginning eight days after the bleomycin injury. Rapamycin-treatment increased weight loss and decreased survival of bleomycin-treated +/+ and −/− mice. Rapamycin did not reduce the fibrotic disease in the prophylactic or rescue experiments of either genotype of mice. Further, rapamycin treatment augmented airway resistance and reduced lung compliance of bleomycin-treated −/− mice. Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-γ. These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD/IPF.

  15. Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: erdosteine and N-acetylcysteine.

    Yildirim, Zeki; Kotuk, Mahir; Iraz, Mustafa; Kuku, Irfan; Ulu, Ramazan; Armutcu, Ferah; Ozen, Suleyman


    Antioxidant therapy may be useful in diseases with impaired oxidant antioxidant balance such as lung fibrosis. The effects of sulfhydryl-containing antioxidant agents N-acetylcysteine (NAC) and erdosteine on the bleomycin-induced lung fibrosis were compared in rats. The animals were divided into four groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + (10 mg/kg), and bleomycin + NAC (3 mmol/kg). Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology which is almost completely prevented by erdosteine and NAC. Hydroxyproline content was 18.7 +/- 3.5 and 11.2 +/- 0.6 mg/g dried tissue in bleomycin and saline treated rats, respectively (P erdosteine and NAC pretreated, respectively. Erdosteine and NAC significantly reduced depletion of glutathione peroxidase, and prevented increases in myeloperoxidase activities, nitric oxide, and malondialdehyde levels in lung tissue produced by bleomycin. Data presented here indicate that erdosteine and NAC similarly prevented bleomycin-induced lung fibrosis and their antioxidant effects were also similar in this experiment.

  16. Effects of N-acetyl-L-cysteine on bleomycin induced oxidative stress in malignant testicular germ cell tumors.

    Cort, Aysegul; Ozdemir, Evrim; Timur, Mujgan; Ozben, Tomris


    Testicular cancer is a very common cancer in males aged 15-44 years. Bleomycin is used in chemotherapy regimens in the treatment of patients having testicular germ-cell tumor. Bleomycin generates oxygen radicals, induces oxidative cleavage of DNA strand and induces apoptosis in cancer cells. There is no study in the literature investigating effects of N-Acetyl-L-Cysteine (NAC) on bleomycin-induced oxidative stress in testicular germ cell tumors. For this reason, we studied effects of NAC on oxidative stress produced in wild-type NTera-2 and p53-mutant NCCIT testis cancer cells incubated with bleomycin and compared the results with H(2)O(2) which directly produces oxidative stress. We determined protein carbonyl content, thiobarbituric acid reactive substances (TBARS), glutathione (GSH), 8-isoprostane, lipid hydroperoxide levels and total antioxidant capacity in both testicular cancer cells. Bleomycin and H(2)O(2) significantly increased 8-isoprostane, TBARS, protein carbonyl and lipid hydroperoxide levels in NTera-2 and NCCIT cells. Bleomycin and H(2)O(2) significantly decreased antioxidant capacity and GSH levels in both cell lines. Co-incubation with NAC significantly decreased lipid hydroperoxide, 8-isoprostane, protein carbonyl content and TBARS levels increased by bleomycin and H(2)O(2). NAC enhanced GSH levels and antioxidant capacity in the NTera-2 and NCCIT cells. It can be concluded that NAC diminishes oxidative stress in human testicular cancer cells induced by bleomycin and H(2)O(2).

  17. Protective Effect of Pistacia lentiscus Oil Against Bleomycin-Induced Lung Fibrosis and Oxidative Stress in Rat.

    Abidi, Anouar; Aissani, Nadhem; Sebai, Hichem; Serairi, Raja; Kourda, Nadia; Ben Khamsa, Saloua


    We aimed in the present study to investigate the protective effect of Pistacia lentiscus oil against bleomycin-induced lung fibrosis as well as the involvement of oxidative stress in such protection. In this respect, adult male Wistar rats were used and divided into three groups of twenty each: control (NaCl, 0.9%), bleomycin, and bleomycin (4 mg/kg b.w.) + P. lentiscus oil (3 g/kg, b.w.). Animals were pretreated for 30 days before the induction of fibrosis by bleomycin and 1 wk after the induction of fibrosis. The oil principal compounds detected by gas chromatography analysis are: Linoleic and palmitic acids (70.6 and 24.7%, respectively). Our data demonstrated that P. lentiscus oil protected against bleomycin-induced fibrosis as evidenced by TGFβ immunostaining increase in lungs fibrocytes as well as inflammatory infiltrate. We also showed that acute bleomycin-induced fibrosis was accompanied by an oxidative stress in lung tissue as assessed by an increase of lipid peroxidation as well as antioxidant enzyme activities depletion such as superoxide dismutase (SOD) and catalase (CAT). More importantly, P. lentiscus oil treatment reversed all bleomycin-induced oxidative stress parameters disturbances. In conclusion, we suggest that P. lentiscus oil had potent protective effects against bleomycin-induced fibrosis due in part to its antioxidant properties.

  18. Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

    Lili eGao


    Full Text Available Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA, a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition and activation of tansforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

  19. Antioxidant ability and radiosensitivity in malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle irradiation%α粒子诱发BEP2D细胞恶性转化中抗氧化能力和辐射敏感性研究

    苟巧; 张伟; 王春燕; 苏旭


    Objective To investigate the antioxidant ability and radiosensitivity in the malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle exposure.Methods Glutathione Peroxidase (GPX),Catalase (CAT) and Glutathione (GSH) assay kits were employed to detect GPX and CAT enzyme abilities and the levels of GSH in BEP2D,RH21 ( passage 21 of α-particle-irradiated BEP2D cells),and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from cells of passage 35 of α-particle-irradiated BEP2D cells).MTT assay were used to test the growth rate of BEP2D,RH21 and BERP35T-1 cells treated with 0,30,60,90,120,and 150 μmoL/L H2O2.Colony-forming test and MTT assay were used to examine the cell survival fraction and the growth rate of BEP2D,RH21 and BERP35T-1 cells exposed to 0,2,4,and 8 Gy of γ-rays,respectively.Results GPX and CAT enzyme activities in RH21 and BERP35T-1 cells were obviously lower than in BEP2D( t = 5.75-67.92 ,P < 0.05 ).CAT enzyme activity in BERP35T-1 was lower than that in RH21 cells (t =22.25 ,P <0.01 ).Compared to BEP2D cells,decreased level of GSH was detected in BERP35T-1 cells(t = 7.76,P < 0.05 ),but there was no change in RH21.After treatment with 30,60,90,120,and 150 μmol/L H2O2,the growth rates of BEP2D were all higher than those of BERP35T-1 cells(t = 10.37-58.36,P <0.01 ).Meanwhile,the growth rates of BEP2D were all higher than those of RH21 cells after treatment with 60,90,120,and 150 μ mol/L H2O2 (t = 29.90-84.68,P < 0.01 ).In addition,compared to BEP2D cells,decreased cell survival fraction and growth rate of BERP35T-1 cells were observed after irradiation with 2,4,and 8 Gy of y-rays ( t = 5.87-34.17,P < 0.05 ).The cell survival fraction and growth rate of RH21 were all lower than those of BEP2D cells at 4 and 8 Gy post-irradition( t =6.33- 45.00,P < 0.05 ).Conclusion The function of antioxidant system decreased in the α-particleinduced transformed cells,which could

  20. Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

    Oliveira-Junior, Manoel Carneiro; Assumpção-Neto, Erasmo; Brandão-Rangel, Maysa Alves Rodrigues; Damaceno-Rodrigues, Nilsa Regina; Garcia Caldini, Elia; Velosa, Ana Paula Pereira; Teodoro, Walcy Rosolia; Ligeiro de Oliveira, Ana Paula; Dolhnikoff, Marisa; Eickelberg, Oliver; Vieira, Rodolfo Paula


    Introduction The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin-induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX); (n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1; p<0.01), (IL-1β; p<0.001), (IL-5; p<0.01), (IL-6; p<0.001), (IL-13; p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15–44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model. PMID:27677175

  1. The Proposed Tiebreaker Rule in OECD/G20 BEPS Action 6: A Critical Examination of the Possible Motives and Means, and a Potential Alternative

    Sanghavi, Dhruv


    In this article, the author critically examines the proposed tiebreaker rule in the OECD’s Final Report on Action 6 of the Base Erosion and Profit Shifting (BEPS) project, and the motives behind the proposal. The author concludes by suggesting an alternative, which he argues is a more effective mean

  2. Beamed-Energy Propulsion (BEP): Considerations for Beaming High Energy-Density Electromagnetic Waves Through the Atmosphere

    Manning, Robert M.


    A study to determine the feasibility of employing beamed electromagnetic energy for vehicle propulsion within and outside the Earth's atmosphere was co-funded by NASA and the Defense Advanced Research Projects Agency that began in June 2010 and culminated in a Summary Presentation in April 2011. A detailed report entitled "Beamed-Energy Propulsion (BEP) Study" appeared in February 2012 as NASA/TM-2012-217014. Of the very many nuances of this subject that were addressed in this report, the effects of transferring the required high energy-density electromagnetic fields through the atmosphere were discussed. However, due to the limitations of the length of the report, only a summary of the results of the detailed analyses were able to be included. It is the intent of the present work to make available the complete analytical modeling work that was done for the BEP project with regard to electromagnetic wave propagation issues. In particular, the present technical memorandum contains two documents that were prepared in 2011. The first one, entitled "Effects of Beaming Energy Through the Atmosphere" contains an overview of the analysis of the nonlinear problem inherent with the transfer of large amounts of energy through the atmosphere that gives rise to thermally-induced changes in the refractive index; application is then made to specific beamed propulsion scenarios. A brief portion of this report appeared as Appendix G of the 2012 Technical Memorandum. The second report, entitled "An Analytical Assessment of the Thermal Blooming Effects on the Propagation of Optical and Millimeter- Wave Focused Beam Waves For Power Beaming Applications" was written in October 2010 (not previously published), provides a more detailed treatment of the propagation problem and its effect on the overall characteristics of the beam such as its deflection as well as its radius. Comparisons are then made for power beaming using the disparate electromagnetic wavelengths of 1.06 microns and 2

  3. A designer bleomycin with significantly improved DNA cleavage activity.

    Huang, Sheng-Xiong; Feng, Zhiyang; Wang, Liyan; Galm, Ute; Wendt-Pienkowski, Evelyn; Yang, Dong; Tao, Meifeng; Coughlin, Jane M; Duan, Yanwen; Shen, Ben


    The bleomycins (BLMs) are used clinically in combination with a number of other agents for the treatment of several types of tumors, and the BLM, etoposide, and cisplatin treatment regimen cures 90-95% of metastatic testicular cancer patients. BLM-induced pneumonitis is the most feared, dose-limiting side effect of BLM in chemotherapy, which can progress into lung fibrosis and affect up to 46% of the total patient population. There have been continued efforts to develop new BLM analogues in the search for anticancer drugs with better clinical efficacy and lower lung toxicity. We have previously cloned and characterized the biosynthetic gene clusters for BLMs from Streptomyces verticillus ATCC15003, tallysomycins from Streptoalloteichus hindustanus E465-94 ATCC31158, and zorbamycin (ZBM) from Streptomyces flavoviridis SB9001. Comparative analysis of the three biosynthetic machineries provided the molecular basis for the formulation of hypotheses to engineer novel analogues. We now report engineered production of three new analogues, 6'-hydroxy-ZBM, BLM Z, and 6'-deoxy-BLM Z and the evaluation of their DNA cleavage activities as a measurement for their potential anticancer activity. Our findings unveiled: (i) the disaccharide moiety plays an important role in the DNA cleavage activity of BLMs and ZBMs, (ii) the ZBM disaccharide significantly enhances the potency of BLM, and (iii) 6'-deoxy-BLM Z represents the most potent BLM analogue known to date. The fact that 6'-deoxy-BLM Z can be produced in reasonable quantities by microbial fermentation should greatly facilitate follow-up mechanistic and preclinical studies to potentially advance this analogue into a clinical drug.

  4. Metformin Reduces Bleomycin-induced Pulmonary Fibrosis in Mice.

    Choi, Sun Mi; Jang, An Hee; Kim, Hyojin; Lee, Kyu Hwa; Kim, Young Whan


    Metformin has anti-inflammatory and anti-fibrotic effects. We investigated whether metformin has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis in a murine model. A total of 62 mice were divided into 5 groups: control, metformin (100 mg/kg), BLM, and BLM with metformin (50 mg/kg or 100 mg/kg). Metformin was administered to the mice orally once a day from day 1. We sacrificed half of the mice on day 10 and collected the bronchoalveolar lavage fluid (BALF) from their left lungs. The remaining mice were sacrificed and analyzed on day 21. The right lungs were harvested for histological analyses. The messenger RNA (mRNA) levels of epithelial-mesenchymal transition markers were determined via analysis of the harvested lungs on day 21. The mice treated with BLM and metformin (50 mg/kg or 100 mg/kg) showed significantly lower levels of inflammatory cells in the BALF compared with the BLM-only mice on days 10 and 21. The histological examination revealed that the metformin treatment led to a greater reduction in inflammation than the treatment with BLM alone. The mRNA levels of collagen, collagen-1, procollagen, fibronectin, and transforming growth factor-β in the metformin-treated mice were lower than those in the BLM-only mice on day 21, although statistical significance was observed only in the case of procollagen due to the small number of live mice in the BLM-only group. Additionally, treatment with metformin reduced fibrosis to a greater extent than treatment with BLM alone. Metformin suppresses the inflammatory and fibrotic processes of BLM-induced pulmonary fibrosis in a murine model.

  5. Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury.

    Rey-Parra, G J; Vadivel, A; Coltan, L; Hall, A; Eaton, F; Schuster, M; Loibner, H; Penninger, J M; Kassiri, Z; Oudit, G Y; Thébaud, B


    Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.

  6. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.

    Mata, M; Ruíz, A; Cerdá, M; Martinez-Losa, M; Cortijo, J; Santangelo, F; Serrano-Mollar, A; Llombart-Bosch, A; Morcillo, E J


    Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model.

  7. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis.

    Cabrera, Sandra; Maciel, Mariana; Herrera, Iliana; Nava, Teresa; Vergara, Fabián; Gaxiola, Miguel; López-Otín, Carlos; Selman, Moisés; Pardo, Annie


    Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses.

  8. Efficient Nuclear DNA Cleavage in Human Cancer Cells by Synthetic Bleomycin Mimics

    Li, Qian; van der Wijst, Monique G. P.; Kazemier, Hinke G.; Rots, Marianne G.; Roelfes, Gerard


    Iron complexes of N,N-bis(2-Pyridylmethyl)-N-bis(2-pyridyl)-methylamine (N4Py) have proven to be excellent synthetic mimics of the Bleomycins (BLMs), which are a family of natural antibiotics used clinically in the treatment of certain cancers. However, most investigations of DNA cleavage activity o

  9. Evaluating the ameliorative potential of plant flavonoids and their nanocomposites in bleomycin induced idiopathic pulmonary fibrosis

    Srabani Kar


    Full Text Available Introduction: Pulmonary Fibrosis can severely disrupt lung function. The cause of Idiopathic Pulmonary Fibrosis (IPF is still unclear. The treatment currently available for IPF provides minimal benefits. Bleomycin is used in research to induce experimental pulmonary fibrosis in animals. Plant flavonoids such as fisetin and curcumin are known for their anti-inflammatory properties. The aim was to demonstrate the path of physiological changes in bleomycin induced IPF and to further evaluate the reversal and ameliorative potentials of some plant flavonoids and their nanocomposites. Bleomycin administration is known to damage the lung epithelial cells resulting in lower cell numbers. Results: Our colony forming assay in BALF also demonstrated a reduction (1.65 fold in colony-forming unit after bleomycin administration. The number of colonies increased upon treatment with fisetin(1.20 fold and curcumin (1.13 fold respectively. MTT proliferation assay demonstrated a significant increase in the number of viable cells upon treatment with curcumin (1.42 fold and fisetin (1.74 fold respectively, in the lung. The NBT assay demonstrated a significant effect of curcumin in BALF, lung and peripheral blood. A significant effect of fisetin was observed in BALF and peripheral blood. Conclusion: These findings were also supported by the histological analyses of the lung samples. Curcumin showed highestpotential for the treatment of IPF and fisetin showed its ameliorative effect. [Biomed Res Ther 2016; 3(7.000: 707-722

  10. Studies on bleomycin-induced repair DNA synthesis in permeable mouse ascites sarcoma cells.



    Full Text Available To study the mechanism of DNA excision repair, a DNA repair system employing permeable mouse sarcoma (SR-C3H/He cells was established and characterized. SR-C3H/He cells were permeabilized with a 0.0175% Triton X-100 solution. The permeable cells were treated with 1 mM ATP and 0.11 mM bleomycin, and then washed thoroughly to remove ATP and bleomycin. Repair DNA synthesis occurred in the bleomycin-damaged, permeable SR-C3H/He cells when incubated with ATP and four deoxyribonucleoside triphosphates. The repair nature of the DNA synthesis was confirmed by the BrdUMP density shift technique, and by the reduced sensitivity of the newly synthesized DNA to Escherichia coli exonuclease III. The DNA synthesis was optimally enhanced by addition of 0.08 M NaCl. Studies using selective inhibitors of DNA synthesis showed that aphidicolin-sensitive DNA polymerase (DNA polymerase alpha and/or delta and DNA polymerase beta were involved in the repair process. The present DNA repair system is thought to be useful to study nuclear DNA damage by bleomycin, removal of the damaged ends by an exonuclease, repair DNA synthesis by DNA polymerases and repair patch ligation by DNA ligase(s.

  11. Effects of erdosteine on bleomycin-induced lung fibrosis in rats.

    Boyaci, Haşim; Maral, Hale; Turan, Gupse; Başyiğit, Ilknur; Dillioğlugil, Meltem O; Yildiz, Füsun; Tugay, Melih; Pala, Ayşe; Erçin, Cengiz


    This study was designed to examine the effects of erdosteine on bleomycin (BLM)-induced lung fibrosis in rats. Thirty-three Sprague-Dawley rats were divided randomly into three groups, bleomycin alone (BLM), bleomycin + erdosteine (BLM + ERD), and saline alone (control). The BLM and BLM + ERD groups, were given 2.5 mg/kg BLM intratracheally. The first dose of oral erdosteine (10 mg/kg/day) in the BLM + ERD group was started 2 days before BLM administration and continued until animals were sacrificed. Animals were sacrificed 14 days after intratracheal instillation of BLM. The effect of erdosteine on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and biochemical measurements of lung tissue superoxide dismutase (SOD) and glutathione (GSH) as antioxidants, malondialdehyde (MDA) as an index for lipid peroxidation, and nitrite/nitrate levels. Bleomycin-induced lung fibrosis as determined by lung histology was prevented with erdosteine (grades of fibrosis were 4.9, 2.3, and 0.2 in BLM, BLM + ERD, and control groups, respectively). Erdosteine also prevented bleomycin-induced increase in MDA (MDA levels were 0.50 +/- 0.15, 0.11 +/- 0.02, and 0.087+/- 0.03 nmol/mg protein in BLM, BLM + ERD, and control groups, respectively) and nitrite/nitrate (nitrite/nitrate levels were 0.92 +/- 0.06, 0.60 +/- 0.09, and 0.56+/- 0.1 micromol/mg protein in BLM, BLM + ERD, and control groups respectively) levels. Bleomycin-induced decrease in GSH and SOD levels in the lung tissue also prevented by erdosteine [(GSH levels were 213.5 +/- 12.4, 253.2+/- 25.2, and 287.9+/- 34.4 nmol/mg protein) (SOD levels were 1.42+/- 0.12, 1.75+/- 0.17, and 1.89+/- 0.09 U/mg protein) in BLM, BLM + ERD, and control groups respectively]. Erdosteine prevented bleomycin-induced increases in total cell number and neutrophil content of the BAL fluid. In conclusion, oral erdosteine is effective in prevention of BLM-induced lung fibrosis in rats possibly via the

  12. Evaluation of Efficacy and Safety of BEP Regimen in the Treatment of High-risk Gestational Trophoblastic Tumor%BEP方案治疗高危型妊娠滋养细胞肿瘤的疗效及安全性评价



    Objective:To explore the clinical efficacy and safety of BEP regimen in the treatment of high-risk gestational trophoblastic tumor. Method:40 cases of patients with high-risk gestational trophoblastic tumor were treated with bleomycin+etoposide+cisplatin(BEP)from February 2005 to September 2012.Result:The course of treatment was(6.1±0.2)chemotherapy cycle.36 cases of patients achieved complete remission,accounted for 90%.4 cases of patients had drug resistance,accounted for 10%.The average time of drug resistance occured in(4.7±0.1)chemotherapy cycle,and then treated with cyclophosphamide+vincristine(CO)/etoposide+methotrexate+put red of actinomycin D(EMA).On basis of chemotherapy,1 case of patients was treated with operation,2 cases of patients were treated with radiotherapy,and 1 case died,3 cases of patients achieved complete remission. The main adverse reaction included hair loss,gastrointestinal discomfort and bone marrow suppression,secondary adverse reaction included liver function damage and peripheral neuritis,the differences were statistically significant(P<0.05).Conclusion:BEP regimen have good clinical efficacy and safety in the treatment of high-risk gestational trophoblastic tumor,and has very important application value.%  目的:探讨高危型妊娠滋养细胞肿瘤采用BEP方案治疗的临床效果及安全性。方法:本次研究选择的对象共40例,均为本院2005年2月-2012年9月收治的高危型妊娠滋养细胞肿瘤的患者,给予博来霉素+依托泊苷+顺铂(BEP)方案救治,并回顾分析其临床资料。结果:本组40例患者,平均接受BEP方案化疗(6.1±0.2)个疗程,其中完全缓解36例,占90%;耐药者4例,占10%。耐药患者平均进行(4.7±0.1)个疗程时出现耐药,均改用环磷酰胺+长春新碱(CO)/依托泊苷+甲氨蝶呤+放红菌素D(EMA)方案化疗,辅以手术治疗1例,辅以放疗治疗2例,后死亡1例,完全缓解3

  13. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment.

    Degryse, Amber L; Tanjore, Harikrishna; Xu, Xiaochuan C; Polosukhin, Vasiliy V; Jones, Brittany R; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P; McMahon, Frank B; Gleaves, Linda A; Blackwell, Timothy S; Lawson, William E


    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4(+)/β-gal(+)) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine.

  14. Therapeutic evaluation of cisplatin, etoposide, and bleomycin chemotherapy regimen in high-risk gestational trophoblastic neoplasia%BEP方案治疗高危型妊娠滋养细胞肿瘤的疗效及安全性评价

    宋水勤; 张国楠


    Objective To evaluate the effectiveness and safety of combination chemotherapy with bleomycin,etoposide and cisplatin (BEP) regimen on the patients with high-risk gestational trophoblastic neoplasia (GTN).Methods Forty-two patients with high-risk GTN admitted in Sichuan Cancer Hospital between Jan.1997 and Oct.2011 were analyzed retrospectively.The International Federation of Gynecology and Obstetrics (FIGO) prognostic score of all patients was more than 7.The mean age of patients was 30.2years (range 20 -49 years).All patients were treated with more than two cycles BEP regimen and followed up to the patients' death or at the end of Feb.2012.The clinical response,toxicity and the occurrence of secondary tumors were investigated.Results Forty-two high-risk GTN patients received the total of 251courses of the BEP regimen,the average number of courses for each patient was 6.0 courses.Thirty-seven patients achieved complete remission and 5 patients showed drug-resistant.The total complete remission rate of BEP regimen was 88% ( 37/42 ).Among the complete remission patients,the total courses of BEP regimen of cases getting normal serum β-hCG level was 129 courses ( average 3.5 courses),and the total courses of cases achieving complete remission was 227 courses (average 6.1 courses ).Among the 37 complete remission patients,31 cases were treated with BEP regimen chemotherapy alone,4 patients with BEP regimen chemotherapy combined with surgical treatment (1 case had no cancer after surgery) and 2 cases with BEP regimen chemotherapy combined with radiation therapy.Therefore,the complete remission rate of BEP regimen chemotherapy alone was 74% (31/42 ).There were 5 patients who showed drug-resistance after 24 courses of BEP regimen chemotherapy (average 4.8 courses),then received etoposide,methotrexate and dactinomycin( EMA )/cyclophosphamide and vincristine sulfate ( CO ) regimen chemotherapy after drugresistance,2 cases combined with radiation therapy,1 case combined

  15. Bleomycin-induced chromosome aberrations in head and neck cancer patients analyzed by classical cytogenetics and FISH.

    Zych, M; Schlade-Bartusiak, K; Chorostkowska, A; Stembalska, A; Krêcicki, T; Sasiadek, M


    Individual sensitivity to mutagens has been considered to play an important role in head-and-neck squamous cells carcinoma (HNSCC) development. The bleomycin test was introduced for establishing constitutional susceptibility to mutagens (T.C. Hsu, D.A. Johnston, L.M. Cherry, D. Ramkisson, S.P. Schantz, J.M. Jessup, R.J. Winn, L. Shirley, C. Furlong, Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis, Int. J. Cancer 43 (1989) 403-409). Its criteria are based on scoring of chromosome aberrations (CAs, mainly breaks) in Giemsa-stained chromosomes. Fluorescence in situ hybridization (FISH) offers an easy method for analysis of translocations, acentric fragments and dicentrics. In the present study FISH was applied in the analysis of bleomycin-induced CAs of the HNSCC patients and controls. The results proved that FISH is a complementary method to the classical staining in monitoring of bleomycin-induced CAs.

  16. Precision measurement of the $^{7}$Be(p, $\\gamma$)$\\,^{8}$B cross section with an implanted $^{7}$Be target

    Baby, L T; Goldring, G; Hass, M; Weissman, L; Fedosseev, V; Köster, U; Nir-El, Y; Haquin, G; Gäggeler, H W; Weinreich, R


    The $^{7}$Be(p, $\\gamma$) $\\,^{8}$B reaction plays a central role in the evaluation of solar neutrino fluxes. We report on a new precision measurement of the cross section of this reaction, following our previous experiment with an implanted $^{7}$Be target, a raster- scanned beam, and the elimination of the backscattering loss. The new measurement incorporates a more abundant $^{7}$Be target and a number of improvements in design and procedure. The point at E$_{lab}$ = 991 keV was measured several times under varying experimental conditions, yielding a value of S$_{17}$(E$_{c.m.}$ = 850 keV) = 24.0 $\\pm$ 0.5 eV b. Measurements were carried out at lower energies as well. Because of the precise knowledge of the implanted $^{7}$Be density profile, it was possible to reconstitute both the off- and on-resonance parts of the cross section and to obtain from the entire set of measurements an extrapolated value of S$_{17}$(0)=21.2 $\\pm$ 0.7 eV b.

  17. Angiotensin-converting enzyme: an indicator of bleomycin-induced pulmonary toxicity in humans?

    Sørensen, Peter G; Rømer, F K; Cortes, Dina


    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiolog......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical...... or radiological evidence of pulmonary damage. While the static and dynamic lung function parameters were unchanged, carbon monoxide diffusion capacity (DLCO) decreased significantly (P less than 0.01) during a total of 126 days of pulsed regimen, indicating damage to the alveolar-endothelial membrane. S...

  18. Air leak: An unusual manifestation of organizing pneumonia secondary to bleomycin

    Namitha, R; Nimisha, KP; Yusuf, Nasser; Rauf, CP


    Organizing pneumonia (OP) is a less common interstitial lung disease with varying clinical picture. The development of pulmonary air leak in a case of OP is an extremely rare complication. Here, we report the case of a 46-year-old female with carcinoma ovary, postchemotherapy who developed respiratory distress with pneumomediastinum, and subcutaneous emphysema. Lung biopsy showed evidence of OP. This turned out to be a rare case of OP, secondary to bleomycin chemotherapy, presenting with pulmonary air leak. PMID:28360468

  19. Indium 111-A-bleomycin--a new tracer for imaging orofacial neoplasms

    Kment, G.; Matejka, M.; Porteder, H.; Sinzinger, H.


    Forty-six patients with maxillofacial squamous cell cancer of variable keratinization underwent radioisotope diagnosis using Indium 111-A-bleomycin. This new technique was applied to expand the battery of diagnostic tools available for detecting maxillofacial neoplasms. Its high specificity (100%) and sensitivity (96%) make it well suited for detection of both local and distant recurrences as well as tumor regrowth. Preliminary whole body retention measurements also indicate that this technique looks promising for potential therapeutic use.

  20. Radiation nephritis following combined abdominal radiation and chemotherapy (bleomycin-vinblastine)

    Churchill, D.N.; Hong, K.; Gault, M.H.


    A 29-year-old man presented with acute glomerulonephritis five weeks following completion of combined chemotherapy (bleomycin-vinblastine) and abdominal radiation for testicular carcinoma. There was no evidence for a post-infectious cause or a systemic collagen disorder. The renal biopsy showed changes consistent with radiation nephritis. The combined radiation and chemotherapy may have, by additive or synergistic action, caused the early appearance of radiation nephritis.

  1. Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice

    Trivedi, Ruchit; Redente, Elizabeth F.; Thakur, Ashish; Riches, David W. H.; Kompella, Uday B.


    Our purpose was to assess sustained delivery and enhanced efficacy of pirfenidone-loaded nanoparticles after intratracheal instillation. Poly(lactide-co-glycolide) nanoparticles containing pirfenidone (NPs) were prepared and characterized. Biodistribution of NPs and solution was assessed using LC-MS after intratracheal administration in C57Bl/6 mice at 3 and 24 h and 1 week post-administration. Efficacy was tested in C57Bl/6 mice in a bleomycin-induced pulmonary fibrosis model. Mice received 10 μg pirfenidone intratracheally in solution or NPs, once a week, for 3 weeks after bleomycin administration. Drug effects were monitored on day 28. Lung hydroxyproline content, total number of cells, and numbers of macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage (BAL) were assessed. Numbers of macrophages, lymphocytes, and neutrophils were assessed in the lung as well. NPs sustained significantly higher levels of pirfenidone in the lungs and BAL at 24 h and 1 week, compared to the solution group. Pirfenidone solution and NPs significantly reduced hydroxyproline levels by 57 and 81%, respectively, compared to bleomycin alone. At the end of 4 weeks, BAL cellularity was reduced by 25.4% and 56% with solution and NP treatment, respectively. The numbers of lymphocytes and neutrophils in the BAL were also reduced by 58.9 and 82.4% for solution and 74.5% and 89.7% for NPs, respectively. The number of inflammatory macrophages in the lung was reduced by 62.8% and the number of neutrophils was reduced by 59.1% in the NP group and by 37.7% and 44.5%, respectively, in the solution group, compared to bleomycin alone. In conclusion, nanoparticles sustain lung pirfenidone delivery and enhance its anti-fibrotic efficacy.


    Jin-ming Gao; Bao Lu; Zi-jian Guo


    Objective To investigate the role of CXC chemokine receptor 3(CXCR3 ) in bleomycin-induced lung injury by using CXCR3 gene deficient mice.Methods Sex-, age-, and weight-matched C57BL/6 CXCR3 gene knockout mice and C57BL/6 wide type mice were challenged by injection of bleomycin via trachea. Lung tissue was stained with HE method. Airway resistance was measured. Bronchoalveolar lavage (BAL) was performed using phosphate buffered saline twice, cell number and differentials were counted by Diff-Qnick staining. Interleukin(IL)-4, IL-5, IL-12p40, and interfon-γ in BAL fluid and lung homogenate were measured by enzyme-linked immunosorbent assay. Unpaired t test was explored to compare the difference between two groups.Results On day 7 after bleomycin injection via trachea, CXCR3 knockout mice were protected from bleomycininduced lung injury as evidenced by fewer accumulation of inflammatory cells in the airway and lung interstitium compared with their wild type littermates ( P<0.05 ). Airway resistance was also lower in CXCR3 knockout mice compared with wild type mice (P<0.01 ). Significantly lower level of inflammatory cytokines release, including the altered production of IL-4 and IL-5 both in BAL fluid and lung tissue was seen in CXCR3 knockout mice than in wild type mice (both P<0.05).Conclusion CXCR3 signaling promotes inflammatory cells recruiting and initiates inflammatory cytokines cascade following endotracheal bleomycin administration, indicating that CXCR3 might be a therapeutic target for pulmonary injury.

  3. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J


    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

  4. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Chad S Boomershine; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.


    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice tha...

  5. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis.

    François, Antoine; Gombault, Aurélie; Villeret, Bérengère; Alsaleh, Ghada; Fanny, Manoussa; Gasse, Paméla; Adam, Sylvain Marchand; Crestani, Bruno; Sibilia, Jean; Schneider, Pascal; Bahram, Seiamak; Quesniaux, Valérie; Ryffel, Bernhard; Wachsmann, Dominique; Gottenberg, Jacques-Eric; Couillin, Isabelle


    Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1β, BAFF and IL-17A.

  6. The Human Carnitine Transporter SLC22A16 Mediates High Affinity Uptake of the Anticancer Polyamine Analogue Bleomycin-A5*

    Aouida, Mustapha; Poulin, Richard; Ramotar, Dindial


    Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae l-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human l-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, l-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients. PMID:20037140

  7. The human carnitine transporter SLC22A16 mediates high affinity uptake of the anticancer polyamine analogue bleomycin-A5.

    Aouida, Mustapha; Poulin, Richard; Ramotar, Dindial


    Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae L-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human L-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, L-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients.

  8. A cell-free system for studying a priming factor involved in repair of bleomycin-damaged DNA.



    Full Text Available A simple cell-free system for studying a priming factor involved in the repair of bleomycin-damaged DNA was established. The template-primer used for the repair DNA synthesis was prepared by treating the closed circular, superhelical form of pUC19 plasmid DNA with 2.2 microM bleomycin and 20 microM ferrous ions. Single-strand breaks were introduced into pUC19 DNA by the bleomycin treatment, and the DNA was consequently converted largely into the open circular form. A system for repair of this bleomycin-damaged DNA was constructed with a priming factor, DNA polymerase (DNA polymerase beta or Klenow fragment of DNA polymerase I, ATP, T4 DNA ligase and four deoxynucleoside triphosphates. After incubation, the conformation of the DNA was analyzed by agarose gel electrophoresis and electron microscopy. The open circular DNA was largely converted to the closed circular DNA, indicating that the single-strand breaks of DNA were repaired. When the priming factor was omitted, DNA repair did not occur. The present system seemed to be applicable to the study of priming factors involved in the repair of DNA with single-strand breaks caused not only by bleomycin but also by ionizing radiation or active oxygen.

  9. Administration of bleomycin via the oropharyngeal aspiration route leads to sustained lung fibrosis in mice and rats as quantified by UTE-MRI and histology.

    Christine Egger

    Full Text Available Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In the present study, we investigated the oropharyngeal aspiration of bleomycin as an alternative route for the induction of lung fibrosis in rats and mice. The development of lung injury was followed in vivo by ultrashort echo time magnetic resonance imaging (UTE-MRI and by post-mortem analyses (histology of collagen, hydroxyproline determination, and qRT-PCR. In C57BL/6 mice, oropharyngeal aspiration of bleomycin led to more prominent lung fibrosis as compared to intranasal administration. Consequently, the oropharyngeal aspiration route allowed a dose reduction of bleomycin and, therewith, a model refinement. Moreover, the distribution of collagen after oropharyngeal aspiration of bleomycin was more homogenous than after intranasal administration: for the oropharyngeal aspiration route, fibrotic areas appeared all over the lung lobes, while for the intranasal route fibrotic lesions appeared mainly around the largest superior airways. Thus, oropharyngeal aspiration of bleomycin induced morphological changes that were more comparable to the human disease than the intranasal administration route did. Oropharyngeal aspiration of bleomycin led to a homogeneous fibrotic injury also in rat lungs. The present data suggest oropharyngeal aspiration of bleomycin as a less invasive means to induce homogeneous and sustained fibrosis in the lungs of mice and rats.

  10. Bleomycin-induced DNA synthesis in a cell-free system using a permeable mouse sarcoma cell Extract.



    Full Text Available To investigate factors involved in excision repair DNA synthesis, a soluble extract was prepared from permeable mouse sarcoma (SR-C3H/He cells by homogenization and ultracentrifugation. DNA synthesis measured by using native calf thymus DNA as the template-primer and the extract as the polymerase source showed low activity. The DNA synthesis was enhanced more than ten-fold by the addition of an appropriate concentration of bleomycin, a radiomimetic DNA-damaging drug. Using selective inhibitors of DNA polymerases, it was shown that the DNA polymerase involved in the bleomycin-induced DNA synthesis was DNA polymerase beta. In addition to DNA polymerase beta, an exonuclease which converts bleomycin-damaged DNA into suitable template-primers for repair DNA synthesis appeared to be present in the permeable cell extract.

  11. BEPS: quo vadis Nederland?

    Cornelisse, R.P.C.


    Schrijver blikt vooruit op de ontwikkelingen die dit jaar in de fiscale wereld gaan plaatsvinden. Hij stelt de vraag aan de orde of Nederland de ontwikkelingen op dit terrein moet afwachten of dat het verstandiger is juist niet af te wachten maar pro-actief haar fiscale stelsel op korte termijn zoda

  12. Increased Cellular NAD+ Level through NQO1 Enzymatic Action Has Protective Effects on Bleomycin-Induced Lung Fibrosis in Mice

    Oh, Gi-Su; Lee, Su-Bin; Karna, Anjani; Kim, Hyung-Jin; Shen, AiHua; Pandit, Arpana; Lee, SeungHoon


    Background Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to NAD+ by various quinones and thereby elevates the intracellular NAD+ levels. In this study, we examined the effect of increase in cellular NAD+ levels on bleomycin-induced lung fibrosis in mice. Methods C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with β-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor β1 (TGF-β1) and β-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results β-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-β1, α-smooth muscle actin accumulation. In addition, β-lapachone showed a protective role in TGF-β1–induced ECM expression and EMT in A549 cells. Conclusion Our results suggest that β-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-β1–induced EMT in vitro, by elevating the NAD+/NADH ratio through NQO1 activation.

  13. Treatment Options for Testicular Cancer, by Type and Stage

    ... nodes, chemo is often recommended. Chemotherapy with the BEP regimen (bleomycin, etoposide, and cisplatin) for 2 cycles. ... chemo is recommended, with either 3 cycles of BEP or 4 cycles of EP (etoposide and cisplatin). ...

  14. Effects of 1,25( OH)2D3 on bleomycin-induced pulmonary fibrosis in mice



    Objective To observe the effects of 1,25(OH)2D3on bleomycin-induced pulmonary fibrosis in mice and to explore its mechanisms.Methods Ninety male C57BL/6mice,6 to 8 weeks old,were randomly divided into 3groups according to the table of random numbers:a control group,a model group and a treatment group(n=30each).Bleomycin was injected to the mice in the latter 2groups by single intratracheal injection to duplicate the pulmonary fibrosis model,while the control group was injected with

  15. Disruption of Calcium Signaling in Fibroblasts and Attenuation of Bleomycin-Induced Fibrosis by Nifedipine.

    Mukherjee, Subhendu; Ayaub, Ehab A; Murphy, James; Lu, Chao; Kolb, Martin; Ask, Kjetil; Janssen, Luke J


    Fibrotic lung disease afflicts millions of people; the central problem is progressive lung destruction and remodeling. We have shown that external growth factors regulate fibroblast function not only through canonical signaling pathways but also through propagation of periodic oscillations in Ca(2+). In this study, we characterized the pharmacological sensitivity of the Ca(2+)oscillations and determined whether a blocker of those oscillations can prevent the progression of fibrosis in vivo. We found Ca(2+) oscillations evoked by exogenously applied transforming growth factor β in normal human fibroblasts were substantially reduced by 1 μM nifedipine or 1 μM verapamil (both L-type blockers), by 2.7 μM mibefradil (a mixed L-/T-type blocker), by 40 μM NiCl2 (selective at this concentration against T-type current), by 30 mM KCl (which partially depolarizes the membrane and thereby fully inactivates T-type current but leaves L-type current intact), or by 1 mM NiCl2 (blocks both L- and T-type currents). In our in vivo study in mice, nifedipine prevented bleomycin-induced fibrotic changes (increased lung stiffness, overexpression of smooth muscle actin, increased extracellular matrix deposition, and increased soluble collagen and hydroxyproline content). Nifedipine had little or no effect on lung inflammation, suggesting its protective effect on lung fibrosis was not due to an antiinflammatory effect but rather was due to altering the profibrotic response to bleomycin. Collectively, these data show that nifedipine disrupts Ca(2+) oscillations in fibroblasts and prevents the impairment of lung function in the bleomycin model of pulmonary fibrosis. Our results provide compelling proof-of-principle that interfering with Ca(2+) signaling may be beneficial against pulmonary fibrosis.

  16. Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.

    Quintyne, Keith Ian


    The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

  17. Prolonged Drainage and Intrapericardial Bleomycin Administration for Cardiac Tamponade Secondary to Cancer-Related Pericardial Effusion.

    Numico, Gianmauro; Cristofano, Antonella; Occelli, Marcella; Sicuro, Marco; Mozzicafreddo, Alessandro; Fea, Elena; Colantonio, Ida; Merlano, Marco; Piovano, Pierluigi; Silvestris, Nicola


    Malignant pericardial effusion (MPE) is a serious complication of several cancers. The most commonly involved solid tumors are lung and breast cancer. MPE can give rise to the clinical picture of cardiac tamponade, a life threatening condition that needs immediate drainage. While simple pericardiocentesis allows resolution of the symptoms, MPE frequently relapses unless further procedures are performed. Prolonged drainage, talcage with antineoplastic agents, or surgical creation of a pleuro-pericardial window are the most commonly suggested ones. They all result in MPE resolution and high rates of long-term control. Patients suitable for further systemic treatments can have a good prognosis irrespective of the pericardial site of disease. We prospectively enrolled patients with cardiac tamponade treated with prolonged drainage associated with Bleomycin administration. Twenty-two consecutive patients with MPE and associated signs of hemodynamical compromise underwent prolonged drainage and subsequent Bleomycin administration. After injection of 100 mg lidocaine hydrochloride, 10 mg Bleomycin was injected into the pericardial space. The catheter was clumped for 48 h and then reopened. Removal was performed when the drainage volume was <25 mL daily. Twelve patients (54%) achieved complete response and 9 (41%) a partial response. Only 1 (5%) had a treatment failure and underwent a successful surgical procedure. Acute toxicity was of a low degree and occurred in 7 patients (32%). It consisted mainly in thoracic pain and supraventricular arrhythmia. The 1-year pericardial effusion progression-free survival rate was 74.0% (95% confidence interval [CI]: 51.0-97.3). At a median follow-up of 75 months, a pericardial progression was detected in 4 patients (18%). One- and two-year overall survival rates were 33.9% (95% CI: 13.6-54.2) and 14.5% (95% CI: 0.0-29.5), respectively, with lung cancer patients having a shorter survival than breast cancer patients. The worst

  18. Phylogenomic analyses of nuclear genes reveal the evolutionary relationships within the BEP clade and the evidence of positive selection in Poaceae.

    Zhao, Lei; Zhang, Ning; Ma, Peng-Fei; Liu, Qi; Li, De-Zhu; Guo, Zhen-Hua


    BEP clade of the grass family (Poaceae) is composed of three subfamilies, i.e. Bambusoideae, Ehrhartoideae, and Pooideae. Controversies on the phylogenetic relationships among three subfamilies still persist in spite of great efforts. However, previous evidence was mainly provided from plastid genes with only a few nuclear genes utilized. Given different evolutionary histories recorded by plastid and nuclear genes, it is indispensable to uncover their relationships based on nuclear genes. Here, eleven species with whole-sequenced genome and six species with transcriptomic data were included in this study. A total of 121 one-to-one orthologous groups (OGs) were identified and phylogenetic trees were reconstructed by different tree-building methods. Genes which might have undergone positive selection and played important roles in adaptive evolution were also investigated from 314 and 173 one-to-one OGs in two bamboo species and 14 grass species, respectively. Our results support the ((B, P) E) topology with high supporting values. Besides, our findings also indicate that 24 and nine orthologs with statistically significant evidence of positive selection are mainly involved in abiotic and biotic stress response, reproduction and development, plant metabolism and enzyme etc. from two bamboo species and 14 grass species, respectively. In summary, this study demonstrates the power of phylogenomic approach to shed lights on the evolutionary relationships within the BEP clade, and offers valuable insights into adaptive evolution of the grass family.

  19. Phylogenomic analyses of nuclear genes reveal the evolutionary relationships within the BEP clade and the evidence of positive selection in Poaceae.

    Lei Zhao

    Full Text Available BEP clade of the grass family (Poaceae is composed of three subfamilies, i.e. Bambusoideae, Ehrhartoideae, and Pooideae. Controversies on the phylogenetic relationships among three subfamilies still persist in spite of great efforts. However, previous evidence was mainly provided from plastid genes with only a few nuclear genes utilized. Given different evolutionary histories recorded by plastid and nuclear genes, it is indispensable to uncover their relationships based on nuclear genes. Here, eleven species with whole-sequenced genome and six species with transcriptomic data were included in this study. A total of 121 one-to-one orthologous groups (OGs were identified and phylogenetic trees were reconstructed by different tree-building methods. Genes which might have undergone positive selection and played important roles in adaptive evolution were also investigated from 314 and 173 one-to-one OGs in two bamboo species and 14 grass species, respectively. Our results support the ((B, P E topology with high supporting values. Besides, our findings also indicate that 24 and nine orthologs with statistically significant evidence of positive selection are mainly involved in abiotic and biotic stress response, reproduction and development, plant metabolism and enzyme etc. from two bamboo species and 14 grass species, respectively. In summary, this study demonstrates the power of phylogenomic approach to shed lights on the evolutionary relationships within the BEP clade, and offers valuable insights into adaptive evolution of the grass family.

  20. A spatially explicit hydro-ecological modeling framework (BEPS-TerrainLab V2.0): Model description and test in a boreal ecosystem in Eastern North America

    Govind, Ajit; Chen, Jing Ming; Margolis, Hank; Ju, Weimin; Sonnentag, Oliver; Giasson, Marc-André


    SummaryA spatially explicit, process-based hydro-ecological model, BEPS-TerrainLab V2.0, was developed to improve the representation of ecophysiological, hydro-ecological and biogeochemical processes of boreal ecosystems in a tightly coupled manner. Several processes unique to boreal ecosystems were implemented including the sub-surface lateral water fluxes, stratification of vegetation into distinct layers for explicit ecophysiological representation, inclusion of novel spatial upscaling strategies and biogeochemical processes. To account for preferential water fluxes common in humid boreal ecosystems, a novel scheme was introduced based on laboratory analyses. Leaf-scale ecophysiological processes were upscaled to canopy-scale by explicitly considering leaf physiological conditions as affected by light and water stress. The modified model was tested with 2 years of continuous measurements taken at the Eastern Old Black Spruce Site of the Fluxnet-Canada Research Network located in a humid boreal watershed in eastern Canada. Comparison of the simulated and measured ET, water-table depth (WTD), volumetric soil water content (VSWC) and gross primary productivity (GPP) revealed that BEPS-TerrainLab V2.0 simulates hydro-ecological processes with reasonable accuracy. The model was able to explain 83% of the ET, 92% of the GPP variability and 72% of the WTD dynamics. The model suggests that in humid ecosystems such as eastern North American boreal watersheds, topographically driven sub-surface baseflow is the main mechanism of soil water partitioning which significantly affects the local-scale hydrological conditions.

  1. Serum bleomycin-detectable iron in patients with thalassemia major with normal range of serum iron.

    Han,Khin Ei


    Full Text Available "Free" iron, a potentially radical-generating low mass iron, and not found in normal human blood, was increased in the serum of blood-transfused thalassemia major patients seen in the Yangon General Hospital, Yangon, Myanmar (Burma. The low mass iron was detected by the bleomycin assay. Fifty-one blood samples were analyzed (from 28 males and 23 females. High "free" iron was detected in 47 sera samples from thalassemia patients. Serum ferritin, which reflects the body store iron, was higher than the normal range (10-200 ng/ml in 49 patients. On the other hand, serum iron of 39 sera samples fell within the normal range (50-150 micrograms/dl. Four were less than 50 micrograms/dl and eight were more than 150 micrograms/dl. Almost all the patients' sera of normal or higher serum iron level contained "free" iron. Thus, almost all the sera from thalassemic patients from Myanmar contain bleomycin-detectable iron, even when serum iron is within the normal range. In developing countries where undernutrition is prevalent (serum albumin in these patients was 3.6 +/- 0.4 g/dl, P < 0.0001 vs. control value of 4.0 - 4.8 g/dl, normal serum iron does not preclude the presence of free iron in the serum.

  2. An Escherichia coli mutant resistant to phleomycin, bleomycin, and heat inactivation is defective in ubiquinone synthesis.

    Collis, C M; Grigg, G W


    A mutant of Escherichia coli, selected for resistance to the antibiotic and antitumor agent phleomycin, has been characterized, and the phleomycin resistance determinant has been identified. The mutant is equally resistant to bleomycins. The resistance to phleomycin is strongly dependent on the nature of the C-terminal amine of the drug, with the greatest resistance being shown to phleomycins and bleomycins with the most basic terminal amines. The mutation also confers resistance to the lethal effects of heating at 52 degrees C. Other characteristics of the phleomycin-resistant strain include a slow growth rate, an inability to grow on succinate as the sole carbon source (Suc- phenotype), cross resistance to aminoglycoside antibiotics, and a slight sensitivity to hydrogen peroxide, methyl methanesulfonate, and gamma-irradiation. Some of these characteristics, together with mapping data, suggested that the phleomycin resistance and Suc- determinant probably lies within the ubiF gene coding for an enzyme effecting a step in the biosynthesis of ubiquinone. The phenotypes of known mutants defective in this and other steps of the ubiquinone pathway were found to be closely similar to those of the original phleomycin-resistant strain. PMID:2475481

  3. Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice.

    Brewer, George J; Ullenbruch, Matthew R; Dick, Robert; Olivarez, Leovigildo; Phan, Sem H


    Tetrathiomolybdate (TM), a drug developed for the treatment of Wilson's disease, produces an antiangiogenic effect by reducing systemic copper levels. Several angiogenic cytokines appear to depend on normal levels of copper for activity. In both animal tumor models and in cancer patients, TM therapy has proved effective in inhibiting the growth of tumors. We have hypothesized that the activities of fibrotic and inflammatory cytokines are also subject to modulation by the availability of copper in a manner similar to angiogenic cytokines. As a first step in evaluating whether TM plays a therapeutic role in diseases of inflammation and fibrosis, we studied the effects of TM on a murine model of bleomycin-induced pulmonary fibrosis. Oral TM therapy resulted in dose-dependent reduction in serum ceruloplasmin, a surrogate marker of systemic copper levels. Significant decreases in systemic copper levels were associated with marked reduction in lung fibrosis as determined on the basis of histopathologic findings and a biochemical measure of fibrosis. The protection afforded by TM was also reflected in significantly reduced bleomycin-induced body-weight loss. In the next phase of this work, we will seek to determine the mechanisms by which TM brings about this therapeutic benefit.

  4. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

    Citro Gennaro


    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  5. The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induced fibrosis.

    Abdulaleem Alnajar

    Full Text Available Fibrogenesis is usually initiated when regenerative processes have failed and/or chronic inflammation occurs. It is characterised by the activation of tissue fibroblasts and dysregulated synthesis of extracellular matrix proteins. FHL2 (four-and-a-half LIM domain protein 2 is a scaffolding protein that interacts with numerous cellular proteins, regulating signalling cascades and gene transcription. It is involved in tissue remodelling and tumour progression. Recent data suggest that FHL2 might support fibrogenesis by maintaining the transcriptional expression of alpha smooth muscle actin and the excessive synthesis and assembly of matrix proteins in activated fibroblasts. Here, we present evidence that FHL2 does not promote bleomycin-induced lung fibrosis, but rather suppresses this process by attenuating lung inflammation. Loss of FHL2 results in increased expression of the pro-inflammatory matrix protein tenascin C and downregulation of the macrophage activating C-type lectin receptor DC-SIGN. Consequently, FHL2 knockout mice developed a severe and long-lasting lung pathology following bleomycin administration due to enhanced expression of tenascin C and impaired activation of inflammation-resolving macrophages.

  6. Enhancement of antioxidant defense system by epigallocatechin-3-gallate during bleomycin induced experimental pulmonary fibrosis.

    Sriram, Narayanan; Kalayarasan, Srinivasan; Sudhandiran, Ganapasam


    Oxidative stress resulting from an imbalance between radical-generating and radical scavenging systems plays an important role in the pathogenesis of pulmonary fibrosis. Epigallocatechin-3-gallate (EGCG), a polyphenol and a major component of green tea, possess a potent antioxidant property. This study was designed to evaluate the potential antioxidative activity of EGCG in the plasma and lungs during bleomycin induced experimental pulmonary fibrosis. Intratracheal administration of bleomycin (6.5 U/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Elevations in lung W/D (wet weight/dry weight) ratio, hydroxyproline content was observed with a synchronized increase in lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides). Intraperitoneal administration of EGCG at a dose of 20 mg/kg body weight significantly improved the body weight, enzymic and non enzymic antioxidants and considerably decreased the W/D ratio, hydroxyproline and lipid peroxidation marker levels. Histological observations also correlated with the biochemical parameters. Thus, this study confirms the beneficial use of EGCG in alleviating the oxidative stress induced during pulmonary fibrosis.

  7. Chemical activity of anticancer compounds : computational studies on the mechanism of bleomycin and the recognition of flavonoids

    Karawajczyk, Anna


    The thesis is focused on the DNA-cleaving antibiotic bleomycin that is successfully used in the chemotherapy against several types of cancer like head and neck cancer or certain lymphomas and testicular cancer. Although it has been in use for more than two decades, the mechanism of its action is not

  8. Interactions of radiation and adriamycin, bleomycin, mitomycin C or cis-diamminedichloroplatinum II in intestinal crypt cells

    von der Maase, H


    The interactions of radiation and adriamycin (ADM), bleomycin (BLM), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) in mouse jejunal crypt cells were studied using the microcolony survival assay. ADM administered from 24 h before to 48 h after irradiation resulted in an almost...

  9. A protective role for IL-13 receptor α 1 in bleomycin-induced pulmonary injury and repair.

    Karo-Atar, D; Bordowitz, A; Wand, O; Pasmanik-Chor, M; Fernandez, I E; Itan, M; Frenkel, R; Herbert, D R; Finkelman, F D; Eickelberg, O; Munitz, A


    Molecular mechanisms that regulate lung repair vs. progressive scarring in pulmonary fibrosis remain elusive. Interleukin (IL)-4 and IL-13 are pro-fibrotic cytokines that share common receptor chains including IL-13 receptor (R) α1 and are key pharmacological targets in fibrotic diseases. However, the roles of IL-13Rα1 in mediating lung injury/repair are unclear. We report dysregulated levels of IL-13 receptors in the lungs of bleomycin-treated mice and to some extent in idiopathic pulmonary fibrosis patients. Transcriptional profiling demonstrated an epithelial cell-associated gene signature that was homeostatically dependent on IL-13Rα1 expression. IL-13Rα1 regulated a striking array of genes in the lung following bleomycin administration and Il13ra1 deficiency resulted in exacerbated bleomycin-induced disease. Increased pathology in bleomycin-treated Il13ra1(-/-) mice was due to IL-13Rα1 expression in structural and hematopoietic cells but not due to increased responsiveness to IL-17, IL-4, IL-13, increased IL-13Rα2 or type 1 IL-4R signaling. These data highlight underappreciated protective roles for IL-13Rα1 in lung injury and homeostasis.

  10. Amniotic fluid stem cells inhibit the progression of bleomycin-induced pulmonary fibrosis via CCL2 modulation in bronchoalveolar lavage.

    Orquidea Garcia

    Full Text Available The potential for amniotic fluid stem cell (AFSC treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF, is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0 or chronic (day 14 intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL, but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events.

  11. The anti-tumor drug bleomycin preferentially cleaves at the transcription start sites of actively transcribed genes in human cells.

    Murray, Vincent; Chen, Jon K; Galea, Anne M


    The genome-wide pattern of DNA cleavage at transcription start sites (TSSs) for the anti-tumor drug bleomycin was examined in human HeLa cells using next-generation DNA sequencing. It was found that actively transcribed genes were preferentially cleaved compared with non-transcribed genes. The 143,600 identified human TSSs were split into non-transcribed genes (82,596) and transcribed genes (61,004) for HeLa cells. These transcribed genes were further split into quintiles of 12,201 genes comprising the top 20, 20-40, 40-60, 60-80, and 80-100 % of expressed genes. The bleomycin cleavage pattern at highly transcribed gene TSSs was greatly enhanced compared with purified DNA and non-transcribed gene TSSs. The top 20 and 20-40 % quintiles had a very similar enhanced cleavage pattern, the 40-60 % quintile was intermediate, while the 60-80 and 80-100 % quintiles were close to the non-transcribed and purified DNA profiles. The pattern of bleomycin enhanced cleavage had peaks that were approximately 200 bp apart, and this indicated that bleomycin was identifying the presence of phased nucleosomes at TSSs. Hence bleomycin can be utilized to detect chromatin structures that are present at actively transcribed genes. In this study, for the first time, the pattern of DNA damage by a clinically utilized cancer chemotherapeutic agent was performed on a human genome-wide scale at the nucleotide level.

  12. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

    Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott


    Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression.

  13. Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis.

    Habgood, Anthony N; Tatler, Amanda L; Porte, Joanne; Wahl, Sharon M; Laurent, Geoffrey J; John, Alison E; Johnson, Simon R; Jenkins, Gisli


    Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-β (TGF-β) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lung is tightly regulated by protease inhibitors, particularly secretory leukocyte protease inhibitor (SLPI). The bleomycin model of lung fibrosis was used to determine the effect of increased protease activity in the lungs of Slpi(-/-) mice following injury. Slpi(-/-), and wild-type, mice received oropharyngeal administration of bleomycin (30 IU) and the development of pulmonary fibrosis was assessed. Pro and active forms of matrix metalloproteinase (MMP)-2 and MMP-9 were measured. Lung fibrosis was determined by collagen subtype-specific gene expression, hydroxyproline concentration, and histological assessment. Alveolar TGF-β activation was measured using bronchoalveolar lavage cell pSmad2 levels and global TGF-β activity was assessed by pSmad2 immunohistochemistry. The active-MMP-9 to pro-MMP-9 ratio was significantly increased in Slpi(-/-) animals compared with wild-type animals, demonstrating enhanced metalloproteinase activity. Wild-type animals showed an increase in TGF-β activation following bleomycin, with a progressive and sustained increase in collagen type I, alpha 1 (Col1α1), III, alpha 1(Col3α1), IV, alpha 1(Col4α1) mRNA expression, and a significant increase in total lung collagen 28 days post bleomycin. In contrast Slpi(-/-) mice showed no significant increase of alveolar TGF-β activity following bleomycin, above their already elevated levels, although global TGF-β activity did increase. Slpi(-/-) mice had impaired collagen gene expression but animals demonstrated minimal reduction in lung fibrosis compared with wild-type animals. These data suggest that enhanced proteolysis does not further enhance TGF-β activation, and inhibits sustained Col1α1, Col3α1, and Col4α1 gene expression

  14. Histology protocols

    CarloAlberto Redi


    Full Text Available Tim D. Hewitson & Ian A. Darby (Eds Humana press, Totowa, New Jersey (USA Series: Springer Protocols Methods in Molecular Biology, Volume 611, 2010 Pages: 230; € 83.15 ISBN: 978-1-60327-344-2 Impressive as it can sounds in the era that Biology see a clear dominance of reductionism with the idea that complexity can be disentagled more and more thanks to the use of molecular tools, the reader will remain fascinated by this slim and agile volume devoted to bring together what apparently are two separeted words: molecular biology and histology. Simply remembering to the youngest scientists.....

  15. BlmB and TlmB provide resistance to the bleomycin family of antitumor antibiotics by N-acetylating metal-free bleomycin, tallysomycin, phleomycin, and zorbamycin.

    Coughlin, Jane M; Rudolf, Jeffrey D; Wendt-Pienkowski, Evelyn; Wang, Liyan; Unsin, Claudia; Galm, Ute; Yang, Dong; Tao, Meifeng; Shen, Ben


    The bleomycin (BLM) family of glycopeptide-derived antitumor antibiotics consists of BLMs, tallysomycins (TLMs), phleomycins (PLMs), and zorbamycin (ZBM). The self-resistant elements BlmB and TlmB, discovered from the BLM- and TLM-producing organisms Streptomyces verticillus ATCC15003 and Streptoalloteichus hindustanus E465-94 ATCC31158, respectively, are N-acetyltransferases that provide resistance to the producers by disrupting the metal-binding domain of the antibiotics required for activity. Although each member of the BLM family of antibiotics possesses a conserved metal-binding domain, the structural differences between each member, namely, the bithiazole moiety and C-terminal amine of BLMs, have been suggested to instill substrate specificity within BlmB. Here we report that BlmB and TlmB readily accept and acetylate BLMs, TLMs, PLMs, and ZBM in vitro but only in the metal-free forms. Kinetic analysis of BlmB and TlmB reveals there is no strong preference or rate enhancement for specific substrates, indicating that the structural differences between each member of the BLM family play a negligible role in substrate recognition, binding, or catalysis. Intriguingly, the zbm gene cluster from Streptomyces flavoviridis ATCC21892 does not contain an N-acetyltransferase, yet ZBM is readily acetylated by BlmB and TlmB. We subsequently established that S. flavoviridis lacks the homologue of BlmB and TlmB, and ZbmA, the ZBM-binding protein, alone is sufficient to provide ZBM resistance. We further confirmed that BlmB can indeed confer resistance to ZBM in vivo in S. flavoviridis, introduction of which into wild-type S. flavoviridis further increases the level of resistance.

  16. Nucleobase-Based Barbiturates: Their Protective Effect against DNA Damage Induced by Bleomycin-Iron, Antioxidant, and Lymphocyte Transformation Assay

    Bhaveshkumar D. Dhorajiya


    Full Text Available A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, 1H NMR, 13C NMR, HMBC, and UV spectroscopy and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3-TBA manifested the best protective effect against DNA damage induced by bleomycin.

  17. Therapeutic use of fisetin, curcumin, and mesoporous carbaon nanoparticle loaded fisetin in bleomycin-induced idiopathic pulmonary fibrosis

    Srabani Kar


    Full Text Available Idiopathic pulmonary fibrosis (IPF is a devastating disease of unknown etiology, for which there is no curative pharmacological therapy. Bleomycin, an anti-neoplastic agent that causes lung fibrosis in human patients has been used extensively in rodent models to mimic IPF. The conventional therapy has been steroids and immunosuppressive agents. But only a minority of patients responds to such a therapy. IPF is a progressive, ultimately fatal disorder for which substantive medical therapy is desperately needed. Fisetin is a flavonol which inhibits the activity of several pro-inflammatory cytokines. The polyphenol curcumin is used to treat inflammatory diseases, abdominal disorders, and a variety of other ailments. The aim of this study was to evaluate the beneficial effect of fistine, curcumin and mesoporous carbaon nanoparticle (MCN loaded fisetin as an anti-inflammatory agents against bleomycin-induced changes in mice with IPF. In our study, flavonoids showed their anti fibrotic action. The inflammatory cell count was greatly increased for bleo treated individuals and effectiveness of fisein was increased after addition of MCN particles with it, curcumin also showed anti- inflammatory effects. In another experiment, bleomycin effectively inhibits the cellular recruitment to the spleen and treatment with fisetin, and curcumin increases the cellular recruitment in spleen. Colony count was also increased in MCN+fisetin treated groups, and it was statistically significant. We also observed the increased level of cytokines with fisetin treatment, with curcumin treatment and with MCN +fisetin treatment as compared to the bleo treated sample. In conclusion, the present research suggests that fisetin and curcumin and MCN loaded fisetin may be a promising therapeutic agent for bleomycin-induced changes in mice with IPF. This will open up new perspectives for a potential role of these drugs as a molecular target in Idiopathic pulmonary fibrosis. [Biomed

  18. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille;


    electroporation and electrochemotherapy. METHODS: The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore...... survival at similar applied voltage parameters. The effect of calcium electroporation is independent of calcium compound. GENERAL SIGNIFICANCE: This study strongly supports the use of calcium electroporation as a potential cancer therapy and the results may aid in future clinical trials....

  19. Effects of Spaceflight on Molecular and Cellular Responses to Bleomycin-Induced DNA Damages in Confluent Human Fibroblasts

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu


    Spaceflights expose human beings to various risk factors. Among them are microgravity related physiological stresses in immune, cytoskeletal, and cardiovascular systems, and space radiation related elevation of cancer risk. Cosmic radiation consists of energetic protons and other heavier charged particles that induce DNA damages. Effective DNA damage response and repair mechanism is important to maintain genomic integrity and reduce cancer risk. There were studies on effects of spaceflight and microgravity on DNA damage response in cell and animal models, but the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on molecular and cellular responses to DNA damages, bleomycin, an anti-cancer drug and radiomimetic reagent, was used to induce DNA damages in confluent human fibroblasts flown to the International Space Station (ISS) and on ground. After exposure to 1.0 µg/ml bleomycin for 3 hours, cells were fixed for immunofluorescence assays and for RNA preparation. Extents of DNA damages were quantified by foci and pattern counting of phosphorylated histone protein H2AX (?-H2AX). The cells on the ISS showed modestly increased average foci counts per nucleus while the distribution of patterns was similar to that on the ground. PCR array analysis showed that expressions of several genes, including CDKN1A and PCNA, were significantly changed in response to DNA damages induced by bleomycin in both flight and ground control cells. However, there were no significant differences in the overall expression profile of DNA damage response genes between the flight and ground samples. Analysis of cellular proliferation status with Ki-67 staining showed a slightly higher proliferating population in cells on the ISS than those on ground. Our results suggested that the difference in ?-H2AX focus counts between flight and ground was due to the higher percentage of proliferating cells in space, but spaceflight did not significantly affect

  20. Spironolactone attenuates bleomycin-induced pulmonary injury partially via modulating mononuclear phagocyte phenotype switching in circulating and alveolar compartments.

    Wen-Jie Ji

    Full Text Available BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20 mg/kg/day by oral gavage revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson' trichrome staining in bleomycin treated (2.5 mg/kg, via oropharyngeal instillation male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+ of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c- remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.

  1. Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores

    Jin, Gong Yong; Bok, Se Mi; Han, Young Min [Department of Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Chung, Myung Ja [Department of Pathology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Yoon, Kwon-Ha [Department of Radiology, Iksan Hospital, Iksan (Korea, Republic of); Kim, So Ri [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Yong Chul, E-mail: [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of)


    Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR{gamma} agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

  2. Resonance Rayleigh scattering study of the interaction of bleomycinA5 with nucleic acids and its analytical application

    LIU; JiangTao; LIU; ZhongFang; LIU; ShaoPu


    The interaction of bleomycinA5 with nucleic acids has been investigated by using resonance Rayleigh scattering (RRS), molecular absorption and fluorescence spectra. The result shows that in near pH 2.2 buffer medium and absence of any metal ions, nucleic acids are capable of binding with bleomycinA5 (BLMA5) to form complexes which can remarkably enhance the RRS intensity and result in bathochromic and hyperchromic molecular absorption of nucleic acids and fluorescence quenching of bleomycinA5. The RRS spectral characteristics for the binding products of bleomycinA5 with various DNA and RNA are similar, and the maximum RRS peaks are at 301 nm for ctDNA and sDNA, 370 nm for hsDNA, 310 nm for RNAtypeVI and RNAtypeIII, respectively. The increments of RRS intensity are greatly different in which DNA enhances greatly and RNA enhances lightly. In this work, the optimum conditions of the interaction and some influencing factors have been investigated. The reaction mechanism and a binding model for the interaction of BLMA5 with the nucleic acids are discussed. In addition, a highly sensitive, simple and rapid new method for the determination of DNA has been developed. The detection limits (3σ) are 5.7 ng/mL for ctDNA, 7.4 ng/mL for sDNA and 9.2 ng/mL for hsDNA, respectively. The method can be applied to determination of trace amounts of DNA.

  3. Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro.

    Sailaja Polavarapu

    Full Text Available In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs tested on human neuroblastoma IMR-32 (0.5 × 10(4 cells/100 µl of IMR cells (EPA > DHA > ALA = GLA = AA > DGLA = LA: ∼ 60, 40, 30, 10-20% respectively at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2 and leukotrienes (LTD4 and LTE4 tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4, 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA and 10(S,17(S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S,17(SDiHDoHE, metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.

  4. Changes of global terrestrial carbon budget and major drivers in recent 30 years simulated using the remote sensing driven BEPS model

    Ju, W.; Chen, J.; Liu, R.; Liu, Y.


    The process-based Boreal Ecosystem Productivity Simulator (BEPS) model was employed in conjunction with spatially distributed leaf area index (LAI), land cover, soil, and climate data to simulate the carbon budget of global terrestrial ecosystems during the period from 1981 to 2008. The BEPS model was first calibrated and validated using gross primary productivity (GPP), net primary productivity (NPP), and net ecosystem productivity (NEP) measured in different ecosystems across the word. Then, four global simulations were conducted at daily time steps and a spatial resolution of 8 km to quantify the global terrestrial carbon budget and to identify the relative contributions of changes in climate, atmospheric CO2 concentration, and LAI to the global terrestrial carbon sink. The long term LAI data used to drive the model was generated through fusing Moderate Resolution Imaging Spectroradiometer (MODIS) and historical Advanced Very High Resolution Radiometer (AVHRR) data pixel by pixel. The meteorological fields were interpolated from the 0.5° global daily meteorological dataset produced by the land surface hydrological research group at Princeton University. The results show that the BEPS model was able to simulate carbon fluxes in different ecosystems. Simulated GPP, NPP, and NEP values and their temporal trends exhibited distinguishable spatial patterns. During the period from 1981 to 2008, global terrestrial ecosystems acted as a carbon sink. The averaged global totals of GPP NPP, and NEP were 122.70 Pg C yr-1, 56.89 Pg C yr-1, and 2.76 Pg C yr-1, respectively. The global totals of GPP and NPP increased greatly, at rates of 0.43 Pg C yr-2 (R2=0.728) and 0.26 Pg C yr-2 (R2=0.709), respectively. Global total NEP did not show an apparent increasing trend (R2= 0.036), averaged 2.26 Pg C yr-1, 3.21 Pg C yr-1, and 2.72 Pg C yr-1 for the periods from 1981 to 1989, from 1990 to 1999, and from 2000 to 2008, respectively. The magnitude and temporal trend of global

  5. Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10.

    Emilio García-Prieto

    Full Text Available BACKGROUND: Matrix metalloproteinases (MMPs may have pro and antifibrotic roles within the lungs, due to its ability to modulate collagen turnover and immune mediators. MMP-8 is a collagenase that also cleaves a number of cytokines and chemokines. METHODOLOGY AND PRINCIPAL FINDINGS: To evaluate its relevance in lung fibrosis, wildtype and Mmp8(-/- mice were treated with either intratracheal bleomycin or saline, and lungs were harvested at different time points. Fibrosis, collagen, collagenases, gelatinases, TGFβ and IL-10 were measured in lung tissue. Mmp8(-/- mice developed less fibrosis than their wildtype counterparts. This was related to an increase in lung inflammatory cells, MMP-9 and IL-10 levels in these mutant animals. In vitro experiments showed that MMP-8 cleaves murine and human IL-10, and tissue from knockout animals showed decreased IL-10 processing. Additionally, lung fibroblasts from these mice were cultured in the presence of bleomycin and collagen, IL-10 and STAT3 activation (downstream signal in response to IL-10 measured by western blotting. In cell cultures, bleomycin increased collagen synthesis only in wildtype mice. Fibroblasts from knockout mice did not show increased collagen synthesis, but increased levels of unprocessed IL-10 and STAT3 phosphorylation. Blockade of IL-10 reverted this phenotype, increasing collagen in cultures. CONCLUSIONS: According to these results, we conclude that the absence of MMP-8 has an antifibrotic effect by increasing IL-10 and propose that this metalloprotease could be a relevant modulator of IL-10 metabolism in vivo.

  6. Comparison of therapeutic response of keloids and hypertrophic scars to cryotherapy plus intralesional steroid and bleomycin tattoo

    Farahnaz Fatemi


    Full Text Available Keloids and hypertrophic scars are abnormal responses of body to skin injuries. Overproduction of compacted fibrous tissue is the basic cause of these lesions. In this study the result of treatment of these skin conditions with bleomycin tattoo are compared with cryotherapy and triamcinolone injection. This study involved 45 patients with hypertrophic scar or keloid. Patients were divided into two groups consecutively. Group A (23 patients was treated with bleomycin tattoo and the group B with cryotherapy and triamcinolone injection. There were four therapeutic sessions one month apart. All patients were followedup for three month after the end of treatment .The therapeutic response was determined as reduction of lesion size or flattening relative to initial size. Therapeutic response was 88.3±14% in group A and 67.4 ±22.5% in group B (p<0.001. In group A 69%, but in group B only 49% of patients were asymptomatic after the end of treatment. In group A there was no relation between therapeutic response and lesion size (p=0.58 but in group B lesions those were smaller (<100mm2 had better therapeutic response than larger ones (p=0.007. It was concluded that bleomycin tattoo is more effective in treatment of hypertrophic scar and keloid than traditional treatment, cryotherapy plus triamcinolone injection especially in larger ones.

  7. Serial micro-CT assessment of the therapeutic effects of rosiglitazone in a bleomycin-induced lung fibrosis mouse model

    Choi, Eun Jung; Jin, Gong Yong; Bok, Se Mi; Han, Young Min; Lee, Young Sun; Jung, Myung Ja; Kwon, Keun Sang [Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Institute for Medical Sciences, Jeonju (Korea, Republic of)


    The aim of this study was to assess the therapeutic effects of rosiglitazone with serial micro-CT findings before and after rosiglitazone administration in a lung fibrosis mouse model induced with bleomycin. We instilled the bleomycin solution directly into the trachea in twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice were closely observed for 3 weeks and then all mice were scanned using micro-CT without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days 21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the rosiglitazone treatment completion. We assessed the abnormal CT findings (ground glass attenuation, consolidation, bronchiectasis, reticular opacity, and honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed ranked test. The micro-CT findings were correlated with the histopathologic results. One out of nine (11.1%) mice improved completely. In terms of consolidation, all mice (100%) showed marked decrease from 3.1 ± 1.4 at 3 weeks to 0.9 ± 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6, 66.7%), mild reticular opacity (n 7, 77.8%) and mild honeycomb patterns (n = 3, 33.3%) appeared. A serial micro-CT enables the evaluation of drug effects in a lung fibrosis mouse model.

  8. Bleomycin induced sensitivity to TRAIL/Apo-2L-mediated apoptosis in human seminomatous testicular cancer cells is correlated with upregulation of death receptors.

    Timur, Mujgan; Cort, Aysegul; Ozdemir, Evrim; Sarikcioglu, Sureyya Bilmen; Sanlioglu, Salih; Sanlioglu, Ahter Dilsad; Ozben, Tomris


    The most common solid tumor is testicular cancer among young men. Bleomycin is an antitumor antibiotic used for the therapy of testicular cancer. TRAIL is a proapoptotic cytokine that qualified as an apoptosis inducer in cancer cells. Killing cancer cells selectively via apoptosis induction is an encouraging therapeutic strategy in clinical settings. Combination of TRAIL with chemotherapeutics has been reported to enhance TRAIL-mediated apoptosis of different kinds of cancer cell lines. The molecular ground for sensitization of tumour cells to TRAIL by chemotherapeutics might involve upregulation of TRAIL-R1 (TR/1, DR4) and/or TRAIL-R2 (TR/2, DR5) receptors or activation of proapoptotic proteins including caspases. The curative potential of TRAIL to eradicate cancer cells selectively in testicular cancer has not been studied before. In this study, we investigated apoptotic effects of bleomycin, TRAIL, and their combined application in NTera-2 and NCCIT testicular cancer cell lines. We measured caspase 3 levels as an apoptosis indicator, and TRAIL receptor expressions using flow cytometry. Both NTera-2 and NCCIT cells were fairly resistant to TRAIL's apoptotic effect. Incubation of bleomycin alone caused a significant increase in caspase 3 activity in NCCIT. Combined incubation with bleomycin and TRAIL lead to elevated caspase 3 activity in Ntera-2. Exposure to 72 h of bleomycin increased TR/1, TR/2, and TR/3 cell-surface expressions in NTera-2. Elevation in TR/1 cell-surface expression was evident only at 24 h of bleomycin application in NCCIT. It can be concluded that TRAIL death receptor expressions in particular are increased in testicular cancer cells via bleomycin treatment, and TRAIL-induced apoptosis is initiated.

  9. The triterpenoid CDDO-Me inhibits bleomycin-induced lung inflammation and fibrosis.

    Ajit A Kulkarni

    Full Text Available Pulmonary Fibrosis (PF is a devastating progressive disease in which normal lung structure and function is compromised by scarring. Lung fibrosis can be caused by thoracic radiation, injury from chemotherapy and systemic diseases such as rheumatoid arthritis that involve inflammatory responses. CDDO-Me (Methyl 2-cyano-3,12-dioxooleana-1,9(11dien-28-oate, Bardoxolone methyl is a novel triterpenoid with anti-fibrotic and anti-inflammatory properties as shown by our in vitro studies. Based on this evidence, we hypothesized that CDDO-Me would reduce lung inflammation, fibrosis and lung function impairment in a bleomycin model of lung injury and fibrosis. To test this hypothesis, mice received bleomycin via oropharyngeal aspiration (OA on day zero and CDDO-Me during the inflammatory phase from days -1 to 9 every other day. Bronchoalveolar lavage fluid (BALF and lung tissue were harvested on day 7 to evaluate inflammation, while fibrosis and lung function were evaluated on day 21. On day 7, CDDO-Me reduced total BALF protein by 50%, alveolar macrophage infiltration by 40%, neutrophil infiltration by 90% (p≤0.01, inhibited production of the inflammatory cytokines KC and IL-6 by over 90% (p≤0.001, and excess production of the pro-fibrotic cytokine TGFβ by 50%. CDDO-Me also inhibited α-smooth muscle actin and fibronectin mRNA by 50% (p≤0.05. On day 21, CDDO-Me treatment reduced histological fibrosis, collagen deposition and αSMA production. Lung function was significantly improved at day 21 by treatment with CDDO-Me, as demonstrated by respiratory rate and dynamic compliance. These new findings reveal that CDDO-Me exhibits potent anti-fibrotic and anti-inflammatory properties in vivo. CDDO-Me is a potential new class of drugs to arrest inflammation and ameliorate fibrosis in patients who are predisposed to lung injury and fibrosis incited by cancer treatments (e.g. chemotherapy and radiation and by systemic autoimmune diseases.

  10. Brucella ovis PA mutants for outer membrane proteins Omp10, Omp19, SP41, and BepC are not altered in their virulence and outer membrane properties.

    Sidhu-Muñoz, Rebeca S; Sancho, Pilar; Vizcaíno, Nieves


    Mutants in several genes have been obtained on the genetic background of virulent rough (lacking O-polysaccharide) Brucella ovis PA. The target genes encode outer membrane proteins previously associated with the virulence of smooth (bearing O-polysaccharide chains in the lipopolysaccharide) Brucella strains. Multiple attempts to delete omp16, coding for a homologue to peptidoglycan-associated lipoproteins, were unsuccessful, which suggests that Omp16 is probably essential for in vitro survival of B. ovis PA. Single deletion of omp10 or omp19-that encode two other outer membrane lipoproteins--was achieved, but the simultaneous removal of both genes failed, suggesting an essential complementary function between both proteins. Two other deletion mutants, defective in the Tol-C-homologue BepC or in the SP41 adhesin, were also obtained. Surprisingly when compared to previous results obtained with smooth Brucella, none of the B. ovis mutants showed attenuation in the virulence, either in the mouse model or in cellular models of professional and non-professional phagocytes. Additionally, and in contrast to the observations reported with smooth Brucella strains, several properties related to the outer membrane remained almost unaltered. These results evidence new distinctive traits between naturally rough B. ovis and smooth brucellae.

  11. [Effects of erdosteine on inflammation and fibrosis in rats with pulmonary fibrosis induced by bleomycin].

    Erden, Ersin Sükrü; Kirkil, Gamze; Deveci, Figen; Ilhan, Nevin; Cobanoğlu, Bengü; Turgut, Teyfik; Muz, Mehmet Hamdi


    We aimed to investigate the levels of some chemokines, inflammatory cell counts in bronchoalveolar lavage (BAL) fluid, histopathological changes in lung tissue, to determine the effect of erdosteine on acute inflammatory changes and fibrosis in a rat fibrosis model induced by bleomycine (BLM). Forty-five Wistar male rats were taken into the study. On day 0, intratracheal saline to control group (group 1, n= 15), intratracheal BLM 7.5 U/kg to BLM (group 2, n= 15) and erdosteine group (group 3, n= 15) was administered. In group 3, oral erdosteine (10 mg/kg/day) was applied two days before BLM. On day 0, 14, and 29th five rats in each groups were sacrificed, BAL fluid was performed. Malonyldialdehyde (MDA), macrophage inflammatory protein (MIP)-1alpha, MIP-2 levels in BAL fluid, hydroxyproline levels in lung tissue were measured. Histopathological examination was performed. When BLM group compared to erdosteine group, the levels of MDA, MIP-1alpha, MIP-2, and neutrophil counts, the hydroxyproline (OH-P) level of lung tissue were decreased in erdosteine group on acute inflammatory phase (day 14) (perdosteine group than BLM group on day 29 (p= 0.01). We conclude that erdosteine may prevent the acute lung inflammation and fibrosis by suppressing the accumulation of neutrophils, inhibition of lipid peroxydation, chemokine production, and release.

  12. Paracetamol Supplementation Does Not Alter The Antitumor Activity and Lung Toxicity of Bleomycin

    Ghada M. Suddek


    Full Text Available Bleomycin (BLM is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Hyperpyrexia following injection of BLM was reported thus, paracetamol is sometimes administered with BLM as antipyretic drug. Actually, paracetamol was found to interfere with cytotoxicity of some drugs. This study was conducted to investigate the effect of paracetamol administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma (EAC cells. Paracetamol did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-hydroxytryptamine (5-HT and increase in the contractility of tracheal smooth muscles induced by acetylcholine (ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in reduced glutathione (GSH level. Pretreatment with paracetamol did not significantly change lipid peroxidation, GSH level, percent survival of rats or the response of pulmonary arterial rings and tracheal smooth muscles to 5-HT and ACh respectively. The results of the present study indicated that paracetamol neither modified the antitumor effect of BLM nor changed drug-induced lung toxicity.

  13. Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice.

    Shi, Keyun; Jiang, Jianzhong; Ma, Tieliang; Xie, Jing; Duan, Lirong; Chen, Ruhua; Song, Ping; Yu, Zhixin; Liu, Chao; Zhu, Qin; Zheng, Jinxu


    Our objective was to investigate the pathogenesis pathways of idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) induced animal models of experimental lung fibrosis were used. CHIP assay was executed to find the link between Smad3 and IL-31, and the expressions of TGF-β1, Smad3, IL-31 and STAT1 were detected to find whether they were similar with each other. We found that in the early injury or inflammation of the animal model, BLM promoted the development of inflammation, leading to severe pulmonary fibrosis. Then the expression of TGF-β1 and Smad3 increased. Activated Smad3 bound to the IL-31 promoter region, followed by the activation of JAK-STAT pathways. The inhibitor of TGF-β1 receptor decreased the IL-31 expression and knocking-down of IL-31 also decreased the STAT1 expression. We conclude that there is a pathway of pathogenesis in BLM-induced mouse model that involves the TGF-β, IL-31 and JAKs/STATs pathway.

  14. Evaluating the Ameliorative Potential of Quercetin against the Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats

    Ramesh Verma


    Full Text Available The current study deals with the effect of a dietary flavanoid quercetin on fibrotic lung tissue in rats. Bleomycin was administered by single intratracheal instillation to Wistar rats to induce lung fibrosis. The pathologies associated with this included significantly reduced antioxidant capacity, ultimately leading to protracted inflammation of the lung tissue. The hallmark of this induced fibrosis condition was an excessive collagen deposition in peribronchial and perialveolar regions of the lung. Oral quercetin treatment over a period of twenty days resulted in significant reversal of the pathologies. The antioxidant defense in lung tissue was revived. Moreover, activity of the collagenase MMP-7, which was high in fibrotic tissue, was seen restored after quercetin administration. Trichome staining of lung tissue sections showed high collagen deposition in fibrotic rats, which may be a direct result of increased mobilization of collagen by MMP-7. This was appreciably reduced in quercetin treated animals. These results point towards an important protective role of quercetin against idiopathic lung fibrosis, which remains a widely prevalent yet incurable condition in the present times.

  15. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

    Yoon Hee Cho


    Full Text Available Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM, a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL, the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

  16. Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs.

    Reed, S D; Fulmer, A; Buckholz, J; Zhang, B; Cutrera, J; Shiomitsu, K; Li, S


    On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform, was associated with repair of bone lysis in cured dogs, improved quality of life for dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

  17. Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes

    Benkhaled, L.; Xuncla, M.; Caballin, M.R. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain); Barrios, L. [Universitat Autonoma de Barcelona, Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia (Spain); Barquinero, J.F. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain)], E-mail:


    Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation ({approx}0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.

  18. Role of thioredoxin nitration in bleomycin-induced pulmonary fibrosis in rats.

    Wang, Lei; Song, Yimin; Li, Xiankui; Guo, Haizhou; Zhang, Guojun


    Oxidant stimulation has been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our study aimed to investigate the role and mechanisms of thioredoxin (Trx) nitration during the development of IPF. A rat model of IPF was established by intratracheal instillation of bleomycin (BLM). Male Wistar rats were randomly distributed among the control group and BLM-treated group, in which rats were intratracheally instilled with a single dose of BLM (5.0 mg/kg body mass in 1.0 mL phosphate-buffered saline). At 7 or 28 days after instillation the rats were euthanized. Histopathological and biochemical examinations were performed. The activity and protein level of thioredoxin were assessed. The thioredoxin nitration level was determined using immunoprecipitation and immunoblotting techniques. Our results demonstrated that protein tyrosine nitration increased in the BLM-treated group compared with the control group. Trx activity decreased in the BLM group compared with control group, whereas Trx expression and nitration level increased dramatically in the BLM group compared with the control group. Our results indicated that Trx nitration might be involved in the pathogenesis of IPF.

  19. Bleomycin Loaded Magnetite Nanoparticles Functionalized by Polyacrylic Acid as a New Antitumoral Drug Delivery System

    Yue Xu


    Full Text Available Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs coated with polyacrylic acid (PAA as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM, vibrating sample magnetometer (VSM, and Fourier transform infrared spectroscopy (FTIR. The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30 nm exhibit a saturation magnetization of 87 emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24 h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23 hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors.

  20. Expression of PEPT2 mRNA in the lung of rat with bleomycin-induced pulmonary fibrosis

    Li Li; Dianhua Wang; Xuan Zhang; Xing Song


    Objective:Pulmonary fibrosis is a common pathological phenomena in lung cancer patients after chemotherapy or radiotherapy, which is a key factor hindering to transport ion of high concentrated drug to the lung tissue, peptide trans-porter has become targets of the rational design of peptides and peptide drug. The purpose of the study is to investigate the expression of PEPT2 mRNA in the lung of rats with bleomycin (BLM)-induced pulmonary fibrosis. Methods:Fifty healthy adult Spragne-Dawley rats were randomized into five groups, the rats in BLM 7d, 14d and 28d groups were treated with a single instil ation of 5 mg/kg of BLM, to induced pulmonary fibrosis models. On days 7, 14 and 28, the animals were kil ed by exsan-guination respectively. Normal saline (NS) group were treated by NS, on days 14, the animals were kil ed by exsanguinations. Control group were untreated. The lung samples were processed for light microscopy and determined the hydroxyproline (HYP) concentration. The expression of PEPT2 mRNA were measured by RT-PCR. PEPT2 cDNA fragments were tested by dideoxy chain termination. Results:Compared with control and NS group, HYP levels increased on day 7 of BLM group, but there was no statistical significant dif erence (P>0.05). HYP levels markedly increased on days 14 and 28 of BLM group, there was statistical significant dif erence (P0.05). Conclusion:The pulmonary fibrosis models of SD rats can be induced by a single instil ation of 5 mg/kg of bleomycin on 28d. There were no significant changes of PEPT2 mRNA expression in the lung of rats with bleomycin-induced pulmonary fibrosis.

  1. Effects of Spaceflight on Molecular and Cellular Responses to Bleomycin-induced DNA Damages in Confluent Human Fibroblasts

    Lu, Tao; Wu, Honglu; Karouia, Fathi; Stodieck, Louis; Zhang, Ye; Wong, Michael


    Spaceflights expose human beings to various risk factors. Among them are microgravity related physiological stresses in immune, cytoskeletal, and cardiovascular systems, and space radiation related elevation of cancer risk. Cosmic radiation consists of energetic protons and other heavier charged particles that induce DNA damages. Effective DNA damage response and repair mechanism is important to maintain genomic integrity and reduce cancer risk. There were studies on effects of spaceflight and microgravity on DNA damage response in cell and animal models, but the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on molecular and cellular responses to DNA damages, bleomycin, an anti-cancer drug and radiomimetic reagent, was used to induce DNA damages in confluent human fibroblasts flown to the International Space Station (ISS) and on ground. After exposure to 1.0 mg/ml bleomycin for 3 hours, cells were fixed for immunofluorescence assays and for RNA preparation. Extents of DNA damages were quantified by focus pattern and focus number counting of phosphorylated histone protein H2AX (γg-H2AX). The cells on the ISS showed modestly increased average focus counts per nucleus while the distribution of patterns was similar to that on the ground. PCR array analysis showed that expressions of several genes, including CDKN1A and PCNA, were significantly changed in response to DNA damages induced by bleomycin in both flight and ground control cells. However, there were no significant differences in the overall expression profiles of DNA damage response genes between the flight and ground samples. Analysis of cellular proliferation status with Ki-67 staining showed a slightly higher proliferating population in cells on the ISS than those on ground. Our results suggested that the difference in γg-H2AX focus counts between flight and ground was due to the higher percentage of proliferating cells in space, but spaceflight did not

  2. Effect of intramuscular injection of hepatocyte growth factor plasmid DNA with electroporation on bleomycin-induced lung fibrosis in rats

    LONG Xiang; XIONG Sheng-dao; XIONG Wei-ning; XU Yong-jian


    Background So far, there is no efficient treatment for pulmonary fibrosis. The objective of this study was to determine whether intramuscular injection of the hepatocyte growth factor (HGF) plasmid DNA by in vivo electroporation could prevent bleomycin-induced pulmonary fibrosis in rats, and to investigate the possible mechanisms.Methods Twenty male Wistar rats were randomly divided into four groups: control group(group C), model group (group M), early intervention group (group Ⅰ ) and late intervention group (groupⅡ). Groups M, Ⅰ and Ⅱ were intratracheally infused with bleomycin, then injected the plasmid pcDNA3.1-hHGF to group Ⅰ on day 7, 14 and 21. Group Ⅱ received the same treatment like Group Ⅰ on day 14 and 21. All the rats were killed on day 28 after bleomycin injection. We detected Homo HGF expression in the rats with ELISA method and estimated the pathological fibrosis score of lung tissue using hematoxylin eosin (HE) and Massion staining. The mRNA expression of transforming growth factor-β1 (TGF-β1),cycloxygenase-2 (COX-2), and rat HGF in rat pulmonary parenchyma were evaluated by RT-PCR.Immunohistochemistry and Western blotting were performed to determine the protein expression of transforming TGF-β1 and COX-2 in lung parenchyma.Results The plasmid pcDNA3.1-hHGF could express hHGF in NIH3T3 cells and the hHGF protein is secreted into the culture medium. The expression of hHGF protein could be monitored in quadriceps muscle, plasma and lung in Groups Ⅰ and Ⅱ. Pulmonary fibrosis levels of Groups Ⅰ and Ⅱ were obviously lower than that of group M (P<0.05).Expression of TGF-β1 protein and mRNA in lung tissue was markedly decreased in Groups Ⅰ and Ⅱ compared with Group M (P<0.05). The level of expression of HGF and COX-2 mRNA was higher in Groups Ⅰ and Ⅱ than in Group M (P<0.05).Conclusions Injection of the plasmid pcDNA3.1-hHGF into skeletal muscle with electroporation has a potential role in the treatment of bleomycin

  3. Effect of early treatment with transcutaneous electrical diaphragmatic stimulation (TEDS on pulmonary inflammation induced by bleomycin

    Laisa A. Santos


    Full Text Available BACKGROUND : Bleomycin (B is an antineoplastic drug that has pulmonary fibrosis as a side effect. There are few experimental studies about the effects of physical therapy treatment in this case. OBJECTIVE: The objective was to study rat lungs treated with B and precocious intervention by transcutaneous electrical diaphragmatic stimulation (TEDS. METHOD : Wistar rats were divided into 4 groups (n=5: a control group (C; a stimulated group (TEDS; a group treated with a single dose of B (intratracheally, 2.5 mg/kg (B; and a group treated with B and electric stimulation (B + TEDS. After the B instillation, the electrical stimulation was applied for 7 days, for a duration of 20 minutes. Lung fragments were histologically processed with hematoxylin and eosin (HE and 8-isoprostane-PGF2α (8-iso-PGF2α. The density of the alveolar area was determined by planimetry, the inflammatory profile was defined by the number of cells, and the level of oxidative stress in the pulmonary tissue was evaluated by 8-iso-PGF2α. For statistical analysis of the data, the Shapiro-Wilk test was used, followed by a one-way ANOVA with the post-hoc Bonferroni test (p≤0.05. RESULTS : The B group exhibited a significant reduction in the area density, and the acute treatment with B + TEDS prevented this reduction. There were increased numbers of fibroblasts, leukocytes, and macrophages in the B group, as well as increased lipid peroxidation, which was observed only in this group. CONCLUSION : B promoted a reduction in the alveolar density area, thereby inducing the inflammatory process and increasing the production of free radicals. These effects were minimized by the application of TEDS at the initial treatment stage.

  4. Histopathologic observation of anti-tumor effect of bleomycin and irradiation on cancers of tongue

    Kohmura, Yuji (Aichi-Gakuin Univ., Nagoya (Japan). School of Dentistry); Hosoda, Syun; Kawabe, Yoshitaka; Isojima, Genzo


    Nine cases of squamous cell carcinoma of the tongue were treated by either intramuscular or local injections of total 60 to 200 mg of Bleomycin (BLM), and 7 cases by total doses of 1,200 to 5,320 rads of irradiation, followed by surgical removal of primary neoplasm. The histologic examination was done focussing on the antitumor effect of both treatments. In the cases with keratinizing component more than 25 % in the biopsy specimens, the earliest change due to BLM was vacuolar degeneration of proliferating cells either at the base of superficial cancer epithelia or at the periphery of invading cancer foci. When the proliferating cancer cells disappeared, an appearance of invading cancer foci resembled that of ectopic islands of normal squamous epithelium. These foci of differentiated squamous cell carcinoma gradually underwent morphological change into the so-called cancer pearls. Finally, the cancer pearls degenerated, leaving foreign bodies consisting of concreted keratin. The stromal reaction was characterized by the formation of granulation tissues accompanying significant numbers of foreign body giant cells. In the cases of lingual carcinoma with poor squamous differentiation, these processes were indistinct. Instead, the proliferating anaplastic cancer cells were markedly reduced and the remaining cancer cells transformed into large bizarre cells, probably at degenerative stage. On the histologic level, irradiation showed essentially similar antitumor effect to BLM, except for the rapid formation of concreted keratin bodies accompanying more abundant foreign body giant cells and the presence of irregular granulation tissues at different stages. We concluded that both BLM and irradiation had a powerful antitumor action on squamous cell carcinoma of the tongue.

  5. Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion.

    Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Mogami, Sachiko; Yamada, Chihiro; Iizuka, Seiichi; Hattori, Tomohisa; Nakazato, Masamitsu


    Cachexia is a frequent complication in patients with respiratory failure, such as lung fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Reductions in body weight and skeletal muscle mass are key features of cachexia that are resistant to current therapies. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to stimulate ghrelin secretion. By using bleomycin (BLM)-induced lung fibrosis mice in this study, we tested our hypothesis that RKT administration could ameliorate pulmonary cachexia. After BLM administration, mice were provided with either RKT or distilled water on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller reductions of food intake and body weight. Skeletal muscle weights were retained in the RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the lysates of skeletal muscle found in lung fibrosis. Rikkunshito administration restored the plasma concentrations of ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a ghrelin receptor antagonist. Rikkunshito administration did not decrease the degree of loss of body weight or food intake reduction in either ghrelin-deficient mice or growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung fibrosis.

  6. Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages.

    Xiang, Juan; Cheng, Si; Feng, Tianlong; Wu, Yan; Xie, Weina; Zhang, Mian; Xu, Xianghong; Zhang, Chaofeng


    Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-β1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100μM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-β1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100μM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages.

  7. Protocol Implementation Generator

    Carvalho Quaresma, Jose Nuno; Probst, Christian W.


    necessary tools. In this paper, we present the Protocol Implementation Generator (PiG), a framework that can be used to add protocol generation to protocol negotiation, or to easily share and implement new protocols throughout a network. PiG enables the sharing, verification, and translation...... of communication protocols. With it, partners can suggest a new protocol by sending its specification. After formally verifying the specification, each partner generates an implementation, which can then be used for establishing communication. We also present a practical realisation of the Protocol Implementation...... Generator framework based on the LySatool and a translator from the LySa language into C or Java....

  8. Influence of pH and length of post-treatment incubation on bleomycin-induced DNA damage

    Moore, C.W.; Vossler, D.A.


    The dependence of the extent of DNA damage by anticancer bleomycin on pH and length of post-treatment incubation was studied in yeast. Bleomycin was always removed from cells after 20-min exposures, and cells were washed prior to incubation in non-nutrient buffer. Following exposures of late stationary-phase cells to the very low dose of only 3, 1.5 h incubation in non-nutrient buffer, pH 5, had hardly any effect on profiles derived from alkaline sucrose gradient sedimentation of nucleic acids released from spheroplasts. In contrast, after incubation of cells for 1.5 h in buffer, pH 7, DNA was all low molecular weight. Thus, even after extensive washing of cells, pH strongly influences the drug's action on DNA. At pH 5, washed cells were increasingly susceptible to DNA damage up to 26 h in non-nutrient buffer.

  9. The resonance Rayleigh scattering of the interaction of copper(Ⅱ)-bleomycinA2 with DNA and its analytical application


    The forming of bleomycinA2-Cu(Ⅱ) cationic chelate and the interaction of the chelate with DNA have been investigated by using resonance Rayleigh scattering(RRS),molecular absorption and fluorescence spectra.The result shows that in aqueous solution,bleomycinA2(BLMA2) can react with Cu(Ⅱ) to form 1:1 cationic chelate which contributes to the changes of the absorption spectra and the quenched fluorescence of BLMA2.When the cationic chelate further bound with DNA to form ternary ion-association complexes,the remarkable enhancement of the RRS intensity was observed.In this work,the optimum conditions for the coordination reaction of BLMA2 with Cu(Ⅱ) and some influencing factors have been investigated.The reaction mechanism of BLMA2-Cu(Ⅱ) binding with DNA was suggested and a binding model was proposed.In addition,the fluorescence quenching type of BLMA2 was investigated.A highly sensitive,simple and rapid new method for the determination of DNA by using BLMA2-Cu(Ⅱ) as RRS probe has been developed.The detection limits(3σ) are 7.2 ng/mL for ctDNA,7.1 ng/mL for sDNA and 18 ng/mL for hsDNA.The method can be applied to the determination of trace amounts of DNA.

  10. Definition of the intermediates and mechanism of the anticancer drug bleomycin using nuclear resonance vibrational spectroscopy and related methods

    Liu, Lei V.; Bell, Caleb B.; Wong, Shaun D.; Wilson, Samuel A.; Kwak, Yeonju; Chow, Marina S.; Zhao, Jiyong; Hodgson, Keith O.; Hedman, Britt; Solomon, Edward I.


    Bleomycin (BLM) is a glycopeptide anticancer drug capable of effecting single- and double-strand DNA cleavage. The last detectable intermediate prior to DNA cleavage is a low spin FeIII peroxy level species, termed activated bleomycin (ABLM). DNA strand scission is initiated through the abstraction of the C-4′ hydrogen atom of the deoxyribose sugar unit. Nuclear resonance vibrational spectroscopy (NRVS) aided by extended X-ray absorption fine structure spectroscopy and density functional theory (DFT) calculations are applied to define the natures of FeIIIBLM and ABLM as (BLM)FeIII─OH and (BLM)FeIII(η1─OOH) species, respectively. The NRVS spectra of FeIIIBLM and ABLM are strikingly different because in ABLM the δFe─O─O bending mode mixes with, and energetically splits, the doubly degenerate, intense O─Fe─Nax transaxial bends. DFT calculations of the reaction of ABLM with DNA, based on the species defined by the NRVS data, show that the direct H-atom abstraction by ABLM is thermodynamically favored over other proposed reaction pathways. PMID:21149675

  11. Effects of Thermal-Oxidative Aging Time on Properties of PA6/LGF/BEP%热氧老化时间对PA6/LGF/BEP复合材料性能的影响


    探究了160℃温度下不同热氧老化时间对溴化环氧树脂(BEP)阻燃长玻纤增强尼龙6(PA6/LGF/BEP)复合材料性能的影响.通过热重分析(TGA)、氧指数(LOI)及锥形量热仪测试,分析了不同热氧老化时间下PA6/LGF/BEP复合材料的热稳定性、阻燃性能、燃烧性能.结果表明:热氧老化时间的延长对PA6/LGF/BEP复合材料的热稳定性影响不大,但热氧老化时间的延长使复合材料的氧指数由25%降低到23.2%,最大热释放速率由138 kW/m2增加到316 kW/m2,火势增长指数由1.31 kW/(m2 ·s)增加到3.01 kW/(m2·s),这表明随着热氧老化时间的延长,该复合材料的阻燃性能下降,火灾安全性逐渐降低.

  12. Codon 64 of K-ras gene mutation pattern in hepatocellular carcinomas induced by bleomycin and 1-nitropyrene in A/J mice.

    Bai, Feng; Nakanishi, Yoichi; Takayama, Koichi; Pei, Xin-Hai; Inoue, Koji; Harada, Taishi; Izumi, Miiru; Hara, Nobuyuki


    Bleomycin is a radiomimetic antitumor agent with unique genotoxic properties. 1-nitropyrene is an environmental mutagen and carcinogen that undergoes both oxidative and reductive metabolism. In the present study, hepatocellular carcinomas were induced in male A/J mice by the intraperitoneal injection of bleomycin (120 mg/kg) followed by the intraperitoneal administration of 1-nitropyrene (total dose: 1,575 mg/kg). In order to understand the mechanism by which these two compounds induce hepatocellular carcinomas, the incidence and spectrum of mutations in the K-ras proto-oncogene in these hepatocellular carcinomas were analyzed. The hepatocellular carcinomas were induced by the administration of bleomycin and 1-nitropyrene were evaluated for point mutations in exon 1 and exon 2 of the K-ras gene by the polymerase chain reaction and a sequencing analysis. No mutation was found in the hotspots regions of the K-ras gene codon 12, 13, or 61. However, the codon 64 of the K-ras gene mutation was identified in 10 of 10 (100%) hepatocellular carcinomas. All mutations showed the same pattern, which was TAC-CAC transition. Codon 64 of the K-ras gene mutation may thus play an important role in the induction of hepatocellular carcinomas by bleomycin in the existence of 1-nitropyrene. As far as we know, this is the first report of a codon 64 mutation in the K-ras gene in a chemically induced tumor.

  13. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)


    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

  14. The valence state of technetium-99 in its complexes with bleomycin, 1-hydroxy-ethylidene-1,1-diphosphonate and human serum albumin

    Korteland, J.; Dekker, B.G.; Ligny, C.L. de


    The valence state of technetium-99 in its complexes with bleomycin, 1-hydroxy-ethylidene-1,1-diphosphonate and human serum albumin was determined by titration of 99TcO4− with Sn(II) in the presence of these complexing agents. Both direct titration, and addition of an excess of Sn(II) and back-titrat

  15. Atorvastatin Attenuates Bleomycin-Induced Pulmonary Fibrosis via Suppressing iNOS Expression and the CTGF (CCN2/ERK Signaling Pathway

    Bo Zhu


    Full Text Available Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-induced lung fibrosis and to further explore the possible underlying mechanisms. Our results showed that atorvastatin administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA level and lung indices. Atorvastatin also markedly decreased the expression of inducible nitric oxide synthase (iNOS in lung tissues and, thus, prevented nitric oxide (NO release in response to bleomycin challenge. Furthermore, atorvastatin exhibited target down-regulation of connective tissue growth factor (CTGF (CCN2 and phosphorylation extracellular regulated protein kinases (p-ERK expression. Taken together, atorvastatin significantly ameliorated bleomycin-induced pulmonary fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2/ERK signaling pathway. The present study provides evidence that atorvastatin may be a potential therapeutic reagent for the treatment of lung fibrosis.

  16. The response of normal and ataxia-telangiectasia cells to bleomycin: relationships between chromosome damage, cell cycle delay and cell killing.

    Zampetti-Bosseler, F; Scott, D


    In agreement with our earlier observation (Scott and Zampetti-Bosseler, 1982) on X-irradiated normal and ataxia-telangiectasia (A-T) fibroblasts, we now report that after bleomycin or neocarzinostatin treatment also, A-T cells exhibit less G2 delay than normal cells. We confirm that A-T cells sustain more chromosome damage and lethality than normal cells after bleomycin. These observations support the hypothesis (Painter and Young, 1980) that A-T cells are defective in the recognition of certain lesions which normally lead to delays in progression through the cell cycle, during which they are repaired, and which, if unrepaired, lead to cell-lethal chromosome damage. However, we find that after bleomycin, as opposed to X-rays, the contribution of this type of lesion to cell death is minimal. The predominant lesions leading to cell death after bleomycin are not manifested at chromosome aberrations and do not lead to G2 delay or DNA-synthesis inhibition. A-T cells are defective in the recognition and/or repair of both types of lesion.

  17. Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in the skin in a murine model of scleroderma, bleomycin-induced fibrosis.

    Katebi, Majid; Fernandez, Patricia; Chan, Edwin S L; Cronstein, Bruce N


    Peripheral blood fibrocytes are a newly identified circulating leukocyte subpopulation that migrates into injured tissue where it may display fibroblast-like properties and participate in wound healing and fibrosis of skin and other organs. Previous studies in our lab demonstrated that A(2A) receptor-deficient and A(2A) antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis, thus the aim of this study was to determine whether the adenosine A(2A) receptor regulates recruitment of fibrocytes to the dermis in this bleomycin-induced model of dermal fibrosis. Sections of skin from normal mice and bleomycin-treated wild type, A(2A) knockout and A(2A) antagonist-treated mice were stained for Procollagen alpha2 Type I and CD34 and the double stained cells, fibrocytes, were counted in the tissue sections. There were more fibrocytes in the dermis of bleomycin-treated mice than normal mice and the increase was abrogated by deletion or blockade of adenosine A(2A) receptors. Because fibrocytes play a central role in tissue fibrosis these results suggest that diminished adenosine A(2A) receptor-mediated recruitment of fibrocytes into tissue may play a role in the pathogenesis of fibrosing diseases of the skin. Moreover, these results provide further evidence that adenosine A(2A) receptors may represent a new target for the treatment of such fibrosing diseases as scleroderma or nephrogenic fibrosing dermopathy.


    Xin-lun Tian; Wei Yao; Zi-jian Guo; Li Gu; Yuan-jue Zhu


    Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and matrix metalloproteinase-13 (MMP-13) in lung tissue.Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone (25-800 mg·kg-1·d-1), dexamethasone (3 mg/kg), or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg·kg -1·d-1 at 7 days or 14 days after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in lung tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxyproline. Expression of proteins of TGF-β, TIMP-1, and MMP-13 were detected by Western blotting.Results At doses of 25, 50, and 100 mg·kg-1·d-1, pirfenidone had significant anti-fibrofic effects for bleomycin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50mg·kg-1 1d-1 (HE: P<0.01, P<0.01, and P =0.064; sirius red: P<0.05, P<0.01, and P<0. 05; hydroxyproline: P=0.595, P<0.01, and P=0.976). Pirfenidone at a dosage of 50 mg·kg -1·d-1 inhibited protein expression of TGF-β1 and TIMP-1 in lung tissue in the early phase (0.79 and 0.75 times of control group), but had no effect on expression of MMP-13.Conclusion Low dose pirfenidone, especially at dosage of 50 mg·kg-1·d-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-β1 and TIMP-1 in lung tissue.

  19. Dysregulated macrophages are present in bleomycin-induced murine laryngotracheal stenosis

    Hillel, Alexander T.; Samad, Idris; Ma, Garret; Ding, Dacheng; Sadler, Kaitlyn; Powell, Jonathan D.; Lane, Andrew P.; Horton, Maureen R.


    Objective To define the inflammatory cell infiltrate preceding fibrosis in a laryngotracheal stenosis (LTS) murine model. Study Design Prospective controlled murine study. Setting Tertiary care hospital in a research university. Subjects and Methods Chemomechanical injury mice (n=44) sustained bleomycin-coated wire-brush injury to the laryngotracheal complex while mechanical injury controls (n=42) underwent PBS-coated wire-brush injury. Mock surgery controls (n=34) underwent anterior transcervical tracheal exposure only. Inflammatory and fibrosis protein and gene expression was assessed in each condition. Immunohistochemistry served as a secondary outcome. Results In chemomechanical injury mice, there was an up-regulation of: Collagen I (p<0.0001, p<0.0001), Tgf-β (p=0.0023, p=0.0008), and elastin (p<0.0001, p<0.0001) on Day 7, acute inflammatory gene: Il1β (p=0.0027, p=0.0008) on Day 1, and macrophage gene: CD11b (p=0.0026, p=0.0033) on Day 1 versus mechanical and mock controls respectively. M1 marker iNOS expression decreased (p=0.0014) while M2 marker arg1 (p=0.0002) increased on Day 7 compared to mechanical controls. Flow cytometry demonstrated increased macrophages (p=0.0058, day 4) and M1 macrophages (p=0.0148, day 4, p=0.0343, day 7, p=0.0229, day 10) compared to mock controls. There were similarities between chemomechanical and mechanical injury mice with an increase in M2 macrophages at day 10 (p=0.0196). Conclusions The mouse model demonstrated increased macrophages involved with the development of LTS. Macrophage immunophenotype suggested that dysregulated M2 macrophages have a role in abnormal laryngotracheal wound healing in both species. These results support this animal model as a representation for human disease. Furthermore, this data delineates inflammatory cells and signaling pathways in LTS that may potentially be modulated to lessen fibroblast proliferation and collagen deposition. PMID:26084828

  20. Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats

    Ke Zhang


    Full Text Available Rhodiola rosea L. (RRL possesses a wide range of pharmacological properties, including lung-protective activity, and has been utilized in folk medicine for several 100 years. However, the lung-protective mechanism remains unclear. This study investigated the possible lung-protective activity mechanism of RRL in a pulmonary fibrosis (PF rat model. Lung fibrotic injury was induced in Sprague–Dawley rats by single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg. The rats were administered 125, 250, or 500 mg/kg of a 95% ethanol extract of RRL for 28 days. The animals were killed to detect changes in body weight, serum levels of glutathione (GSH and total superoxide dismutase (T-SOD, as well as lung tissue hydroxyproline (HYP content. Tumor necrosis factor-α (TNF-α, transforming growth factor-β1 (TGF-β1, and interleukin 6 (IL-6 levels were measured in bronchoalveolar lavage fluid (BALF by enzyme-linked immunosorbent assay. Hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining were performed to observe the histopathological changes in lung tissues. Additionally, target-related proteins were measured by Western blotting. RRL alleviated the loss of body weight induced by instilling BLM in PF rats, particularly at the 500 mg/kg per day dose. RRL reduced HYP (p < 0.01 and increased GSH and T-SOD contents. BALF levels of TNF-α, TGF-β1, and IL-6 decreased significantly in the RRL-treated groups. Expression levels of matrix metalloproteinase-9 (MMP-9 and α-smooth muscle actin decreased significantly in a dose-dependent manner in response to RRL. Moreover, the levels of TGF-β1 and tissue inhibitor of metalloproteinase-1 in lung tissues also decreased in the RRL-treated groups. RRL alleviated BLM-induced PF in rats. Our results reveal that the protective effects of RRL against fibrotic lung injury in rats are correlated with its anti-inflammatory, antioxidative, and anti-fibrotic properties. MMP-9 may

  1. Research on Protocol Migration

    汪芸; 顾冠群; 等


    This paper elaborates the concept and model of protocol migration in network interconnection.Migration strategies and principles are discussed and several cases are studied in detail which show the basic procedure and techniques used in protocol migration.

  2. Gene Expression Profile Changes and Cellular Responses to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Lu, Tao; Zhang, Ye; Kidane, Yared; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Rohde, Larry; Wu, Honglu


    Living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. In addition, DNA in space can be damaged by toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage affects the accuracy of the radiation risk assessment for astronauts and the mutation rate in microorganisms. Although possible synergistic effects of space radiation and microgravity have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate the effects of spaceflight on cellular responses to DNA damage, confluent human fibroblast cells (AG1522) flown on the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB). Damages in the DNA were quantified by immunofluorescence staining for ?-H2AX, which showed similar percentages of different types of stained cells between flight and ground. However, there was a slight shift in the distribution of the ?-H2AX foci number in the flown cells with countable foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. A microarray analysis of gene expressions in response to bleomycin treatment was also performed. Comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. Similar responses at the RNA level between different gravity conditions were also observed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly

  3. Topological Design of Protocols

    Jaffe, Arthur; Wozniakowski, Alex


    We give a topological simulation for tensor networks that we call the two-string model. In this approach we give a new way to design protocols, and we discover a new multipartite quantum communication protocol. We introduce the notion of topologically compressed transformations. Our new protocol can implement multiple, non-local compressed transformations among multi-parties using one multipartite resource state.

  4. Pneumomediastinum, subcutaneous emphysema, and pneumothorax after a pulmonary function testing in a patient with bleomycin-induced interstitial pneumonitis

    Mariana Sponholz Araujo


    Full Text Available Spontaneous pneumomediastinum is an uncommon event, the clinical picture of which includes retrosternal chest pain, subcutaneous emphysema, dyspnea, and dysphonia. The pathophysiological mechanism involved is the emergence of a pressure gradient between the alveoli and surrounding structures, causing alveolar rupture with subsequent dissection of the peribronchovascular sheath and infiltration of the mediastinum and subcutaneous tissue with air. Known triggers include acute exacerbations of asthma and situations that require the Valsalva maneuver. We described and documented with HRCT scans the occurrence of pneumomediastinum after a patient with bleomycin-induced interstitial lung disease underwent pulmonary function testing. Although uncommon, the association between pulmonary function testing and air leak syndromes has been increasingly reported in the literature, and lung diseases, such as interstitial lung diseases, include structural changes that facilitate the occurrence of this complication.

  5. Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice

    Min-Hua Zheng; Bao-Ming Yu; Bo Feng; Jian-Wen Li; Ai-Guo Lu; Ming-Liang Wang; Wei-Guo Hu; Ji-Yuan Sun; Yan-Yan Hu; Jun-Jun Ma


    AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT.METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay.RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (χ2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups.CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer.The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

  6. Epithelium-specific deletion of TGF-β receptor type II protects mice from bleomycin-induced pulmonary fibrosis.

    Li, Min; Krishnaveni, Manda Sai; Li, Changgong; Zhou, Beiyun; Xing, Yiming; Banfalvi, Agnes; Li, Aimin; Lombardi, Vincent; Akbari, Omid; Borok, Zea; Minoo, Parviz


    Idiopathic pulmonary fibrosis (IPF) is a chronic fibroproliferative pulmonary disorder for which there are currently no treatments. Although the etiology of IPF is unknown, dysregulated TGF-β signaling has been implicated in its pathogenesis. Recent studies also suggest a central role for abnormal epithelial repair. In this study, we sought to elucidate the function of epithelial TGF-β signaling via TGF-β receptor II (TβRII) and its contribution to fibrosis by generating mice in which TβRII was specifically inactivated in mouse lung epithelium. These mice, which are referred to herein as TβRIINkx2.1-cre mice, were used to determine the impact of TβRII inactivation on (a) embryonic lung morphogenesis in vivo; and (b) the epithelial cell response to TGF-β signaling in vitro and in a bleomycin-induced, TGF-β-mediated mouse model of pulmonary fibrosis. Although postnatally viable with no discernible abnormalities in lung morphogenesis and epithelial cell differentiation, TβRIINkx2.1-cre mice developed emphysema, suggesting a requirement for epithelial TβRII in alveolar homeostasis. Absence of TβRII increased phosphorylation of Smad2 and decreased, but did not entirely block, phosphorylation of Smad3 in response to endogenous/physiologic TGF-β. However, TβRIINkx2.1-cre mice exhibited increased survival and resistance to bleomycin-induced pulmonary fibrosis. To our knowledge, these findings are the first to demonstrate a specific role for TGF-β signaling in the lung epithelium in the pathogenesis of pulmonary fibrosis.

  7. Bone marrow stem cells expressing keratinocyte growth factor via an inducible lentivirus protects against bleomycin-induced pulmonary fibrosis.

    Susana Aguilar

    Full Text Available Many common diseases of the gas exchange surface of the lung have no specific treatment but cause serious morbidity and mortality. Idiopathic Pulmonary Fibrosis (IPF is characterized by alveolar epithelial cell injury, interstitial inflammation, fibroblast proliferation and collagen accumulation within the lung parenchyma. Keratinocyte Growth Factor (KGF, also known as FGF-7 is a critical mediator of pulmonary epithelial repair through stimulation of epithelial cell proliferation. During repair, the lung not only uses resident cells after injury but also recruits circulating bone marrow-derived cells (BMDC. Several groups have used Mesenchymal Stromal Cells (MSCs as therapeutic vectors, but little is known about the potential of Hematopoietic Stem cells (HSCs. Using an inducible lentiviral vector (Tet-On expressing KGF, we were able to efficiently transduce both MSCs and HSCs, and demonstrated that KGF expression is induced in a regulated manner both in vitro and in vivo. We used the in vivo bleomycin-induced lung fibrosis model to assess the potential therapeutic effect of MSCs and HSCs. While both populations reduced the collagen accumulation associated with bleomycin-induced lung fibrosis, only transplantation of transduced HSCs greatly attenuated the histological damage. Using double immunohistochemistry, we show that the reduced lung damage likely occurs through endogenous type II pneumocyte proliferation induced by KGF. Taken together, our data indicates that bone marrow transplantation of lentivirus-transduced HSCs can attenuate lung damage, and shows for the first time the potential of using an inducible Tet-On system for cell based gene therapy in the lung.

  8. EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-β signaling in lung fibroblasts

    Inagaki Hirofumi


    Full Text Available Abstract Background Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice. Methods Seven-week-old male ICR mice were used. All experiments used eight mice/group, unless otherwise noted in the figure legends. Bleomycin was administered intravenously to the mice on day 0. EM703 was orally administered daily to mice. All groups were examined for cell populations in the bronchoalveolar lavage (BAL fluid and for induction of messenger RNA (mRNA of Smad3 and Smad4 in the lung tissues by reverse transcriptase (RT-polymerase chainreaction (PCR on day 7. Fibroblastic foci were assessed histologically, and the hydroxyproline content was chemically determined in the lung tissues on day 28. We performed assay of proliferation and soluble collagen production, and examined the induction of mRNA of Smad3 and Smad4 by RT-PCR in murine lung fibroblast cell line MLg2908. We also examined Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3 protein assay by western blotting in MLg2908. Results Bleomycin-induced lung fibrosis, and the infiltration of macrophages and neutrophils into the airspace were inhibited by EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast proliferation and the collagen production in lung fibroblasts induced by Transforming growth factor-beta (TGF-β. The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-β, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF

  9. A young male with shortness of breath

    Khan Fahmi


    Full Text Available We report a case of primary mediastinal seminoma, which presented initially with shortness of breath and a swelling in upper part of anterior chest wall. The diagnosis of primary mediastinal seminoma was established on the basis of histologic findings and was confirmed by immunohistochemical analysis. Abdominal, pelvis and cerebral CT scan, testicular ultrasound and TC-99 MDP bone scintigraphy were negative. Chemotherapy was initiated with B.E.P. protocol (Bleomycin, Etoposide, Cisplatinum; the patient received four cycles of chemotherapy. After 8 months, the patient was seen in the clinic; he was well.

  10. Resistance to Bleomycin in Cancer Cell Lines Is Characterized by Prolonged Doubling Time, Reduced DNA Damage and Evasion of G2/M Arrest and Apoptosis

    Qi Wang; Kangping Cui; Osvaldo Espin-Garcia; Dangxiao Cheng; Xiaoping Qiu; Zhuo Chen; Malcolm Moore; Bristow, Robert G.; Wei Xu; Der, Sandy; Geoffrey Liu


    BACKGROUND: To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell ...

  11. Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

    Kalayarasan, Srinivasan, E-mail:; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam, E-mail:


    Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

  12. Multiparty Quantum Cryptographic Protocol

    M. Ramzan; M. K. Khan


    We propose a multiparty quantum cryptographic protocol. Unitary operators applied by Bob and Charlie, on their respective qubits of a tripartite entangled state encoding a classical symbol that can be decoded at Alice's end with the help of a decoding matrix. Eve's presence can be detected by the disturbance of the decoding matrix. Our protocol is secure against intercept-resend attacks. Furthermore, it is efficient and deterministic in the sense that two classical bits can be transferred per entangled pair of qubits. It is worth mentioning that in this protocol, the same symbol can be used for key distribution and Eve's detection that enhances the effciency of the protocol.

  13. Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.

    Qi Wang

    Full Text Available BACKGROUND: To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell lines. RESULTS: Compared with parental cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50 and a mean doubling time increase of 147 % (range 64 %-352% in BLM-resistant sub-clones (p<0.05 for both. Higher maintenance BLM concentrations were associated with higher IC50 and increased doubling times (p<0.05. Significantly reduced DNA damage (COMET and γ-H2AX assays, G2/M arrest, and apoptosis (p<0.05 for each set of comparison following high-dose acute BLM exposure was observed in resistant sub-clones, compared with their BLM-sensitive parental counterparts. Three weeks of BLM-free culturing resulted in a partial return to BLM sensitivity in 3/7 BLM-resistant sub-clones (p<0.05. CONCLUSION: Bleomycin resistance may be associated with reduced DNA damage after bleomycin exposure, resulting in reduced G2/M arrest, and reduced apoptosis.

  14. Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response

    Pazit Y. Cohen


    Full Text Available Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1− myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days, as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1+ lymphocytes and Thy1− myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.

  15. Fibroblast-specific expression of AC6 enhances beta-adrenergic and prostacyclin signaling and blunts bleomycin-induced pulmonary fibrosis.

    Liu, Xiaoqiu; Li, Fengying; Sun, Shu Qiang; Thangavel, Muthusamy; Kaminsky, Joseph; Balazs, Louisa; Ostrom, Rennolds S


    Pulmonary fibroblasts regulate extracellular matrix production and degradation and are critical in maintenance of lung structure, function, and repair, but they also play a central role in lung fibrosis. cAMP-elevating agents inhibit cytokine- and growth factor-stimulated myofibroblast differentiation and collagen synthesis in pulmonary fibroblasts. In the present study, we overexpressed adenylyl cyclase 6 (AC6) in pulmonary fibroblasts and measured cAMP production and collagen synthesis. AC6 overexpression enhanced cAMP production and the inhibition of collagen synthesis mediated by isoproterenol and beraprost, but not the responses to butaprost or PGE(2). To examine if increased AC6 expression would impact the development of fibrosis in an animal model, we generated transgenic mice that overexpress AC6 under a fibroblast-specific promoter, FTS1. Lung fibrosis was induced in FTS1-AC6(+/-) mice and littermate controls by intratracheal instillation of saline or bleomycin. Wild-type mice treated with bleomycin showed extensive peribronchial and interstitial fibrosis and collagen deposition. By contrast, FTS1-AC6(+/-) mice displayed decreased fibrotic development, lymphocyte infiltration (as determined by pathological scoring), and lung collagen content. Thus, AC6 overexpression inhibits fibrogenesis in the lung by reducing pulmonary fibroblast-mediated collagen synthesis and myofibroblast differentiation. Because AC6 overexpression does not lead to enhanced basal or PGE(2)-stimulated levels of cAMP, we conclude that endogenous catecholamines or prostacyclin is produced during bleomycin-induced lung fibrosis and that these signals have antifibrotic potential.

  16. Transport Protocol Throughput Fairness

    Saleem Bhatti


    Full Text Available Interest continues to grow in alternative transport protocols to the Transmission Control Protocol (TCP. These alternatives include protocols designed to give greater efficiency in high-speed, high-delay environments (so-called high-speed TCP variants, and protocols that provide congestion control without reliability. For the former category, along with the deployed base of ‘vanilla’ TCP – TCP NewReno – the TCP variants BIC and CUBIC are widely used within Linux: for the latter category, the Datagram Congestion Control Protocol (DCCP is currently on the IETF Standards Track. It is clear that future traffic patterns will consist of a mix of flows from these protocols (and others. So, it is important for users and network operators to be aware of the impact that these protocols may have on users. We show the measurement of fairness in throughput performance of DCCP Congestion Control ID 2 (CCID2 relative to TCP NewReno, and variants Binary Increase Congestion control (BIC, CUBIC and Compound, all in “out-of-the box” configurations. We use a testbed and endto- end measurements to assess overall throughput, and also to assess fairness – how well these protocols might respond to each other when operating over the same end-to-end network path. We find that, in our testbed, DCCP CCID2 shows good fairness with NewReno, while BIC, CUBIC and Compound show unfairness above round-trip times of 25ms.

  17. Coded Splitting Tree Protocols

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar


    This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each...... instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early...... as possible. Evaluations show that the proposed protocol provides considerable gains over the standard tree splitting protocol applying SIC. The improvement comes at the expense of an increased feedback and receiver complexity....

  18. Rapamycin attenuates bleomycin-induced pulmonary fibrosis in rats and the expression of metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in lung tissue

    Jin Xiaoguang; Dai Huaping; Ding Ke; Xu Xuefeng; Pang Baosen; Wang Chen


    Background Idiopathic pulmonary fibrosis (IPF) is the most common and devastating form of interstitial lung disease (ILD) in the clinic.There is no effective therapy except for lung transplantation.Rapamycin is an immunosuppressive drug with potent antifibrotic activity.The purpose of this study was to examine the effects of rapamycin on bleomycininduced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).Methods Sprague-Dawley rats were treated with intratracheal injection of 0.3 ml of bleomycin (5 mg/kg) in sterile 0.9% saline to make the pulmonary fibrosis model.Rapamycin was given at a dose of 0.5 mg/kg per gavage,beginning one day before bleomycin instillation and once daily until animal sacrifice.Ten rats in each group were sacrificed at 3,7,14,28 and 56 days after bleomycin administration.Alveolitis and pulmonary fibrosis were semi-quantitatively assessed after HE staining and Masson staining under an Olympus BX40 microscope with an IDA-2000 Image Analysis System.Type Ⅰ and Ⅲ collagen fibers were identified by Picro-sirius-polarization.Hydroxyproline content in lung tissue was quantified by a colorimetric-based spectrophotometric assay,MMP-9 and TIMP-1 were detected by immunohistochemistry and by realtime quantitative reverse transcriptase polymerase chain reaction (RT-PCR).Results Bleomycin induced alveolitis and pulmonary fibrosis of rats was inhibited by rapamycin.Significant inhibition of alveolitis and hydroxyproline product were demonstrated when daily administration of rapamycin lasted for at least 14 days.The inhibitory efficacy on pulmonary fibrosis was unremarkable until rapamycin treatment lasted for at least 28 days (P <0.05).It was also demonstrated that rapamycin treatment reduced the expression of MMP-9 and TIMP-1 in lung tissue that was increased by bleomycin.Conclusion These results highlight the significance of rapamycin in alleviating

  19. STAT1 Antisense Oligonucleotides Attenuate the Proinflammatory Cytokine Release of Alveolar Macrophages in Bleomycin-Induced Fibrosis

    Xianming Fan; Zengli Wang


    To investigate the effect of signal transducers and activators of transcription 1 (STAT1) antisense oligonucleotides (ASON) on concentrations of TNF-α, IL-8, NO secreted by alveolar macrophages (AMs) in bleomycin-induced rat pulmonary fibrosis, five adult female Wistar rats were intratracheally instilled with bleomycin. After 7 days, the rats were killed by right ventricle of heart exsanguinations under ketamine anaesthesia and bronchoalveolar lavage (BAL) was performed to obtain AMs. AMs were divided into four groups, treated with STAT1 ASON, STAT1 sense oligonucleotides (SON), dexamethasone (DEX) and medium alone (control), respectively. AMs and media were collected after culture for 36 h. The mRNA and protein expressions of STAT1 and ICAM-1 in AMs were detected by RT-PCR and ELISA, respectively. The concentrations of TNF-α, IL-8, NO in cultured medium were detected.The STAT1 mRNA expression by AMs in the STAT1 ASON group was lower than those of AMs in the STAT1 SON group, the DEX group and the control group (p < 0.05). Moreover, the STAT1 mRNA expression by AMs in the DEX group was also lower than those of AMs in the STAT1 SON group and the control group (p < 0.05), but the STAT1 mRNA expression by AMs in the STAT1 SON group was not different from that of the control group (p >0.05). The protein expressions of STAT1 and ICAM-1 and the mRNA expression of ICAM-1 showed similar changes to the STAT1 mRNA expression by AMs. The concentrations of TNF-α, IL-8, NO in cultured medium from STAT1 ASON group were lower than those from STAT1 SON, DEX and the control groups (p < 0.05). Moreover,the concentrations of TNF-α, IL-8, NO in cultured medium from DEX group were also lower than those from the control and STAT1 SON group (p < 0.05), but no difference between STAT1 SON group and the control (p > 0.05).The results suggest that STAT1 ASON could inhibit the secretion of TNF-α, IL-8, NO in AMs, and STAT1 could become a target of treating pulmonary fibrosis.

  20. Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts

    Zhang Dongwei


    Full Text Available Abstract Background Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycin-induced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression and activity of cathepsins which have been implicated in the development of fibrotic lung diseases. Methods We investigated the effects of curcumin administration to bleomycin stimulated C57BL/6 mice and human fetal lung fibroblasts (HFL-1 on the expression of cathepsins K and L which have been implicated in matrix degradation, TGF-β1 modulation, and apoptosis. Lung tissues were evaluated for their contents of cathepsins K and L, collagen, and TGF-β1. HFL-1 cells were used to investigate the effects of curcumin and cathepsin inhibition on cell proliferation, migration, apoptosis, and the expression of cathepsins K and L and TGF-β1. Results Collagen deposition in lungs was decreased by 17-28% after curcumin treatment which was accompanied by increased expression levels of cathepsins L (25%-39% and K (41%-76% and a 30% decrease in TGF-β1 expression. Moreover, Tunel staining of lung tissue revealed a 33-41% increase in apoptotic cells after curcumin treatment. These in vivo data correlated well with data obtained from the human fibroblast line, HFL-1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGF-β1 decreased by 34%. Furthermore, curcumin significantly decreased cell proliferation and migration and increased the expression of surrogate markers of apoptosis. In contrast, these curcumin effects were partly reversed by a potent cathepsin inhibitor. Conclusion This study demonstrates that

  1. IPv6 Protocol Analyzer


    With the emerging of next generation Intemet protocol (IPv6), it is expected to replace the current version of Internet protocol (IPv4) that will be exhausted in the near future. Besides providing adequate address space, some other new features are included into the new 128 bits of IP such as IP auto configuration, quality of service, simple routing capability, security, mobility and multicasting. The current protocol analyzer will not be able to handle IPv6 packets. This paper will focus on developing protocol analyzer that decodes IPv6 packet. IPv6 protocol analyzer is an application module,which is able to decode the IPv6 packet and provide detail breakdown of the construction of the packet. It has to understand the detail construction of the IPv6, and provide a high level abstraction of bits and bytes of the IPv6 packet.Thus it increases network administrators' understanding of a network protocol,helps he/she in solving protocol related problem in a IPv6 network environment.

  2. ATM and Internet protocol

    Bentall, M; Turton, B


    Asynchronous Transfer Mode (ATM) is a protocol that allows data, sound and video being transferred between independent networks via ISDN links to be supplied to, and interpreted by, the various system protocols.ATM and Internet Protocol explains the working of the ATM and B-ISDN network for readers with a basic understanding of telecommunications. It provides a handy reference to everyone working with ATM who may not require the full standards in detail, but need a comprehensive guide to ATM. A substantial section is devoted to the problems of running IP over ATM and there is some discussion o

  3. Playing With Population Protocols

    Xavier Koegler


    Full Text Available Population protocols have been introduced as a model of sensor networks consisting of very limited mobile agents with no control over their own movement: A collection of anonymous agents, modeled by finite automata, interact in pairs according to some rules. Predicates on the initial configurations that can be computed by such protocols have been characterized under several hypotheses. We discuss here whether and when the rules of interactions between agents can be seen as a game from game theory. We do so by discussing several basic protocols.

  4. Linear Logical Voting Protocols

    DeYoung, Henry; Schürmann, Carsten


    . In response, we promote linear logic as a high-level language for both specifying and implementing voting protocols. Our linear logical specifications of the single-winner first-past-the-post (SW- FPTP) and single transferable vote (STV) protocols demonstrate that this approach leads to concise......Current approaches to electronic implementations of voting protocols involve translating legal text to source code of an imperative programming language. Because the gap between legal text and source code is very large, it is difficult to trust that the program meets its legal specification...... implementations that closely correspond to their legal specification, thereby increasing trust....

  5. Biochemical evaluation of a 108-member deglycobleomycin library: viability of a selection strategy for identifying bleomycin analogues with altered properties.

    Ma, Qian; Xu, Zhidong; Schroeder, Benjamin R; Sun, Wenyue; Wei, Fang; Hashimoto, Shigeki; Konishi, Kazuhide; Leitheiser, Christopher J; Hecht, Sidney M


    The bleomycins (BLMs) are clinically used glycopeptide antitumor antibiotics that have been shown to mediate the sequence-selective oxidative damage of both DNA and RNA. Previously, we described the solid-phase synthesis of a library of 108 unique analogues of deglycoBLM A6, a congener that cleaves DNA analogously to BLM itself. Each member of the library was assayed for its ability to effect single- and double-strand nicking of duplex DNA, sequence-selective DNA cleavage, and RNA cleavage in the presence and absence of a metal ion cofactor. All of the analogues tested were found to mediate concentration-dependent plasmid DNA relaxation to some extent, and a number exhibited double-strand cleavage with an efficiency comparable to or greater than deglycoBLM A6. Further, some analogues having altered linker and metal-binding domains mediated altered sequence-selective cleavage, and a few were found to cleave a tRNA3Lys transcript both in the presence and in the absence of a metal cofactor. The results provide insights into structural elements within BLM that control DNA and RNA cleavage. The present study also permits inferences to be drawn regarding the practicality of a selection strategy for the solid-phase construction and evaluation of large libraries of BLM analogues having altered properties.

  6. Gamma rays and bleomycin nick DNA and reverse the DNase I sensitivity of beta-globin gene chromatin in vivo

    Villeponteau, B.; Martinson, H.G.


    The active beta-globin genes in chicken erythrocytes, like all active genes, reside in large chromatin domains which are preferentially sensitive to digestion by DNase I. We have recently proposed that the special structure of chromatin in active domains is maintained by torsional stress in the DNA. This hypothesis predicts that nicking of the DNA within any such chromosomal domain in vivo will relax the DNA and lead to loss of the special DNase I-sensitive state. Here we have tested this prediction by using gamma irradiation and bleomycin treatment to cleave DNA within intact chicken embryo erythrocytes. Both treatments cause reversal of DNase I sensitivity. Moreover, reversal occurs at approximately one nick per 150 kilobase pairs for both agents despite their entirely unrelated modes of cell penetration and DNA attack. These results suggest that the domain of DNase I sensitivity surrounding the beta-globin genes comprises 150 kilobase pairs of chromatin under torsional stress and that a single DNA nick in this region is sufficient to reverse the DNase I sensitivity throughout the entire domain.

  7. Intratracheal Bleomycin Aerosolization: The Best Route of Administration for a Scalable and Homogeneous Pulmonary Fibrosis Rat Model?

    Alexandre Robbe


    Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic disease with a poor prognosis and is characterized by the accumulation of fibrotic tissue in lungs resulting from a dysfunction in the healing process. In humans, the pathological process is patchy and temporally heterogeneous and the exact mechanisms remain poorly understood. Different animal models were thus developed. Among these, intratracheal administration of bleomycin (BML is one of the most frequently used methods to induce lung fibrosis in rodents. In the present study, we first characterized histologically the time-course of lung alteration in rats submitted to BLM instillation. Heterogeneous damages were observed among lungs, consisting in an inflammatory phase at early time-points. It was followed by a transition to a fibrotic state characterized by an increased myofibroblast number and collagen accumulation. We then compared instillation and aerosolization routes of BLM administration. The fibrotic process was studied in each pulmonary lobe using a modified Ashcroft scale. The two quantification methods were confronted and the interobserver variability evaluated. Both methods induced fibrosis development as demonstrated by a similar progression of the highest modified Ashcroft score. However, we highlighted that aerosolization allows a more homogeneous distribution of lesions among lungs, with a persistence of higher grade damages upon time.

  8. Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury.

    Liebler, Janice M; Lutzko, Carolyn; Banfalvi, Agnes; Senadheera, Dinithi; Aghamohammadi, Neema; Crandall, Edward D; Borok, Zea


    We studied the capacity of adult human bone marrow-derived cells (BMDC) to incorporate into distal lung of immunodeficient mice following lung injury. Immunodeficient NOD/SCID and NOD/SCID/beta(2) microglobulin (beta(2)M)(null) mice were administered bleomycin (bleo) or saline intranasally. One, 2, 3 and 4 days after bleo or saline, human BMDC labeled with CellTracker Green CMFDA (5-chloromethylfluorescein diacetate) were infused intravenously. Retention of CMFDA(+) cells was maximal when delivered 4 days after bleo treatment. Seven days after bleo, cells from NOD/SCID mice were CMFDA(+), which increased 10- to 100-fold in NOD/SCID/beta(2)M(null) mice. Preincubation of BMDC with Diprotin A, a reversible inhibitor of CD26 peptidase activity that enhances the stromal-derived factor-1 (SDF-1/CXCL12)/CXCR4 axis, resulted in a 30% increase in the percentage of CMFDA(+) cells retained in the lung. These data indicate that human BMDC can be identified in lungs of mice following injury, albeit at low levels, and this may be modestly enhanced by manipulation of the SDF-1/CXCR4 axis. Given the overall low number of human cells detected, methods to increase homing and retention of adult BMDC, and consideration of other stem cell populations, will likely be required to facilitate engraftment in the treatment of lung injury.

  9. 1996 : Track Count Protocol

    US Fish and Wildlife Service, Department of the Interior — The goal of St. Vincent National Wildlife Refuge's Track Count Protocol is to provide an index to the population size of game animals inhabiting St. Vincent Island.

  10. Quantum deniable authentication protocol

    Shi, Wei-Min; Zhou, Yi-Hua; Yang, Yu-Guang


    The proposed quantum identity authentication schemes only involved authentication between two communicators, but communications with deniability capability are often desired in electronic applications such as online negotiation and electronic voting. In this paper, we proposed a quantum deniable authentication protocol. According to the property of unitary transformation and quantum one-way function, this protocol can provide that only the specified receiver can identify the true source of a given message and the specified receiver cannot prove the source of the message to a third party by a transcript simulation algorithm. Moreover, the quantum key distribution and quantum encryption algorithm guarantee the unconditional security of this scheme. Security analysis results show that this protocol satisfies the basic security requirements of deniable authentication protocol such as completeness and deniability and can withstand the forgery attack, impersonation attack, inter-resend attack.

  11. Unconditionally Secure Protocols

    Meldgaard, Sigurd Torkel

    the secure computation. Especially we look at the communication complexity of protocols in this model, and perfectly secure protocols. We show general protocols for any finite functionality with statistical security and optimal communication complexity (but exponential amount of preprocessing). And for two......This thesis contains research on the theory of secure multi-party computation (MPC). Especially information theoretically (as opposed to computationally) secure protocols. It contains results from two main lines of work. One line on Information Theoretically Secure Oblivious RAMS, and how...... they are used to speed up secure computation. An Oblivious RAM is a construction for a client with a small $O(1)$ internal memory to store $N$ pieces of data on a server while revealing nothing more than the size of the memory $N$, and the number of accesses. This specifically includes hiding the access pattern...

  12. USA-USSR protocol


    On 30 November the USA Atomic Energy Commission and the USSR State Committee for the Utilization of Atomic Energy signed, in Washington, a protocol 'on carrying out of joint projects in the field of high energy physics at the accelerators of the National Accelerator Laboratory (Batavia) and the Institute for High Energy Physics (Serpukhov)'. The protocol will be in force for five years and can be extended by mutual agreement.

  13. Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis.

    Conte, Enrico; Fagone, Evelina; Gili, Elisa; Fruciano, Mary; Iemmolo, Maria; Pistorio, Maria Provvidenza; Impellizzeri, Daniela; Cordaro, Marika; Cuzzocrea, Salvatore; Vancheri, Carlo


    In this study, the bleomycin model of pulmonary fibrosis was utilized to investigate putative anti-fibrotic activity of Ac-SDKP in vivo. Male CD-1 mice received intra-tracheal bleomycin (BLEO, 1 mg/kg) instillation in the absence or presence of Ac-SDKP (a dose of 0.6 mg/kg delivered intra-peritoneally on the day of BLEO treatment, d0, followed by bi-weekly additional doses). To evaluate therapeutic effects in a subset of mice, Ac-SDKP was administered one week after BLEO instillation (d7). Animals were sacrificed at one, two, or three weeks later. Measurement of fluid and collagen content in the lung, Broncho Alveolar Lavage Fluid (BALF) analysis, lung histology, immunohistochemistry (IHC), and molecular analysis were performed. Compared to BLEO-treated mice, animals that received also Ac-SDKP (at both d0 and d7) had significantly decreased mortality, weight loss, inflammation (edema, and leukocyte lung infiltration), lung damage (histological evidence of lung injury), and fibrosis (collagen histological staining and soluble collagen content in the lung) at up to 21 days. Moreover, IHC and quantitative RT-PCR results demonstrated a significant decrease in BLEO-induced IL-17 and TGF-β expression in lung tissue. Importantly, α-SMA expression, the hallmark of myofibroblast differentiation, was also decreased. This is the first report showing not only a preventive protective role of Ac-SDKP but also its significant therapeutic effects in the bleomycin model of pulmonary fibrosis, thus supporting further preclinical and clinical studies.

  14. Absence of O sup 6 -alkylguanine-DNA alkyltransferase induction in chick embryo liver and brain following X-irradiation or treatment with bleomycin

    Stammberger, I.; Tempel, K. (Munich Univ. (Germany). Faculty of Veterinary Medicine)


    The presence of O{sup 6}-alkylguanine-DNA alkyltransferase (AT) in liver and brain of chick embryos, chicks and hens was demonstrated. An induction of AT activity has only been found in the liver of chicks and hens 48 h after X-irradiation. The administration of methylmethanesulphonate to the chick embryo resulted 3-24 hr later in strong inhibition of AT activity accompanied by DNA alkylation. Under the same conditions, X-irradiation, dimethylnitrosamine and bleomycin exhibited no effect. The results are compared with those obtained in mouse, rat and human foetal tissues. (author).

  15. DNA repair protocols

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  16. Blind Cognitive MAC Protocols

    Mehanna, Omar; Gamal, Hesham El


    We consider the design of cognitive Medium Access Control (MAC) protocols enabling an unlicensed (secondary) transmitter-receiver pair to communicate over the idle periods of a set of licensed channels, i.e., the primary network. The objective is to maximize data throughput while maintaining the synchronization between secondary users and avoiding interference with licensed (primary) users. No statistical information about the primary traffic is assumed to be available a-priori to the secondary user. We investigate two distinct sensing scenarios. In the first, the secondary transmitter is capable of sensing all the primary channels, whereas it senses one channel only in the second scenario. In both cases, we propose MAC protocols that efficiently learn the statistics of the primary traffic online. Our simulation results demonstrate that the proposed blind protocols asymptotically achieve the throughput obtained when prior knowledge of primary traffic statistics is available.

  17. Cytoskeleton - Methods and Protocols

    CarloAlberto Redi


    Full Text Available Cytoskeleton - Methods and ProtocolsSecond edition, 2010; Ray H. Gavin (Ed; Springer Protocols methods in molecular biology, vol. 586 Humana press, Totowa, New Jersey (USA; Pages: 390; €95.44; ISBN: 978-1-60761-375-6Ray H. Gavin, from the Brooklyn College of The City University of New York, Brooklyn, NY, USA, wrote a few line as preface of this book. This is quite understandable: there is not a great need of words when there are facts that sustain and favour the dissemination of a cultural product. This is the case of the second edition of Cytoskeleton - Methods and Protocols, which appears just ten years after the first edition...

  18. Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast

    Hoffmann, George R. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)], E-mail:; Gessner, Gabrielle S.; Hughes, Jennifer F.; Ronan, Matthew V.; Sylvia, Katelyn E.; Willett, Christine J. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)


    The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve

  19. Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina.

    Bolzán, Alejandro D; Bianchi, Martha S; Giménez, Esteban M; Flaqué, María C Díaz; Ciancio, Vicente R


    Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (paircrew and controls are equally sensitive to BLM G2 clastogenic effects, since both groups exhibited a similar frequency of chromatid breaks per cell (p>0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (paircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals.

  20. Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina

    Bolzan, Alejandro D. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina)], E-mail:; Bianchi, Martha S. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina); Gimenez, Esteban M.; Flaque, Maria C. Diaz [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Ciancio, Vicente R. [Universidad Nacional de La Plata, Facultad de Ciencias Medicas, 120 y 60, 1900 La Plata (Argentina)


    Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p < 0.05). BLM sensitivity test showed that aircrew and controls are equally sensitive to BLM G2 clastogenic effects, since both groups exhibited a similar frequency of chromatid breaks per cell (p > 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals.

  1. Lung inflammation and thymic atrophy after bleomycin are controlled by the prostaglandin D2 receptor DP1.

    van den Brule, Sybille; Huaux, François; Uwambayinema, Francine; Ibouraadaten, Saloua; Yakoub, Yousof; Palmai-Pallag, Mihaly; Trottein, François; Renauld, Jean-Christophe; Lison, Dominique


    Acute lung injury (ALI) can be accompanied by secondary systemic manifestations. In a model of ALI induced by bleomycin (bleo), we examined the response of D prostanoid receptor 1 (DP1)-deficient mice (DP1(-/-)) to better understand these processes. DP1 deficiency aggravated the toxicity of bleo as indicated by enhanced body weight loss, mortality, and lung inflammation including bronchoalveolar permeability and neutrophilia. Thymic atrophy was also observed after bleo and was strongly exacerbated in DP1(-/-) mice. This resulted from the enhanced depletion of immature T lymphocytes in the thymus of DP1(-/-) mice, a phenomenon usually related to increased glucocorticoid release in blood. Serum corticosterone was more elevated in DP1(-/-) mice after bleo than in wild-type (wt) mice. Thymocytes of DP1(-/-) mice were not more sensitive to dexamethasone in vitro, and systemic delivery of dexamethasone or peritoneal inflammation after LPS induced a similar thymic atrophy in wt and DP1(-/-) mice, indicating that pulmonary DP1 was critical to the control of thymic atrophy after bleo. DP1(-/-) mice showed increased lung and/or blood mediators involved in neutrophil recruitment and/or glucocorticoid production/thymic atrophy (osteopontin, leukemia inhibitory factor, and keratinocyte-derived chemokine) after bleo. Finally, local pulmonary DP1 activation or inhibition in wt mice abrogated or amplified thymic atrophy after bleo, respectively. Altogether, our data reveal that ALI can perturb the systemic T-cell pool by inducing thymic atrophy and that both pathological processes are controlled by the pulmonary DP1 receptor. This new pathway represents a potential therapeutic target in ALI.

  2. VEGFmRNA and eNOSmRNA expression in immature rabbits with bleomycin-induced pulmonary hypertension

    龚方戚; 林幼敏; 汤宏峰; 顾伟忠; 汪伟; 康曼丽


    Objective: To investigate the evolution of pulmonary hypertension, the pathological changes of pulmonary arteries, and the expression of VEGFmRNA and eNOSmRNA of pulmonary arterial endothelial cells in immature rabbits treated with intratracheal bleomycin (BLM). Methods: Immature rabbits were divided into control and BLM group. Two and four weeks after intratracheal normal saline or BLM injection, the systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter; the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE and in situ hybridization.Results: Two and four weeks after intratracheal injection of BLM, the PASP, PADP and MPAP increased 53%, 49%, 52%in 2 weeks, and 43%, 89%, 56% in 4 weeks; the wall thickness increased and the cavity in middle and small pulmonary arteries became narrow; the Thickness Index (TI) and Area Index (AI) increased 25%, 14% in 2 weeks, and 22%, 24% in 4 weeks; the level of VEGFmRNA and eNOSmRNA expression decreased 46%, 43% in 2 weeks, and 43%, 51% in 4 weeks.There was no significant difference between 2 weeks and 4 weeks BLM groups. Conclusion: The pulmonary artery pressure was elevated, the thickness of wall increased and the cavity became narrow in middle and small pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbits after 2 weeks and 4 weeks of intratracheal 4 U/kg BLM injection.

  3. Apoptosis - Methods and Protocols

    CarloAlberto Redi


    Full Text Available Apoptosis - Methods and ProtocolsSecond edition, 2009; Peter Erhardt and Ambrus Toth (Eds; Springer Protocols - Methods in molecular biology, vol. 559; Humana press, Totowa, New Jersey (USA; Pages: 400; €88.35; ISBN: 978-1-60327-016-8The editors rightly begin the preface telling us that: “The ability to detect and quantify apoptosis, to understand its biochemistry and to identify its regulatory genes and proteins is crucial to biomedical research”. Nowadays this is a grounding concept of biology and medicine. What is particularly remarkable...

  4. IP Routing Protocols

    Nolasco Pinto, Armando


    Uyless Black is a widely known expert in computer networks and data communications. He is author of more than ten books in the communication technologies field, which puts him in a good position to address this topic. In IP Routing Protocols he starts by providing the background and concepts required for understanding TCP/IP technology. This is done clearly and assumes little prior knowledge of the area. As might be expected, he emphasizes the IP route discovery problem. Later he details several routing protocols.

  5. Protocol Materials: A Clarification.

    Innerd, Wilfred; O'Gorman, David

    "Protocol materials" are records or recordings of a wide variety of behavioral situations. Characteristically they are neither simulated nor extensively edited. They are to be used for the empirical verification of concepts derived from both educational theory and the social sciences. They are attempts to capture reality so that it may be studied…


    Allegra, Carmen J.


    During the past decade, biomedical technologies have undergone an explosive evolution---from the publication of the first complete human genome in 2003, after more than a decade of effort and at a cost of hundreds of millions of dollars---to the present time, where a complete genomic sequence can be available in less than a day and at a small fraction of the cost of the original sequence. The widespread availability of next generation genomic sequencing has opened the door to the development of precision oncology. The need to test multiple new targeted agents both alone and in combination with other targeted therapies, as well as classic cytotoxic agents, demand the development of novel therapeutic platforms (particularly Master Protocols) capable of efficiently and effectively testing multiple targeted agents or targeted therapeutic strategies in relatively small patient subpopulations. Here, we describe the Master Protocol concept, with a focus on the expected gains and complexities of the use of this design. An overview of Master Protocols currently active or in development is provided along with a more extensive discussion of the Lung Master Protocol (Lung-MAP study). PMID:26433553

  7. Principles of Protocol Design

    Sharp, Robin

    This is a new and updated edition of a book first published in 1994. The book introduces the reader to the principles used in the construction of a large range of modern data communication protocols, as used in distributed computer systems of all kinds. The approach taken is rather a formal one...

  8. Security Protocol Design: A Case Study Using Key Distribution Protocols

    Reiner Dojen


    Full Text Available Nowadays security protocols are a key component in providing security services for fixed and mobile networks. These services include data confidentiality, radio link encryption, message integrity, mobile subscriber authentication, electronic payment, certified e-mail, contract signing and nonrepudiation. This paper is concerned with design of effective security protocols. Security protocols are introduced and some common attacks against security protocols are discussed. The vulnerabilities that lead to theattacks are analyzed and guidelines for effective security protocol design are proposed. The presented guidelines are applied to the Andrew Secure RPC protocol and its adapted versions. It is demonstrated that compliance with the guidelines successfully avoidsfreshness and parallel session attacks.

  9. Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis.

    Ah-Mee Park

    Full Text Available Heat shock protein 27 (HSP27 is a member of the small molecular weight HSP family. Upon treatment with transforming growth factor β1 (TGF-β1, we observed upregulation of HSP27 along with that of α-smooth muscle actin (α-SMA, a marker of myofibroblast differentiation, in cultured human and mouse lung fibroblasts. Furthermore, by using siRNA knockdown, we demonstrated that HSP27 was involved in cell survival and upregulation of fibronectin, osteopontin (OPN and type 1 collagen, all functional markers of myofibroblast differentiation, in TGF-β1-treated MRC-5 cells. In lung tissues of bleomycin-treated mice, HSP27 was strongly upregulated and substantially co-localized with α-SMA, OPN and type I collagen but not with proSP-C (a marker of type II alveolar epithelial cells, E-cadherin (a marker of epithelial cells or F4/80 (a marker of macrophages. A similar co-localization of HSP27 and α-SMA was observed in lung tissues of patients with idiopathic pulmonary fibrosis. Furthermore, airway delivery of HSP27 siRNA effectively suppressed bleomycin-induced pulmonary fibrosis in mice. Collectively, our findings indicate that HSP27 is critically involved in myofibroblast differentiation of lung fibroblasts and may be a promising therapeutic target for lung fibrotic diseases.

  10. A family of quantum protocols

    Devetak, I; Winter, A


    We introduce two dual, purely quantum protocols: for entanglement distillation assisted by quantum communication (``mother'' protocol) and for entanglement assisted quantum communication (``father'' protocol). We show how a large class of ``children'' protocols (including many previously known ones) can be derived from the two by direct application of teleportation or super-dense coding. Furthermore, the parent may be recovered from most of the children protocols by making them ``coherent''. We also summarize the various resource trade-offs these protocols give rise to.

  11. Symmetric cryptographic protocols

    Ramkumar, Mahalingam


    This book focuses on protocols and constructions that make good use of symmetric pseudo random functions (PRF) like block ciphers and hash functions - the building blocks for symmetric cryptography. Readers will benefit from detailed discussion of several strategies for utilizing symmetric PRFs. Coverage includes various key distribution strategies for unicast, broadcast and multicast security, and strategies for constructing efficient digests of dynamic databases using binary hash trees.   •        Provides detailed coverage of symmetric key protocols •        Describes various applications of symmetric building blocks •        Includes strategies for constructing compact and efficient digests of dynamic databases

  12. Mitosis Methods & Protocols

    CarloAlberto Redi


    Full Text Available Mitosis Methods & Protocols Andrew D. McAinsh (Edt Humana press, Totowa, New Jersey (USA Series: Springer Protocols Methods in Molecular Biology, Volume 545, 2009 ISBN: 978-1-60327-992-5   It is quite clear from the contents of this book that the remarkably fascinating phenomenon of mitosis (that captured, and still is capturing, the attention of entire generations of scientists is still open to research. This is mainly due to our lack of knowledge of so many multifaced events of this extraordinarly complex process. The reader giving a glace through the Contents and Contributors sections is speechless: All of the first-class models (i.e., budding yeast, Caenorabditis, Drosophila, Xenopus and Human are presented..... 

  13. Cognitive Protocol Stack Design


    SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park , NC 27709-2211 cognitive...related to mobility and topology changes in a wireless multi-hop ad hoc network. (xv) We used a cross-layer formulation to design transmission...the transmission parameters, the implemented protocol and the network topology . The solution adopted involves a heuristic metric to measure how the

  14. Dysphonia risk screening protocol

    Katia Nemr


    Full Text Available OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children, 29.25 (adult women, 22.75 (adult men, and 27.10 (seniors. CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics.

  15. Bach1 siRNA attenuates bleomycin-induced pulmonary fibrosis by modulating oxidative stress in mice

    Liu, Yuan; Zheng, Yi


    Oxidative stress plays an essential role in inflammation and fibrosis. Bach1 is an important transcriptional repressor that acts by modulating oxidative stress and represents a potential target in the treatment of pulmonary fibrosis (PF). In this study, we knocked down Bach1 using adenovirus-mediated small interfering RNA (siRNA) to determine whether the use of Bach1 siRNA is an effective therapeutic strategy in mice with bleomycin (BLM)-induced PF. Mouse lung fibroblasts (MLFs) were incubated with transforming growth factor (TGF)-β1 (5 ng/ml) and subsequently infected with recombined adenovirus-like Bach1 siRNA1 and Bach1 siRNA2, while an empty adenovirus vector was used as the negative control. The selected Bach1 siRNA with higher interference efficiency was used for the animal experiments. A mouse model of BLM-induced PF was established, and Bach1 siRNA (1×109 PFU) was administered to the mice via the tail vein. The results revealed that the Bach1 mRNA and protein levels were significantly downregulated by Bach1 siRNA. Furthermore, the MLFs infected with Bach1 siRNA exhibited increased mRNA and protein expression levels of heme oxygenase-1 and glutathione peroxidase 1, but decreased levels of TGF-β1 and interleukin-6 in the cell supernatants compared with the cells exposed to TGF-β1 alone. Bach1 knockdown by siRNA also enhanced the expression of antioxidant factors, but suppressed that of fibrosis-related cytokines in mice compared with the BLM group. Finally, the inflammatory infiltration of alveolar and interstitial cells and the destruction of lung structure were significantly attenuated in the mide administered Bach1 siRNA compared with those in the BLM group. On the whole, our findings demonstrate that Bach1 siRNA exerts protective effects against BLM-induced PF in mice. Our data may provide the basis for the development of novel targeted therapeutic strategies for PF. PMID:27959382

  16. Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats.

    Altintas, Nejat; Erboga, Mustafa; Aktas, Cevat; Bilir, Bulent; Aydin, Murat; Sengul, Aysun; Ates, Zehra; Topcu, Birol; Gurel, Ahmet


    We aimed to investigate the preventive effect of Infliximab (IFX), a tumor necrosis factor (TNF)-α inhibitor, on bleomycin (BLC)-induced lung fibrosis in rats. Rats were assigned into four groups as follows: I-BLC group, a single intra-tracheal BLC (2.5 mg/kg) was installed; II-control group, a single intra-tracheal saline was installed; III-IFX + BLC group, a single-dose IFX (7 mg/kg) was administered intraperitoneally (i.p.), 72 h before the intra-tracheal BLC installation; IV-IFX group, IFX (7 mg/kg) was administered alone i.p. on the same day with IFX + BLC group. All animals were sacrificed on the 14th day of BLC installation. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin (IL)-6, periostin, YKL-40, nitric oxide (NO) in rat serum were measured, as well as, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and reduced glutathione (GSH), hydroxyproline, malondialdehyde (MDA) content in lung homogenates. Lung tissues were stained with hematoxylin and eosin (H&E) for quantitative histological evaluation. The inducible nitric oxide synthase (iNOS) expression and cell apoptosis in the lung tissues were determined quantitatively by immunohistochemical staining (INOS) and by TUNNEL staining, respectively. BLC installation worsened antioxidant status (such as SOD, CAT, GPx, GSH, MPO), while it increased the serum TNF-α, TGF-β, IL-6, periostin, YKL-40, and lipid peroxidation, and collagen deposition, measured by MDA and hydroxyproline, respectively. IFX pretreatment improved antioxidant status as well as BLC-induced lung pathological changes, while it decreased the TNF-α, TGF-β, IL-6, periostin, YKL-40, lipid peroxidation and collagen deposition. Finally, histological, immunohistochemical, and TUNNEL evidence also supported the ability of IFX to prevent BLC-induced lung fibrosis. The results of the present study indicate that IFX pretreatment can attenuate

  17. Boswellic acids extract attenuates pulmonary fibrosis induced by bleomycin and oxidative stress from gamma irradiation in rats

    Mansour Somaya


    Full Text Available Abstract Background Interstitial pulmonary fibrosis is characterized by an altered cellular composition of the alveolar region with excessive deposition of collagen. Lung inflammation is also common in pulmonary fibrosis. This study aims to test the inhibition of 5-lipooxygenase (5-LOX by boswellic acid (BA extract in an experimental model of pulmonary fibrosis using bleomycin (BL. Methods Boswellic acid extract (1 g/kg was force-fed to rats seven days prior to administration of BL or gamma irradiation or both. BL (0.15 U/rat in 25 μl of 0.9% normal saline (NS or 0.9% NS alone was administered intratracheally. Rats were exposed to two fractionated doses of gamma irradiation (0.5 Gy/dose/week with a gamma cell-40 (Cesium-137 irradiation units, Canada during the last two weeks of the experiment. BA was administered during BL or irradiation treatment or both. After the animals were sacrificed, bronchoalveolar lavage was performed; lungs were weighed and processed separately for biochemical and histological studies. Results In rats treated with BL, levels of transforming growth factor-β1 (TGF-β1 and tumor necrosis factor-α (TNF-α were significantly elevated (P = 0.05 and P = 0.005. Hydroxyproline was highly and extensively expressed. Immunoreactive compounds were abundantly expressed, represented in the levels of macrophages infiltrate, accumulation of eosinophils and neutrophils in the lung as well as the aggregation of fibroblasts in the fibrotic area. The levels of lipoxygenase enzyme activity were significantly increased (P = 0.005. Antioxidant activities measured in BL-treated rats deteriorated, coupled with the elevation of both levels of plasma lipid peroxide (LP content and bronchoalveolar lavage lactate dehydrogenase activity. BA-treated rats had reduced number of macrophages, (P = 0.01, neutrophils in bronchoalveolar lavage (P = 0.01 and protein (P = 0.0001. Moreover, the hydroxyproline content was significantly lowered in BA

  18. Bleomycin-induced epithelial–mesenchymal transition in sclerotic skin of mice: Possible role of oxidative stress in the pathogenesis

    Zhou, Cheng-Fan, E-mail: [Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China); Zhou, Deng-Chuan [Department of Emergency Medicine and Critical Care Medicine, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Zhang, Jia-Xiang; Wang, Feng; Cha, Wan-Sheng [Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China); Wu, Chang-Hao [Department of Biochemistry and Physiology, Faculty of Health and Medical Sciences, University of Surrey (United Kingdom); Zhu, Qi-Xing, E-mail: [Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China)


    Epithelial–mesenchymal transition (EMT) derived myofibroblasts are partly responsible for the increased collagen synthesis and deposition that occur in tissue fibrosis; however EMT occurrence in skin fibrosis and its mechanism remain unknown. The aim of this study was to investigate whether epithelial cells undergo EMT and determine the role of oxidative stress in this process. BALB/c mice were subcutaneously injected with bleomycin (BLM) or phosphate buffer saline (PBS) into the shaved back daily for 2, 3, and 4 weeks. Skin collagen deposition was evaluated by histopathology and Western blotting. EMT characteristics in the skin were determined by histopathology and immunofluorescent staining for E-cadherin and vimentin, which were further evaluated by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the role of oxidative stress in EMT, the antioxidant N-acetylcysteine (NAC) was intraperitoneally (100 mg/kg body weight/day) injected daily for 3 weeks. The epithelial suprabasal cells were detached from the basement membrane zone (BMZ) in the sclerotic skin treated with BLM. Immunofluorescent staining indicated vimentin-positive epithelial cells frequently occurring in the thickened epidermis of BLM-treated mice. Western blotting and RT-PCR showed that the expression of E-cadherin was significantly decreased but that of vimentin significantly increased in the skin treated with BLM. NAC attenuated BLM induced oxidative damage, changes in E-cadherin and vimentin expressions and collagen deposition in the sclerotic skin of mice. This study provides the first evidence that BLM induces the EMT of the epithelial cells superficial to the basement membrane zone in the skin fibrosis. Oxidative stress may contribute, at least in part, to BLM induced EMT and skin fibrosis in mice. - Highlights: • We provided the first evidence that EMT occurred in BLM-induced skin fibrosis. • Epithelial cells superficial to the BMZ underwent

  19. Automatic Validation of Protocol Narration

    Bodei, Chiara; Buchholtz, Mikael; Degano, Pierpablo;


    We perform a systematic expansion of protocol narrations into terms of a process algebra in order to make precise some of the detailed checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we...

  20. Meiotic and Mitotic Phenotypes Conferred by the blm1-1 Mutation in Saccharomyces cerevisiae and MSH4 Suppression of the Bleomycin Hypersusceptibility

    Carol Wood Moore


    Full Text Available Abstract: Oxidative damage can lead to a number of diseases, and can be fatal. The blm1-1 mutation of Saccharomyces cerevisiae confers hypersusceptibility to lethal effects of the oxidative, anticancer and antifungal agent, bleomycin. For the current report, additional defects conferred by the mutation in meiosis and mitosis were investigated. The viability of spores produced during meiosis by homozygous normal BLM1/BLM1, heterozygous BLM1/blm1-1, and homozygous mutant blm1-1/blm1-1 diploid strains was studied and compared. Approximately 88% of the tetrads derived from homozygous blm1-1/blm1-1 mutant diploid cells only produced one or two viable spores. In contrast, just one tetrad among all BLM1/BLM1 and BLM1/blm1-1 tetrads only produced one or two viable spores. Rather, 94% of BLM1/BLM1 tetrads and 100% of BLM1/blm1-1 tetrads produced asci with four or three viable spores. Thus, at least one copy of the BLM1 gene is essential for the production of four viable spores after meiosis. During mitotic growth, mutant blm1-1 strains grew at reduced rates and produced cells with high frequencies of unusual morphologies compared to wild-type strains. These results indicated BLM1 is also essential for normal mitotic growth. We also investigated the suppression by the MSH4 gene, a meiosis-specific MutS homolog, of the bleomycin hypersusceptibility of blm1-1 mutant cells, and the relationship of MSH4 to BLM1. We screened a genomic library, and isolated the MSH4 gene on the basis of its ability to suppress lethal effects of bleomycin in blm1-1 cells. However, genetic mapping studies indicated that BLM1 and MSH4 are not the same gene. The possibility that chromosomal nondisjunction could be the basis for the inability of blm1-1/blm1-1 mutant cells to produce four viable spores after meiosis is discussed.

  1. CT protocol review and optimization.

    Kofler, James M; Cody, Dianna D; Morin, Richard L


    To reduce the radiation dose associated with CT scans, much attention is focused on CT protocol review and improvement. In fact, annual protocol reviews will soon be required for ACR CT accreditation. A major challenge in the protocol review process is determining whether a current protocol is optimal and deciding what steps to take to improve it. In this paper, the authors describe methods for pinpointing deficiencies in CT protocols and provide a systematic approach for optimizing them. Emphasis is placed on a team approach, with a team consisting of at least one radiologist, one physicist, and one technologist. This core team completes a critical review of all aspects of a CT protocol and carefully evaluates proposed improvements. Changes to protocols are implemented only with consensus of the core team, with consideration of all aspects of the CT examination, including image quality, radiation dose, patient care and safety, and workflow.


    Division des Ressources Humaines; Human Resources Division; Tel. 74683-79494


    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.


    Division du Personnel


    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

  4. Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.

    Kis, Erika; Baltás, Eszter; Kinyó, Agnes; Varga, Erika; Nagy, Nikoletta; Gyulai, Rolland; Kemény, Lajos; Oláh, Judit


    Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

  5. Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles.

    Lee, Changkyu; Seo, Jisoo; Hwang, Ha Shin; Thao, Le Quang; Lee, Seunghyun; Lee, Eun Seong; Lee, Eun Hee; Choi, Han-Gon; Youn, Yu Seok


    Pulmonary fibrosis is a chronic lung disease characterized by inflammation and collagen deposition, with an estimated mortality rate exceeding 70%. Here, we evaluated the therapeutic effectiveness of inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles (chitosan TAC PLGA-NPs) in a bleomycin-induced pulmonary fibrosis mouse model. Chitosan TAC PLGA-NPs were fabricated using an o/w emulsification diffusion method, and uncoated TAC PLGA-NPs and chitosan TAC PLGA-NPs were spherical with approximate diameters of 320 and 441 nm, respectively. The zeta potential of chitosan TAC PLGA-NPs (+13.6 mV) was increased significantly by chitosan-coating versus uncoated TAC PLGA-NPs (-28.3 mV). The incorporation efficiency of tacrolimus was 37.7%, and the tacrolimus was gradually released until about 5 day. Direct inhalation of chitosan TAC PLGA-NPs (TAC 180 μg/mouse) twice a week produced marked anti-fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from daily oral administration (TAC 300 μg/mouse) on the basis of hematoxylin/eosin and Masson's trichrome staining assessments. Imaging of lung deposition showed that chitosan TAC PLGA-NPs were located well in the lungs and gradually faded over 96 h. The pulmonary delivery of tacrolimus could be therapeutically efficacious for treating pulmonary fibrosis. TAC-loaded PLGA nanoparticles should be considered to be an efficient sustained-release type inhalation system that reduces administration frequency and relevant side effects.

  6. Knock out of S1P3 receptor signaling attenuates inflammation and fibrosis in bleomycin-induced lung injury mice model.

    Ken Murakami

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid metabolite involved in many critical cellular processes, including proliferation, migration, and angiogenesis, through interaction with a family of five G protein-coupled receptors (S1P1-5. Some reports have implicated S1P as an important inflammatory mediator of the pathogenesis of airway inflammation, but the role of S1P3 in the pathogenesis of lung diseases is not completely understood. We used S1P3-deficient (knockout (KO mice to clarify the role of S1P3 receptor signaling in the pathogenesis of pulmonary inflammation and fibrosis using a bleomycin-induced model of lung injury. On the seventh day after bleomycin administration, S1P3 KO mice exhibited significantly less body weight loss and pulmonary inflammation than wild-type (WT mice. On the 28th day, there was less pulmonary fibrosis in S1P3 KO mice than in WT mice. S1P3 KO mice demonstrated a 56% reduction in total cell count in bronchoalveolar lavage fluid (BALF collected on the seventh day compared with WT mice; however, the differential white blood cell profiles were similar. BALF analysis on the seventh day showed that connective tissue growth factor (CTGF levels were significantly decreased in S1P3 KO mice compared with WT mice, although no differences were observed in monocyte chemotactic protein-1 (MCP-1 or transforming growth factor β1 (TGF-β1 levels. Finally, S1P levels in BALF collected on the 7th day after treatment were not significantly different between WT and S1P3 KO mice. Our results indicate that S1P3 receptor signaling plays an important role in pulmonary inflammation and fibrosis and that this signaling occurs via CTGF expression. This suggests that this pathway might be a therapeutic target for pulmonary fibrosis.

  7. MAP3K19 Is a Novel Regulator of TGF-β Signaling That Impacts Bleomycin-Induced Lung Injury and Pulmonary Fibrosis.

    Stefen A Boehme

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive, debilitating disease for which two medications, pirfenidone and nintedanib, have only recently been approved for treatment. The cytokine TGF-β has been shown to be a central mediator in the disease process. We investigated the role of a novel kinase, MAP3K19, upregulated in IPF tissue, in TGF-β-induced signal transduction and in bleomycin-induced pulmonary fibrosis. MAP3K19 has a very limited tissue expression, restricted primarily to the lungs and trachea. In pulmonary tissue, expression was predominantly localized to alveolar and interstitial macrophages, bronchial epithelial cells and type II pneumocytes of the epithelium. MAP3K19 was also found to be overexpressed in bronchoalveolar lavage macrophages from IPF patients compared to normal patients. Treatment of A549 or THP-1 cells with either MAP3K19 siRNA or a highly potent and specific inhibitor reduced phospho-Smad2 & 3 nuclear translocation following TGF-β stimulation. TGF-β-induced gene transcription was also strongly inhibited by both the MAP3K19 inhibitor and nintedanib, whereas pirfenidone had a much less pronounced effect. In combination, the MAP3K19 inhibitor appeared to act synergistically with either pirfenidone or nintedanib, at the level of target gene transcription or protein production. Finally, in an animal model of IPF, inhibition of MAP3K19 strongly attenuated bleomycin-induced pulmonary fibrosis when administered either prophylactically ortherapeutically. In summary, these results strongly suggest that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease.

  8. Stream Control Transmission Protocol Steganography

    Fraczek, Wojciech; Szczypiorski, Krzysztof


    Stream Control Transmission Protocol (SCTP) is a new transport layer protocol that is due to replace TCP (Transmission Control Protocol) and UDP (User Datagram Protocol) protocols in future IP networks. Currently, it is implemented in such operating systems like BSD, Linux, HP-UX or Sun Solaris. It is also supported in Cisco network devices operating system (Cisco IOS) and may be used in Windows. This paper describes potential steganographic methods that may be applied to SCTP and may pose a threat to network security. Proposed methods utilize new, characteristic SCTP features like multi-homing and multistreaming. Identified new threats and suggested countermeasures may be used as a supplement to RFC 5062, which describes security attacks in SCTP protocol and can induce further standard modifications.

  9. Protocols for Scholarly Communication

    Pepe, Alberto; Pepe, Alberto; Yeomans, Joanne


    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should naturally guide authors towards OA publication and CERN wants to help reach a full...




    Full Text Available A Prospective randomized Clinical study of outcome of labour following. “A Programmed labour. Protocol” was done at Department of OBG, MRMC Gulbarga. The Protocol was aimed with dual. Objective of Providing Pain relief during labour and teaching the goal of safe motherhood by optimizing objective outcome. AIMS AND OBJECTIVES: Shortening of duration of labour. Effect of labour analgesia. Monitoring of the events during labour. Lowering the incidence of operative deliveries. METHODS: 100 cases primi pregnant women admitted in labour room are randomly selected. It is designed to apply to low risk primi parous, singleton cephalic presentation without evidence of CPD and spontaneous onset of labour. RESULTS: Shortened duration of all the stages of Labour, especially significant reduction in duration of active phase of labour. CONCLUSION: The programmed labour is simple easy and effective method for painless and safe delivery.

  11. Survey protocol for invasive species

    Menza, Charles


    This protocol was developed by the Biogeography Branch of NOAA’s Center for Coastal Monitoring and Assessment to support invasive species research by the Papahānaumokuākea Marine National Monument. The protocol’s objective is to detect Carijoa riisei and Hypnea musciformis in deepwater habitats using visual surveys by technical divers. Note: This protocol is designed to detect the presence or absence of invasive species. A distinct protocol is required to collect information on abundance ...

  12. New Progress of International Tax Administration in Australia and Its Enlightenment to China: Against the Background of BEPS Action Plan%澳大利亚国际税收管理工作的进展及借鉴——在全球BEPS行动计划背景下




  13. Static Validation of Security Protocols

    Bodei, Chiara; Buchholtz, Mikael; Degano, P.;


    We methodically expand protocol narrations into terms of a process algebra in order to specify some of the checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we demonstrate that these techniques ...... suffice to identify several authentication flaws in symmetric and asymmetric key protocols such as Needham-Schroeder symmetric key, Otway-Rees, Yahalom, Andrew secure RPC, Needham-Schroeder asymmetric key, and Beller-Chang-Yacobi MSR...

  14. 应用博莱霉素治疗儿童颜面部海绵状血管瘤%Treatment of orofacial cavernous haemangioma in children by bleomycin

    陆东辉; M.Jiddawei



  15. Internet Protocol Television (IPTV

    Lokesh Mittal


    Full Text Available IPTV is one of the mostly used technology of Internet and IP application. IPTV is a service for the delivery of broadcast TV, movies on demand and other interactive multimedia services over a secure, end-to-end operator managed broadband IP data network with desired QoS to the public with a broadband Internet connection. IPTV system may also include Internet services such as Web access and VoIP where it may be called Triple Play and is typically supplied by a broadband operator using the same infrastructure. IPTV is not the Internet Video that simply allows users to watch videos, like movie previews and web-cams, over the Internet in a best effort fashion. IPTV technology offers revenue-generating opportunities for the telecom and cable service providers. For traditional telephone service providers, Triple Play is delivered using a combination of optical fiber and Digital Subscriber Line (DSL technologies to its residential base. IPTV is a system where a digital television service is delivered by using Internet Protocol over a network infrastructure, which may include delivery by a broadband connection. A general definition of IPTV is television content that, instead of being delivered through traditional broadcast and cable formats, is received by the viewer through the technologies used for computer networks. In this paper I am trying to discuss this topic as my knowledge, including what is IPTV, how it works, its advantages and its applications

  16. Persistent improved results after adding vincristine and bleomycin to a cyclophosphamide/hydroxorubicin/Vm-26/prednisone combination (CHVmP) in stage III-IV intermediate- and high-grade non-Hodgkin's lymphoma. The EORTC Lymphoma Cooperative Group.

    Meerwaldt, J H; Carde, P; Somers, R; Thomas, J; Kluin-Nelemans, J C; Bron, D; Noordijk, E M; Cosset, J M; Bijnens, L; Teodorovic, I; Hagenbeek, A


    CHOP has been and still is regarded by many as the 'standard' treatment of advanced non-Hodgkin's lymphoma. In 1980 the EORTC Lymphoma Cooperative Group started a study to evaluate the addition of vincristine and bleomycin to its standard four-drug combination chemotherapy, CHVmP (cyclophosphamide, hydroxorubicin, Vm-26, prednisone). Eligible patients were stage III or IV, intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation E-I). One-hundred-eighty-nine patients were entered, of whom 140 were eligible and evaluable. A previous report showed an improved response rate and failure-free survival (FFS) and overall survival for the combination CHVmP-VB. At ten years, the outcome still favors the addition of vincristine and bleomycin. The FFS was 34% vs. 23% and the overall survival 34% vs 22%. This difference was mainly due to a difference in CR rate (74% vs. 49%), Relapse-free survival for patients reaching a CR was the same in both arms. When the patients were grouped according to the International Prognostic Factor Index, no statistically significant difference could be observed in favor of one treatment within either group. This trial clearly demonstrates the benefit gained by the addition of vincristine and bleomycin to 'standard' chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma.

  17. Virtual Communities for Protocol Development and Discussion.

    Teytelman, Leonid; Stoliartchouk, Alexei; Kindler, Lori; Hurwitz, Bonnie L


    The detailed know-how to implement research protocols frequently remains restricted to the research group that developed the method or technology. This knowledge often exists at a level that is too detailed for inclusion in the methods section of scientific articles. Consequently, methods are not easily reproduced, leading to a loss of time and effort by other researchers. The challenge is to develop a method-centered collaborative platform to connect with fellow researchers and discover state-of-the-art knowledge. is an open-access platform for detailing, sharing, and discussing molecular and computational protocols that can be useful before, during, and after publication of research results.



    In 1999, Seo and Sweeney proposed a simple authenticated key agreement protocol that was designed to act as a Diffie-Hellman key agreement protocol with user authentication.Various attacks on this protocol are described and enhanced in the literature. Recently, Ku and Wang proposed an improved authenticated key agreement protocol, where they asserted the protocol could withstand the existing attacks. This paper shows that Ku and Wang's protocol is still vulnerable to the modification attack and presents an improved authenticated key agreement protocol to enhance the security of Ku and Wang's protocol. The protocol has more efficient performance by replacing exponentiation operations with message authentication code operations.

  19. SIP protocol model for OMNET++

    Jan Kucerak


    Full Text Available The article describes our new SIP protocol implementation for the OMNeT++ simulation framework. OMNeT++ simulation framework provides an extensive support of IP related protocols, nevertheless a working SIP protocol implementation is missing. Real measurements were also done using a SIPp traffic generator and the results are compared to those obtained by our new SIP model. Since this work is a part of bigger project concerned strictly on measuring "first response times" over networks with a faulty transmission links, the actually collected statistics are focused only this way.

  20. Interoperation between AODV protocol and AOHR protocol for mobile ad hoc networks

    Wu, Shaochuan; Wang, Changhong; Zhang, Jiayan


    Although AOHR protocol has some excellent performance, no actual network utilizes AOHR as routing protocol. It is because that this protocol cannot interoperate with AODV protocol, which is the most famous routing protocol and used all over the world. The cost will be very huge to replace AODV protocol with AOHR protocol for existing networks, so the only feasible method is to modify AOHR protocol to interoperate with AODV as introduced in this paper. The simulation results prove that the modified AOHR protocol can help the existing AODV protocol provide routing service, and the interoperation of these two routing protocols is realized.

  1. Process for Reviewing Survey Protocols

    US Fish and Wildlife Service, Department of the Interior — This document describes the process for conducting two types of reviews of survey protocols. A quick assessment is used to acknowledge and describe to potential...

  2. Assessment of Established Survey Protocols

    US Fish and Wildlife Service, Department of the Interior — A form and instructions for quickly and briefly assessing a previously (prior to 2013) reviewed or approved survey protocol for use as a National or Regional survey...

  3. National Elk Refuge vaccination protocol

    US Fish and Wildlife Service, Department of the Interior — Proposal by the State of Wyoming, Wyoming Game and Fish Department, to vaccinate elk on the National Elk Refuge. The proposal provides a protocol for vaccinating elk...

  4. Improved Authenticated Multi-Key Agreement Protocol

    ZHANG Hua; YUAN Zheng; WEN Qiaoyan


    Zhou et al give an attack on Harn's modified authenticated multi-key agreement protocol, and give a protocol that can prevent the unknown key-share attack. The paper points out that the protocol is vulnerable to a concatenation attack. This paper proposes an improved authenticated multi-key agreement protocol which shows how to make Harn's protocol more secure by modifying the signature and verification. And this protocol can escape the concatenation attack.

  5. Formal Modeling of Communication Protocols.


    problems have been developed. 4 FORMAL MODELING OF COMMUNICATION PROTOCOLS The state machine model is motivated by the observation that protocols may be...simplest types of state machine model because they have only a single state variable (the state) which takes on a relatively small range of values. For...grammar, this correspondence is very apparent. For each state of the state machine model , we define a nonterminal symbol in the grammar. The inputs

  6. A genome-wide screen in Saccharomyces cerevisiae reveals altered transport as a mechanism of resistance to the anticancer drug bleomycin.

    Aouida, Mustapha; Pagé, Nicolas; Leduc, Anick; Peter, Matthias; Ramotar, Dindial


    The potent DNA damaging agent bleomycin (BLM) is highly effective for treating various cancers, although, in certain individuals, the development of cellular resistance to the drug can severely diminish its antineoplastic properties. We performed two independent genome-wide screens using a Saccharomyces cerevisiae mutant collection to isolate variants exhibiting either sensitivity or resistance to BLM. This procedure reproducibly identified a relatively large collection of 231 BLM-hypersensitive mutants, representing genes belonging to diverse functional groups. In contrast, only five BLM-resistant mutants could be recovered by our screens. Among these latter mutants, three were deleted for genes involved in plasma membrane transport, including the L-carnitine transporter Agp2, as well as the kinases Ptk2 and Sky1, which are involved in regulating polyamine transport. We further showed that Agp2 acts as a transporter of BLM and that overexpression of this transporter significantly enhances BLM-induced cell killing. Our data strongly implicate membrane transport as a key determinant in BLM resistance in yeast. This finding is critical, given that very little is known about BLM transport in human cells. Indeed, characterization of analogous mechanisms in humans may ultimately lead to enhancement of the antitumor properties of BLM.

  7. Aerosolized STAT1 Antisense Oligodeoxynucleotides Decrease the Concentrations of Inflammatory Mediators in Bronchoalveolar Lavage Fluid in Bleomycin-Induced Rat Pulmonary Fibrosis

    Ming Zeng; Bin Liao; Chen Zhu; Wenjun Wang; Xiaoqin Zhan; Xianming Fan


    It has been demonstrated that alveolar macrophages (AMs) play a key role in the pathogenesis of pulmonary fibrosis by releasing a variety of cytokines and inflammatory mediators. In addition, abnormal signal transducer and activator of transcription-1 (STAT1) activation in AMs may play a pivotal role in the process of alveolitis and pulmonary fibrosis. In this study, we transfected STAT1 antisense oligodeoxynucleotide (ASON) into rats by aerosolization, and then investigated the effect of STAT1 ASON on inflammatory mediators such as TGF-β, PDGF and TNF-α in bronchoalveolar lavage fluid (BALF) from rats with bleomycin (BLM)-induced rat pulmonary fibrosis. Our results showed that STAT1 ASON by aerosolization could enter into lung tissues and AMs. STAT1 ASON could inhibit mRNA and protein expressions of STATI and ICAM-1 in AMs of rat with pulmonary fibrosis, and had no toxic side effect on liver and kidney. Aerosolized STAT1 ASON could ameliorate the alveolitis through inhibiting the secretion of inflammatory mediators in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis. Cellular & Molecular Immunology. 2008;5(3):219-224.

  8. Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats.

    Togami, Kohei; Chono, Sumio; Tada, Hitoshi


    Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals. Moreover, disrupted epithelial tight junctions, including claudins-1, -3, and -5, were observed in pulmonary fibrotic lesions using immunofluorescence microscopy. In addition, destruction of tight junctions on model alveolar epithelial cells (NCI-H441) by transforming growth factor-β1 treatment enhanced the permeability of 6-CF and FDs through NCI-H441 cell monolayers. These results indicate that aerosolized drugs are easily distributed into the plasma after leakage through damaged tight junctions of alveolar epithelium. Therefore, the development of delivery systems for anti-fibrotic agents to improve intrapulmonary pharmacokinetics may be necessary for effective idiopathic pulmonary fibrosis therapy.

  9. Dose evaluation of therapeutic radiolabeled bleomycin complexes based on biodistribution data in wild-type rats:Effect of radionuclides in absorbed dose of different organs

    Hassan Yousefnia; Samaneh Zolghadri; Amir Reza Jalilian; Mohammad Ghannadi-Maragheh


    Bleomycins (BLMs), as tumor-seeking antibiotics, have been used for over 20 years in treatment of several types of cancers. Several radioisotopes are used in radiolabeling of BLMs for therapeutic and diagnostic purpos-es. An important points in developing new radiopharmaceuticals, especially therapeutic agents, is the absorbed dose delivered in critical organs. In this work, absorbed dose to organs after injection of 153Sm-, 177Lu-and 166Ho-labeled BLM was investigated by radiation dose assessment resource (RADAR) method based on biodis-tribution data in wild-type rats. The absorbed dose effect of the radionuclides was evaluated. The maximum absorbed dose for the complexes was observed in the kidneys, liver and lungs. For all the radiolabeled BLMs, bone and red marrow received considerable absorbed dose. Due to the high energy beta particles emitted by 166Ho, higher absorbed dose is observed for 166Ho-BLM in the most organs. The reported data can be useful for the determination of the maximum permissible injected activity of the radiolabeled BLMs in the treatment planning programs.

  10. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice

    Chow, Leola N.; Schreiner, Petra; Ng, Betina Y. Y.; Lo, Bernard; Hughes, Michael R.; Scott, R. Wilder; Gusti, Vionarica; Lecour, Samantha; Simonson, Eric; Manisali, Irina; Barta, Ingrid; McNagny, Kelly M.; Crawford, Jason; Webb, Murray; Underhill, T. Michael


    Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis. PMID:26998906

  11. Essential roles of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration.

    Ishida, Yuko; Kimura, Akihiko; Kondo, Toshikazu; Hayashi, Takahito; Ueno, Masaya; Takakura, Nobuyuki; Matsushima, Kouji; Mukaida, Naofumi


    We investigated the pathogenic roles of CC chemokine ligand (CCL)3 and its receptors, CC chemokine receptor (CCR)1 and CCR5, in bleomycin (BLM)-induced pulmonary fibrosis (PF). An intratracheal injection of BLM into wild-type (WT) mice caused a massive infiltration of granulocytes and macrophages, followed by the development of diffuse PF with fibrocyte accumulation. Intrapulmonary CCL3 expression was enhanced rapidly and remained at elevated levels until PF developed. Moreover, CCL3 protein was detected mainly in infiltrating granulocytes and macrophages, whereas transforming growth factor-beta1 protein was detected in macrophages and myofibroblasts. Compared with WT mice, collagen accumulation was reduced in CCL3(-/-) and CCR5(-/-) but not CCR1(-/-) mice. Moreover, the BLM-induced increases in intrapulmonary macrophage and fibrocyte numbers were attenuated in CCL3(-/-) and CCR5(-/-) but not CCR1(-/-) mice, although BLM increased bone marrow (BM) fibrocyte number to a similar extent in these strains. BM transplantation from CCR5(-/-) to WT, but not that from WT to CCR5(-/-) mice, recapitulated the phenotypes in CCR5(-/-) mice. Furthermore, CCR5(+/-) mice exhibited a significant reduction in BLM-induced fibrotic changes. These results demonstrated that locally produced CCL3 was involved in BLM-induced recruitment of BM-derived macrophages and fibrocytes, main producers of transforming growth factor-beta1, and subsequent development of PF by interacting mainly with CCR5.

  12. The mesh network protocol evaluation and development

    Pei Ping; PETRENKO Y.N.


    In this paper, we introduce a Mesh network protocol evaluation and development. It has a special protocol. We could easily to understand that how different protocols are used in mesh network. In addition to our comprehension, Multi – hop routing protocol could provide robustness and load balancing to communication in wireless mesh networks.

  13. Cryptographic Protocols under Quantum Attacks

    Lunemann, Carolin


    The realm of this thesis is cryptographic protocol theory in the quantum world. We study the security of quantum and classical protocols against adversaries that are assumed to exploit quantum effects to their advantage. Security in the quantum world means that quantum computation does not jeopardize the assumption, underlying the protocol construction. But moreover, we encounter additional setbacks in the security proofs, which are mostly due to the fact that some well-known classical proof techniques are forbidden by certain properties of a quantum environment. Interestingly, we can exploit some of the very same properties to the benefit of quantum cryptography. Thus, this work lies right at the heart of the conflict between highly potential effects but likewise rather demanding conditions in the quantum world.

  14. Lightweight Distance Bounding Protocol against Relay Attacks

    Kim, Jin Seok; Cho, Kookrae; Yum, Dae Hyun; Hong, Sung Je; Lee, Pil Joong

    Traditional authentication protocols are based on cryptographic techniques to achieve identity verification. Distance bounding protocols are an enhanced type of authentication protocol built upon both signal traversal time measurement and cryptographic techniques to accomplish distance verification as well as identity verification. A distance bounding protocol is usually designed to defend against the relay attack and the distance fraud attack. As there are applications to which the distance fraud attack is not a serious threat, we propose a streamlined distance bounding protocol that focuses on the relay attack. The proposed protocol is more efficient than previous protocols and has a low false acceptance rate under the relay attack.

  15. The Kyoto protocol development; La viabilite du protocole de Kyoto

    Cooper, R. [Harvard Univ., Barrow, AK (United States); Guesneris, R. [College de France, 75 - Paris (France)


    From the author R. Cooper point of view the Kyoto Protocol is a flawed concept. The reasons for dropping Kyoto are presented in this paper insisting that rejecting Kyoto not means to imply that global climate change is not a serious problem. After a presentation of the US policy facing the Climatic Change, some concluding propositions are proposed. (A.L.B.)

  16. Protocol Writing in Clinical Research

    Al-Jundi, Azzam


    Writing a research proposal is probably one of the most challenging and difficult task as research is a new area for the majority of postgraduates and new researchers. The purpose of this article is to summarize the most important steps and necessary guidelines for producing a standard research protocol. Academic and administrative success of any project is usually determined by acquiring a grant for the related field of research. Hence, the quality of a protocol is primarily required to achieve success in this scientific competition. PMID:28050522

  17. Developing protocols for obstetric emergencies.

    Roth, Cheryl K; Parfitt, Sheryl E; Hering, Sandra L; Dent, Sarah A


    There is potential for important steps to be missed in emergency situations, even in the presence of many health care team members. Developing a clear plan of response for common emergencies can ensure that no tasks are redundant or omitted, and can create a more controlled environment that promotes positive health outcomes. A multidisciplinary team was assembled in a large community hospital to create protocols that would help ensure optimum care and continuity of practice in cases of postpartum hemorrhage, shoulder dystocia, emergency cesarean surgical birth, eclamptic seizure and maternal code. Assignment of team roles and responsibilities led to the evolution of standardized protocols for each emergency situation.

  18. Superposition Attacks on Cryptographic Protocols

    Damgård, Ivan Bjerre; Funder, Jakob Løvstad; Nielsen, Jesper Buus


    Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece...... of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security...

  19. The Simplest Protocol for Oblivious Transfer

    Chou, Tung; Orlandi, Claudio


    Oblivious Transfer (OT) is the fundamental building block of cryptographic protocols. In this paper we describe the simplest and most efficient protocol for 1-out-of-n OT to date, which is obtained by tweaking the Diffie-Hellman key-exchange protocol. The protocol achieves UC-security against...... optimizations) is at least one order of magnitude faster than previous work. Category / Keywords: cryptographic protocols / Oblivious Transfer, UC Security, Elliptic Curves, Efficient Implementation...

  20. The Network Protocol Analysis Technique in Snort

    Wu, Qing-Xiu

    Network protocol analysis is a network sniffer to capture data for further analysis and understanding of the technical means necessary packets. Network sniffing is intercepted by packet assembly binary format of the original message content. In order to obtain the information contained. Required based on TCP / IP protocol stack protocol specification. Again to restore the data packets at protocol format and content in each protocol layer. Actual data transferred, as well as the application tier.

  1. High-dose-rate brachytherapy with local injection of bleomycin for N0 oral tongue cancer. Possibilities of the control of tumor implant by inserting applicators and the decrease in tumor dose

    Ohga, Saiji; Uehara, Satoru [National Kyushu Medical Center Hospital, Fukuoka (Japan); Miyoshi, Makoto [Kitakyushu Municipal Medical Center Hospital, Fukuoka (Japan); Jingu, Kenichi [Fukuoka Univ. (Japan). School of Medicine


    Twenty-eight patients with N0 oral tongue cancer were treated with high-dose-rate (HDR) interstitial brachytherapy combined with local injection of bleomycin between December 1997 and June 2001 at the Department of Radiology, National Kyushu Medical Center Hospital. A median dose of 5 mg of bleomycin was injected locally, and 16-20 Gy was delivered to the area surrounding applicators for control of the tumor implant during the initial two days. The two-year local recurrence-free survival rate was 96% [T1, 2: 100% (8/8, 15/15), T3: 80% (4/5)]. The two-year secondary neck node metastasis rate was 7.1% [T1: 12.5% (1/8), T2: 6.7% (1/15), T3: 0% (0/5)]. There were no tumor implants in any patients. We tried to decrease the minimal tumor dose step by step. The groups with median minimal tumor doses of 60 Gy, 50 Gy, and 40 Gy had local recurrence rates of 12.5% (1/8), 0% (0/14), and 0% (0/6), respectively. Local recurrence rates were not increased by decreasing the minimal tumor dose. Two patients (7%) had secondary neck node metastasis. Late adverse effects were tongue ulcer: 11% (3/28), oral floor ulcer: 4% (1/28), and osteonecrosis: 4% (1/28). These results suggest that control of the tumor implant and the decrease in minimal tumor dose below 60 Gy may be possible with the local injection of bleomycin and delivery of doses to the area surrounding the applicators when N0 tongue cancer is treated using {sup 192}Ir-HDR brachytherapy. (author)

  2. Probability Distributions over Cryptographic Protocols


    exception. Cryptyc integrates use of pattern- matching in the spi calculus framework , which in turn allows the specification of nested cryptographic...programs too: the metaheuristic search for security protocols,” Information and Software Technology, vol. 43, pp. 891– 904, December 2001. 131 [9] X

  3. Performance Evaluation of Security Protocols

    Bodei, Chiara; Buchholtz, Mikael; Curti, Michele


    We use a special operational semantics which drives us in inferring quantitative measures on systems describing cryptographis cryptographic protocols. We assign rates to transitions by only looking at these labels. The rates reflect the distributed architecture running applications and the use of...... of possibly different cryptosystems. We then map transition systems to Markov chains and evaluate performance of systems, using standard tools....

  4. A Student Teamwork Induction Protocol

    Kamau, Caroline; Spong, Abigail


    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

  5. Metabolomics protocols for filamentous fungi.

    Gummer, Joel P A; Krill, Christian; Du Fall, Lauren; Waters, Ormonde D C; Trengove, Robert D; Oliver, Richard P; Solomon, Peter S


    Proteomics and transcriptomics are established functional genomics tools commonly used to study filamentous fungi. Metabolomics has recently emerged as another option to complement existing techniques and provide detailed information on metabolic regulation and secondary metabolism. Here, we describe broad generic protocols that can be used to undertake metabolomics studies in filamentous fungi.

  6. From protocol to published report

    Berendt, Louise; Callréus, Torbjörn; Petersen, Lene Grejs


    BACKGROUND: Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and...

  7. Protocol biopsies for renal transplantation

    Rush David


    Full Text Available Protocol biopsies in renal transplantation are those that are procured at predetermined times post renal transplantation, regardless of renal function. These biopsies have been useful to study the natural history of the transplanted kidney as they have detected unexpected - i.e. "subclinical" pathology. The most significant subclinical pathologies that have been detected with protocol biopsies have been acute lesions, such as cellular and antibody mediated rejection, and chronic lesions, such as interstitial fibrosis and tubular atrophy, and transplant glomerulopathy. The potential benefit of early recognition of the above lesions is that their early treatment may result in improved long-term outcomes. Conversely, the identification of normal histology on a protocol biopsy, may inform us about the safety of reduction in overall immunosuppression. Our centre, as well as others, is attempting to develop non-invasive methods of immune monitoring of renal transplant patients. However, we believe that until such methods have been developed and validated, the protocol biopsy will remain an indispensable tool for the complete care of renal transplant patients.

  8. Petri Nets in Cryptographic Protocols

    Crazzolara, Federico; Winskel, Glynn


    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrat...

  9. Recursive Ping-Pong Protocols

    Huttel, Hans; Srba, Jiri


    This paper introduces a process calculus with recursion which allows us to express an unbounded number of runs of the ping-pong protocols introduced by Dolev and Yao. We study the decidability issues associated with two common approaches to checking security properties, namely reachability analys...

  10. Improving the DGK comparison protocol

    Veugen, P.J.M.


    When processing signals in the encrypted domain, homomorphic encryption can be used to enable linear operations on encrypted data. Comparison of encrypted data however requires an additional protocol between the parties and will be relatively expensive. A well-known and frequently used comparison pr

  11. Automata-theoretic protocol programming

    Jongmans, Sung-Shik Theodorus Quirinus


    Parallel programming has become essential for writing scalable programs on general hardware. Conceptually, every parallel program consists of workers, which implement primary units of sequential computation, and protocols, which implement the rules of interaction that workers must abide by. As progr

  12. Bundle Security Protocol for ION

    Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher


    This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

  13. The Kyoto Protocol and China



    The kyoto Protocol is an agreement to the United Nations Framework Convention on CLimate Change (UNFCCC)2,an international treaty on global warming .It is a legally binding agreement under which industrialized countries will reduce their collective emissions of greenhouse gases by an average of 5.2% compared to the level of 1990 during the 2008-12 period.

  14. Formally Generating Adaptive Security Protocols


    a proven version of leader election and 2/3 consensus. In 2011 we did the same for a simple version of Paxos. At each stage of the evolution as our... leader election [2] and authentication [4] would suffice for Paxos as well. In preparation for the harder protocols, we had added expressive power to the

  15. Prehospital thrombolysis in acute myocardial infarction: the Belgian eminase prehospital study (BEPS). BEPS Collaborative Group.


    Interest in early thrombolysis has prompted a study on the feasibility and time course of prehospital thrombolysis in patients with acute myocardial infarction (AMI) in six centres in Belgium. Patients with clinically suspected AMI and with typical ECG changes presenting within 4 h after onset of pain were treated with 30 units of Anisoylated Plasminogen Streptokinase Activator Complex (APSAC, eminase) intravenously by a mobile intensive care unit (MICU). Sixty-two patients were included in the study and an AMI was confirmed in 60. The mean time (+/- 1 SD) from onset of pain to injection of APSAC was 95 +/- 47 min and the mean estimated time gain, calculated as the time difference between the arrival of the MICU at home and the arrival of the MICU at the emergency department, was 50 +/- 17 min. In the prehospital period four patients developed ventricular fibrillation and one cardiogenic shock. During hospital stay severe complications were observed in four patients. Two events were fatal, one diffuse haemorrhage and one septal rupture; two events were non fatal, one feasible and that an estimated time gain of 50 min can be obtained. Potential risks and benefits remain to be demonstrated in a large controlled clinical trial.

  16. Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice

    Hong-Mei Yang


    Full Text Available Bleomycin (BLM, a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22 tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.

  17. Distribution of cells labelled by a novel somatic stem cell-recognizing antibody (A3) in pulmonary genesis and bleomycin induced pulmonary fibrosis in rats.

    Hori, M; Juniantito, V; Izawa, T; Ichikawa, C; Tanaka, M; Tanaka, K; Takenaka, S; Kuwamura, M; Yamate, J


    Stem cells play important roles in organogenesis and remodelling after tissue injury. A monoclonal antibody (A3) has been produced against rat somatic stem cells. The present study investigated the distribution of cells labelled by A3 in the lung of fetal, neonatal and adult rats, as well as in the lung of rats with bleomycin (BLM) induced pulmonary fibrosis. In developing fetal lungs, A3(+) interstitial cells were present around the bronchi/bronchioles and arterioles, while in neonatal and adult lungs, the A3 reactivity of the interstitial cells gradually disappeared and instead, vascular endothelial cells in alveolar capillaries and arterioles expressed A3. By double immunofluorescence labelling, the A3(+) interstitial cells also expressed vimentin (a mesenchymal marker) and CD34 (a marker of immature mesenchymal cells), indicating that the interstitial cells were immature mesenchymal cells concentrated in organs as precursors to cells of connective tissues. A3(+)endothelial cells were co-expressed RECA-1 (a marker of rat endothelial cells) and A3 was localized to the cell membrane and cytoplasm of these cells by immunoelectron microscopy. In BLM induced fibrotic lesions, there were many A3(+) cells, which also expressed vimentin or RECA-1 by dual immunofluorescence labelling. There were few CD34(+)/A3(+) double positive cells. No cells co-expressed A3 and α-smooth muscle actin (a marker of well-differentiated myofibroblastic cells). Although the detailed properties of cells labelled by A3 remain to be discovered, A3 would appear to be a useful marker of immature mesenchymal cells and vascular endothelial cells in developing lungs and in pulmonary fibrosis.

  18. Effect of antisense TIMP-1 cDNA on the expression of TIMP-1 and MMP-2 in lung tissue with pulmonary fibrosis induced by bleomycin.

    Tang, Haiying; Mao, Jingwei; Gao, Lili; Liu, Jia; Wu, Taihua


    The aim of this study was to observe the effect of antisense tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) cDNA on the concentration of hydroxyproline (HYP) and the expression of TIMP-1 and matrix metalloproteinase-2 (MMP-2) in the lung tissue of rats with bleomycin (BLM)‑induced pulmonary fibrosis. Sprague-Dawley rats were randomly divided into 5 groups: the control, pulmonary fibrosis model, sense TIMP-1 transfection, antisense TIMP-1 transfection and empty vector transfection groups. For the transfection groups, following the intratracheal injection of BLM on days 1, 3, 7, 14, 28 and 60, the rats were treated with retroviral vectors and sacrificed on day 28. The control and pulmonary fibrosis groups were treated with normal saline at the same time‑points. The concentration of HYP and the expression levels of TIMP-1 and MMP-2 in the lung tissue were detected. The HYP concentration and lung tissue TIMP-1 expression levels of the antisense TIMP-1 group decreased significantly on days 1 and 3 compared with those of the empty vector and pulmonary fibrosis groups at the same time-points (Ppulmonary fibrosis groups on days 7, 14, 28 and 60. The lung expression levels of MMP-2 in all groups, with the exception of the control group, had no significant differences at all time-points (P>0.05). Antisense TIMP-1 cDNA retroviral vectors are able to suppress the development of pulmonary fibrosis in the early stages.

  19. Atomic resolution structure of EhpR: phenazine resistance in Enterobacter agglomerans Eh1087 follows principles of bleomycin/mitomycin C resistance in other bacteria

    Itzen Aymelt


    Full Text Available Abstract Background The phenazines are redox-active secondary metabolites that a large number of bacterial strains produce and excrete into the environment. They possess antibiotic activity owing to the fact that they can reduce molecular oxygen to toxic reactive oxygen species. In order to take advantage of this activity, phenazine producers need to protect themselves against phenazine toxicity. Whereas it is believed that phenazine-producing pseudomonads possess highly active superoxide dismutases and catalases, it has recently been found that the plant-colonizing bacterium Enterobacter agglomerans expresses a small gene ehpR to render itself resistant towards D-alanyl-griseoluteic acid, the phenazine antibiotic produced by this strain. Results To understand the resistance mechanism installed by EhpR we have determined its crystal structure in the apo form at 2.15 Å resolution and in complex with griseoluteic acid at 1.01 Å, respectively. While EhpR shares a common fold with glyoxalase-I/bleomycin resistance proteins, the ligand binding site does not contain residues that some related proteins employ to chemically alter their substrates. Binding of the antibiotic is mediated by π-stacking interactions of the aromatic moiety with the side chains of aromatic amino acids and by a few polar interactions. The dissociation constant KD between EhpR and griseoluteic acid was quantified as 244 ± 45 μM by microscale thermophoresis measurements. Conclusions The data accumulated here suggest that EhpR confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. It is tempting to speculate that EhpR acts in concert with EhpJ, a transport protein of the major facilitator superfamily that is also encoded in the phenazine biosynthesis operon of E. agglomerans. The low affinity of EhpR for griseoluteic acid may be required for its physiological function.

  20. IL-21 induction of CD4+ T cell differentiation into Th17 cells contributes to bleomycin-induced fibrosis in mice.

    Lei, Ling; Zhong, Xiao-Ning; He, Zhi-Yi; Zhao, Cheng; Sun, Xue-Jiao


    Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs. Th17 cells and interleukin-17 (also called IL-17A) have been found to be increased in peripheral blood and skin in patients with SSc. IL-21 is a potent inducer of Th17 differentiation that is produced by activated T cells, and whose relationship with Th17 cells in SSc is unclear. Here, using a bleomycin (BLM)-induced mouse model of skin fibrosis, we detected the frequency of CD4+/IL-17+ (Th17) cells, CD4+/IL-21+ T cells and IL-21+ Th17 cells in peripheral blood, skin and lungs, as well as the serum content of IL-17A and IL-21. In addition, we assessed the differentiation of CD4+ T cells cultured from these mice into Th17 cells in response to treatment with IL-21. Compared with the control mice, Th17 cell counts and IL-17A levels were significantly increased and correlated with inflammatory and fibrotic indices in the skin and lungs of the BLM-induced fibrosis mice. Moreover, serum levels of CD4+/IL-21+ T cells, IL-21+ Th17 cells, and IL-21 were significantly increased in these mice, and correlated positively with serum levels of Th17 cells. In vitro experiments showed that IL-21 treated CD4+ T cells derived from BLM-induced mice differentiated into Th17 cells. Our results indicate that Th17 cells and IL-17A contributes to inflammatory and fibrotic processes in the skin and lungs in a BLM-induced mouse model of SSc. Moreover, the expansion of the Th17 cell population may be subsequent to IL-21 promotion of the differentiation of CD4+ T cells in these mice.

  1. Performance Evaluation of MANET Routing Protocols Based on Internet Protocols

    Hilal Bello Said,


    Full Text Available The topology of mobile ad hoc network (MANET changes rapidly and unpredictably due to nodes mobility. This makes routing protocols very important to analyze so as to communicate efficiently between the wireless nodes. Another important issue in the MANET is the internet protocols IPv4 and IPV6. The former which have been conventionally in use for long and the latter which is seen as the future standard for network architecture is studied due to its improved protection and huge address space support. In this paper, performance of AODV, DYMO, OLSRv2 and OLSR are analyzed under the IPv4 and IPv6 standards using the Qualnet simulator. Distinct performance metrics viz. Packet delivery ratio, Throughput, Average End-to-End Delay, and Average jitter are selected for the experiment. The results are then analyzed and scrutinized to provide qualitative assessment of their performances.

  2. Improvement In MAODV Protocol Using Location Based Routing Protocol

    Kaur Sharnjeet


    Full Text Available Energy saving is difficult in wireless sensor network (WSN due to limited resources. Each node in WSN is constrained by their limited battery power for their energy. The energy is reduced as the time goes off due to the packet transmission and reception. Energy management techniques are necessary to minimize the total power consumption of all the nodes in the network in order to maximize its life span. Our proposed protocol Location based routing (LBR aimed to find a path which utilizes the minimum energy to transmit the packets between the source and the destination. The required energy for the transmission and reception of data is evaluated in MATLAB. LBR is implemented on Multicast Ad hoc On Demand Distance Vector Routing Protocol (MAODV to manage the energy consumption in the transmission and reception of data. Simulation results of LBR show the energy consumption has been reduced.

  3. Novel analysis and improvement of Yahalom protocol

    CHEN Chun-ling; YU Han; L(U) Heng-shan; WANG Ru-chuan


    The modified version of Yahalom protocol improved by Burrows, Abradi, and Needham (BAN) still has security drawbacks. This study analyzed such flaws in a detailed way from the point of strand spaces, which is a novel method of analyzing protocol's security. First, a mathematical model of BAN-Yahalom protocol is constructed. Second, penetrators' abilities are restricted with a rigorous and formalized definition. Moreover, to increase the security of this protocol against potential attackers in practice, a further improvement is made to the protocol. Future application of this re-improved protocol is also discussed.

  4. Implementation and evaluation of a protocol management system for automated review of CT protocols.

    Grimes, Joshua; Leng, Shuai; Zhang, Yi; Vrieze, Thomas; McCollough, Cynthia


    Protocol review is important to decrease the risk of patient injury and increase the consistency of CT image quality. A large volume of CT protocols makes manual review labor-intensive, error-prone, and costly. To address these challenges, we have developed a software system for automatically managing and monitoring CT proto-cols on a frequent basis. This article describes our experiences in the implementation and evaluation of this protocol monitoring system. In particular, we discuss various strategies for addressing each of the steps in our protocol-monitoring workflow, which are: maintaining an accurate set of master protocols, retrieving protocols from the scanners, comparing scanner protocols to master protocols, reviewing flagged differences between the scanner and master protocols, and updating the scanner and/or master protocols. In our initial evaluation focusing only on abdo-men and pelvis protocols, we detected 309 modified protocols in a 24-week trial period. About one-quarter of these modified protocols were determined to contain inappropriate (i.e., erroneous) protocol parameter modifications that needed to be corrected on the scanner. The most frequently affected parameter was the series description, which was inappropriately modified 47 times. Two inappropriate modifications were made to the tube current, which is particularly important to flag as this parameter impacts both radiation dose and image quality. The CT protocol changes detected in this work provide strong motivation for the use of an automated CT protocol quality control system to ensure protocol accuracy and consistency.

  5. Kioto protocol; Protocolo de Kioto

    Romero, A.


    Atmospheric contamination by greenhouse gases is a global problem, and thus its solution requires global measures. Although the consequences of climate change are questioned and the foreseeable effects are not excessively serious, there are plenty of scientific reasons for all countries to make the necessary efforts to meet the objectives established by the Kyoto Protocol of reducing the six greenhouse gases over the period 2008-2012. Therefore, it seems essential that we understand the nature of the transformation that are occurring in the different systems, what changes they are causing and what costs they incur. Independently of its effectiveness and realism, the Kyoto Protocol is the first regulatory step in the direction of globalization in the environmental field. (Author)

  6. Chapter 14: Chiller Evaluation Protocol

    Tiessen, A.


    This protocol defines a chiller measure as a project that directly impacts equipment within the boundary of a chiller plant. A chiller plant encompasses a chiller--or multiple chillers--and associated auxiliary equipment. This protocol primarily covers electric-driven chillers and chiller plants. It does not include thermal energy storage and absorption chillers fired by natural gas or steam, although a similar methodology may be applicable to these chilled water system components. Chillers provide mechanical cooling for commercial, institutional, multiunit residential, and industrial facilities. Cooling may be required for facility heating, ventilation, and air conditioning systems or for process cooling loads (e.g., data centers, manufacturing process cooling). The vapor compression cycle, or refrigeration cycle, cools water in the chilled water loop by absorbing heat and rejecting it to either a condensing water loop (water cooled chillers) or to the ambient air (air-cooled chillers).

  7. On using Mobile IP Protocols

    Fayza A. Nada


    Full Text Available The recent advances in wireless communication technology and the unprecedented growth of the Internet have paved the way for wireless networking and IP mobility. Mobile Internet protocol has been designed within the IETF to support the mobility of users who wish to connect to the Internet and maintain communications as they move from place to place. This study describes and summarizes the current Internet draft for mobile IP (MIPv4 with its major components: agent discovery, registration and tunneling. In addition, we outline the available encapsulation techniques and route optimization procedure. In the end, we describe the design of the new protocol for transparent routing of IPv6 packets to mobile IPv6 nodes operating in the Internet.

  8. Second-line chemotherapy with bleomycin, methotrexate, and vinorelbine (BMV) for patients with squamous cell carcinoma of the head, neck and esophagus (SCC-HN&E) pretreated with a cisplatin-containing regimen: a phase II study.

    Moroni, M; Giannetta, L; Gelosa, G; Secondino, S; Chillura, G; Colombo, E; Siena, S


    We evaluated the toxicity and activity of bleomycin, methotrexate and vinorelbine (BMV) combination chemotherapy in cisplatin-pretreated patients with squamous cell carcinoma of the head, neck and esophagus (SCC-HN&E) with the aim of identifying a second-line therapy combination and schedule that might offer an improved therapeutic index. BMV (bleomycin 15 I.U., total dose, methotrexate 30 mg/m2, and vinorelbine 30 mg/m2) was administered intravenously every 2 weeks until disease progression, to 26 consecutive patients. Clinical and CT-scan evaluations revealed 7 partial responses (PR) 127%, 95% confidence interval: 9.6%-44.4%], and 13 patients with stable disease (SD) [50%]. The mean progression-free survival for patients who achieved a PR or SD was 6.47 months (range 4-13 months), with 75% of these patients experiencing partial relief of symptoms, mainly pain and dysphagia. BMV, administered second-line in an outpatient setting, has activity similar to that of the taxanes, but with a more acceptable toxicity profile including an absence of alopecia.

  9. Heuristic Methods for Security Protocols

    Qurat ul Ain Nizamani


    Full Text Available Model checking is an automatic verification technique to verify hardware and software systems. However it suffers from state-space explosion problem. In this paper we address this problem in the context of cryptographic protocols by proposing a security property-dependent heuristic. The heuristic weights the state space by exploiting the security formulae; the weights may then be used to explore the state space when searching for attacks.

  10. Building America House Simulation Protocols

    Hendron, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Engebrecht, Cheryn [National Renewable Energy Lab. (NREL), Golden, CO (United States)


    The House Simulation Protocol document was developed to track and manage progress toward Building America's multi-year, average whole-building energy reduction research goals for new construction and existing homes, using a consistent analytical reference point. This report summarizes the guidelines for developing and reporting these analytical results in a consistent and meaningful manner for all home energy uses using standard operating conditions.

  11. Heuristic Methods for Security Protocols

    Qurat ul Ain Nizamani; Emilio Tuosto


    Model checking is an automatic verification technique to verify hardware and software systems. However it suffers from state-space explosion problem. In this paper we address this problem in the context of cryptographic protocols by proposing a security property-dependent heuristic. The heuristic weights the state space by exploiting the security formulae; the weights may then be used to explore the state space when searching for attacks.

  12. New Models for Protocol Security


    protocols and primitives (e.g., Schnorrs identification scheme, commitment schemes secure against selective openings, Chaum Blind Signatures , etc...Theory 156: 246-268 (2015) 5 3. Samantha Leung, Edward Lui, Rafael Pass: Voting with Coarse Beliefs. ITCS 2015: 61 4. Jing Chen, Silvio Micali, Rafael...Schneider: Multi-Verifier Signatures . J. Cryptology 25(2): 310-348 (2012) 7 37. Rafael Pass, Muthuramakrishnan Venkitasubramaniam: A Parallel Repetition

  13. Automatic analysis of distance bounding protocols

    Malladi, Sreekanth; Kothapalli, Kishore


    Distance bounding protocols are used by nodes in wireless networks to calculate upper bounds on their distances to other nodes. However, dishonest nodes in the network can turn the calculations both illegitimate and inaccurate when they participate in protocol executions. It is important to analyze protocols for the possibility of such violations. Past efforts to analyze distance bounding protocols have only been manual. However, automated approaches are important since they are quite likely to find flaws that manual approaches cannot, as witnessed in literature for analysis pertaining to key establishment protocols. In this paper, we use the constraint solver tool to automatically analyze distance bounding protocols. We first formulate a new trace property called Secure Distance Bounding (SDB) that protocol executions must satisfy. We then classify the scenarios in which these protocols can operate considering the (dis)honesty of nodes and location of the attacker in the network. Finally, we extend the const...

  14. DSTC Layering Protocols in Wireless Cooperative Networks

    Elamvazhuthi, P S; Dey, B K


    In adhoc wireless relay networks, layers of relays are used to communicate from a source to a destination to achieve better reliability. In this paper, we consider five protocols derived from an earlier proposed protocol, where the relays do a simple processing before transmitting and as a result achieve distributed space-time code. Four of the protocols discussed utilize more complicated relaying schemes than simple layered protocols proposed in earlier literature. We have analyzed the effectiveness of these protocols in various power loss configurations among the paths. Optimum power allocation of the total power among various transmissions have been found by reasonable fine search for all the protocols. Bit error rate plots are compared under optimum power allocation for these protocols. From the simulation results, we draw some guidelines as to which protocol is good for what kind of environment.

  15. Language, Semantics, and Methods for Security Protocols

    Crazzolara, Federico

    used to give a formal semantics to security protocols which supports proofs of their correctness. More precisely, we give a compositional event-based semantics to an economical, but expressive, language for describing security protocols (SPL); so the events and dependency of a wide range of protocols......Security protocols help in establishing secure channels between communicating systems. Great care needs therefore to be taken in developing and implementing robust protocols. The complexity of security-protocol interactions can hide, however, security weaknesses that only a formal analysis can...... reveal. The last few years have seen the emergence of successful intensional, event-based, formal approaches to reasoning about security protocols. The methods are concerned with reasoning about the events that a security protocol can perform, and make use of a causal dependency that exists between...

  16. The reliable multicast protocol application programming interface

    Montgomery , Todd; Whetten, Brian


    The Application Programming Interface for the Berkeley/WVU implementation of the Reliable Multicast Protocol is described. This transport layer protocol is implemented as a user library that applications and software buses link against.

  17. ACSEPP On-Line Electronic Payment Protocol

    WANG Shao-bin; ZHU Xian; HONG Fan


    With analyzing the existing on-line electronic payment protocols, this paper presents a new on-line electronic payment protocol named ACSEPP: Anonymous, Convenient and Secure Electronic Payment Protocol.Its aim is to design a practical electronic payment protocol which is both secure and convenient.Without using PKI_CA frame, it realized the anonymity of consumer and merchant, the convenient of handling, the low cost of maintenance and the security.

  18. Security Verification of Secure MANET Routing Protocols


    the destination. The route discovery phase is complete upon receipt of the RREP at the requesting node. The DYMO protocol is a simpler version of AODV ...described in this appendix. The protocols are Secure AODV (SAODV), Secure Efficient Distance Vector (SEAD), and Secure Link State Routing Protocol (SLSP...SECURITY VERIFICATION OF SECURE MANET ROUTING PROTOCOLS THESIS Matthew F. Steele, Captain, USAF AFIT/GCS/ENG/12-03 DEPARTMENT OF THE AIR FORCE AIR

  19. A father protocol for quantum broadcast channels

    Dupuis, F; Dupuis, Fr\\'ed\\'eric; Hayden, Patrick


    We present a new protocol for quantum broadcast channels based on the fully quantum Slepian-Wolf protocol. The protocol yields an achievable rate region for entanglement-assisted transmission of quantum information through a quantum broadcast channel that can be considered the quantum analogue of Marton's region for classical broadcast channels. The protocol can be adapted to yield achievable rate regions for unassisted quantum communication and for entanglement-assisted classical communication. Regularized versions of all three rate regions are provably optimal.

  20. Model checking the HAVi leader election protocol

    Romijn, J.M.T.


    The HAVi specification proposes an architecture for audio/video interoperability in home networks. Part of the HAVi specification is a distributed leader election protocol. We have modelled this leader election protocol in Promela and Lotos and have checked several properties with the tools Spin and Xtl (from the Caesar/Aldebaran package). It turns out that the protocol does not meet some safety properties and that there are situations in which the protocol may never converge to designate a l...

  1. Bioinspired Security Analysis of Wireless Protocols

    Petrocchi, Marinella; Spognardi, Angelo; Santi, Paolo


    work, this paper investigates feasibility of adopting fraglets as model for specifying security protocols and analysing their properties. In particular, we give concrete sample analyses over a secure RFID protocol, showing evolution of the protocol run as chemical dynamics and simulating an adversary...

  2. Static Validation of a Voting Protocol

    Nielsen, Christoffer Rosenkilde; Andersen, Esben Heltoft; Nielson, Hanne Riis


    The desired security properties of electronic voting protocols include verifiability, accuracy, democracy and fairness. In this paper we use a static program analysis tool to validate these properties for one of the classical voting protocols under appropriate assumptions. The protocol is formali...

  3. Induced pluripotent stem cells inhibit bleomycin-induced pulmonary fibrosis in mice through suppressing TGF-β1/Smad-mediated epithelial to mesenchymal transition

    Yan Zhou


    Full Text Available Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS cells have been considered as an ideal resource for stem cell-based therapy. Although an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF-β1 signaling pathway, and epithelial to mesenchymal transition (EMT during bleomycin (BLM-induced lung fibrosis. A single intratracheal instillation of BLM (5 mg/kg was performed to induce pulmonary fibrosis in C57BL/6 mice. Then, iPS cells (c-Myc-free were administrated intravenously at 24 h following BLM instillation. Three weeks after BLM administration, pulmonary fibrosis was evaluated. As expected, treatment with iPS cells significantly limited the pathological changes, edema, and collagen deposition in lung tissues of BLM-induced mice. Mechanically, treatment with iPS cells obviously repressed the expression ratios of matrix metalloproteinase-2 (MMP-2 to its tissue inhibitor -2 (TIMP-2 and MMP-9/TIMP-1 in BLM-induced pulmonary tissues. In addition, iPS cell administration remarkably suppressed BLM-induced up-regulation of pulmonary inflammatory mediators, including tumor necrosis factor-α, interleukin (IL-1β, IL-6, inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and prostaglandin E2. We further demonstrated that transplantation of iPS cells markedly inhibited BLM-mediated activation of TGF-β1/Mothers against decapentaplegic homolog 2/3 (Smad2/3 and EMT in lung tissues through up-regulating epithelial marker E-cadherin and down-regulating mesenchymal markers including fibronectin, vimentin and α-smooth muscle actin. Moreover, in vitro, iPS cell-conditioned medium (iPSC-CM profoundly inhibited TGF-β1-induced EMT signaling pathway in mouse

  4. Sequence Patterns of Identity Authentication Protocols

    Tao Hongcai; He Dake


    From the viewpoint of protocol sequence, analyses are made of the sequence patterns of possible identity authentication protocol under two cases: with or without the trusted third party (TTP). Ten feasible sequence patterns of authentication protocol with TTP and 5 sequence patterns without TTP are gained. These gained sequence patterns meet the requirements for identity authentication,and basically cover almost all the authentication protocols with TTP and without TTP at present. All of the sequence patterns gained are classified into unilateral or bilateral authentication. Then , according to the sequence symmetry, several good sequence patterns with TTP are evaluated. The accompolished results can provide a reference to design of new identity authentication protocols.

  5. Analysing ZigBee Key Establishment Protocols

    Yüksel, Ender


    In this report, we present our approach for protocol analysis together with a real example where we find an important flow in a contemporary wireless sensor network security protocol. We start by modelling protocols using a specific process algebraic formalism called LySa process calculus. We then apply an analysis based on a special program analysis technique called control flow analysis. We apply this technique to the ZigBee-2007 End-to-End Application Key Establishment Protocol and with the help of the analysis discover an unknown flaw. Finally we suggest a fix for the protocol, and verify that the fix works by using the same technique.


    C. S. Staley; M. L. Abbott; P. D. Ritter


    Various laws stemming from the Clean Air Act of 1970 and the Clean Air Act amendments of 1990 require air emissions modeling. Modeling is used to ensure that air emissions from new projects and from modifications to existing facilities do not exceed certain standards. For radionuclides, any new airborne release must be modeled to show that downwind receptors do not receive exposures exceeding the dose limits and to determine the requirements for emissions monitoring. For criteria and toxic pollutants, emissions usually must first exceed threshold values before modeling of downwind concentrations is required. This document was prepared to provide guidance for performing environmental compliance-driven air modeling of emissions from Idaho National Engineering and Environmental Laboratory facilities. This document assumes that the user has experience in air modeling and dose and risk assessment. It is not intended to be a "cookbook," nor should all recommendations herein be construed as requirements. However, there are certain procedures that are required by law, and these are pointed out. It is also important to understand that air emissions modeling is a constantly evolving process. This document should, therefore, be reviewed periodically and revised as needed. The document is divided into two parts. Part A is the protocol for radiological assessments, and Part B is for nonradiological assessments. This document is an update of and supersedes document INEEL/INT-98-00236, Rev. 0, INEEL Air Modeling Protocol. This updated document incorporates changes in some of the rules, procedures, and air modeling codes that have occurred since the protocol was first published in 1998.

  7. Effective Protocols for Mobile Communications and Networking

    Espinoza, J.; Sholander, P.; Van Leeuwen, B,


    This report examines methods of mobile communications with an emphasis on mobile computing and wireless communications. Many of the advances in communications involve the use of Internet Protocol (IP), Asynchronous Transfer Mode (ATM), and ad hoc network protocols. However, many of the advances in these protocols have been focused on wired communications. Recently much focus has been directed at advancing communication technology in the area of mobile wireless networks. This report discusses various protocols used in mobile communications and proposes a number of extensions to existing protocols. A detailed discussion is also included on desirable protocol characteristics and evaluation criteria. In addition, the report includes a discussion on several network simulation tools that maybe used to evaluate network protocols.

  8. Authenticating Tripartite Key Agreement Protocol with Pairings

    Sheng-Li Liu; Fang-Guo Zhang; Ke-Fei Chen


    In this paper, an authenticated tripartite key agreement protocol is proposed, which is an ID-based one with pairings. This protocol involves only one round. The authenticity of the protocol is assured by a special signature scheme, so that messages carrying the information of two ephemeral keys can be broadcasted authentically by an entity. Consequently, one instance of the protocol results in eight session keys for three entities. In other word, one instance of the protocol generates a session key, which is eight times longer than those obtained from traditional key agreement protocols. Security attributes of the protocol are presented, and the computational overhead and bandwidth of the broadcast messages are analyzed as well.

  9. Generalized routing protocols for multihop relay networks

    Khan, Fahd Ahmed


    Performance of multihop cooperative networks depends on the routing protocols employed. In this paper we propose the last-n-hop selection protocol, the dual path protocol, the forward-backward last-n-hop selection protocol and the forward-backward dual path protocol for the routing of data through multihop relay networks. The average symbol error probability performance of the schemes is analysed by simulations. It is shown that close to optimal performance can be achieved by using the last-n-hop selection protocol and its forward-backward variant. Furthermore we also compute the complexity of the protocols in terms of number of channel state information required and the number of comparisons required for routing the signal through the network. © 2011 IEEE.

  10. Developing security protocols in χ-Spaces

    Crazzolara, Federico; Milicia, Giuseppe


    of formal protocol verification. Verification, however, is usually carried out on an abstract model not at all related with a protocol’s implementation. Experience shows that security breaches introduced in implementations of successfully verified models are rather common. The χ-Spaces framework...... is an implementation of SPL (Security Protocol Language), a formal model for studying security protocols. In this paper we discuss the use of χ-Spaces as a tool for developing robust security protocol implementations. To make the case, we take a family of key-translation protocols due to Woo and Lam and show how χ-Spaces......It is of paramount importance that a security protocol effectively enforces the desired security requirements. The apparent simplicity of informal protocol descriptions hides the inherent complexity of their interactions which, often, invalidate informal correctness arguments and justify the effort...

  11. A Secure Short Message Communication Protocol

    Chao-Wen Chang; Heng Pan; Hong-Yong Jia


    According to the security requirement of the short message service (SMS) industry application, a secure short message communication protocol is proposed. This is an application level protocol constructed on the standard SMS communication protocol using public key authentication and key agreement without the need of wireless public key infrastructure (WPKI). Secure short message transmission and dynamic key agreement between mobile terminals and the accessing gateway are realized. The security of the proposed protocol is validated through the BAN logic. Compared with the standard SMS protocol, the effective payload rate of our protocol can reach 91.4%, and subscriber identity module (SIM) tool kit (STK) applications based on our protocol suit well for all kinds of mobile terminals in practical application.

  12. Tool Supported Analysis of Web Services Protocols

    Marques, Abinoam P.; Ravn, Anders Peter; Srba, Jiri


    e.g. in the design of web services protocols, into an intermediate XML format. We further translate this format into a network of communicating state machines directly suitable for verification in the model checking tool UPPAAL. We introduce two types of communication media abstractions in order......We describe an abstract protocol model suitable for modelling of web services and other protocols communicating via unreliable, asynchronous communication channels. The model is supported by a tool chain where the first step translates tables with state/transition protocol descriptions, often used...... to ensure the finiteness of the protocol state-spaces while still being able to verify interesting protocol properties. The translations for different kinds of communication media have been implemented and successfully tested, among others, on agreement protocols from WS-Business Activity....

  13. Research on Container Behaviors Protocol


    With the development of middleware technology, there are some new features to be adopted on demand in middleware platform based on container component. Aiming at the adaptation of middleware platform, from the nature of component container, this paper begins with behaviors features of EJB (Enterprise Java Bean) container, extracts general behaviors protocol of container, and defines its formal behaviors specification. In the end, the interactive relationship of components is described by WRIGHT language, and the configuration of whole system is shown. The method proposed in this paper mines the hidden features of framework of component container, and applies to refactor middleware platform in reflection and aspect-oriented programming technology.

  14. New Models for Population Protocols

    Michail, Othon


    Wireless sensor networks are about to be part of everyday life. Homes and workplaces capable of self-controlling and adapting air-conditioning for different temperature and humidity levels, sleepless forests ready to detect and react in case of a fire, vehicles able to avoid sudden obstacles or possibly able to self-organize routes to avoid congestion, and so on, will probably be commonplace in the very near future. Mobility plays a central role in such systems and so does passive mobility, that is, mobility of the network stemming from the environment itself. The population protocol model was

  15. Experimental quantum multiparty communication protocols

    Smania, Massimiliano; Elhassan, Ashraf M.; Tavakoli, Armin; Bourennane, Mohamed


    Quantum information science breaks limitations of conventional information transfer, cryptography and computation by using quantum superpositions or entanglement as resources for information processing. Here we report on the experimental realisation of three-party quantum communication protocols using single three-level quantum system (qutrit) communication: secret-sharing, detectable Byzantine agreement and communication complexity reduction for a three-valued function. We have implemented these three schemes using the same optical fibre interferometric setup. Our realisation is easily scalable without compromising on detection efficiency or generating extremely complex many-particle entangled states.

  16. A structured data transfer protocol

    Barrett, P.; Rots, A.


    The transfer of data between different computers and programs can be a major obstacle during data analysis. We present a new data transfer protocol which is based on a simple structure containing a value, an error, and a unit. Each of these members can be arrays or another structure. The ability to nest structures allows for the concept of objects. When using an object-oriented language such as C++, reference can be made to the object name instead of each element explicitly. Prototype code has been written which implements the basic design with enhancements planned for the future.

  17. Analyzing the effect of routing protocols on media access control protocols in radio networks

    Barrett, C. L. (Christopher L.); Drozda, M. (Martin); Marathe, A. (Achla); Marathe, M. V. (Madhav V.)


    We study the effect of routing protocols on the performance of media access control (MAC) protocols in wireless radio networks. Three well known MAC protocols: 802.11, CSMA, and MACA are considered. Similarly three recently proposed routing protocols: AODV, DSR and LAR scheme 1 are considered. The experimental analysis was carried out using GloMoSim: a tool for simulating wireless networks. The main focus of our experiments was to study how the routing protocols affect the performance of the MAC protocols when the underlying network and traffic parameters are varied. The performance of the protocols was measured w.r.t. five important parameters: (i) number of received packets, (ii) average latency of each packet, (iii) throughput (iv) long term fairness and (v) number of control packets at the MAC layer level. Our results show that combinations of routing and MAC protocols yield varying performance under varying network topology and traffic situations. The result has an important implication; no combination of routing protocol and MAC protocol is the best over all situations. Also, the performance analysis of protocols at a given level in the protocol stack needs to be studied not locally in isolation but as a part of the complete protocol stack. A novel aspect of our work is the use of statistical technique, ANOVA (Analysis of Variance) to characterize the effect of routing protocols on MAC protocols. This technique is of independent interest and can be utilized in several other simulation and empirical studies.

  18. Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

    Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.


    Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective...... of the study was to explore plasma cytokine concentrations in GCC patients randomized to resistance training or usual care during BEP, in comparison with healthy controls. Design/Setting: This was a randomized controlled trial in GCC patients enrolled from an oncology clinic, including a healthy reference......). Changes in TNF-α correlated with pulmonary toxicity (P BEP display consistently elevated levels of systemic inflammatory markers compared with healthy...

  19. Research on Routing Protocol of Mobile Ad Hoc Network

    Tuo Ming Fu; Che Min


    Routing protocol is an important content of mobile Ad Hoc. The typical mobile Ad Hoc network routing protocols is introduced. The advantages and disadvantages of these routing protocols are analyzed. A hybrid routing protocol is put forward based on this.

  20. 博莱霉素联合局部热疗治疗恶性胸腔积液的临床观察%Clinical observation of bleomycin combined with local thermotherapy in the treatment of malignant pleural effusion

    周洋; 黄河; 张家洪; 龚建化


    Objective To observe the clinical effect of bleomycin combined with local thermotherapy in the treatment of NSCLC patients with malignant pleural effusion. Methods 50 NSCLC patients with malignant pleural effusion were randomly divided into two groups. All patients were treated with thoracentesis and inserted central ve-nous catheter to drainage pleural effusion. After exhaustion of pleural effusion, the control group was treated with ble-omycin by pleural perfusion, and the experiment group was treated with local thermotherapy on the base of the control group. The treatment, side effect and quality of life were compared. Results After the treatment, the KPS scores of living quality and the total effective rate of controlling pleural effusion were better in the experiment group than in the control group (P<0. 05), and the side effect was significant lower in the experiment group than in the control group (P<0. 05). Conclusion Bleomycin combined with local thermotherapy has a synergistic effect in the treatment of NSCLC with malignant pleural effusion.%目的:观察博莱霉素联合局部热疗治疗非小细胞肺癌( NSCLC)恶性胸腔积液的临床疗效。方法将50例NSCLC恶性胸腔积液的患者随机分为两组,采用胸腔穿刺术置入中心静脉导管引流胸腔积液,待排尽胸腔积液后,对照组给予胸腔灌注博莱霉素,实验组在对照组的基础上给予患者局部热疗,比较两组治疗情况、毒副反应及生活质量改善情况。结果两组患者治疗后,实验组患者的生活质量KPS评分及控制胸水的总有效率均明显高于对照组(P<0.05),且不良反应明显少于对照组(P<0.05)。结论博莱霉素联合局部热疗治疗NSCLC恶性胸腔积液具有协同作用,值得临床推广。

  1. VANET Routing Protocols: Pros and Cons

    Paul, Bijan; Bikas, Md Abu Naser


    VANET (Vehicular Ad-hoc Network) is a new technology which has taken enormous attention in the recent years. Due to rapid topology changing and frequent disconnection makes it difficult to design an efficient routing protocol for routing data among vehicles, called V2V or vehicle to vehicle communication and vehicle to road side infrastructure, called V2I. The existing routing protocols for VANET are not efficient to meet every traffic scenarios. Thus design of an efficient routing protocol has taken significant attention. So, it is very necessary to identify the pros and cons of routing protocols which can be used for further improvement or development of any new routing protocol. This paper presents the pros and cons of VANET routing protocols for inter vehicle communication.

  2. Developing practice protocols for advanced practice nursing.

    Paul, S


    In most states, the role of an advanced practice nurse is dependent on practice protocols that provide an organized method for analyzing and managing a disease or major symptom. They are also used to control the process of medical care and to specify steps in the delivery of that care. Creating appropriate practice protocols is one of the most important precursors to implementing the advanced practice role, because they virtually drive the clinician's ability to treat or manage clinical situations or disease states. This article outlines the steps involved in developing practice protocols and discusses the content that should be included in a protocol, providing an example of narrative and algorithm format protocols. Pros and cons, as well as legal issues related to practice protocols, are also presented.

  3. Merging Multiparty Protocols in Multiparty Choreographies

    Fabrizio Montesi


    Full Text Available Choreography-based programming is a powerful paradigm for defining communication-based systems from a global viewpoint. A choreography can be checked against multiparty protocol specifications, given as behavioural types, that may be instantiated indefinitely at runtime. Each protocol instance is started with a synchronisation among the involved peers. We analyse a simple transformation from a choreography with a possibly unbounded number of protocol instantiations to a choreography instantiating a single protocol, which is the merge of the original ones. This gives an effective methodology for obtaining new protocols by composing existing ones. Moreover, by removing all synchronisations required for starting protocol instances, our transformation reduces the number of communications and resources needed to execute a choreography.

  4. Symmetric cryptographic protocols for extended millionaires' problem

    LI ShunDong; WANG DaoShun; DAI YiQi


    Yao's millionaires' problem is a fundamental problem in secure multiparty computation, and its solutions have become building blocks of many secure multiparty computation solutions. Unfortunately,most protocols for millionaires' problem are constructed based on public cryptography, and thus are inefficient. Furthermore, all protocols are designed to solve the basic millionaires' problem, that is,to privately determine which of two natural numbers is greater. If the numbers are real, existing solutions do not directly work. These features limit the extensive application of the existing protocols. This study introduces and refines the first symmetric cryptographic protocol for the basic millionaires' problem, and then extends the symmetric cryptographic protocol to privately determining which of two real numbers is greater, which are called the extended millionaires' problem, and proposes corresponding Constructed based on symmetric cryptography, these protocols are very efficient.

  5. E-Cash Payment Protocols

    Shweta Srivastava


    Full Text Available E-cash is a payment system designed and implemented for making purchases over open networks such as the Internet. Need of a payment system which enables the electronic transactions are growing at the same time that the use of Internet is growing in our daily life. Present days electronic payment systems have a major problem, they cannot handle the security and the users anonymity and at the same time these systems are secure on the cost of their users anonymity. This paper shows the payment protocols for digital cash and discusses how a digital cash system can be formed by presenting a few of the present days digital cash systems in details. We also provide a comparison and determine them together to see which one of them fulfils the properties for digital cash and the required security level.

  6. Analysing Protocol Stacks for Services

    Gao, Han; Nielson, Flemming; Nielson, Hanne Riis


    We show an approach, CaPiTo, to model service-oriented applications using process algebras such that, on the one hand, we can achieve a certain level of abstraction without being overwhelmed by the underlying implementation details and, on the other hand, we respect the concrete industrial...... standards used for implementing the service-oriented applications. By doing so, we will be able to not only reason about applications at different levels of abstractions, but also to build a bridge between the views of researchers on formal methods and developers in industry. We apply our approach...... to the financial case study taken from Chapter 0-3. Finally, we develop a static analysis to analyse the security properties as they emerge at the level of concrete industrial protocols....

  7. Secure Multi-Player Protocols

    Fehr, Serge

    secret sharing in terms of simple algebraic conditions on the integer sharing coefficients, and we propose a black-box secret sharing scheme with minimal expansion factor. Note that, in contrast to the classical field-based secret sharing schemes, a black-box secret sharing scheme allows to share......, MPC can be based on arbitrary finite rings. This is in sharp contrast to the literature where essentially all MPC protocols require a much stronger mathematical structure, namely a field. Apart from its theoretical value, this can lead to efficiency improvements since it allows a greater freedom...... ones. We also construct a noninteractive distributed-verifier proof of circuit satisfiability, which—in principle—allows to prove anything that can be proven without giving away the proof....

  8. [Climate change and Kyoto protocol].

    Ergasti, G; Pippia, V; Murzilli, G; De Luca D'Alessandro, E


    Due to industrial revolution and the heavy use of fossil fuels, the concentration of greenhouse gases in the atmosphere has increased dramatically during the last hundred years, and this has lead to an increase in mean global temperature. The environmental consequences of this are: the melting of the ice caps, an increase in mean sea-levels, catastrophic events such as floodings, hurricanes and earthquakes, changes to the animal and vegetable kingdoms, a growth in vectors and bacteria in water thus increasing the risk of infectious diseases and damage to agriculture. The toxic effects of the pollution on human health are both acute and chronic. The Kyoto Protocol is an important step in the campaign against climatic changes but it is not sufficient. A possible solution might be for the States which produce the most of pollution to adopt a better political stance for the environment and to use renewable resources for the production of energy.

  9. [The research protocol. Part I].

    Miranda-Novales, María Guadalupe; Villasís-Keever, Miguel Ángel


    One of the principal aims in research is the publication of the study in scientific journals. This implies two challenges: the first one, the election of an adequate research design, and the second one, the concrete and simple wording of the results for the study to be accepted in the most appropriate journal according to the scope. Despite numerous supporting documents are available for both issues, the publication process is long, tiresome, and can discourage the most enthusiastic researcher. This is the first of a series of articles with the objective to describe the steps from the research question to the publication of the study. First of all, the importance of the research design will be addressed. The structure of the protocol is essential to achieve the objectives, and provides a way to organize the investigation in a logic, comprehensible and efficient manner.

  10. Failure of Kak quantum key distribution protocol

    Ching-Nung Yang; Su-Hsuan Chu; Bing-Ling Lu


    Kak's quantum key distribution (QKD) protocol provides not only the distribution but also the integrity of secret key simultaneously in quantum channel. Consequently the additional exchange of information, used to check whether an eavesdropper exists, is unnecessary. In this comment, we will point out the failure of Kak's protocol and show that Kak's protocol does not have the joint distribution and integration that the author declares in [1].

  11. The Braid-Based Bit Commitment Protocol

    WANG Li-cheng; CAO Zhen-fu; CAO Feng; QIAN Hai-feng


    With recent advances of quantum computation, new threats have closed in upon to the classical public key cryptosystems. In order to build more secure bit commitment schemes, this paper gave a survey of the new coming braid-based cryptography and then brought forward the first braid-based bit commitment protocol. The security proof manifests that the proposed protocol is computationally binding and information-theoretically hiding.Furthermore, the proposed protocol is also invulnerable to currently known quantum attacks.

  12. Reasoning about Protocol Change and Knowledge

    Wang, Yanjing

    In social interactions, protocols govern our behaviour and assign meaning to actions. In this paper, we investigate the dynamics of protocols and their epistemic effects. We develop two logics, inspired by Propositional Dynamic Logic (PDL) and Public Announcement Logic (PAL), for reasoning about protocol change and knowledge updates. We show that these two logics can be translated back to the standard PDL and PAL respectively.

  13. An Identity- Based Key- Exchange Protocol

    ZHANG Ya-juan; ZHU Yue-fei; HUANG Qiu-sheng


    An identity-based key-exchange protocol using a bilinear map is proposed and it is proved SK-secure(session key secure) in the AM (authenticated links adversarial model)provided the BDDH (bilinear Diffie-Hellmen) assumption is correct. Then we apply the signature-based authenticator to our protocol and obtain an identity-Based key-exchange protocol that is SK-secure in the UM (unauthenticated links adversarial model) provided the BDDH assumption is correct.

  14. Traffic Performance Analysis of Manet Routing Protocol

    Rajeswari, S; 10.5121/ijdps.2011.2306


    The primary objective of this research work is to study and investigate the performance measures of Gossip Routing protocol and Energy Efficient and Reliable Adaptive Gossip routing protocols. We use TCP and CBR based traffic models to analyze the performance of above mentioned protocols based on the parameters of Packet Delivery Ratio, Average End-to-End Delay and Throughput. We will investigate the effect of change in the simulation time and Number of nodes for the MANET routing protocols. For Simulation, we have used ns-2 simulator.

  15. Secure Key Management Protocol in WIMAX

    Noudjoud Kahya


    Full Text Available The Worldwide Interoperability for Microwave Access (WIMAX /IEEE 802.16, is new technology basedon wireless metropolitan area network. Security of connections access in WIMAX /IEEE 802.16 iscomplete with respect to the Privacy Key Management (PKM protocol. The protocol is responsible forproviding the secure distribution of keying data from Base Station (BS to Subscriber Station (SS. In thispaper we provide the formal analysis of PKMv2 using Scyther tool to verify the security properties. Wefound that PKMv2 is vulnerable to replay, DoS, Man-in-the middle attacks. At last we have proposed asecure protocol (SPKM to prevent the authorization protocol from such attacks.

  16. Status Report on the UNIDROIT Space Protocol

    Larsen, Paul B.


    In my status report on the UNIDROIT Space Protocol I will describe the history and purpose of the Space Protocol; I will state the Protocol's relationship to the UNIDROIT Convention on International Interests in Mobile Equipment in particular after the 2001 Cape Town Diplomatic Conference on the Convention. I will describe the COPUOS study of possible conflicts with the existing space law treaties and explain UNIDROIT's objective of avoiding conflicts between existing space law and the Space Protocol. Finally I will describe future steps to be taken.

  17. A formal model of fair exchange protocols

    QING Sihan; LI Gaicheng


    Based on the study of existing fair exchange protocols, this paper sets up an accurate formal model by stepwise refinement. In the process of refinement an unreliable channel is employed to simulate an attack behavior. The model provides a novel formal definition of exchanged items, and presents the formal goals for fairness, accountability,etc., reflecting the inherent requirements for fair exchange protocols across-the-board. In order to check, prove, and design fair exchange protocols effectively and efficiently, the model puts forward a novel property of abuse-freeness which applies to all fair exchange protocols, gives a formal definition for trust strand of the third party, and presents general criteria of designing a secure and effective fair exchange protocol. Taking a typical fair exchange protocol as an example, this paper presents the analysis steps of fair exchange protocols appealing to our model. An unknown attack is uncovered. The analysis reveals the process of a complete attack, discovering deeper reasons for causing an attack.Finally, we modify the flawed protocol and the revised protocol ensures the desirable properties.

  18. Mac protocols for cyber-physical systems

    Xia, Feng


    This book provides a literature review of various wireless MAC protocols and techniques for achieving real-time and reliable communications in the context of cyber-physical systems (CPS). The evaluation analysis of IEEE 802.15.4 for CPS therein will give insights into configuration and optimization of critical design parameters of MAC protocols. In addition, this book also presents the design and evaluation of an adaptive MAC protocol for medical CPS, which exemplifies how to facilitate real-time and reliable communications in CPS by exploiting IEEE 802.15.4 based MAC protocols. This book wil

  19. Wireless sensors networks MAC protocols analysis

    Chaari, Lamia


    Wireless sensors networks performance are strictly related to the medium access mechanism. An effective one, require non-conventional paradigms for protocol design due to several constraints. An adequate equilibrium between communication improvement and data processing capabilities must be accomplished. To achieve low power operation, several MAC protocols already proposed for WSN. The aim of this paper is to survey and to analyze the most energy efficient MAC protocol in order to categorize them and to compare their performances. Furthermore we have implemented some of WSN MAC protocol under OMNET++ with the purpose to evaluate their performances.

  20. Multimode Communication Protocols Enabling Reconfigurable Radios

    Berlemann Lars


    Full Text Available This paper focuses on the realization and application of a generic protocol stack for reconfigurable wireless communication systems. This focus extends the field of software-defined radios which usually concentrates on the physical layer. The generic protocol stack comprises common protocol functionality and behavior which are extended through specific parts of the targeted radio access technology. This paper considers parameterizable modules of basic protocol functions residing in the data link layer of the ISO/OSI model. System-specific functionality of the protocol software is realized through adequate parameterization and composition of the generic modules. The generic protocol stack allows an efficient realization of reconfigurable protocol software and enables a completely reconfigurable wireless communication system. It is a first step from side-by-side realized, preinstalled modes in a terminal towards a dynamic reconfigurable anymode terminal. The presented modules of the generic protocol stack can also be regarded as a toolbox for the accelerated and cost-efficient development of future communication protocols.

  1. A New Watermarking Protocol against Conspiracy

    ZHANG Jun; KOU Weidong; FAN Kai; CAO Xuefei


    A trusted third party introduced in watermarking protocols would decrease the security and affect the implementation of the protocols. In this paper, a new watermarking protocol with an un-trusted third party (UTTP) was proposed. Based on the idea of all-or-nothing disclosure of secret (ANDOS), all of the buyer, the seller and the third party didn't know the exact watermark, which was embedded in a digital content for tracing piracy. The proposed protocol provided mechanisms to trace piracy and protect customer's right. In addition, the problem that a seller colluded with UTTP to frame the buyer, namely, the conspiracy problem, could be avoided.

  2. Efficient secure two-party protocols

    Hazay, Carmit


    The authors present a comprehensive study of efficient protocols and techniques for secure two-party computation -- both general constructions that can be used to securely compute any functionality, and protocols for specific problems of interest. The book focuses on techniques for constructing efficient protocols and proving them secure. In addition, the authors study different definitional paradigms and compare the efficiency of protocols achieved under these different definitions.The book opens with a general introduction to secure computation and then presents definitions of security for a

  3. Experimental Study on Effect of Compound Biejia Ruangan Prescription(复方鳖甲软肝方) on High-Resolution Computerized Tomographic Images in Bleomycin Induced Pulmonary Fibrosis Rats

    张东伟; 王继峰; 牛建昭; 高宝华; 李贡宇


    Objective: To study the therapeutic effect of Compound Biejia Ruangan prescription (CBRP) on rat model with pulmonary fibrosis induced by bleomycin. Methods: Fifty-four male Sprague-Dawley rats were randomly divided into 6 groups (9 rats in each group). From the first day to the 28th day of the experiment, except to those in the sham-model control group that were treated with normal saline, the same amount of bleomycin injection as the normal saline given to the control group was given through endotracheal instillation to all the rats in all the other groups. From the 29th day of the modeling, CBRP solution of different dosages was respectively injected into the rats in the high, moderate and low CBRP dose group, while equal volume of normal saline was given to those in the sham-model control group and the model control group, and an equal volume of prednisone solution was given to rats in the prednisone group. On the 80th day, the high-resolution computerized tomographic (HRCT) images were observed on an equal footing, and HRCT-pathology was correlatively studied. Results: Different HRCT pathological changes were shown in the rats with pulmonary fibrosis, such as lung consolidation, thickening of interlobular septum and interlobular mesenchyma as well as lobular deformation, nodule shadow, abnormal brochiovascular tract, thickened pleura with irregular junction and polished glass-like dense shadows. Honeycomb lung was observed in some cases. Pathological sections showed fibrotic proliferation of lung tissues and noticeable pulmonary interstitial fibrosis. CBRP could improve HRCT images of rats with pulmonary fibrosis, and lower fibrotic proliferation of the lung tissue.Conclusion: CBRP plays its therapeutic role possibly through its effect on the structure of the lung in rats with pulmonary fibrosis.

  4. Wind power agreement protocol; Protocole d'accord eolien



    The aim of this protocol of agreement is to propose to wind turbine fitters some models of contracts allowing the setting up of wind turbines on agricultural lots. These documents, which make an indissociable ensemble, apply to both phases of development of a wind power project: the feasibility study phase, for a duration comprised between 2 and 5 years (studies, administrative procedures, precise definition of the project), and the construction, exploitation and dismantling phase. These documents will serve as common guidelines for both the farmers and the wind turbine designers. Both parties agree to meet together in the future to propose some modifications of these texts if necessary. The four models of contracts are attached to the document: contract for the feasibility study phase, first contract between the landlord and the farmer for the cancellation of the rural lease, second contract between the landlord and the wind power exploitation company for the common right lease, and the third contract between the farmer and the wind power company for the indemnification convention. (J.S.)

  5. Comment on "flexible protocol for quantum private query based on B92 protocol"

    Chang, Yan; Zhang, Shi-Bin; Zhu, Jing-Min


    In a recent paper (Quantum Inf Process 13:805-813, 2014), a flexible quantum private query (QPQ) protocol based on B92 protocol is presented. Here we point out that the B92-based QPQ protocol is insecure in database security when the channel has loss, that is, the user (Alice) will know more records in Bob's database compared with she has bought.

  6. Mobile IPv6 Protocols and Implementation

    Li, Qing; Shima, Keiichi


    Mobile IPv6 has become the key enabling technology for mobile data and multimedia services and devices worldwide. This book covers the IPv6 host mobility protocol known as 'mobile IPv6' and begins with a basic description of mobile IPv6 and then details protocol specifications and data structures as well as actual implementation.

  7. Performance of a connectionless protocol over ATM

    Heijenk, Geert J.; Moorsel, van Aad P.A.; Niemegeers, Ignas G.


    Recent studies show the existence of a demand for a connectionless broadband service. In order to cope with this demand, a connectionless protocol for the B-ISDN needs to be designed. Such a protocol should make use of ATM and the ATM Adaptation Layer. It needs to specify destination and bandwidth o

  8. Algebraic techniques for low communication secure protocols

    Haan, Robbert de


    This thesis discusses new results in two areas within cryptography; securely transmitting a message between two parties and securely computing a function on the inputs of multiple parties. For both of these areas we mainly consider perfectly secure protocols, which are protocols that have a zero err

  9. Summary Report on Rational Cryptographic Protocols

    Alwen, Joël; Cachin, Christian; Pereira, Olivier

    This report gives an overview of some of the models and techniques in rational cryptography, an emerging research area which in particular uses the methodologies and techniques of game theory to analyze cryptographic protocols and which uses cryptographic protocol theory to implement game theoretic...

  10. Secure Geographic Routing Protocols: Issues and Approaches

    sookhak, Mehdi; Haghparast, Mahboobeh; ISnin, Ismail Fauzi


    In the years, routing protocols in wireless sensor networks (WSN) have been substantially investigated by researches. Most state-of-the-art surveys have focused on reviewing of wireless sensor network .In this paper we review the existing secure geographic routing protocols for wireless sensor network (WSN) and also provide a qualitative comparison of them.

  11. Beveiliging Internet Protocol beter en beter

    Luiijf, H.A.M.


    Iedereen die gebruik maakt van e-mail, internet, intranet of extranet maakt gebruik van het in de jaren 7O ontworpen IP het Internet Protocol. Dit protocol zorgt ervoor dat toegang tot de diverse internetdiensten mogelijk is. Iedere computer die op internet wordt aangesloten, krijgt een eigen IP-adr

  12. Analysis of a security protocol in ?CRL

    Pang, J.


    Needham-Schroeder public-key protocol; With the growth and commercialization of the Internet, the security of communication between computers becomes a crucial point. A variety of security protocols based on cryptographic primitives are used to establish secure communication over insecure open netwo

  13. Diagrammatization of the Transmission Control Protocol

    Sabah Al-Fedaghi


    Full Text Available With the wide spread of Internet services, developers and users need a greater understanding of the technology of networking. Acquiring a clear understanding of communication protocols is an important step in understanding how a network functions; however, many protocols are complicated, and explaining them can be demanding. In addition, protocols are often explained in terms of traffic analysis and oriented toward technical staff and those already familiar with network protocols. This paper aims at proposing a diagrammatic methodology to represent protocols in general, with a focus on the Transmission Control Protocol and Secure Sockets Layer in particular. The purpose is to facilitate understanding of protocols for learning and communication purposes. The methodology is based on the notion of flow of primitive things in a system with six stages: creation, release, transfer, arrival, acceptance, and processing. Though the method presents a basic description of protocols without in-depth analysis of all aspects and mechanisms, the resultant conceptual description is a systematic specification that utilizes a few basic notions that assist in illustrating functionality and support comprehension.

  14. Network Coding Protocols for Smart Grid Communications

    Prior, Rui; Roetter, Daniel Enrique Lucani; Phulpin, Yannick


    We propose a robust network coding protocol for enhancing the reliability and speed of data gathering in smart grids. At the heart of our protocol lies the idea of tunable sparse network coding, which adopts the transmission of sparsely coded packets at the beginning of the transmission process b...

  15. Concurrent Validity of a Pragmatic Protocol.

    Duncan, Julie Condon; Perozzi, Joseph A.


    The scores of 11 non-handicapped kindergarten children on the Pragmatic Protocol (used in assessing language-handicapped children) were correlated with their ratings by five experienced judges on a 7-point equal-appearing interval scale of communicative competence. The concurrent validity of the Protocol and interobserver reliability were…

  16. The Formal Specifications for Protocols of Decoders

    YUAN Meng-ting; WU Guo-qing; SHU Feng-di


    This paper presents a formal approach, FSPD (Formal Specifications for Protocols of Decoders), to specify decoder communication protocols. Based on axiomatic, FSPD is a precise language with which programmers could use only one suitable driver to handle various types of decoders. FSPD is helpful for programmers to get high adaptability and reusability of decoder-driver software.

  17. A Survey on Distance Vector Routing Protocols

    Tang, Linpeng


    In this paper we give a brief introduction to five different distance vector routing protocols (RIP, AODV, EIGRP, RIP-MTI and Babel) and give some of our thoughts on how to solve the count to infinity problem. Our focus is how distance vector routing protocols, based on limited information, can prevent routing loops and the count to infinity problem.

  18. Welfare monitroing system : assessment protocol for horses

    Livestock Research,


    This document describes the protocol for horses in more detail. For the development of the protocol the Welfare Quality® framework was used. For each measure there is a description how to assess the measure including the method of classification.

  19. Model checking the HAVi leader election protocol

    Romijn, J.M.T.


    The HAVi specification proposes an architecture for audio/video interoperability in home networks. Part of the HAVi specification is a distributed leader election protocol. We have modelled this leader election protocol in Promela and Lotos and have checked several properties with the tools Spin a

  20. Secure Geographic Routing Protocols: Issues and Approaches

    Mehdi sookhak


    Full Text Available In the years, routing protocols in wireless sensor networks (WSN have been substantially investigated by researches Most state-of-the-art surveys have focused on reviewing of wireless sensor network .In this paper we review the existing secure geographic routing protocols for wireless sensor network (WSN and also provide a qualitative comparison of them.

  1. Treatment protocols for cervical cancer

    Vujkov Tamara


    Full Text Available Introduction Cervical cancer is the second most common cancer in women worldwide and the second cause of cancer death among women. About 95% (90% in developed countries of invasive carcinomas are of sqamous types, and 5% (10% in developed countries are adenocarcinomas. FIGO classification of cervical carcinomas, based on clinical staging and prognostic factor dictate therapeutic procedures and help in designing treatment protocols. Therapeutic modalities Surgical therapy includes conization, radical hysterectomy with pelvic lymphadenectomy and palliative operation urinary diversion and colostomy. Radiotherapy, brachytherapy and teletherapy are most recently combined with chemotherapy as concurrent chemoradiation. Discussion and conclusion No change in therapeutic modalities will ever decrease mortality rate of cervical carcinoma as much as education, prevention and early screening. The 5-year survival for locally advanced disease has not improved during the last 40 years as a result of failure to deliver therapy to the paraaortic region. Paraaortic lymph nodes should be evaluated before therapy planning by different imaging procedures, or more exactly by surgical staging: laparoscopy or laparotomy. Radical operations of cervical carcinoma should be performed by experienced surgeons, educated for this type of operation, with sufficient number of cases.

  2. Security Weaknesses in Arbitrated Quantum Signature Protocols

    Liu, Feng; Zhang, Kejia; Cao, Tianqing


    Arbitrated quantum signature (AQS) is a cryptographic scenario in which the sender (signer), Alice, generates the signature of a message and then a receiver (verifier), Bob, can verify the signature with the help of a trusted arbitrator, Trent. In this paper, we point out there exist some security weaknesses in two AQS protocols. Our analysis shows Alice can successfully disavow any of her signatures by a simple attack in the first protocol. Furthermore, we study the security weaknesses of the second protocol from the aspects of forgery and disavowal. Some potential improvements of this kind of protocols are given. We also design a new method to authenticate a signature or a message, which makes AQS protocols immune to Alice's disavowal attack and Bob's forgery attack effectively.

  3. Cryptanalysis of the arbitrated quantum signature protocols

    Gao, Fei; Qin, Su-Juan; Guo, Fen-Zhuo; Wen, Qiao-Yan


    As a new model for signing quantum messages, arbitrated quantum signature (AQS) has recently received a lot of attention. In this paper we study the cryptanalysis of previous AQS protocols from the aspects of forgery and disavowal. We show that in these protocols the receiver, Bob, can realize existential forgery of the sender's signature under known message attack. Bob can even achieve universal forgery when the protocols are used to sign a classical message. Furthermore, the sender, Alice, can successfully disavow any of her signatures by simple attack. The attack strategies are described in detail and some discussions about the potential improvements of the protocols are given. Finally we also present several interesting topics on AQS protocols that can be studied in future.

  4. Cryptanalysis of the arbitrated quantum signature protocols

    Gao, Fei; Guo, Fen-Zhuo; Wen, Qiao-Yan


    As a new model for signing quantum message, arbitrated quantum signature (AQS) has recently received a lot of attention. In this paper we study the cryptanalysis of previous AQS protocols from the aspects of forgery and disavowal. We show that in these protocols the receiver Bob can realize existential forgery of the sender's signature under known message attack. Bob can even achieve universal forgery when the protocols are used to sign a classical message. Furthermore, the sender Alice can successfully disavow any of her signatures by simple attack. The attack strategies are described in detail and some discussions about the potential improvements of the protocols are given. Finally we also present several interesting topics in future study on AQS protocols.

  5. Quantum Communication Attacks on Classical Cryptographic Protocols

    Damgård, Ivan Bjerre

    In the literature on cryptographic protocols, it has been studied several times what happens if a classical protocol is attacked by a quantum adversary. Usually, this is taken to mean that the adversary runs a quantum algorithm, but communicates classically with the honest players. In several cases......, one can show that the protocol remains secure even under such an attack. However, there are also cases where the honest players are quantum as well, even if the protocol uses classical communication. For instance, this is the case when classical multiparty computation is used as a “subroutine......” in quantum multiparty computation. Furthermore, in the future, players in a protocol may employ quantum computing simply to improve efficiency of their local computation, even if the communication is supposed to be classical. In such cases, it no longer seems clear that a quantum adversary must be limited...

  6. Quantum Communication Complexity of Quantum Authentication Protocols

    Guedes, Elloá B


    In order to perform Quantum Cryptography procedures it is often essencial to ensure that the parties of the communication are authentic. Such task is accomplished by quantum authentication protocols which are distributed algorithms based on the intrinsic properties of Quantum Mechanics. The choice of an authentication protocol must consider that quantum states are very delicate and that the channel is subject to eavesdropping. However, even in face of the various existing definitions of quantum authentication protocols in the literature, little is known about them in this perspective, and this lack of knowledge may unfavor comparisons and wise choices. In the attempt to overcome this limitation, in the present work we aim at showing an approach to evaluate quantum authentication protocols based on the determination of their quantum communication complexity. Based on our investigation, no similar methods to analyze quantum authentication protocols were found in the literature. Pursuing this further, our approa...

  7. Similarity based mixed transaction concurrency control protocol

    PAN Yi; LU Yan-sheng


    Due to the various performance requirements and data access restrictions of different types of real-time transactions, concurrency control protocols which had been designed for the systems with single type of transactions are not sufficient for mixed real-time database systems (MRTDBS), where different types of real-time transactions coexist in the systems concurrently. In this paper, a new concurrency control protocol MRTT_CC for mixed real-time transactions is proposed. The new strategy integrates with different concurrency control protocols to meet the deadline requirements of different types of real-time transactions. The data similarity concept is also explored in the new protocol to reduce the blocking time of soft real-time transactions, which increases their chances to meet the deadlines. Simulation experiments show that the new protocol has gained good performance.

  8. Multicast Protocol for Uni-Directional Networks

    黄皓; 陈贵海; 谢立; 孙钟秀


    A very inexpensive receive-only satellite receiver can receive high bandwidth traffic from a feeder. Therefore the connection between the feeder and the receiver is uni-directional. The existing routing protocols, such as Link-State and Distance-Vector, are designed on the premise that any links are bidirectional and they cannot handle the uni-directional links. In this paper, a dynamic multicast routing protocol is proposed, which can handle uni-directional networks. This protocol can also adapt to the dynamic change of the topology of the network and has good scalability. A formal description of the protocol by Petri net is given. Liveness,deadlock free and other properties of the protocol are proved.

  9. Chemotherapy-induced hypercoagulability and biomarkers for prediction of thromboembolic events in patients with metastatic testicular cancer

    Lubberts, S.; Boer, H.; Altena, R.; Meijer, C.; Lefrandt, J.D.; Nuver, J.; Mulder, A.B.; Lisman, T.; Kamphuisen, P.W.; Gietema, J.A.


    The majority of patients with disseminated testicular cancer can be cured with combination chemotherapy consisting of bleomycin, etoposide and cisplatin (BEP). Because of this success, focus shifts to adverse effects of this treatment. The incidences of venous and arterial thromboembolism (VTE and A

  10. A Comparison Between Inter-Asterisk eXchange Protocol and Jingle Protocol: Session Time

    H. S. Haj Aliwi


    Full Text Available Over the last few years, many multimedia conferencing and Voice over Internet Protocol (VoIP applications have been developed due to the use of signaling protocols in providing video, audio and text chatting services between at least two participants. This paper compares between two widely common signaling protocols: InterAsterisk eXchange Protocol (IAX and the extension of the eXtensible Messaging and Presence Protocol (Jingle in terms of delay time during call setup, call teardown, and media sessions.

  11. Universally composable protocols with relaxed set-up assumptions

    Barak, Boaz; Canetti, Ran; Nielsen, Jesper Buus;


    A desirable goal for cryptographic protocols is to guarantee security when the protocol is composed with other protocol instances. Universally composable (UC) protocols provide this guarantee in a strong sense: A protocol remains secure even when composed concurrently with an unbounded number...

  12. Snakebite management in Iran: Devising a protocol

    Seyed Mostafa Monzavi


    Full Text Available Background: Snakebite in Iran has been a health concern. However, management of snakebite is not standardized and varies from center to center. This study is aimed at devising an evidence-based comprehensive protocol for snakebite management in Iran, to reduce unnecessary variations in practice. Materials and Methods: A narrative search in electronic databases was performed. Fifty peer-reviewed articles, guidelines, and textbooks were reviewed and practical details were extracted. Our currently used protocol in the Mashhad Toxicology Center was supplemented with this information. Consequently an improved wide-range protocol was developed. The protocol was then discussed and amended within a focus group comprised of medical toxicologists and internal medicine specialists. The amended version was finally discussed with expert physicians specialized in different areas of medicine, to be optimized by supplementing other specific considerations. Results: During a one-year process, the protocol was finalized. The final version of the protocol, which was designed in six steps, comprised of three components: A schematic algorithm, a severity grading scale, and instructions for supportive and adjunctive treatments. The algorithm pertains to both Viperidae and Elapidae snakebite envenomations and consists of a planned course of action and dosing of antivenom, based on the severity of the envenomation. Conclusion: Snakebite envenomation is a clinical toxicologic emergency, which needs to be treated in a timely and organized manner. Hence, a multi-aspect protocol was designed to improve the clinical outcomes, reduce unnecessary administration of antivenom, and help physicians make more proper clinical judgments.

  13. Efficient Privacy Preserving Protocols for Similarity Join

    Bilal Hawashin


    Full Text Available During the similarity join process, one or more sources may not allow sharing its data with other sources. In this case, a privacy preserving similarity join is required. We showed in our previous work [4] that using long attributes, such as paper abstracts, movie summaries, product descriptions, and user feedbacks, could improve the similarity join accuracy using supervised learning. However, the existing secure protocols for similarity join methods can not be used to join sources using these long attributes. Moreover, the majority of the existing privacy‐preserving protocols do not consider the semantic similarities during the similarity join process. In this paper, we introduce a secure efficient protocol to semantically join sources when the join attributes are long attributes. We provide two secure protocols for both scenarios when a training set exists and when there is no available training set. Furthermore, we introduced the multi‐label supervised secure protocol and the expandable supervised secure protocol. Results show that our protocols can efficiently join sources using the long attributes by considering the semantic relationships among the long string values. Therefore, it improves the overall secure similarity join performance.

  14. A fully efficient secure quantum cryptography protocol

    Xiang Bin Wang


    Since Bennett and Brassard suggested their quantum key distribution protocol(BB84 protocol) in 1984, the subject has been extensively studied both theoretically and experimentally. The protocol allows two remote parties Alice and Bob to create and share a secret key using a quantum channel and public authenticated communications. The quantum key created in this way is in principle secure because eavesdroppers have no way to tap the quantum channel without disturb it. In the protocol, two level quantum bits are measured in two basis, $X$ and $Z$ randomly by Bob. So at least half of the measurement results will be discarded because Bob has a half probability taking the measurement in a wrong basis. On the other hand, the security is not the maximum in BB84 protocol. To increase the security, one may straightforwardly increase the number of basis used in the protocol. For example, six state protocol was proposed recently for two level system. However, in this way, it seems to be the case that the higher the secu...

  15. α-粒子诱发BEP2D细胞癌变系的DNA断裂重接修复缺陷与XRCCs修复基因mRNA表达研究%The studies of DNA double-strand break (DSB) rejoining and mRNA expression of repair gene XRCCs in malignant transformed cell lines of human bronchial epithelial cells generated by α-particles

    孙敬芬; 隋建丽; 耿煜; 周平坤; 吴德昌


    目的研究α粒子诱发人支气管上皮细胞(BEP2D)癌变细胞系BERP35T-1和BERP35T- 4的DNA断裂损伤修复能力,分析其DNA断裂修复基因XRCCs系列的mRNA表达.方法脉冲电场凝胶电泳法检测DNA双链断裂,RT-PCR分析DNA修复基因的mRNA表达.结果恶性转化细胞系BERP35T-1和BERP35T-4受0~150 Gy γ射线照射后修复4 h的DNA断裂残留损伤显著高于亲本BEP2D细胞,mRNA表达分析显示修复基因XRCC2、XRCC3和Ku80(XRCC5)表达下调 2 5~6 5倍,而BERP35T-4细胞中DNA -PKcs(XRCC7)表达上调2.4倍.结论 α粒子诱发恶性转化细胞系的DNA链断裂修复机理缺陷,其中部分原因是DNA修复基因的表达抑制.DNA修复缺陷将导致细胞基因组不稳定性,α粒子诱发细胞恶性转化机理可能与此相关.

  16. Analysis of Enhanced Associativity Based Routing Protocol

    Said A. Shaar


    Full Text Available This study introduces an analysis to the performance of the Enhanced Associativity Based Routing protocol (EABR based on two factors; Operation complexity (OC and Communication Complexity (CC. OC can be defined as the number of steps required in performing a protocol operation, while CC can be defined as the number of messages exchanged in performing a protocol operation[1]. The values represent the worst-case analysis. The EABR has been analyzed based on CC and OC and the results have been compared with another routing technique called ABR. The results have shown that EABR can perform better than ABR in many circumstances during the route reconstruction.

  17. Advanced Internet Protocols, Services, and Applications

    Oki, Eiji; Tatipamula, Mallikarjun; Vogt, Christian


    Today, the internet and computer networking are essential parts of business, learning, and personal communications and entertainment. Virtually all messages or transactions sent over the internet are carried using internet infrastructure- based on advanced internet protocols. Advanced internet protocols ensure that both public and private networks operate with maximum performance, security, and flexibility. This book is intended to provide a comprehensive technical overview and survey of advanced internet protocols, first providing a solid introduction and going on to discu


    Yu Guanding; Zhang Zhaoyang; Qiu Peiliang


    A novel Automatic repeat ReQuest (ARQ) protocol called cooperative ARQ is presented in this letter, where a relay terminal is requested to retransmit an erroneously received packet, instead of the source terminal. The data link layer Packet Error Rate (PER) performance of cooperative ARQ is derived in correlated wireless channel. The results show that even though the relay-destination channel is worse than the sourcedestination channel, the new protocol outperforms the traditional one as long as the average SNR of the relaydestination channel is better than a certain threshold. It is also demonstrated that a second order diversity gain can be achieved with the cooperative ARQ protocol.


    Amit Rana


    Full Text Available The Internet Engineering Task Force (IETF has proposednew protocols for highly secured wireless networking. Thepurpose of this paper is to implement one such proposedsecurity protocol - PEAP (Protected ExtensibleAuthentication Protocol [1]. PEAP was jointly developedby Microsoft, Cisco and RSA security. The protocolimplementation is done on the server end of a Client/Servernetwork model on a RADIUS server (RemoteAuthentication Dial-in User Service. The proposedprotocol - PEAP provides for Client identity protection andkey generation thus preventing unauthorized user accessand protecting or encrypting the data against maliciousactivities.

  20. Analyzing security protocols in hierarchical networks

    Zhang, Ye; Nielson, Hanne Riis


    Validating security protocols is a well-known hard problem even in a simple setting of a single global network. But a real network often consists of, besides the public-accessed part, several sub-networks and thereby forms a hierarchical structure. In this paper we first present a process calculus...... capturing the characteristics of hierarchical networks and describe the behavior of protocols on such networks. We then develop a static analysis to automate the validation. Finally we demonstrate how the technique can benefit the protocol development and the design of network systems by presenting a series...

  1. Comparison of a kayaking ergometer protocol with an arm crank protocol for evaluating peak oxygen consumption.

    Forbes, Scott C; Chilibeck, Philip D


    The purpose of this study was to compare a kayak ergometer protocol with an arm crank protocol for determining peak oxygen consumption (V(.-)O2). On separate days in random order, 10 men and 5 women (16-24 years old) with kayaking experience completed the kayak ergometer protocol and a standardized arm crank protocol. The kayak protocol began at 70 strokes per minute and increased by 10 strokes per minute every 2 minutes until volitional fatigue. The arm crank protocol consisted of a crank rate of 70 revolutions per minute, initial loading of 35 W and subsequent increases of 35 W every 2 minutes until volitional fatigue. The results showed a significant difference (p kayak ergometer and the arm crank protocols for relative peak V(.-)O2 (47.5 +/- 3.9 ml x kg(-1) x min(-1) vs. 44.2 +/- 6.2 ml x kg(-1) x min(-1)) and absolute peak V(.-)O2 (3.38 L x min(-1) +/- 0.53 vs. 3.14 +/- 0.64 L x min(-1)). The correlation between kayak and arm crank protocol was 0.79 and 0.90, for relative and absolute V(.-)O2 peak, respectively (both p kayak ergometer may be due to the greater muscle mass involved compared to the arm crank ergometer. The kayak ergometer protocol may therefore be more specific to the sport of kayaking than an arm crank protocol.

  2. Privacy-Preserving Protocols for Eigenvector Computation

    Pathak, Manas A


    In this paper, we present a protocol for computing the dominant eigenvector of a collection of private data distributed across multiple parties, with the individual parties unwilling to share their data. Our proposed protocol is based on secure multiparty computation with a trusted third-party arbitrator who deals with data encrypted by the other parties using an additive homomorphic cryptosystem. We also augment the protocol with randomization to make it difficult, with a high probability, for any party to estimate properties of the data belonging to other parties from the intermediate steps. The previous approaches towards this problem were based on expensive QR decomposition of correlation matrices, we present an efficient algorithm using the power iteration method. We present an analysis of the correctness, security, efficiency of protocol and experiments over a prototype implementation.

  3. Multicast Routing Protocols in Adhoc Mobile networks



    Full Text Available The majority of applications are in areas where rapid deployment and dynamic reconfiguration are necessary and a wire line network is not available. These include military battlefields, emergency search and rescue sites, classrooms, and conventions where participants share information dynamically using their mobile devices. Well established routing protocols do exist to offer efficient multicasting service in conventional wired networks. These protocols, having been designed for fixed networks, may fails to keep up with node movements and frequent topology changes in a MANET. Therefore, adapting existing wired multicast protocols as such to a MANET, which completely lacks infrastructure, appear less promising. Providing efficient multicasting over MANET faces many challenges, includes scalability,quality of service, reliable service, security, Address configuration, Applications for multicast over MANET. The existing multicast routing protocol do not addresses these issues effectively over Mobile Adhoc Networks (MANET.

  4. Rethinking low extra delay background transport protocols

    Carofiglio, Giovanna; Rossi, Dario; Testa, Claudio; Valenti, Silvio


    BitTorrent has recently introduced LEDBAT, a novel application-layer congestion control protocol for data exchange. The protocol design starts from the assumption that network bottlenecks are at the access of the network, and that thus user traffic competes creating self-inducing congestion. To relieve from this phenomenon, LEDBAT is designed to quickly infer that self-induced congestion is approaching (by detecting relative changes of the one-way delay in the transmission path), and to react by reducing the sending rate prior that congestion occurs. Prior work has however shown LEDBAT to be affected by a latecomer advantage, where newly arriving connections can starve already existing flows. In this work, we propose modifications to the congestion window update mechanism of the LEDBAT protocol that aim at solving this issue, guaranteeing thus intra-protocol fairness and efficiency. Closed-form expressions for the stationary throughput and queue occupancy are provided via a fluid model, whose accuracy is conf...

  5. Standardized North American Marsh Bird Monitoring Protocol

    US Fish and Wildlife Service, Department of the Interior — This document describes monitoring protocols for marshbirds in North America. Monitoring parameters, field procedures, survey methods, timing of surveys, recording...

  6. Reparable Key Distribution Protocols for Internet Environments


    It has claimed that any practical way to achieve perfect reparability for key distribution protocol (KDP) could only be futile. Fortunately, this paper presents reparable KDPs for internet environments with the use of the concept of timestamps.

  7. Identity-based authentication protocol for grid

    Li Hon; Sun Shixin; Yang Homiao


    Current grid authentication frameworks are achieved by applying the standard SSL authentication protocol(SAP).The authentication process is very complicated,and therefore,the grid user is in a heavily loaded point both in computation and in communication.Based on identity-based architecture for grid(IBAG)and corre-sponding encryption and signature schemes,an identity-based authentication protocol for grid is proposed.Being certificate-free,the authentication protocol aligns well with the demands of grid computing.Through simulation testing,it is seen that the authentication protocol is more lightweight and efficient than SAP,especially the more lightweight user side.This contributes to the larger grid scalability.

  8. ARC Code TI: Geometry Manipulation Protocol (GMP)

    National Aeronautics and Space Administration — The Geometry Manipulation Protocol (GMP) is a library which serializes datatypes between XML and ANSI C data structures to support CFD applications. This library...

  9. Protocol to Exploit Waiting Resources for UASNs

    Li-Ling Hung


    Full Text Available The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  10. Protocol to Exploit Waiting Resources for UASNs.

    Hung, Li-Ling; Luo, Yung-Jeng


    The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN) is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  11. National Wildlife Refuge System Survey Protocol Template

    US Fish and Wildlife Service, Department of the Interior — This template was developed for drafting National Wildlife Refuge System (NWRS) Survey Protocols. The template is arranged in the same order as the eight basic...

  12. Comparison of on Demand Routing Protocols

    Bharat Bhushan


    Full Text Available A routing protocol is used to facilitate communication in ad hoc network. The primary goal of such a routing protocol is to provide an efficient and reliable path between a pair of nodes. The routing protocols for ad hoc network can be categorized into three categories: table driven, on demand and hybrid routing. The table driven and hybrid routing strategies require periodic exchange of hello messages between nodes of the ad hoc network and thus have high processing and bandwidth requirements. On the other hand on demand routing strategy creates routes when required and hence is very much suitable for ad hoc network. This paper therefore examines the performance of three on demand routing protocols at application layer using QualNet-5.01 simulator.

  13. Information Flow in Secret Sharing Protocols

    Kashefi, Elham; Mhalla, Mehdi; Perdrix, Simon


    The entangled graph states have emerged as an elegant and powerful quantum resource, indeed almost all multiparty protocols can be written in terms of graph states including measurement based quantum computation (MBQC), error correction and secret sharing amongst others. In addition they are at the forefront in terms of implementations. As such they represent an excellent opportunity to move towards integrated protocols involving many of these elements. In this paper we look at expressing and extending graph state secret sharing and MBQC in a common framework and graphical language related to flow. We do so with two main contributions. First we express in entirely graphical terms which set of players can access which information in graph state secret sharing protocols. These succinct graphical descriptions of access allow us to take known results from graph theory to make statements on the generalisation of the previous schemes to present new secret sharing protocols. Second, we give a set of necessary condit...

  14. How To Develop Survey Protocols: A Handbook

    US Fish and Wildlife Service, Department of the Interior — This handbook provides a standard and guidance for developing and reviewing survey protocols used in the National Wildlife Refuge System. In the handbook, survey...

  15. Saudi Arabia and CERN sign protocol


    On 9 May 2008, Mohammed I. Al Suwaiyel, President of the King Abdulaziz City of Science and Technology, representing the Government of Saudi Arabia, and CERN Director-General, Robert Aymar, signed a protocol to the 2006 cooperation agreement between CERN and Saudi Arabia. Members of the Saudi Arabian Government visit ATLAS.The purpose of the protocol is to define the operational framework needed to carry out various specific tasks provided for in the cooperation agreement in order to promote the development of a high energy particle physics community in Saudi Arabia and its ultimate visible participation as a member of the global CERN community. Signing the protocol, Mohammed I. Al-Suwaiyel said: "The Saudi Arabian Government has taken a number of initiatives to promote R&D in the interests of our country’s development and the advancement of science. Thanks to this protocol, Saudi scientists will be able to work towards this go...

  16. Probabilistic Model--Checking of Quantum Protocols

    Gay, S; Papanikolaou, N; Gay, Simon; Nagarajan, Rajagopal; Papanikolaou, Nikolaos


    We establish fundamental and general techniques for formal verification of quantum protocols. Quantum protocols are novel communication schemes involving the use of quantum-mechanical phenomena for representation, storage and transmission of data. As opposed to quantum computers, quantum communication systems can and have been implemented using present-day technology; therefore, the ability to model and analyse such systems rigorously is of primary importance. While current analyses of quantum protocols use a traditional mathematical approach and require considerable understanding of the underlying physics, we argue that automated verification techniques provide an elegant alternative. We demonstrate these techniques through the use of PRISM, a probabilistic model-checking tool. Our approach is conceptually simpler than existing proofs, and allows us to disambiguate protocol definitions and assess their properties. It also facilitates detailed analyses of actual implemented systems. We illustrate our techniqu...

  17. Hybrid protocol of remote implementations of quantum operations

    Zhao, Ning Bo; Wang, An Min


    We propose a protocol of remote implementations of quantum operations by hybridizing bidirectional quantum-state teleportation (BQST) [Huelga , Phys. Rev. A 63, 042303 (2001)] and the Wang protocol [Wang, Phys. Rev. A 74, 032317 (2006)]. The protocol is available for remote implementations of quantum operations in the restricted sets specified in the paper. We also give a proof of the protocol and point out its optimization. As an extension, this hybrid protocol can be reduced to the BQST and Wang protocols.

  18. Adaptive Baud Protocol For Wireless Communication

    Eskafi, F. H.; Nassiri-toussi, K.; G. Liu


    In this paper, the authors propose an algorithm that increases and decreases the transmission speed according to a user-specified function. The design objective is to regulate baud as efficiently as possible and ensure that in each transmission interval, transmitter and receiver bauds are equal for some period of time during data transmission. An equivalent discrete-time version of the protocol is verified by using the COSPAN software. Application for this adaptive baud protocol for wireless ...

  19. Dose protocols of acetylcholine test in Chinese

    向定成; 龚志华; 何建新; 洪长江; 邱建; 马骏


    @@ Acetylcholine test has been widely used clinically in several countries as a practical test provoking coronary artery spasm.1-3 Although it has also been launched recently in a few hospitals in China, the dose protocol for acetylcholine test used in these hospitals were from abroad.4,5 This study was aimed at developing a dose protocol for acetylcholine test suitable for Chinese people.

  20. Quantum Key Distribution Protocol with User Authentication

    Lee, H; Lee, D; Lim, J; Yang, H J; Lee, Hwayean; Lee, Sangjin; Lee, Donghoon; Lim, Jongin; Yang, HyungJin


    We propose a quantum key distribution protocol with quantum based user authentication. User authentication is executed by validating the correlation of GHZ states. Alice and Bob can distribute a secure key using the remaining GHZ states after authentication. This secret key does not leak even to the arbitrator by the properties of the entanglement. We will show that our protocol is secure against the cloning attack.

  1. Protocol for communications in potentially noisy environments

    Boyd, Gerlad M.; Farrow, Jeffrey


    A communications protocol that is designed for transmission of data in networks that are subjected to harsh conditions is described herein. A network includes a plurality of devices, where the devices comprise respective nodes. The nodes are in communication with one another by way of a central network hub. The protocol causes the nodes to transmit data over a network bus at different data rates depending upon whether the nodes are operating normally or an arbitration procedure has been invoked.

  2. Secure Fingerprint Alignment and Matching Protocols

    Bayatbabolghani, Fattaneh; Blanton, Marina; Aliasgari, Mehrdad; Goodrich, Michael


    We present three secure privacy-preserving protocols for fingerprint alignment and matching, based on what are considered to be the most precise and efficient fingerprint recognition algorithms-those based on the geometric matching of "landmarks" known as minutia points. Our protocols allow two or more honest-but-curious parties to compare their respective privately-held fingerprints in a secure way such that they each learn nothing more than a highly-accurate score of how well the fingerprin...

  3. Mutual Authentication Protocols for RFID Systems

    Ashrar A. Omer; Johnson P. Thomas; Ling Zhu


    With the availability of low-cost radio frequency identification (RFID) tags, security becomes an increasing concern.However, such tags do not permit complex eryptographic functions due to their computational, communications, and storage limitations.In this paper, we investigate the security issues and requirements of RFID systems, and propose ultra-light weight and light weight protocols for low-cost RFID tags. The proposed protocols has been applied to a supply chain management system.

  4. Trust Authentication Protocol on the Web


    It is unsuitable to use traditional identity-based authentication on the Web where entities are not foreknown to each other. Trust relationship must be established between strangers before authentication. To achieve trust authentication, the resource-constrained trust negotiation is addressed, and traditional authentication key exchange protocol is extended. Owing to avoiding the heavy computational demands the public key cryptography operations bring about, the authentication protocol is well-suited for security authentication on the Web.

  5. OAuth protocol for CERN Web Applications

    Kleszcz, Emil; Rodriguez Fernandez, Luis; Marescaux, Nicolas Bernard


    Project Specification The CERN Authentication service has recently increased his offer of SSO protocols/frameworks with OAuth2 standard. The purpose of the work is to explain the need for an authorization standard and explain how does OAuth2 protocol addresses our requirements. OAuth is an open standard for authorization which provides a secure access to server resources that belongs to a user. As a wide known and relatively new standard (2012) is used by big players in the industry a...

  6. Equilibria of Generalized Cut and Choose Protocols

    Branzei, Simina; Caragiannis, Ioannis; Kurokawa, David

    Classic cake cutting protocols — which fairly allocate a divisible good among agents with heterogeneous preferences — are susceptible to manipulation. Do their strategic outcomes still guarantee fairness? To answer this question we adopt a novel algo rithmic approach, proposing a concrete computa...... the stronger fairness notion of envy-freeness. Finally, we show that under an obliviousness restriction, which still allows the computation of approximately envy-free allocations, GCC protocols are guaranteed to have exact subgame perfect Nash equilibria...

  7. Field Monitoring Protocol: Heat Pump Water Heaters

    Sparn, B.; Earle, L.; Christensen, D.; Maguire, J.; Wilson, E.; Hancock, E.


    This document provides a standard field monitoring protocol for evaluating the installed performance of Heat Pump Water Heaters in residential buildings. The report is organized to be consistent with the chronology of field test planning and execution. Research questions are identified first, followed by a discussion of analysis methods, and then the details of measuring the required information are laid out. A field validation of the protocol at a house near the NREL campus is included for reference.

  8. Field Monitoring Protocol. Heat Pump Water Heaters

    Sparn, B. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Earle, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Christensen, D. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Maguire, J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Wilson, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hancock, C. E. [Mountain Energy Partnership, Longmont, CO (United States)


    This document provides a standard field monitoring protocol for evaluating the installed performance of Heat Pump Water Heaters in residential buildings. The report is organized to be consistent with the chronology of field test planning and execution. Research questions are identified first, followed by a discussion of analysis methods, and then the details of measuring the required information are laid out. A field validation of the protocol at a house near the NREL campus is included for reference.

  9. Network-topology-adaptive quantum conference protocols

    Zhang Sheng; Wang Jian; Tang Chao-Jing; Zhang Quan


    As an important application of the quantum network communication,quantum multiparty conference has made multiparty secret communication possible.Previous quantum multiparty conference schemes based on quantum data encryption are insensitive to network topology.However,the topology of the quantum network significantly affects the communication efficiency,e.g.,parallel transmission in a channel with limited bandwidth.We have proposed two distinctive protocols,which work in two basic network topologies with efficiency higher than the existing ones.We first present a protocol which works in the reticulate network using Greeberger-Horne-Zeilinger states and entanglement swapping.Another protocol,based on quantum multicasting with quantum data compression,which can improve the efficiency of the network,works in the star-like network.The security of our protocols is guaranteed by quantum key distribution and one-time-pad encryption.In general,the two protocols can be applied to any quantum network where the topology can be equivalently transformed to one of the two structures we propose in our protocols.

  10. EAR Protocol-Towards Fair Optimistic Non-Repudiation Exchange

    WANG Hai-yan; WANG Ru-chuan


    Fairness is of crucial importance for the exchange protocols via Internet. Non-repudiation therefore becomes one of the vital premises, which are essential in the exchange of sensitive and important messages. This paper is to propose a new exchange protocol, termed "EAR" Exchange Protocol as it consists of three sub-protocols: Exchange sub-protocol, Abort sub-protocol and Recovery sub-protocol. It is to be argued that the incorporation of these three sub-protocols may effectively enables EAR to assure non-repudiation, strong fairness, timeliness, confidentiality and the minimized involvement of the Trusted Third Party (TTP).

  11. Security Analysis of Broadcaster Group Key Exchange Protocols

    LI Li; ZHANG Huanguo


    Group key exchange protocols are basic protocols to provide privacy and integrity in secure group communication. This paper discusses the security of one type of group key exchange protocols and defines the kind of protocols as broadcaster group protocols. It points out two attacks on this kind of protocols. The first attack can be avoided by using fresh values in each action during one session of the group protocol. The second attack should be related with concrete application. It also proposes a dynamic key agreement protocol as an example of solutions at the last part of the paper.

  12. Antagonistic effect of vitamin E and taurine on mutagenesis of bleomycin%维生素E、牛黄酸等抗氧化剂对博莱霉素致突变性的拮抗作用

    宗传龙; 周白云; 郭淼; 刘景升; 李效良


    目的观察抗氧化剂(维生素E、牛黄酸、二甲亚砜和维生素C)针对博莱霉素(Bleomycin,BLM)的拮抗作用.方法在人外周血淋巴细胞培养物中注入一定剂量的BLM并一定剂量的抗氧化剂,然后观察淋巴细胞的姐妹染色单体交换率(sister chromatid exchanges,SCE rate)的变化.结果维生素E浓度为5μl/ml时,可显著地拮抗BLM(28.6 nmol/ml)的致突变作用(P<0.05);而维生素E浓度为10μl/ml时,可极显著地拮抗BLM的作用(P<0.01);当加入牛黄酸的终浓度为100和200μg/rl时,均可显著地拮抗BLM(28.6nmol/m1)的致突变作用(P<0.05).结论一定剂量的维生素E和牛黄酸对BLM的致突变性存在着拮抗作用.%Objective: To observe antagonistic effect of vitamin E, taurine and some other antioxidants on mutagenesis of bleomycin. Methods: The changes of SCE (sister chromatid exchanges) rates of human blood lymphocytes were observed when vitamin E and taurine had been added into the culture medium for human blood lymphocytes. Results: Vitamin E(5μl/ml)or taurine(100 or 200μg/ml) had a significant effect on lowering SCE of lymphocytes treated by BLM(28.6 nmol/rml) (P <0.05); While vitamin E( 10μl/ml) has a very significant effect on lowering SCE of lymphocytes treated by BLM(28.6 nmol/ml) (P <0.01). Conclusion: A certain dosage of either vitamin E or taurine has a significant effect on antagonizing mutagenesis of BLM by lowering SCE of human blood lymphocytes.

  13. Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees

    Li, Rebecca H.; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann


    A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency...

  14. Internetworking with Internet Protocol (IP) and Transmission Control Protocol (TCP) within the Military

    Eikenberg, Bruce R.


    Approved for public release; distribution is unlimited. The backbone of the internetworking technology widely used by the military, as well as many civilian installations, is commonly referred to as TCP/IP. Transmission Control Protocol (TCP) and Internet Protocol (IP) are the two standard communication protocols from which TCP/IP receives its name. By utilizing TCP/IP, the majority of technical issues of interconnecting various computer technologies have become transparent to the user. Th...

  15. Epidemic Protocols for Pervasive Computing Systems - Moving Focus from Architecture to Protocol

    Mogensen, Martin


    Pervasive computing systems are inherently running on unstable networks and devices, subject to constant topology changes, network failures, and high churn. For this reason, pervasive computing infrastructures need to handle these issues as part of their design. This is, however, not feasible...... epidemic protocols as distribution mechanism for pervasive systems. The nature of epidemic protocols make them easy to implement, easy to deploy, and resilient to failures. By using epidemic protocols, it is possible to mitigate a wide range of the potential issues on the protocol layer. The result...... is lower complexity of building pervasive systems and higher robustness....

  16. Simulation and Evaluation of CTP and Secure-CTP Protocols

    P. Pecho


    Full Text Available The paper discusses characteristics and qualities of two routing protocols – Collection Tree Protocol and its secure modification. The original protocol, as well as other protocols for wireless sensors, solves only problems of ra- dio communication and limited resources. Our design of the secure protocol tries to solve also the essential security ob- jectives. For the evaluation of properties of our protocol in large networks, a TOSSIM simulator was used. Our effort was to show the influence of the modification of the routing protocol to its behavior and quality of routing trees. We have proved that adding security into protocol design does not necessarily mean higher demands for data transfer, power consumption or worse protocol efficiency. In the paper, we manifest that security in the protocol may be achieved with low cost and may offer similar performance as the original protocol.

  17. Protocol Independent Multicast Based States Allocation

    G Hemalatha


    Full Text Available In this paper the Protocol Independent Multicast (PIM protocol is being used. The PIM protocol avoids the packet drop and diverting problem. The PIM protocol is not dependent on any specific unicast routing protocol. It is IP routing independent protocol. The PIM uses the unicast and multicast information to create a distribution tree along the reverse path from the receivers towards the source. The PIM protocol consists of three modes such as sparse mode, dense mode and bidirectional mode. The sparse mode is used to sends the file from router to a receiver. The dense mode is used to sends the file from router to multiple receivers. The bidirectional mode is used to sends the message from router to sender and then continue the other process depending on the sender requirements. The client sends the file from sender to destination via the router. First the sender selects the file name and receiver name for transmission. Then the state is assigned automatically depend upon the user selection. The state can be defined by the number of destination selected to transmit the file from the source. If the sender selects single destination, it will assign “Without forwarding state router” for transmission. Otherwise it will assign “Forwarding state router” for transmission. If the receiver is not available, the router sends a message to sender such that “the requested receiver is not available”. Then the client will decide the file is transfer or not, it will reply with transfer the file, then the file will be transferred until the file will be discarded at client side. If the sender tries the same process after two times, the router will display the warning message as “the requested receiver is not available, this file will be discarded at client side”. Then it continues the other process.

  18. Eccentricity in Zone Routing Protocol for MANET

    Mrs Komal Nair


    Full Text Available A Mobile Ad-Hoc Network (MANET is a decentralized network of autonomous mobile nodes, able to communicate with each other over wireless links. Due to the mobility of the nodes, the topology ofthe network changes spontaneously, therefore use of conventional routing tables maintained at fixed points (routers is not suggested. Such a network may operate in a standalone fashion. There are variousrouting protocols available for MANETs. The most popular ones are DSR, DSDV and ZRP .The zone routing protocol (ZRP is a hybrid routing protocol that proactively maintains routes within a localregion of the network. ZRP can be configured for a particular network through adjustment of a single parameter, the routing zone radius. In this paper, we address the issue of configuring the ZRP to providethe best performance for a particular network at any time with the concept of eccentricity. The results illustrate the important characteristics of different protocols based on their performance and thus suggest some improvements in the respective protocol. The tools used for the simulation are NS2 which is the main simulator, NAM (Network Animator and Tracegraph which is used for preparing the graphs from the trace files.

  19. Controlled Delegation Protocol in Mobile RFID Networks

    Yang MingHour


    Full Text Available To achieve off-line delegation for mobile readers, we propose a delegation protocol for mobile RFID allowing its readers access to specific tags through back-end server. That is to say, reader-tag mutual authentication can be performed without readers being connected to back-end server. Readers are also allowed off-line access to tags' data. Compared with other delegation protocols, our scheme uniquely enables back-end server to limit each reader's reading times during delegation. Even in a multireader situation, our protocol can limit reading times and reading time periods for each of them and therefore makes back-end server's delegation more flexible. Besides, our protocol can prevent authorized readers from transferring their authority to the unauthorized, declining invalid access to tags. Our scheme is proved viable and secure with GNY logic; it is against certain security threats, such as replay attacks, denial of service (DoS attacks, Man-in-the-Middle attacks, counterfeit tags, and breaches of location and data privacy. Also, the performance analysis of our protocol proves that current tags can afford the computation load required in this scheme.

  20. Manet Load Balancing Parallel Routing Protocol

    Hesham Arafat Ali


    Full Text Available In recent years, multi-path routing protocols have attained more attention in mobile ad hoc networks as compared to other routing schemes due to their abilities and efficiency in improving bandwidth of communication, increasing delivery reliability, responding to congestion and heavy traffic. Several protocols have been developed to address multi path routing, but it always has a problem that the discovered paths may be not 100% disjoint and sending data is done in only one path until it's broken; the discovery of multiple paths also generates more overhead on the network. Load Balancing Parallel Routing Protocol [LBPRP] tried to solve previous multi path problems, distributing traffic among multiple paths sending data in parallel form as it uses all paths in the same time. We employed a simple test scenario to be sure of proposed model efficiency and to validate the proposed Load Balancing Parallel Routing Protocol. [LBPRP] will achieve load balancing in sending data, decreasing the end-to-end delay and increasing the packet delivery ratio and throughput, thus the performance of multi-path routing protocols can be improved consequently.

  1. A Lightweight Buyer-Seller Watermarking Protocol

    Yongdong Wu


    Full Text Available The buyer-seller watermarking protocol enables a seller to successfully identify a traitor from a pirated copy, while preventing the seller from framing an innocent buyer. Based on finite field theory and the homomorphic property of public key cryptosystems such as RSA, several buyer-seller watermarking protocols (N. Memon and P. W. Wong (2001 and C.-L. Lei et al. (2004 have been proposed previously. However, those protocols require not only large computational power but also substantial network bandwidth. In this paper, we introduce a new buyer-seller protocol that overcomes those weaknesses by managing the watermarks. Compared with the earlier protocols, ours is n times faster in terms of computation, where n is the number of watermark elements, while incurring only O(1/lN times communication overhead given the finite field parameter lN. In addition, the quality of the watermarked image generated with our method is better, using the same watermark strength.

  2. Performance Evaluation of Routing Protocols in MANET

    Smitha Sunny


    Full Text Available Mobile Ad-Hoc Network (MANET is an autonomous system that is composed of the mobile nodes which communicates through wireless links without any preexisting infrastructure. MANET is a collection of mobile nodes which can self-organize freely and dynamically into arbitrary and temporary network topologies. Mobile nodes in ad-hoc networks function as a router and can dynamically establish routes among themselves by means of a routing protocol. Routing protocols in mobile ad-hoc network helps node to send and receive packets. Therefore, selection of an appropriate routing protocol is an integral part of establishing a MANET. A suitable and effective routing mechanism helps to extend the successful deployment of mobile ad-hoc networks. An attempt has been made to compare the performance between on-demand reactive routing protocols namely AODV, DSR and proactive routing protocol namely DSDV for Constant Bit Rate (CBR traffic by varying network scope i.e. number of participating nodes as well as by varying the speed. The parameters used for evaluation are Packet delivery ratio (PDR, Normalized routing overhead, Average end to end delay (Delay, Throughput and Average Energy consumption. The simulations are carried out using Network Simulator NS2:34.

  3. Two Cheers for the Trafficking Protocol

    Anne T Gallagher


    Full Text Available The Trafficking Protocol makes an easy target for attack. Its origins lie in an attempt to control a particularly exploitative form of migration that was challenging the ability of States to control their own borders. Its parent instrument is a framework agreement to address transnational organised crime. While paying fleeting attention to the rights of victims, the Protocol, with its emphasis on criminalisation and border protection is nowhere near being a human rights treaty. On top of all that it does not even have a credible enforcement mechanism, allowing states parties wide latitude in interpreting and applying their obligations. Strangely, these seemingly insurmountable flaws have not stopped the Protocol’s emergence as perhaps the single most important development in the fight against human trafficking. Without the Protocol, arguments around definitions would have continued to block the evolution of principles and rules. Without the Protocol it is likely that the human rights system would have continued its shameful tradition of sidelining issues such as forced labour, forced sex, forced marriage and the ritual exploitation of migrant workers through debt. Most critically, the Protocol provided the impetus and template for a series of legal and political developments that, over time, have served to ameliorate some of its greatest weaknesses, including the lack of human rights protections and of a credible oversight mechanism.

  4. Supporting Adaptation of Wireless Communication Protocols



    Full Text Available Pervasive devices such as mobile phones and PDAs (Personal Digital Assistants come with different wireless communication capabilities, for example, WiFi (Wireless Fidelity, Bluetooth, IrDA (Infrared, etc. In order for pervasive devices to interact with each other, they need to have matching (alike communication capabilities, otherwise such heterogeneous devices would not be able to interact with each other. In this paper we address this issue and propose a system that makes devices with heterogeneous wireless communication capabilities communicate with each other. The proposed system supports adaptation of wireless communication protocols through a proxy, which sits between a client and a server, and supports adaptation of wireless communication protocols. Its functionality involves intercepting a request made by a client with a different wireless communication capability (e.g. Bluetooth from what the server has (e.g. WiFi, connecting to the server and then sending results back to the client. We have tested the system by implementing a messaging service application and running it on the system. The proxy supports all Bluetooth protocols, i.e. OBEX (Object Exchange, L2CAP (Logical Link Control and Adaptation Protocol, RFCOM (Radio Frequency Communication and WiFi protocol and can run on (J2MW (Java 2 Micro Edition enabled mobile phones which support both Bluetooth and WiFi capabilities

  5. Operational protocols for controlling accelerator equipment

    Bailey, R.; Baribaud, G.; Benincasa, G.P.; Burla, P.; Casalegno, L.; Coudert, G.; Gelato, G.; Kuhn, H.K.; Saban, R.; Spinks, A. (European Organization for Nuclear Research, Geneva (Switzerland). LEP Div.)


    The equipment used to operate an accelerator is varied. However, the different devices may be divided into a limited number of classes for which operational protocols can be defined. Operational protocols permit: (i) a uniform operation, (ii) a clear definition of responsibility between the various specialists, (iii) independent development of programs and use of the most appropriate technology, (iv) the change of hardware and the transportability of software, and (v) the fabrication of devices by industry for general use. An operational protocol should be independent of any given control system and it must not be confused with a transmission protocol. As a first step, one defines an operational model of the device to be controlled. The model must represent a high-level description of the device as seen by the user. It will be characterized by a set of parameters and a set of rules. Although the particular requirements of specialists are not included in the operational protocol, allowances should be made for them. Emphasis will be placed on studies carried out on power converters and beam instrumentation. A general-purpose control message architecture is reported. (orig.).

  6. Operational protocols for controlling accelerator equipment

    Bailey, R.; Baribaud, G.; Benincasa, G. P.; Burla, P.; Casalegno, L.; Coudert, G.; Gelato, G.; Kuhn, H. K.; Saban, R.; Spinks, A.


    The equipment used to operate an accelerator is varied. However, the different devices may be divided into a limited number of classes for which operational protocols can be defined. Operational protocols permit: (i) a uniform operation, (ii) a clear definition of responsibility between the various specialists, (iii) independent development of programs and use of the most appropriate technology, (iv) the change of hardware and the transportability of software, and (v) the fabrication of devices by industry for general use. An operational protocol should be independent of any given control system and it must not be confused with a transmission protocol. As a first step, one defines an operational model of the device to be controlled. The model must represent a high-level description of the device as seen by the user. It will be characterized by a set of parameters and a set of rules. Although the particular requirements of specialists are not included in the operational protocol, allowances should be made for them. Emphasis will be placed on studies carried out on power converters and beam instrumentation. A general-purpose control message architecture is reported.

  7. The cannabinoid quinol VCE-004.8 alleviates bleomycin-induced scleroderma and exerts potent antifibrotic effects through peroxisome proliferator-activated receptor-γ and CB2 pathways.

    del Río, Carmen; Navarrete, Carmen; Collado, Juan A; Bellido, M Luz; Gómez-Cañas, María; Pazos, M Ruth; Fernández-Ruiz, Javier; Pollastro, Federica; Appendino, Giovanni; Calzado, Marco A; Cantarero, Irene; Muñoz, Eduardo


    Scleroderma is a group of rare diseases associated with early and transient inflammation and vascular injury, followed by fibrosis affecting the skin and multiple internal organs. Fibroblast activation is the hallmark of scleroderma, and disrupting the intracellular TGFβ signaling may provide a novel approach to controlling fibrosis. Because of its potential role in modulating inflammatory and fibrotic responses, both PPARγ and CB2 receptors represent attractive targets for the development of cannabinoid-based therapies. We have developed a non-thiophilic and chemically stable derivative of the CBD quinol (VCE-004.8) that behaves as a dual agonist of PPARγ and CB2 receptors, VCE-004.8 inhibited TGFβ-induced Col1A2 gene transcription and collagen synthesis. Moreover, VCE-004.8 inhibited TGFβ-mediated myofibroblast differentiation and impaired wound-healing activity. The anti-fibrotic efficacy in vivo was investigated in a murine model of dermal fibrosis induced by bleomycin. VCE-004.8 reduced dermal thickness, blood vessels collagen accumulation and prevented mast cell degranulation and macrophage infiltration in the skin. These effects were impaired by the PPARγ antagonist T0070907 and the CB2 antagonist AM630. In addition, VCE-004.8 downregulated the expression of several key genes associated with fibrosis, qualifying this semi-synthetic cannabinoid as a novel compound for the management of scleroderma and, potentially, other fibrotic diseases.

  8. Non-apoptotic programmed cell death with paraptotic-like features in bleomycin-treated plant cells is suppressed by inhibition of ATM/ATR pathways or NtE2F overexpression.

    Smetana, Ondřej; Široký, Jiří; Houlné, Guy; Opatrný, Zdeněk; Chabouté, Marie-Edith


    In plants, different forms of programmed cell death (PCD) have been identified, but they only partially correspond to those described for animals, which is most probably due to structural differences between animal and plant cells. Here, the results show that in tobacco BY-2 cells, bleomycin (BLM), an inducer of double-strand breaks (DSBs), triggers a novel type of non-apoptotic PCD with paraptotic-like features. Analysis of numerous PCD markers revealed an extensive vacuolization, vacuolar rupture, and chromatin condensation, but no apoptotic DNA fragmentation, fragmentation of the nuclei, or sensitivity to caspase inhibitors. BLM-induced PCD was cell cycle regulated, occurring predominantly upon G(2)/M cell cycle checkpoint activation. In addition, this paraptotic-like PCD was at least partially inhibited by caffeine, a known inhibitor of DNA damage sensor kinases ATM and ATR. Interestingly, overexpression of one NtE2F transcriptional factor, whose homologues play a dual role in animal apoptosis and DNA repair, reduced PCD induction and modulated G(2)/M checkpoint activation in BY-2 cells. These observations provide a solid ground for further investigations into the paraptotic-like PCD in plants, which might represent an ancestral non-apoptotic form of PCD conserved among animals, protists, and plants.

  9. Animation of Natural Language Specifications of Authentication Protocols

    Mabroka A. Mayouf


    Full Text Available Problem Statement: A few visualization tools have been created for protocol design and analysis. Although these tools provide an environment for designing security protocols, each one has its own protocol definition language (its also called informal specification language. The problem is that the user should understand the language which related to the used tool in order to define an exist protocol or design a new one. For specification, a language needs to be intuitive as well as easily usable and understandable by the security protocol engineer. It must be able to precisely and unambiguously specify the behavior of security protocol. Approach: In this study, we propose an approach for protocol specification based on the Natural language definitions of protocol semantics. By using programmatic semantics together with animations, representational flexibility of different protocol demonstration is retained for as long as it is needed. Result: This study provides an environment that can be used by protocols designers to develop and investigate different scenarios of security protocols especially authentication protocols. Natural Language Protocol Specifications (NLPS approach is used to define the protocol. The environment accepts the natural language text of protocol specifications and converts it to animations of protocol behavior. Conclusions/Recommendations: NLPS environment can really help protocol designer to consider and investigate the behavior of security protocols. It can also be used for teaching-learning security protocol concepts. In further, we will consider the possibility of analyzing security protocols using our NLPS environment and animation techniques in order to improve the correctness; that is determining whether or not the intended security properties of a protocol do hold.

  10. Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

    Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E


    A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval.

  11. Performance Evaluation of MANET Routing Protocols

    Hrituparna Paul


    Full Text Available The task of finding and sustaining routes in Mobile Ad-hoc Networks (MANETS is an important factor in determining the efficiency of any MANET protocol. MANET characteristically is an autonomous system of mobile nodes connected by wireless links without any centralised infrastructure. Absence of fixed infrastructures and host mobility thus network may experience rapid and unpredictable topology changes. Hence, routing is required in order to perform communication among the entire network. There are several routing protocols namely proactive, reactive and hybrid etc. In this paper we will discuss the active research work on these routing protocols and its performance evaluation. To this end, we adopt a simulation approach, which is more suitable to this kind of analysis

  12. Efficient Controlled Quantum Secure Direct Communication Protocols

    Patwardhan, Siddharth; Moulick, Subhayan Roy; Panigrahi, Prasanta K.


    We study controlled quantum secure direct communication (CQSDC), a cryptographic scheme where a sender can send a secret bit-string to an intended recipient, without any secure classical channel, who can obtain the complete bit-string only with the permission of a controller. We report an efficient protocol to realize CQSDC using Cluster state and then go on to construct a (2-3)-CQSDC using Brown state, where a coalition of any two of the three controllers is required to retrieve the complete message. We argue both protocols to be unconditionally secure and analyze the efficiency of the protocols to show it to outperform the existing schemes while maintaining the same security specifications.

  13. Demarcation of Security in Authentication Protocols

    Ahmed, Naveed; Jensen, Christian D.


    Security analysis of communication protocols is a slippery business; many “secure” protocols later turn out to be insecure. Among many, two complains are more frequent: inadequate definition of security and unstated assumptions in the security model. In our experience, one principal cause...... for such state of affairs is an apparent overlap of security and correctness, which may lead to many sloppy security definitions and security models. Although there is no inherent need to separate security and correctness requirements, practically, such separation is significant. It makes security analysis...... easier, and enables us to define security goals with a fine granularity. We present one such separation, by introducing the notion of binding sequence as a security primitive. A binding sequence, roughly speaking, is the only required security property of an authentication protocol. All other...

  14. Summary Report on Unconditionally Secure Protocols

    Damgård, Ivan Bjerre; Salvail, Louis; Cachin, Christian

    level. In noisy-channel cryptography security proofs are based on the assumption that a given physical means of communication is at a sufficiently low level inherently noisy. In bounded-storage cryptography security proofs are based on the assumption that there exists streams of information, generated...... by computers or other physical phenomena, so intense that no one is able to fully store them. In quantum cryptography security proofs are based on the assumption that nature behaves consistently with quantum mechanics. In the following we describe the state of the art and some main open problems in the three......This document describes the state of the art snd some of the main open problems in the area of unconditionally secure cryptographic protocols. The most essential part of a cryptographic protocol is not its being secure. Imagine a cryptographic protocol which is secure, but where we do not know...

  15. Chapter 15: Commercial New Construction Protocol

    Keates, S.


    This protocol is intended to describe the recommended method when evaluating the whole-building performance of new construction projects in the commercial sector. The protocol focuses on energy conservation measures (ECMs) measures (or packages of measures) where evaluators can best analyze impacts using building simulation. These ECMs typically require the use of calibrated building simulations under Option D of the International Performance Measurement and Verification Protocol. Examples of such measures include Leadership in Energy and Environmental Design building certification, novel and/or efficient heating, ventilation, and air conditioning system designs, and extensive building controls systems. In general, it is best to evaluate any ECM (or set of measures) expected to significantly interact with other systems within the building and with savings sensitive to seasonal variations in weather.



    Military tactical network is one of the most important applications of ad hoc network. Currently the existing routing protocols are put forward based on the simple and universal network model which has the ability of multi-hop routing but cannot work efficiently in the special military applications. The narrow bandwidth and limited energy of the wireless network make general routing protocols seem to be more redundant.In order to satisfy military needs properly, this letter makes a detailed analysis of physical nodes and traffic distribution in military network, uses cross-layer design concept for reference, combines traffic characteristic of application layer with routing protocol design. It categorized routing problem as crucial routes and non-crucial routes which adopted separate maintenance methods. It not only realizes basic transmission function but also works efficiently. It is quite fit for military application.

  17. Zero-Knowledge Protocols and Multiparty Computation

    Pastro, Valerio

    in a finite field, in which the third one is the product of the first two. We extend this protocol in two ways: first we consider the case where the values are integers, and then we consider tuples of values that satisfy more general algebraic relations. Our basic scheme achieves optimal amortized......This thesis presents results in two branches of cryptography. In the first part we construct two general multiparty computation protocols that can evaluate any arithmetic circuit over a finite field. Both are built in the preprocessing model and achieve active security in the setting of a dishonest......+ 13] yields a more efficient protocol than that originally proposed in [DPSZ12]. Our preprocessing phases make use of a somewhat homomorphic encryption scheme, and significantly improve on the previous state of the art, both asymptotically and in practice. The online phase we present relies...

  18. Insights From Verbal Protocols: A Case Study

    Margaret Kumar


    Full Text Available This study explores a postgraduate student writer’s responses and reactions through verbal protocols as she attends to teacher feedback. Teacher feedback has been heralded as an important element in process writing. Numerous studies have been carried out on various aspects of teacher feedback such as on the effectiveness of feedback, students’ preferences for teacher feedback and students’ perceptions of feedback. However, there is still a gap in the literature in determining how students respond as they engage with teacher feedback. This paper reports on one postgraduate student’s responses on and her reactions to teacher feedback. Concurrent verbal protocols used in complement with written drafts and teacher commentaries were the main sources of data for this study. The analyses reveal that attending to feedback is a recursive process that fosters self-reflection which, in turn promotes planning for revision. Keywords: Verbal protocols, Teacher written feedback; Recursion; Reflection; Planning

  19. Chapter 22: Compressed Air Evaluation Protocol

    Benton, N.


    Compressed-air systems are used widely throughout industry for many operations, including pneumatic tools, packaging and automation equipment, conveyors, and other industrial process operations. Compressed-air systems are defined as a group of subsystems composed of air compressors, air treatment equipment, controls, piping, pneumatic tools, pneumatically powered machinery, and process applications using compressed air. A compressed-air system has three primary functional subsystems: supply, distribution, and demand. Air compressors are the primary energy consumers in a compressed-air system and are the primary focus of this protocol. The two compressed-air energy efficiency measures specifically addressed in this protocol are: high-efficiency/variable speed drive (VSD) compressor replacing modulating compressor; compressed-air leak survey and repairs. This protocol provides direction on how to reliably verify savings from these two measures using a consistent approach for each.

  20. Protocol for emergency EPR dosimetry in fingernails.

    Trompier, F; Kornak, L; Calas, C; Romanyukha, A; Leblanc, B; Mitchell, C A; Swartz, H M; Clairand, I


    There is an increased need for after-the-fact dosimetry because of the high risk of radiation exposures due to terrorism or accidents. In case of such an event, a method is needed to make measurements of dose in a large number of individuals rapidly and with sufficient accuracy to facilitate effective medical triage. Dosimetry based on EPR measurements of fingernails potentially could be an effective tool for this purpose. This paper presents the first operational protocols for EPR fingernail dosimetry, including guidelines for collection and storage of samples, parameters for EPR measurements, and the method of dose assessment. In a blinded test of this protocol application was carried out on nails freshly sampled and irradiated to 4 and 20 Gy; this protocol gave dose estimates with an error of less than 30%.

  1. Analysis of Security Protocols by Annotations

    Gao, Han

    The trend in Information Technology is that distributed systems and networks are becoming increasingly important, as most of the services and opportunities that characterise the modern society are based on these technologies. Communication among agents over networks has therefore acquired a great...... deal of research interest. In order to provide effective and reliable means of communication, more and more communication protocols are invented, and for most of them, security is a significant goal. It has long been a challenge to determine conclusively whether a given protocol is secure or not....... The development of formal techniques, e.g. control flow analyses, that can check various security properties, is an important tool to meet this challenge. This dissertation contributes to the development of such techniques. In this dissertation, security protocols are modelled in the process calculus LYSA...

  2. Self Fault-Tolerance of Protocols: A Case Study


    The prerequisite for the existing protocols' correctness is that protocols can be normally operated under the normal conditions, rather than dealing with abnormal conditions.In other words, protocols with the fault-tolerance can not be provided when some fault occurs. This paper discusses the self fault-tolerance of protocols. It describes some concepts and methods for achieving self fault tolerance of protocols. Meanwhile, it provides a case study, investigates a typical protocol that does not satisfy the self fault-tolerance, and gives a new redesign version of this existing protocol using the proposed approach.

  3. A Cryptographic Moving-Knife Cake-Cutting Protocol

    Yoshifumi Manabe


    Full Text Available This paper proposes a cake-cutting protocol using cryptography when the cake is a heterogeneous good that is represented by an interval on a real line. Although the Dubins-Spanier moving-knife protocol with one knife achieves simple fairness, all players must execute the protocol synchronously. Thus, the protocol cannot be executed on asynchronous networks such as the Internet. We show that the moving-knife protocol can be executed asynchronously by a discrete protocol using a secure auction protocol. The number of cuts is n-1 where n is the number of players, which is the minimum.

  4. Objective and automated protocols for the evaluation of biomedical search engines using No Title Evaluation protocols

    Campagne Fabien


    Full Text Available Abstract Background The evaluation of information retrieval techniques has traditionally relied on human judges to determine which documents are relevant to a query and which are not. This protocol is used in the Text Retrieval Evaluation Conference (TREC, organized annually for the past 15 years, to support the unbiased evaluation of novel information retrieval approaches. The TREC Genomics Track has recently been introduced to measure the performance of information retrieval for biomedical applications. Results We describe two protocols for evaluating biomedical information retrieval techniques without human relevance judgments. We call these protocols No Title Evaluation (NT Evaluation. The first protocol measures performance for focused searches, where only one relevant document exists for each query. The second protocol measures performance for queries expected to have potentially many relevant documents per query (high-recall searches. Both protocols take advantage of the clear separation of titles and abstracts found in Medline. We compare the performance obtained with these evaluation protocols to results obtained by reusing the relevance judgments produced in the 2004 and 2005 TREC Genomics Track and observe significant correlations between performance rankings generated by our approach and TREC. Spearman's correlation coefficients in the range of 0.79–0.92 are observed comparing bpref measured with NT Evaluation or with TREC evaluations. For comparison, coefficients in the range 0.86–0.94 can be observed when evaluating the same set of methods with data from two independent TREC Genomics Track evaluations. We discuss the advantages of NT Evaluation over the TRels and the data fusion evaluation protocols introduced recently. Conclusion Our results suggest that the NT Evaluation protocols described here could be used to optimize some search engine parameters before human evaluation. Further research is needed to determine if NT

  5. A Protocol for Evaluating Contextual Design Principles

    Arthur Stamps


    Full Text Available This paper explains how scientific data can be incorporated into urban design decisions, such as evaluating contextual design principles. The recommended protocols are based on the Cochrane Reviews that have been widely used in medical research. The major concepts of a Cochrane Review are explained, as well as the underlying mathematics. The underlying math is meta-analysis. Data are reported for three applications and seven contextual design policies. It is suggested that use of the Cochrane protocols will be of great assistance to planners by providing scientific data that can be used to evaluate the efficacies of contextual design policies prior to implementing those policies.

  6. Study Application of RADIUS Protocol on Ethernet

    GUO Fang; YANG Huan-yu; LI Hong


    This paper presents how to apply the RADIUS (Remote Authentication Dial In User Service)protocol ,which is generally applied to dial-up network, to the authentication & charge of Broad Band accessing control system on Ethernet. It is provided that the Broad Band accessing control system included a self-designed communication protocol is used in communicating between an terminal user and Network Access Server .The interface module on the servers side and the Radius system is also given in this article.

  7. Explicit Protocol for Deterministic Entanglement Concentration

    GU Yong-Jian; GAO Peng; GUO Guang-Can


    @@ We present an explicit protocol for extraction of an EPR pair from two partially entangled pairs in a deterministic fashion via local operations and classical communication. This protocol is constituted by a local measurement described by a positive operator-valued measure (POVM), one-way classical communication, and a corresponding local unitary operation or a choice between the two pairs. We explicitly construct the required POVM by the analysis of the doubly stochastic matrix connecting the initial and the final states. Our scheme might be useful in future quantum communication.

  8. A molecular protocol for diagnosing myotonic dystrophy.

    Guida, M; Marger, R S; Papp, A C; Snyder, P J; Sedra, M S; Kissel, J T; Mendell, J R; Prior, T W


    Myotonic dystrophy (DM) is an autosomal dominant genetic disease caused by an unstable CTG repeat sequence in the 3' untranslated region of the myotonin protein kinase gene. The CTG repeat is present 5-30 times in the normal population, whereas DM patients have CTG expansions of 50 to several thousand repeats. The age of onset of the disorder and the severity of the phenotype is roughly correlated with the size of the CTG expansion. We developed a molecular protocol for the diagnosis of DM based on an initial polymerase chain reaction screen to detect normal-sized alleles and small expansions, followed by an improved Southern protocol to detect larger expansions.

  9. Social Protocols for Agile Virtual Teams

    Picard, Willy

    Despite many works on collaborative networked organizations (CNOs), CSCW, groupware, workflow systems and social networks, computer support for virtual teams is still insufficient, especially support for agility, i.e. the capability of virtual team members to rapidly and cost efficiently adapt the way they interact to changes. In this paper, requirements for computer support for agile virtual teams are presented. Next, an extension of the concept of social protocol is proposed as a novel model supporting agile interactions within virtual teams. The extended concept of social protocol consists of an extended social network and a workflow model.

  10. Social Protocols for Agile Virtual Teams

    Picard, Willy


    Despite many works on collaborative networked organizations (CNOs), CSCW, groupware, workflow systems and social networks, computer support for virtual teams is still insufficient, especially support for agility, i.e. the capability of virtual team members to rapidly and cost efficiently adapt the way they interact to changes. In this paper, requirements for computer support for agile virtual teams are presented. Next, an extension of the concept of social protocol is proposed as a novel model supporting agile interactions within virtual teams. The extended concept of social protocol consists of an extended social network and a workflow model.

  11. Communication Protocols Augmentation in VLSI Design Applications

    Kanhu Charan Padhy


    Full Text Available With the advancement in communication System, the use of various protocols got a sharp rise in the different applications. Especially in the VLSI design for FPGAs, ASICS, CPLDs, the application areas got expanded to FPGA based technologies. Today, it has moved from commercial application to the defence sectors like missiles & aerospace controls. In this paper the use of FPGAs and its interface with various application circuits in the communication field for data (textual & visual & control transfer is discussed. To be specific, the paper discusses the use of FPGA in various communication protocols like SPI, I2C, and TMDS in synchronous mode in Digital System Design using VHDL/Verilog.

  12. Building multiservice Internet protocol virtual private networks

    Cheung, William


    Multiservice Internet Protocol-based Virtual Private Networks (MIP- VPNs) with Quality of Service (QoS) are becoming a reality due to the availability of new standards from the Internet Engineering Task Force (IETF). This paper describes how components including security models, IP tunneling protocols, and service differentiation schemes fit together in order to construct such a VPN. First, the concept and rationale of VPN is presented, followed by a discussion of its supporting components. A comparison is made among the various VPN technologies.

  13. Quantum Private Comparison Protocol with Linear Optics

    Luo, Qing-bin; Yang, Guo-wu; She, Kun; Li, Xiaoyu


    In this paper, we propose an innovative quantum private comparison(QPC) protocol based on partial Bell-state measurement from the view of linear optics, which enabling two parties to compare the equality of their private information with the help of a semi-honest third party. Partial Bell-state measurement has been realized by using only linear optical elements in experimental measurement-device-independent quantum key distribution(MDI-QKD) schemes, which makes us believe that our protocol can be realized in the near future. The security analysis shows that the participants will not leak their private information.

  14. The covert channel over HTTP protocol

    Graniszewski, Waldemar; Krupski, Jacek; Szczypiorski, Krzysztof


    The paper presents a new steganographic method - the covert channel is created over HTTP protocol header, i.e. trailer field. HTTP protocol is one of the most frequently used in the Internet. The popularity of the Web servers and network traffic from, and to them, is one of the requirements for undetectable message exchange. To study this kind of the information hiding technique an application in Javascript language based on the Node.js framework was written. The results of the experiment that was performed to send a message in the covert channel are also presented.

  15. NADA protocol: integrative acupuncture in addictions.

    Carter, Kenneth; Olshan-Perlmutter, Michelle


    National Acupuncture Detoxification Association (NADA) acupuncture is a simple, standardized, 1- to 5-point auricular needling protocol that originated as a grass-roots response to the opiate epidemic of the 1970s. NADA acupuncture is increasingly recognized as a universally useful intervention in the treatment of addictions specifically and in behavior health more generally. It is recognized as a best practice in the treatment of substance use disorders. Integrative programs using the NADA protocol are likely to see improvements in engagement, retention, decreased drug cravings, anxiety, and less physical symptoms.

  16. A New Route Maintenance in Dynamic Source Routing Protocol

    Shukla, Ashish


    Mobile ad-hoc network (MANET) is infrastructureless, self-organizable, multi hop packet switched network. A number of routing protocols for MANETs have been proposed in recent years. Dynamic Source Routing (DSR) protocol is one of the most popular routing protocol for ad hoc networks. This paper presents a novel method to enhance route maintenance part of DSR protocol. Our proposed route maintenance significantly increases the efficiency of the protocol at the time of route failures.

  17. Energy Consumption in Location Sharing Protocols for Android Applications

    Prihodko, Mihails


    This thesis studies the Message Queue Telemetry Transport protocol (MQTT) as an application layer protocol in geographical location sharing applications using third generation cellular communication (3G). The MQTT protocol is compared in terms of energy efficiency and amount of data generated with the Hypertext Transfer Protocol (HTTP), which is currently used in typical location sharing applications. In order to compare the communication energy efficiency of both protocols a location sharing...

  18. Comparison of Two Hierarchical Routing Protocols for Heterogeneous MANET


    protocols (e.g. Ad-Hoc On-Demand Distance Vector routing protocol , AODV ) search for and maintain routes to destination nodes upon demand from...the time it takes to find a route when data needs to be sent. Protocols such as OLSR and AODV support nodes having multiple interfaces. However they...hierarchical ad hoc routing protocols are derived from a “flat” ad routing protocol . For instance, H- AODV [8] and H-DSR [11] are examples

  19. Modify AODV Routing Protocol to Improve Motorway Surveillance System Performance

    Layth Abdulkareem Hassnawi; R. Badlishah Ahmad; Abid Yahya


    This paper presents an algorithm to modify the Ad Hoc On-Demand Distance Vector (AODV) routing protocol in order to improve the routing performance in motorway surveillance systems. The proposed protocol has all the characteristics of the original AODV routing protocol since it follows all the steps of the route discovery and route maintenance mechanism of the original AODV routing protocol. The Modified AODV (MAODV) is different from the original AODV protocol in that it modifies the origina...

  20. BEPS Action 2: Neutralizing the Effects on Hybrid Mismatch Arrangements

    de Boer, R.; Marres, O.


    Curbing tax arbitrage is one of the main priorities of the Organization for Economic Cooperation and Development (OECD) (endorsed by the G20 and the G8) ever since the public debate on base erosion fully erupted. Neutralizing the effect of hybrid mismatch arrangements has become Action No. 2 of the


    Muhammad Yusuf


    Full Text Available Break event point or the break-even point can be defined as a situation where the operating company does not make a profit and not a loss. The goal is to provide the knowledge to increase knowledge about the break event point (the point of principal and its relationship with the company profit and to know how the results of the. Analysis break event point is very important for the leadership of the company to determine the production rate how much the cost will be equal to the amount of sales or in other words to determine the break event point we will determine the relationship between sales, production, selling price, cost, loss or profit, making it easier for leaders to take discretion.DOI: 10.15408/ess.v4i1.1955 

  2. Selective induction of glutathione S-transferases in round spermatids from the Brown-Norway rat by the chemotherapeutic regimen for testicular cancer.

    Delbès, Geraldine; Chan, Donovan; Hales, Barbara F; Trasler, Jacquetta M; Robaire, Bernard


    Chemotherapeutic drugs can affect DNA in male germ cells, thereby impacting on the integrity of the genome transmitted to offspring. Drug metabolizing enzymes can protect cells from xenobiotic insult. We analyzed the expression pattern of such enzymes in isolated round spermatids from rats exposed to drugs used to treat testicular cancer: bleomycin, etoposide, and cisplatin (BEP). The number of isozymes expressed and the overall relative expression values were highest for the glutathione S-transferases (GSTs). Moreover, BEP treatment significantly increased the expression of 8 GSTs and 3 aldehyde dehydrogenases. Increased expression of GST isozymes was confirmed by qRT-PCR and Western blot analysis. Although Gst genes can be targets for epigenetic modifications, promoter DNA methylation was not affected by BEP treatment. As GSTs are involved in drug resistance mechanisms, we hypothesize that BEP induction of GST expression may lead to the survival of damaged germ cells and the production of abnormal sperm.

  3. Real-time communication protocols: an overview

    Hanssen, Ferdy; Jansen, Pierre G.


    This paper describes several existing data link layer protocols that provide real-time capabilities on wired networks, focusing on token-ring and Carrier Sense Multiple Access based networks. Existing modifications to provide better real-time capabilities and performance are also described. Finally

  4. Real-time communication protocols: an overview

    Hanssen, Ferdy; Jansen, Pierre G.


    This paper describes several existing data link layer protocols that provide real-time capabilities on wired networks, focusing on token-ring and Carrier Sense Multiple Access based networks. Existing modifications to provide better real-time capabilities and performance are also described. Finally the pros and cons regarding the At-Home Anywhere project are discussed.

  5. Strong Robustness of Randomized Rumor Spreading Protocols

    Doerr, Benjamin; Levavi, Ariel


    Randomized rumor spreading is a classical protocol to disseminate information across a network. At SODA 2008, a quasirandom version of this protocol was proposed and competitive bounds for its run-time were proven. This prompts the question: to what extent does the quasirandom protocol inherit the second principal advantage of randomized rumor spreading, namely robustness against transmission failures? In this paper, we present a result precise up to $(1 \\pm o(1))$ factors. We limit ourselves to the network in which every two vertices are connected by a direct link. Run-times accurate to their leading constants are unknown for all other non-trivial networks. We show that if each transmission reaches its destination with a probability of $p \\in (0,1]$, after $(1+\\e)(\\frac{1}{\\log_2(1+p)}\\log_2n+\\frac{1}{p}\\ln n)$ rounds the quasirandom protocol has informed all $n$ nodes in the network with probability at least $1-n^{-p\\e/40}$. Note that this is faster than the intuitively natural $1/p$ factor increase over th...

  6. Security Protocols: Specification, Verification, Implementation, and Composition

    Almousa, Omar

    their security. Among others, tools like OFMC [MV09b] and Proverif [Bla01] are quite efficient for the automatic formal verification of a large class of protocols. These tools use different approaches such as symbolic model checking or static analysis. Either approach has its own pros and cons, and therefore, we...

  7. An acid-catalyzed macrolactonization protocol.

    Trost, Barry M; Chisholm, John D


    [reaction: see text] An efficient macrolactonization protocol devoid of any base was developed derived from the use of vinyl esters in transesterification. Subjecting a hydroxy acid and ethoxyacetylene to 2 mol % [RuCl(2)(p-cymene)](2) in toluene followed by addition of camphorsulfonic acid or inverse addition provided macrolactones in good yields.

  8. Secure communication protocol for mobile multimedia applications

    Komninos, N.; Honary, B.; Darnell, M.


    Data transmission over wireless communication networks is increasing rapidly and security has become a very important issue. The main considerations of secure communication systems are authentication, key distribution, and data transfer. This paper describes a secure communication protocol (SCP), which provides privacy and data integrity for end-to-end data transmission over wireless communication systems.

  9. Recursion vs. Replication in Simple Cryptographic Protocols

    Huttel, Hans; Srba, Jiri


    We use some recent techniques from process algebra to draw several conclusions about the well studied class of ping-pong protocols introduced by Dolev and Yao. In particular we show that all nontrivial properties, including reachability and equivalence checking wrt. the whole van Glabbeek's spect...

  10. A Verifiable Language for Cryptographic Protocols

    Nielsen, Christoffer Rosenkilde

    We develop a formal language for specifying cryptographic protocols in a structured and clear manner, which allows verification of many interesting properties; in particular confidentiality and integrity. The study sheds new light on the problem of creating intuitive and human readable languages...

  11. Recursion Versus Replication in Simple Cryptographic Protocols

    Hüttel, Hans; Srba, Jiri


    We use some very recent techniques from process algebra to draw interesting conclusions about the well studied class of ping-pong protocols introduced by Dolev and Yao. In particular we show that all nontrivial properties, including reachability and equivalence checking wrt. the whole van Glabbee...

  12. Sessions and Separability in Security Protocols

    Carbone, Marco; Guttman, Joshua


    Despite much work on sessions and session types in non- adversarial contexts, session-like behavior given an active adversary has not received an adequate definition and proof methods. We provide a syntactic property that guarantees that a protocol has session-respecting executions. Any uncomprom...

  13. Plant Fungal Pathogens: Methods and Protocols

    Bolton, M.D.; Thomma, B.P.H.J.


    Over the course of evolution, fungi have adapted to occupy specific niches, from symbiotically inhabiting the flora of the intestinal tract of mammals to saprophytic growth on leaf litter resting on the forest floor. In Plant Fungal Pathogens: Methods and Protocols, expert researchers in the field d

  14. Implementing the Environmental Protocol Domestically : An Overview

    Bastmeijer, C.J.; Vidas, Davor


    This book - edited by Davor Vidas of the Nansens Institute (Oslo, Norway) - is the first book that comprehensively discusses the implementation of the Environmental Protocol to the Antarctic Treaty. Part V of this book includes a number of chapters describing the measures that have been taken by sel

  15. Knowledge Sharing Protocol for Smart Spaces

    Juha-Pekka Soininen


    Full Text Available In this paper we present a novel knowledge sharing protocol (KSP for semantic technology empowered ubiquitous computing systems. In particular the protocol is designed for M3 which is a blackboard based semantic interoperability solution for smart spaces. The main difference between the KSP and existing work is that KSP provides SPARQL-like knowledge sharing mechanisms in compact binary format that is designed to be suitable also for resource restricted devices and networks. In order to evaluate the KSP in practice we implemented a case study in a prototype smart space, called Smart Greenhouse. In the case study the KSP messages were on average 70.09% and 87.08% shorter than the messages in existing M3 communication protocols. Because the KSP provides a mechanism for automating the interaction in smart spaces it was also possible to implement the case study with fewer messages than with other M3 communication protocols. This makes the KSP a better alternative for resource restricted devices in semantic technology empowered smart spaces.

  16. An evidence based blunt trauma protocol

    Vugt, R. van; Kool, D.R.; Lubeek, S.F.; Dekker, H.M.; Brink, M.; Deunk, J.; Edwards, M.J.R.


    OBJECTIVE: Currently CT is rapidly implemented in the evaluation of trauma patients. In anticipation of a large international multicentre trial, this study's aim was to evaluate the clinical feasibility of a new diagnostic protocol, used for the primary radiological evaluation in adult blunt high-en

  17. Smart environments technology, protocols and applications

    Cook, Diane


    Smart Environments contains contributions from leading researchers, describing techniques and issues related to developing and living in intelligent environments. Reflecting the multidisciplinary nature of the design of smart environments, the topics covered include the latest research in smart environment philosophical and computational architecture considerations, network protocols for smart environments, intelligent sensor networks and powerline control of devices, and action prediction and identification.

  18. A Geographical Heuristic Routing Protocol for VANETs

    Luis Urquiza-Aguiar


    Full Text Available Vehicular ad hoc networks (VANETs leverage the communication system of Intelligent Transportation Systems (ITS. Recently, Delay-Tolerant Network (DTN routing protocols have increased their popularity among the research community for being used in non-safety VANET applications and services like traffic reporting. Vehicular DTN protocols use geographical and local information to make forwarding decisions. However, current proposals only consider the selection of the best candidate based on a local-search. In this paper, we propose a generic Geographical Heuristic Routing (GHR protocol that can be applied to any DTN geographical routing protocol that makes forwarding decisions hop by hop. GHR includes in its operation adaptations simulated annealing and Tabu-search meta-heuristics, which have largely been used to improve local-search results in discrete optimization. We include a complete performance evaluation of GHR in a multi-hop VANET simulation scenario for a reporting service. Our study analyzes all of the meaningful configurations of GHR and offers a statistical analysis of our findings by means of MANOVA tests. Our results indicate that the use of a Tabu list contributes to improving the packet delivery ratio by around 5% to 10%. Moreover, if Tabu is used, then the simulated annealing routing strategy gets a better performance than the selection of the best node used with carry and forwarding (default operation.

  19. A Bayesian approach to optimizing cryopreservation protocols

    Sammy Sambu


    Full Text Available Cryopreservation is beset with the challenge of protocol alignment across a wide range of cell types and process variables. By taking a cross-sectional assessment of previously published cryopreservation data (sample means and standard errors as preliminary meta-data, a decision tree learning analysis (DTLA was performed to develop an understanding of target survival using optimized pruning methods based on different approaches. Briefly, a clear direction on the decision process for selection of methods was developed with key choices being the cooling rate, plunge temperature on the one hand and biomaterial choice, use of composites (sugars and proteins as additional constituents, loading procedure and cell location in 3D scaffolding on the other. Secondly, using machine learning and generalized approaches via the Naïve Bayes Classification (NBC method, these metadata were used to develop posterior probabilities for combinatorial approaches that were implicitly recorded in the metadata. These latter results showed that newer protocol choices developed using probability elicitation techniques can unearth improved protocols consistent with multiple unidimensionally-optimized physical protocols. In conclusion, this article proposes the use of DTLA models and subsequently NBC for the improvement of modern cryopreservation techniques through an integrative approach.




    Full Text Available Electronic Voting play a really vital role in the democracy of our life. In this paper, we propose an electronic voting protocol. Our scheme does not require a special voting channel and communication can occur entirely over the current Internet. This method integrates the Internet convenience and cryptology. In the existing protocol the Tallier has to wait until the decryption key is received from the voter. So it will consume lot of time. But, the proposed protocol is based on the hybrid cryptosystem. In this, the ballot is encrypted using faster secret key algorithm and the digital envelope is encrypted using Tallier’s public key. So, the Tallier will decrypt the digital envelope using his own private key to get the secret key and then the encrypted ballot is decrypted using that secret key. So, comparatively the proposed protocol consumes less time. This paper also analyzes the various security issues involved in an electronic voting like security, privacy, authentication, anonymous, uniqueness, accuracy, fairness, efficiency and uncoercibility.