The Inhibitory Core of the Myostatin Prodomain: Its Interaction with Both Type I and II Membrane Receptors, and Potential to Treat Muscle Atrophy.

Science.gov (United States)

Ohsawa, Yutaka; Takayama, Kentaro; Nishimatsu, Shin-ichiro; Okada, Tadashi; Fujino, Masahiro; Fukai, Yuta; Murakami, Tatsufumi; Hagiwara, Hiroki; Itoh, Fumiko; Tsuchida, Kunihiro; Hayashi, Yoshio; Sunada, Yoshihide

2015-01-01

Myostatin, a muscle-specific transforming growth factor-β (TGF-β), negatively regulates skeletal muscle mass. The N-terminal prodomain of myostatin noncovalently binds to and suppresses the C-terminal mature domain (ligand) as an inactive circulating complex. However, which region of the myostatin prodomain is required to inhibit the biological activity of myostatin has remained unknown. We identified a 29-amino acid region that inhibited myostatin-induced transcriptional activity by 79% compared with the full-length prodomain. This inhibitory core resides near the N-terminus of the prodomain and includes an α-helix that is evolutionarily conserved among other TGF-β family members, but suppresses activation of myostatin and growth and differentiation factor 11 (GDF11) that share identical membrane receptors. Interestingly, the inhibitory core co-localized and co-immunoprecipitated with not only the ligand, but also its type I and type II membrane receptors. Deletion of the inhibitory core in the full-length prodomain removed all capacity for suppression of myostatin. A synthetic peptide corresponding to the inhibitory core (p29) ameliorates impaired myoblast differentiation induced by myostatin and GDF11, but not activin or TGF-β1. Moreover, intramuscular injection of p29 alleviated muscle atrophy and decreased the absolute force in caveolin 3-deficient limb-girdle muscular dystrophy 1C model mice. The injection suppressed activation of myostatin signaling and restored the decreased numbers of muscle precursor cells caused by caveolin 3 deficiency. Our findings indicate a novel concept for this newly identified inhibitory core of the prodomain of myostatin: that it not only suppresses the ligand, but also prevents two distinct membrane receptors from binding to the ligand. This study provides a strong rationale for the use of p29 in the amelioration of skeletal muscle atrophy in various clinical settings.

Chemoembolization (TACE) of Unresectable Intrahepatic Cholangiocarcinoma with Slow-Release Doxorubicin-Eluting Beads: Preliminary Results

International Nuclear Information System (INIS)

Aliberti, Camillo; Benea, Giorgio; Tilli, Massimo; Fiorentini, Giammaria

2008-01-01

The purpose of this study was to evaluate the safety and efficacy of TACE with microspheres preloaded with doxorubicin in unresectable intrahepatic cholangiocarcinoma (UCH). Twenty patients with UCH were observed; 9 refused, preferring other palliative care or chemotherapy, and 11 agreed to be treated with one or more cycles of DC beads loaded with doxorubicin (100-150 mg) in a TACE procedure between February 2006 and September 2007. A total of 29 individual TACE procedures were performed. Follow-up imaging was performed on all patients before, immediately after, and 4 weeks after each TACE procedure to evaluate the response and need for further treatment. Each patient received i.v hydration, antibiotics, and medications against nausea and pain before TACE. Survival rate was calculated using Kaplan-Meier survival curve. A response rate of 100% followed RECIST criteria was observed. Eight of eleven patients are alive, with a median survival of 13 months. TACE was well tolerated by all patients. One patient developed hepatic abscess requiring antibiotic therapy. No evidence of marrow toxicity has been reported. Only one of nine patients treated with chemotherapy or palliative care is alive (with a median survival of 7 months in this group of patients). In conclusion, we suggest that doxorubicin-eluting beads TACE is a feasible and effective treatment in patients with UCH. Survival seems to be clearly prolonged in the treated group with respect to the palliative group. We consider that doxorubicin-eluting beads TACE of 100-150 mg may be an appropriate palliative therapy for these patients. Further studies are warranted to confirm these interesting preliminary data.

Cross-domain inhibition of TACE ectodomain

DEFF Research Database (Denmark)

Tape, Christopher J; Willems, Sofie H; Dombernowsky, Sarah L

2011-01-01

Proteolytic release from the cell surface is an essential activation event for many growth factors and cytokines. TNF-a converting enzyme (TACE) is a membrane-bound metalloprotease responsible for solubilizing many pathologically significant membrane substrates and is an attractive therapeutic...

Correlation of Multislice CT and Histomorphology in HCC Following TACE: Predictors of Outcome

International Nuclear Information System (INIS)

Herber, S.; Biesterfeld, S.; Franz, U.; Schneider, J.; Thies, J.; Schuchmann, M.; Dueber, C.; Pitton, M. B.; Otto, G.

2008-01-01

The purpose of this study was to correlate histopathological with CT findings in patients suffering from hepatocellular carcinoma (HCC) eligible for orthotopic liver transplantation (OLT), with a special focus on the antitumoral effect of transarterial chemoembolization (TACE) therapy. A total of 42 consecutive patients suffering from HCC had been treated prior to OLT by means of TACE. TACE was carried out with a mixture of Lipiodol (10-20 ml) and mitomycin C (max. dosage, 10 mg). TACE was performed at 6- to 8-week intervals. Follow-up investigation included contrast-enhanced multislice CT controls and laboratory control. Liver explants were evaluated macroscopically and microscopically to determine the number and size of the tumor lesions as well as the degree of tumor necrosis. Necrosis was investigated in H and E-stained sections. The degree of necrosis was classified as follows: 0-25%, 26-50%, 51-75%, 75-99%, and complete necrosis. Two hundred thirty-one TACE procedures (5.5 ± 2.9; range, 1-14) were performed. Mean tumor size in CT before and after TACE was 4.1 ± 2.4 (range, 1.0-12.0 cm) and 2.7 ± 1.2 (range, 1.0-6.0 cm; p < 0.001). Mean tumor number before and after TACE in CT was 2.5 ± 1.5 (n = 105; range, 1-8) and 2.4 ± 2.0 (n = 103; range, 1-6; p = 0.99). In the surgical specimen tumor size and tumor number were 2.8 ± 1.6 (range, 1.0-7.0 cm; p = 0.78) and 1.9 ± 1.2 (range, 1-7; p = 0.003). Mean tumor necrosis was 67.8% ± 28.1%. Tumor necrosis was subtotal or complete in 17 of 42 (40.5%) patients. Tumor necrosis correlated significantly with the degree of arterial devascularization in CT (p = 0.001), the amount of Lipiodol washout (p = 0.002), and the number of tumor lesions (i.e., unifocal vs. multifocal). Furthermore, elevated serum levels of bilirubin (p = 0.005) and decreased albumin (p = 0.004) affected the local antitumoral effect. A poor necrosis rate (< 25%) significantly correlated with the number of TACE procedures accomplished (p = 0

Repetitive transarterial chemoembolization (rTACE) of hepatocellular carcinoma: comparisons between an arterial port system and conventional angiographic technique

International Nuclear Information System (INIS)

Hidajat, Nico; Griesshaber, Volker; Hildebrandt, Bert; Hosten, Norbert; Schroeder, Ralf-Juergen; Felix, Roland

2004-01-01

Purpose: To compare the cost and radiation exposure of repetitive transarterial chemoembolization (rTACE) using percutaneously implantable port system with rTACE using conventional catheterization technique. Materials and methods: In five patients with unresectable hepatocellular carcinoma, three cycles of TACE were performed using conventional technique and six cycles using port. The cumulative cost of material and contrast agent and dose area product (DAP) were compared with the cost and DAP that would be expected if the rTACE was performed conventionally. Results: The cost of material and contrast agent was 1002.6 Euro after three cycles of TACE using conventional technique and six cycles using port, but would be 1111.8 Euro if the nine cycles were performed using conventional technique alone. The rTACE with three cycles using conventional technique and six cycles using port led to ∼63% of the cumulative DAP that would be expected in rTACE using conventional technique alone. Conclusion: In rTACE, the use of percutaneously implantable port system might enable a reduction of cost and radiation exposure

Cryotherapy of employing Argon/Helium assisted with TACE in treating unresectable primary liver carcinoma

International Nuclear Information System (INIS)

Zhang Zhiliang; Yang Xuedong; Cao Yongwei; Lin Xiangyang; Zhang Yongping; Liu Yayuan

2004-01-01

Objective: To investigate the effect of cryotherapy of employing Argon/Helium assisted with TACE for the unresectable primary liver carcinoma. Methods: 124 cases with primary liver carcinoma were randomly divided into two groups: 60 cases were treated by TACE and cryotherapy; the other 64 cases were simply done by TACE as control. In general, TACE was undertaken once a month and altogether three times for a course. Cryotherapy was undergone 1-3 times for a course. Results: The total effective rates (CR + PR) were 45.3% for the control group and 68.3% for the combined therapy group, with an obvious difference between the two groups, 0.5, 1, 1.5 years survival rate were 81.3%, 62.5%, 43.8% respectively in the control group; 93.3%, 83.3%, 63.3% respectively for the combined group. There was an obvious difference between the two groups of 1, 1.5 years of survival rates. Conclusions: Cryotherapy of employing Argon/Helium assisted with TACE for the unresectable primary liver carcinoma is feasible with raising the effective rate and prolonging survival time. (authors)

Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer

International Nuclear Information System (INIS)

Xia Jinglin; Ren Zhenggang; Ye Shenglong; Sharma Dilip; Lin Zhiying; Gan Yuhong; Chen Yi; Ge Ninglin; Ma Zengchen; Wu Zhiquan; Fan Jia; Qin Lunxiu; Zhou Xinda; Tang Zhaoyou; Yang Binghui

2006-01-01

Objective: To study severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. Methods: Clinical records of severe and rare complications following TACE in 1348 cases of liver cancer from January 1997 to February 2004 were studied retrospectively. Results: A total of 2012 TACE procedures were performed for 1348 patients. There were 3 cases of spontaneous rupture of liver cancer, 1 case of perforation of duodenum, 3 cases of liver abscess (1 of them was associated with sepsis), 1 case of pulmonary embolism, 1 case of spasm of the hepatic artery, 40 cases of hepatic artery occlusion, 3 cases of femoral nerve injury, 1 case of bilioma and 1 case of acute renal failure. Conclusion: Although the severe complications of TACE are rare, the procedure should be done cautiously including super selection of hepatic artery, slow infusion of lipiodol, careful postoperative observations and early detection and management of complications

In vitro maturation of Drosophila melanogaster Spätzle protein with refolded Easter reveals a novel cleavage site within the prodomain.

Science.gov (United States)

Ursel, Christian; Fandrich, Uwe; Hoffmann, Anita; Sieg, Torsten; Ihling, Christian; Stubbs, Milton T

2013-08-01

Dorsoventral patterning during Drosophila melanogaster embryogenesis is mediated by a well-defined gradient of the mature NGF-like ligand Spätzle. Easter, the ultimate protease of a ventrally-restricted serine protease cascade, plays a key role in the regulation of the morphogenic gradient, catalyzing the activation cleavage of proSpätzle. As a result of alternative splicing, proSpätzle exists in multiple isoforms, almost all of which differ only in their prodomain. Although this domain is unstructured in isolation, it has a stabilizing influence on the mature cystine knot domain and is involved in the binding to the Toll receptor. Here, we report the expression and refolding of Easter, and show that the renatured enzyme performs the activation cleavage of two Spätzle isoforms. We determine the affinity of the prodomain for the cystine knot domain, and show that Easter performs a previously unknown secondary cleavage in each prodomain.

Correlation between serum VEGF level and CT perfusion imaging in patients with primary liver cancer pre-and post TACE

International Nuclear Information System (INIS)

Jia Zhongzhi; Huang Yuanquan; Feng Yaoliang; Shi Haibin

2010-01-01

Objective: To investigate the correlation between serum vascular endothelial growth factor(VEGF) level and CT perfusion parameters in patients with primary liver cancer (PLC) pre-and post-transcatheter arterial chemoembolization (TACE) treatment. Methods: Serum VEGF level was measured and CT perfusion imaging was performed 1 day before and 6 ∼ 8, 32 ∼ 40 days after TACE in 18 patients with PLC. Before and after TACE, the serum VEGF level, the tumor's artery liver perfusion (ALP), the portal vein perfusion (PVP) and the hepatic artery perfusion index (HPI) were measured pre-and post-TACE. The pre-TACE and post-TACE results were compared and statistically analyzed. Results: Based on the therapeutic results, the patients were divided into complete response (CR) group and partial response or stable disease(PR+SD) group. Although no significant difference in serum VEGF level, tumor's ALP, PVP and HPI existed between two groups pre-TACE, there was significant difference in ALP, HPI 6-8 days after TACE (P<0.05). Significant difference in serum VEGF level also existed in CR group (P<0.05), but not in (PR+SD) group, at (32-40) days post-TACE (P=0.221). The serum VEGF level carried a positive correlation with the tumor's ALP and HPI. Conclusion: The serum VEGF level can indirectly reflect the neovascularization of the tumor, while the CTPI can directly and quantitatively reflect the hemodynamic changes of the tumor post-TACE. Moreover, a positive correlation exists between serum VEGF level and ALP, HPI. Therefore, the determination of serum VEGF level together with CTPI is very useful in both evaluating TACE efficacy and making therapeutic schedule. (authors)

Transcatheter Arterial Chemoembolization (TACE) of Colorectal Cancer Liver Metastases by Irinotecan-Eluting Microspheres in a Salvage Patient Population

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Huppert, Peter, E-mail: huppert@klinikum-darmstadt.de [Klinikum Darmstadt GmbH, Department of Diagnostic and Interventional Radiology (Germany); Wenzel, Thorsten [Klinikum Darmstadt GmbH, Department of Medical Oncology (Germany); Wietholtz, Hubertus [Klinikum Darmstadt GmbH, Department of Gastroenterology (Germany)

2013-05-14

PurposeThis prospective study evaluated the effectiveness and safety of TACE using irinotecan loaded superabsorbent polymer (SAP) microspheres for treatment of colorectal cancer liver metastases (CCLM) in a salvage setting of patients.MethodsA total of 71 TACE procedures were performed in 29 patients with liver only or liver-dominant CCLM. In all patients, systemic chemotherapy before TACE had failed. Two hundred milligrams of irinotecan were loaded into 50–100 mg of SAP microspheres (HepaSphere™ Microspheres) considering tumor size and vascularization. TACE was performed selectively with respect to tumor distribution. Response was evaluated following RECIST and EASL criteria, respectively. Median follow-up after last TACE was 8 (range 1–54) months. All patients had died at time of analysis.ResultsAll TACE procedures were performed successfully; 35–400 mg (mean 168.3 mg) of irinotecan loaded in 13–100 mg (mean 48.3 mg) SAP microspheres were injected during individual sessions. No major complications occurred. Three, 6, and 12 months after first TACE complete and partial response was present in 72, 32 %, 0 of patients by EASL criteria and stable disease was seen in 86, 48, and 8 % with no complete and no partial response by RECIST criteria. Median overall survival after first TACE was 8 months, and median time to progression was 5 months. Median overall survival was longer in patients with limited (<25 %) compared with extensive (>50 %) intrahepatic disease (21 vs. 5 months, p < 0.005).ConclusionsTACE using irinotecan loaded SAP microspheres is safe and effective in terms of tumor necrosis. Survival benefit in a salvage setting seems to be limited in patients with advanced intrahepatic tumor load.

[Comparative analysis of TACE alone or plus RFA in the treatment of 167 cases of intermediate and advanced staged primary hepatocellular carcinoma].

Science.gov (United States)

Zhao, Ming; Wang, Jian-peng; Wu, Pei-hong; Zhang, Fu-jun; Huang, Zi-lin; Li, Wang; Zhang, Liang; Pan, Chang-chuan; Li, Chuan-xing; Jiang, Yong

2010-11-09

To evaluate the clinical efficacy and survival rate of transarterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in patients with intermediate or advanced stage primary hepatocellular carcinoma (HCC). In this retrospective study, 467 cases received RFA or TACE plus RFA. Among them, 167 cases with strict clinical procedure (TACE alone or plus RFA) and complete follow-up data were included. Eighty-seven cases received TACE and 80 cases had TACE plus RFA between January 2000 and December 2006. Hierarchical analyses were performed using log-rank tests and survival curve was estimated by Kaplan-Meier method. A total of 167 patients received TACE alone or plus RFA for a follow-up period of 1 to 89 months. In the TACE alone group, the time-to-progression (TTP) was an average of 3.6 months. The median survival was 13 months, one-year survival rate 52.9%, three-year survival rate 11.5% and five-year survival rate 4.6%. In the TACE plus RFA group, the TTP time was an average of 10.8 months. The median survival time was 30 months, one-year survival rate 85.0%, three-year survival rate 45.0% and five-year survival rate 11.3%. In the TACE alone group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 62.2%, three-year survival rate 13.3% and five-year survival rate 4.4%; In the TACE plus RFA group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 90.1%, three-year survival rate 52.9% and five-year survival rate 13.7%. All differences of two groups has statistical significance (P advanced stage HCC, the median survival time was 12 months, one-year survival rate 35%, three-year survival rate 7.1% and five-year survival rate 0 in the TACE alone group versus 28 months, 62.1%, 24.1% and 6.9% in the TACE plus RFA group (P = 0.00). There was significantly statistic difference between both groups in intermediate and advanced staging HCC. Among them, 60/485 (12.4%) patients required a therapy

The effect of TACE plus PSE on the liver function of hepatic cancer with portal hypertension and hypersplenism

International Nuclear Information System (INIS)

Tao Zhenglong; Jin Hongxian; Cheng Yongde; Zhan Yingjiang

2004-01-01

Objective: To evaluate the effect of transcatheter arterial chemoembolization (TACE) plus partial spleen embolization (PSE) on the liver function in patients with hepatocellular carcinoma (HCC). Methods: 85 patients with HCC complicated with portal hypertension and hypersplenism, including group A 45 patients with treatment of TACE plus PSE and group B 40 patients with single TACE were observed. The liver function was evaluated with Child Pugh scores before and after the procedure. Results: There was no difference in the levels of TBIL, ALT, ALB and Child Pugh scores between groups A and B (P>0.05) but remarkable change after therapy was shown at one week later (P<0.05, P<0.01). The liver function tests showed remarkable improvement in the TACE plus PSE group. Conclusion: TACE combined with PSE is a safe and effective procedure for patients with HCC associated with liver cirrhosis, portal hypertension and hypersplenism. (authors)

Dynamic study of efficacy of transcatheter arterial chemoembolization (TACE) of primary liver carcinoma with the MR diffusion-weighted imaging (DWI)

International Nuclear Information System (INIS)

Shang Quanliang; Xiao Enhua; He Zhong; Tan Lihua; Situ Weijun; Bao Moliao; Yuan Shiwen; Du Wanping

2006-01-01

Objective: To dynamically evaluate the efficacy of treatment of primary liver carcinoma (PLC) by transcatheter arterial ehemoembolization(TACE) with the MR diffusion-weighted imaging(DWI). Methods: DWI and the measurement of mean apparent diffusion coeffecient (ADC) value were performed in 25 masses of PLC with the same SE-EPI sequence (b=800 s/mm 2 and 0) at 1.5 T MRI within the 24- 48 hours before TACE (group A) and 36-48 hours, 7-10 days, 30-38 days after TACE (group B, group C, group D). The differences of the mean ADC values of PLC between groups were analyzed. Results: The mean ADC values of the three groups after TACE the mean ADC value of group B: (1.598±0.012) x 10 -3 mm 2 /s, the mean ADC value of group C: (1.723±0.012) x 10 -3 mm 2 /s, the mean ADC value of group D: (1.684±0.012) x 10 -3 mm 2 /s were significantly greater than that of the group before TACE the mean ADC value of group A: (1.376±0.012) x 10 -3 mm 2 /s (p<0.05). The mean ADC values of the group C and the group D were significantly greater than that of the group B (P<0.05). The mean ADC values of the group D was lower than that of the group C (P<0.05). Through contrasting the digital subtraction angiography (DSA) imaging of the second TACE with that of the first TACE, we found that every PLC whose mean ADC value after 30-38 days of the TACE was lower than that after 7-10 days of the TACE could be found the recurrence, especially in those PLC whose mean ADC values were decreased greatly. Conclusion: With the measurement of ADC value of the different time of the PLC we could excellently evaluate the necrosis and the recurrence of the PLC after the operation of the TACE. (authors)

Prospective Evaluation of Transcatheter Arterial Chemoembolization (TACE) with Multiple Anti-Cancer Drugs (Epirubicin, Cisplatin, Mitomycin C, 5-Fluorouracil) Compared with TACE with Epirubicin for Treatment of Hepatocellular Carcinoma

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Sahara, Shinya; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@mail.wakayama-med.ac.jp; Tanaka, Takami; Ikoma, Akira; Nakata, Kouhei; Sanda, Hiroki; Minamiguchi, Hiroki; Nakai, Motoki; Shirai, Shintaro; Sonomura, Tetsuo [Wakayama Medical University, Department of Radiology (Japan)

2012-12-15

Purpose: To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC). Materials and Methods: The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis; Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group. Results: No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019). Conclusion: TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone.

Development of a 'mouse and human cross-reactive' affinity-matured exosite inhibitory human antibody specific to TACE (ADAM17) for cancer immunotherapy.

Science.gov (United States)

Kwok, Hang Fai; Botkjaer, Kenneth A; Tape, Christopher J; Huang, Yanchao; McCafferty, John; Murphy, Gillian

2014-06-01

We previously showed that a human anti-TACE antibody, D1(A12), is a potent inhibitor of TNF-α converting enzyme (TACE) ectodomain proteolysis and has pharmacokinetic properties suitable for studies of the inhibition of TACE-dependent growth factor shedding in relation to possible therapeutic applications. However, the lack of murine TACE immunoreactivity limits pre-clinical in vivo studies to human xenograft models which are poor analogies to in situ pathology and are not considered clinically predictive. Here, to overcome these limitations, we set out to develop a 'mouse and human cross-reactive' specific anti-TACE antibody. We first re-investigated the originally selected anti-TACE ectodomain phage-display clones, and isolated a lead 'mouse-human cross-reactive' anti-TACE scFv, clone A9. We reformatted scFv-A9 into an IgG2 framework for comprehensive biochemical and cellular characterization and further demonstrated that A9 is an exosite TACE inhibitor. However, surface plasmon resonance analysis and quenched-fluorescent (QF) peptide assay indicated that IgG reformatting of A9 caused low binding affinity and an 80-fold reduction in TACE ectodomain inhibition, severely limiting its efficacy. To address this, we constructed second generation phage-display randomization libraries focused on the complementarity-determining region 3, and carried out affinity selections shuffling between human and mouse TACE ectodomain as antigen in addition to an off-rate selection to increase the chance of affinity improvement. The bespoke 'three-step' selections enabled a 100-fold affinity enhancement of A9 IgG, and also improved its IC50 in a QF peptide assay to 0.2 nM. In human and mouse cancer cell assays, matured A9 IgG showed significant cell-surface TACE inhibition as a monotherapy or combination therapy with chemotherapeutic agent. Collectively, these data suggest that we successfully developed an exosite inhibitor of TACE with sub-nanomolar affinity, which possesses both

Randomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Pitton, Michael B.; Kloeckner, Roman; Ruckes, Christian; Wirth, Gesine M.; Eichhorn, Waltraud; Wörns, Marcus A.; Weinmann, Arndt; Schreckenberger, Mathias; Galle, Peter R.; Otto, Gerd; Dueber, Christoph

2015-01-01

PurposeTo prospectively compare SIRT and DEB-TACE for treating hepatocellular carcinoma (HCC).MethodsFrom 04/2010–07/2012, 24 patients with histologically proven unresectable N0, M0 HCCs were randomized 1:1 to receive SIRT or DEB-TACE. SIRT could be repeated once in case of recurrence; while, TACE was repeated every 6 weeks until no viable tumor tissue was detected by MRI or contraindications prohibited further treatment. Patients were followed-up by MRI every 3 months; the final evaluation was 05/2013.ResultsBoth groups were comparable in demographics (SIRT: 8males/4females, mean age 72 ± 7 years; TACE: 10males/2females, mean age 71 ± 9 years), initial tumor load (1 patient ≥25 % in each group), and BCLC (Barcelona Clinic Liver Cancer) stage (SIRT: 12×B; TACE 1×A, 11×B). Median progression-free survival (PFS) was 180 days for SIRT versus 216 days for TACE patients (p = 0.6193) with a median TTP of 371 days versus 336 days, respectively (p = 0.5764). Median OS was 592 days for SIRT versus 788 days for TACE patients (p = 0.9271). Seven patients died in each group. Causes of death were liver failure (n = 4 SIRT group), tumor progression (n = 4 TACE group), cardiovascular events, and inconclusive (n = 1 in each group).ConclusionsNo significant differences were found in median PFS, OS, and TTP. The lower rate of tumor progression in the SIRT group was nullified by a greater incidence of liver failure. This pilot study is the first prospective randomized trial comparing SIRT and TACE for treating HCC, and results can be used for sample size calculations of future studies

Randomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pitton, Michael B., E-mail: michael.pitton@unimedizin-mainz.de; Kloeckner, Roman [Johannes Gutenberg University Medical Center, Department of Diagnostic and Interventional Radiology (Germany); Ruckes, Christian [Johannes Gutenberg University Medical Center, IZKS (Germany); Wirth, Gesine M. [Johannes Gutenberg University Medical Center, Department of Diagnostic and Interventional Radiology (Germany); Eichhorn, Waltraud [Johannes Gutenberg University Medical Center, Department of Nuclear Medicine (Germany); Wörns, Marcus A.; Weinmann, Arndt [Johannes Gutenberg University Medical Center, Department of Internal Medicine (Germany); Schreckenberger, Mathias [Johannes Gutenberg University Medical Center, Department of Nuclear Medicine (Germany); Galle, Peter R. [Johannes Gutenberg University Medical Center, Department of Internal Medicine (Germany); Otto, Gerd [Johannes Gutenberg University Medical Center, Department of Transplantation Surgery (Germany); Dueber, Christoph [Johannes Gutenberg University Medical Center, Department of Diagnostic and Interventional Radiology (Germany)

2015-04-15

PurposeTo prospectively compare SIRT and DEB-TACE for treating hepatocellular carcinoma (HCC).MethodsFrom 04/2010–07/2012, 24 patients with histologically proven unresectable N0, M0 HCCs were randomized 1:1 to receive SIRT or DEB-TACE. SIRT could be repeated once in case of recurrence; while, TACE was repeated every 6 weeks until no viable tumor tissue was detected by MRI or contraindications prohibited further treatment. Patients were followed-up by MRI every 3 months; the final evaluation was 05/2013.ResultsBoth groups were comparable in demographics (SIRT: 8males/4females, mean age 72 ± 7 years; TACE: 10males/2females, mean age 71 ± 9 years), initial tumor load (1 patient ≥25 % in each group), and BCLC (Barcelona Clinic Liver Cancer) stage (SIRT: 12×B; TACE 1×A, 11×B). Median progression-free survival (PFS) was 180 days for SIRT versus 216 days for TACE patients (p = 0.6193) with a median TTP of 371 days versus 336 days, respectively (p = 0.5764). Median OS was 592 days for SIRT versus 788 days for TACE patients (p = 0.9271). Seven patients died in each group. Causes of death were liver failure (n = 4 SIRT group), tumor progression (n = 4 TACE group), cardiovascular events, and inconclusive (n = 1 in each group).ConclusionsNo significant differences were found in median PFS, OS, and TTP. The lower rate of tumor progression in the SIRT group was nullified by a greater incidence of liver failure. This pilot study is the first prospective randomized trial comparing SIRT and TACE for treating HCC, and results can be used for sample size calculations of future studies.

Adverse events and therapeutic efficacy associated with TACE for hepatocellular carcinoma with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension

International Nuclear Information System (INIS)

Araki, Takuji; Okada, Taiki; Kimura, Kazufumi; Sawada, Eiichi; Sano, Katushiro; Araki, Tsutomu

2012-01-01

The aim of this study was to evaluate the short-term adverse events and therapeutic efficacy of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension. Of patients who underwent TACE for unresectable HCCs in 2009 and 2010, twenty-nine and twenty-seven patients underwent TACE using cisplatin-lipiodol suspension (C-LS) and miriplatin-lipiodol suspension (M-LS), respectively. Adverse events of fever, pain, nausea, anorexia, elevation of aspartate aminotransferase (AST), total bilirubin, creatinine and a decrease in platelet count were evaluated by the National Cancer Institute Common Toxicity Criteria Ver.4. to compare the C-LS and M-LS groups. The short-term therapeutic efficacy of both groups was evaluated by the treatment effect (TE) on the CT images three months after TACE according to the General Rules for the Clinical and Pathological Study of Primary Liver Cancer (the 5th edition, Revised Version). With regard to the adverse events, the M-LS group had significantly less fever and anorexia than the C-LS group. No critical adverse events were observed in either group. The therapeutic efficacy was not significantly different between the groups. TACE with M-LS had fewer adverse events than TACE with C-LS, but neither TACE led to any critical adverse events. The short-term therapeutic efficacy of TACE with M-LS was equivalent to that of TACE with C-LS. (author)

The influence of blood supply pattern of hepatic metastases on the short-term effect of TACE

International Nuclear Information System (INIS)

Li Guowen; Liang Zhaoyu; Yu Xiaoping; Gu Shanzhi; Zhang Tiegang; He Qing; Xiong Zhengping; Huang Manping

2010-01-01

Objective: To discuss the influence of blood supply pattern of hepatic metastases on the short-term effect of transcatheter arterial chemoembolization (TACE). Methods: A total of 58 cases of liver metastases who had been treated with TACE were selected, the clinical data and short-term effects were retrospectively analyzed. Results: Based on the DSA findings, 58 cases of liver metastases were divided into the hypervascular pattern (n=14), the isovascular pattern (n=12) and the hypovascular pattern group (n=32). After TACE the clinical effective rate (CR + PR) of hypervascular, isovascular and hypo vascular pattern group was 92.9% (13 /14), 83.3% (10/12) and 9.4% (3/32) respectively, with a significant difference existing between hyper vascular and hypo vascular group as well as between iso vascular and hypo vascular group (P 0.05). The survival rate at half and one year after Tace treatment for all cases was 67.2% and 42.3%, respectively. The survival rate at half and one year for hyper vascular, iso vascular and hypo vascular group was 100% and 78.6%, 100% and 58.3%, 40.6% and 7.6%, respectively. A significant difference in the survival rate existed between hypervascular and hypovascular group as well as between isovascular and hypovascular group (P 0.05). Conclusion: TACE shows much better effectiveness for the hypervascular hepatic metastases, and it is very useful for making an appropriate therapeutic plan to distinguish the blood supply pattern of hepatic metastases. (authors)

Comparing the effectiveness of TWEAK and T-ACE in determining problem drinkers in pregnancy.

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Sarkar, M; Einarson, T; Koren, G

2010-01-01

The TWEAK and T-ACE screening tools are validated methods of identifying problem drinking in a pregnant population. The objective of this study was to compare the effectiveness of the TWEAK and T-ACE screening tools in identifying problem drinking using traditional cut-points (CP). Study participants consisted of women calling the Motherisk Alcohol Helpline for information regarding their alcohol use in pregnancy. In this cohort, concerns surrounding underreporting are not likely as women self-report their alcohol consumption. Participant's self-identification, confirmed by her amount of alcohol use, determined whether she was a problem drinker or not. The TWEAK and T-ACE tools were administered on both groups and subsequent analysis was done to determine if one tool was more effective in predicting problem drinking. The study consisted of 75 problem and 100 non-problem drinkers. Using traditional CP, the TWEAK and T-ACE tools both performed similarly at identifying potential at-risk women (positive predictive value = 0.54), with very high sensitivity rates (100-99% and 100-93%, respectively) but poor specificity rates (36-43% and 19-34%, respectively). Upon comparison, there was no statistical difference in the effectiveness for one test performing better than next using either CP of 2 (P = 0.66) or CP of 3 (P = 0.38). Despite the lack of difference in performance, improved specificity associated with TWEAK suggests that it may be better suited to screen at-risk populations seeking advice from a helpline.

The clinical study on the liver-protection of S-adenosy-methionine in large hepatocellular carcinoma patients after TACE

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Shi Zhenshan; Chen Ziqian; Yang Xizhang; Zhang Hongwen; Dong Qilong; Yang Yongyan; Lei Juan; Zhuang Xi

2008-01-01

Objective: To study effects of S-adenosy-methionine (SAMe) for acute hepatic functional damage after transcatheter chemoembolization in the treatment of primary large HCC. Methods: The clinical data of 51 cases of liver neoplasm after TACE from May 2003 to October 2005 were analyzed retrospectively, including SAMe 1000 mg intravenous drip after TACE daily of the treatment group and diammonium glycyrrhizinate 30 ml intravenous drip after TACE daily of the control group. The two groups were separately assessed the hepatic function on 1st day preoperatively and the 2nd, 4th d and 8th day, postoperatively, and together with the hamilton depression rating scale for derpression (HRSD)and the clinical general impression estimation for the evaluation of the clinical efficiency. Results: All the hepatic functional labels changed markedly after TACE with ALT, AST, TBIL and DBIL rising to a certain extent on the 2nd day postoperatively (P 0.05). There were significant differences of the labels during the same period in the control group (P< 0.05). γ-GT changed irregularly in the two groups. There were also no significant differences of TP and A between 1st d preoperatively and 8th d, postoperatively in the two groups. In the treatment group, 15 patients (60%) showed relief of chief complaints of fatigue, hypodynamia, anxiety, insomnia. The total scores of HRSD also decreased revealing the better cooperation of the patients with treatment. Conclusions: SAMe provides hepatic functional protection for large primary HCC patients after TACE especially for the satisfactory short-term efficiency in acute liver damage with simultaneous anti-depression and enhancing TACE effects, and promoting life quality. (authors)

Workflow optimisation for multimodal imaging procedures: a case of combined X-ray and MRI-guided TACE.

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Fernández-Gutiérrez, Fabiola; Wolska-Krawczyk, Malgorzata; Buecker, Arno; Houston, J Graeme; Melzer, Andreas

2017-02-01

This study presents a framework for workflow optimisation of multimodal image-guided procedures (MIGP) based on discrete event simulation (DES). A case of a combined X-Ray and magnetic resonance image-guided transarterial chemoembolisation (TACE) is presented to illustrate the application of this method. We used a ranking and selection optimisation algorithm to measure the performance of a number of proposed alternatives to improve a current scenario. A DES model was implemented with detail data collected from 59 TACE procedures and durations of magnetic resonance imaging (MRI) diagnostic procedures usually performed in a common MRI suite. Fourteen alternatives were proposed and assessed to minimise the waiting times and improve workflow. Data analysis observed an average of 20.68 (7.68) min of waiting between angiography and MRI for TACE patients in 71.19% of the cases. Following the optimisation analysis, an alternative was identified to reduce waiting times in angiography suite up to 48.74%. The model helped to understand and detect 'bottlenecks' during multimodal TACE procedures, identifying a better alternative to the current workflow and reducing waiting times. Simulation-based workflow analysis provides a cost-effective way to face some of the challenges of introducing MIGP in clinical radiology, highligthed in this study.

Safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) in the treatment of secondary liver malignancies.

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Schicho, Andreas; Pereira, Philippe L; Michalik, Katharina; Beyer, Lukas P; Stroszczynski, Christian; Wiggermann, Philipp

2018-01-01

To evaluate the safety and efficacy of degradable starch microspheres (DSM) as embolic agents in transarterial chemoembolization (TACE) in the treatment of secondary liver metastases. This was a national, multicenter observational study. Primary endpoints were safety and treatment response according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. A total of 77 DSM-TACE procedures were performed in 20 patients. Minor immediate adverse events (AEs) were epigastric pain with an incidence of 45.5% (35/77), and nausea and vomiting at an incidence of 23.4% (18/77). Delayed minor AEs were epigastric pain in 13/77 (16.9%) treatments and nausea and vomiting in 10 (13.0%) treatments. No severe AEs were documented. Therapeutic efficacy of DSM-TACE procedures according to mRECIST was as follows: complete response 0/77, partial response 17/77, stable disease 33/77 and progressive disease 6/77, no data was available for 21/77 treatments. Overall, objective response was achieved in 8 of 20 patients (40.0%). DSM as embolic agent for TACE is safe in the treatment of liver metastases. An objective response in 40.0% of patients and disease control in 64.9% of procedures was achieved, and this should lead to further evaluation of DSM-TACE as treatment option for nonresectable liver metastases.

Expression of porcine myostatin prodomain genomic sequence leads to a decrease in muscle growth, but significant intramuscular fat accretion in transgenic pigs.

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Myostatin, a member of TGF-beta superfamily, is a dominant inhibitor of skeletal muscle development and growth. Previously, skeletal muscle-specific over-expression of myostatin prodomain cDNA (5’-region 886 nucleotide) dramatically increased growth performance and muscle mass in transgenic mice. I...

Radiation Segmentectomy versus TACE Combined with Microwave Ablation for Unresectable Solitary Hepatocellular Carcinoma Up to 3 cm: A Propensity Score Matching Study.

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Biederman, Derek M; Titano, Joseph J; Bishay, Vivian L; Durrani, Raisa J; Dayan, Etan; Tabori, Nora; Patel, Rahul S; Nowakowski, Francis S; Fischman, Aaron M; Kim, Edward

2017-06-01

Purpose To compare the outcomes of radiation segmentectomy (RS) and transarterial chemoembolization (TACE) combined with microwave ablation (MWA) in the treatment of unresectable solitary hepatocellular carcinoma (HCC) up to 3 cm. Materials and Methods This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. From January 2010 to June 2015, a total of 417 and 235 consecutive patients with HCC underwent RS and TACE MWA, respectively. A cohort of 121 patients who had not previously undergone local-regional therapy (RS, 41; TACE MWA, 80; mean age, 65.4 years; 84 men [69.4%]) and who had solitary HCC up to 3 cm without vascular invasion or metastasis was retrospectively identified. Outcomes analyzed included procedure-related complications, laboratory toxicity levels, imaging response, time to progression (TTP), 90-day mortality, and survival. Propensity score matching was conducted by using a nearest-neighbor algorithm (1:1) to account for pretreatment clinical, laboratory, and imaging covariates. Postmatching statistical analysis was performed with conditional logistic regression for binary outcomes and the stratified log-rank test for time-dependent outcomes. Results Before matching, the complication rate was 8.9% and 4.9% in the TACE MWA and RS groups, respectively (P = .46). The overall complete response (CR) rate was 82.9% for RS and 82.5% for TACE MWA (odds ratio, 1.0; 95% confidence interval [CI]: 0.4, 2.8; P = .95). There were 41 (RS, 11; TACE MWA, 30) instances of progression occurring after an initial CR, of which 10 (24%) were classified as target progression (RS, one; TACE MWA, nine). Median overall TTP was 11.1 months (95% CI: 8.8 months, 25.6 months) in the RS group and 12.1 months (95% CI: 7.7 months, 19.1 months) in the TACE MWA group (P > .99). After matching, the overall CR rate (P = .94), TTP (P = .83), and overall survival (P > .99) were not significantly different between

Neoadjuvant TACE before laser induced thermotherapy (LITT) in the treatment of non-colorectal non-breast cancer liver metastases: Feasibility and survival rates

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Vogl, Thomas J., E-mail: T.Vogl@em.uni-frankfurt.de [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Kreutzträger, Martin; Gruber-Rouh, Tatjana; Eichler, Katrin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Nour-Eldin, Nour-Eldin A. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Diagnostic and Interventional Radiology, Cairo University, Cairo (Egypt); Zangos, Stephan [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Radiology, Faculty of Medicine, Alexandria University, Alexandria (Egypt)

2014-10-15

Purpose: To evaluate safety, feasibility and overall survival rates for transarterial chemoembolization (TACE) alone or combined with MR-guided laser-induced-thermotherapy (LITT) in liver metastases of non-colorectal and non-breast cancer origin. Methods and materials: Included were patients with unresectable non-colorectal non-breast cancer liver metastases with progression under systemic chemotherapy. Excluded were patients with Karnofsky score ≤70, respiratory, renal and cardiovascular failure, and general TACE contraindications. TACE using Mitomycin alone, Mitomycin–Gemcitabine or Mitomycin–Gemcitabine–Cisplatin was performed to all patients. After TACE 146 metastases were ablated with MR-guided LITT. To be eligible for LITT metastases should be <5 cm in size and ≤5 in number. Tumor response was evaluated using MRI according to RECIST. Survival was evaluated using Kaplan–Meier analysis. Results: A total of 110 patients (mean age 59.2 years) with 371 metastases received TACE (mean 5.4 sessions/patient, n = 110) with 76 (69%) receiving LITT (mean 1.6 session/patient) afterwards. TACE resulted in a mean decrease of mean maximum diameter of 52% ± 26.6 and volume change of −68.5% ± 22.9 in the 25 patients (23%) with partial response. Stable disease (n = 59, 54%). Progressive disease (n = 26, 23%). The RECIST outcome after LITT showed complete response (n = 13, 17%), partial response (n = 1, 1%), stable situation (n = 41, 54%) and progressive disease (n = 21, 28%). The mean time to progression (TTP) was 8.6 months. Median survival of all patients was 21.1 months. Conclusion: TACE with different protocols alone and in combination with LITT is a feasible palliative treatment option resulting in a median survival of 21.1 months for unresectable liver metastases of non-colorectal and non-breast cancer origin.

Midterm follow-up after DC-BEAD™-TACE of Hepatocellular Carcinoma (HCC)

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Skowasch, Marijke, E-mail: marijkeskowasch@aol.com [Department of Diagnostic and Interventional Radiology, Johannes Gutenberg University of Mainz, Mainz, Langenbeckstrasse 1, 55131 Mainz (Germany); Schneider, Jens, E-mail: jens.schneider@unimedizin-mainz.de [Department of Diagnostic and Interventional Radiology, Johannes Gutenberg University of Mainz, Mainz, Langenbeckstrasse 1, 55131 Mainz (Germany); Otto, Gerd, E-mail: gerd.otto@unimedizin-mainz.de [Department of Hepatobiliary Surgery, Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz (Germany); Weinmann, Arndt, E-mail: weinmann@1-med.klinik.uni-mainz.de [First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz (Germany); Woerns, Markus Alexander, E-mail: marcus-alexander.woerns@unimedizin-mainz.de [First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, 55131 Mainz (Germany); Dueber, Christoph, E-mail: dueber@radiologie.klinik.uni-mainz.de [Department of Diagnostic and Interventional Radiology, Johannes Gutenberg University of Mainz, Mainz, Langenbeckstrasse 1, 55131 Mainz (Germany); Pitton, Michael Bernhard, E-mail: pitton@radiologie.klinik.uni-mainz.de [Department of Diagnostic and Interventional Radiology, Johannes Gutenberg University of Mainz, Mainz, Langenbeckstrasse 1, 55131 Mainz (Germany)

2012-12-15

Aim: To determine local response, its predictors and survival and complication rates after DC-Bead™-TACE in patients with hepatocellular carcinoma (HCC). Materials and methods: DC-Beads™ are non-resorbable, polyvinyl-alcoholic hydrophilic microspheres. They release high amounts of chemotherapeutics directly into the tumour. Delivery is sustained over time, tumour feeders are embolised. We used beads from 100–300 to 500–700 μm loaded with Doxorubicin (max. 150 mg/4 ml). Fifty patients (mean age: 68.5 ± 8.8 years) with HCC were analysed. DC-Bead™-TACE was performed once or repeated in two-month intervals. Imaging scans (CT or MRI) were done one-month following each procedure. To evaluate tumour response EASL and RECIST criteria was applied. If eligible, every patient received a non-selective TACE. Results: 128 DC-Bead™ sessions were performed: 127 showed technical success, 120 successful stasis. Complications occurred in 7% (9/128): active bleeding into the tumour (n = 1), liver failure (n = 1), liver abscess (n = 1) ascites (n = 3), pleural effusion (n = 1), false aneurysm (n = 1) and hypoglycaemia (n = 1). At imaging after the 1st, 2nd, 3rd and 4th–8th session, objective response (complete + partial) was 49%, 67%, 67% and 31%, progressive disease was seen in n = 11/50. Baseline diameter and differentiation significantly impacted response. Median overall survival was 25.1 months (95% [CI]: 18.3–31.9) with an estimated cumulative survival rate at one and two-to-four years of 66.7% and 45.7%, respectively. Conclusion: DC-Beads™ can be safely and effectively control HCC. Survival and response rates are encouraging, complications are low. Many factors are involved in response to treatment like liver function or child state.

Trans-arterial chemoembolization (TACE) in patients with unresectable Hepatocellular carcinoma: Experience from a tertiary care centre in India

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Paul, Shashi Bala; Gamanagatti, Shivanand; Sreenivas, Vishnubhatla; Chandrashekhara, Sheragaru Hanumanhtappa; Mukund, Amar; Gulati, Manpreet Singh; Gupta, Arun Kumar; Acharya, Subrat Kumar

2011-01-01

Aims: To evaluate the outcome following transarterial chemoembolization (TACE) and to identify the predictors of survival in patients with unresectable hepatocellular carcinoma (HCC). Material and Methods: HCC patients reporting to our hospital (2001-2007) were subjected to clinical, biochemical, and radiological examination. TACE was performed in those who fulfilled the inclusion criteria. Follow-up assessment was done with multiphase CT scan of the liver at 1, 3, and 6 months. Tumor response and survival rate were estimated. Univariate and multivariate analyses were done for determinants of survival. Results: A total of 73 patients (69 males, 4 females; mean age 49±13.4 years) were subjected to 123 sessions of TACE. The Child's classification was: A – 56 patients and B – 17 patients. Barcelona Clinic staging was: A – 20 patients, B – 38 patients, and C – 15 patients. Tumor size was ≤5cm in 28 (38%) patients, >5–10 cm in 28 (38%) patients, and >10 cm in 17 (23%) patients. Median follow-up was for 12 months (range: 1–77 months). No significant postprocedure complications were encountered. Overall survival rate was 66%, 47%, and 36.4% at 1, 2, and 3 years, respectively. Tumor size emerged as an important predictor of survival. Conclusion: TACE offers a reasonable palliative therapy for HCC. Initial tumor size is an independent predictor of survival. PMID:21799594

Trans-arterial chemoembolization (TACE in patients with unresectable Hepatocellular carcinoma: Experience from a tertiary care centre in India

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Shashi Bala Paul

2011-01-01

Full Text Available Aims: To evaluate the outcome following transarterial chemoembolization (TACE and to identify the predictors of survival in patients with unresectable hepatocellular carcinoma (HCC. Material and Methods: HCC patients reporting to our hospital (2001-2007 were subjected to clinical, biochemical, and radiological examination. TACE was performed in those who fulfilled the inclusion criteria. Follow-up assessment was done with multiphase CT scan of the liver at 1, 3, and 6 months. Tumor response and survival rate were estimated. Univariate and multivariate analyses were done for determinants of survival. Results: A total of 73 patients (69 males, 4 females; mean age 49±13.4 years were subjected to 123 sessions of TACE. The Child′s classification was: A - 56 patients and B - 17 patients. Barcelona Clinic staging was: A - 20 patients, B - 38 patients, and C - 15 patients. Tumor size was ≤5cm in 28 (38% patients, >5-10 cm in 28 (38% patients, and >10 cm in 17 (23% patients. Median follow-up was for 12 months (range: 1-77 months. No significant postprocedure complications were encountered. Overall survival rate was 66%, 47%, and 36.4% at 1, 2, and 3 years, respectively. Tumor size emerged as an important predictor of survival. Conclusion: TACE offers a reasonable palliative therapy for HCC. Initial tumor size is an independent predictor of survival.

Trans-arterial chemoembolization (TACE) in patients with unresectable Hepatocellular carcinoma: Experience from a tertiary care centre in India

International Nuclear Information System (INIS)

Paul, Shashi Bala; Gamanagatti, Shivanand; Sreenivas, Vishnubhatla; Chandrashekhara, Sheragaru Hanumanhtappa; Mukund, Amar; Gulati, Manpreet Singh; Gupta, Arun Kumar; Acharya, Subrat Kumar

2011-01-01

To evaluate the outcome following transarterial chemoembolization (TACE) and to identify the predictors of survival in patients with unresectable hepatocellular carcinoma (HCC). HCC patients reporting to our hospital (2001-2007) were subjected to clinical, biochemical, and radiological examination. TACE was performed in those who fulfilled the inclusion criteria. Follow-up assessment was done with multiphase CT scan of the liver at 1, 3, and 6 months. Tumor response and survival rate were estimated. Univariate and multivariate analyses were done for determinants of survival. A total of 73 patients (69 males, 4 females; mean age 49±13.4 years) were subjected to 123 sessions of TACE. The Child's classification was: A – 56 patients and B – 17 patients. Barcelona Clinic staging was: A – 20 patients, B – 38 patients, and C – 15 patients. Tumor size was ≤5cm in 28 (38%) patients, >5–10 cm in 28 (38%) patients, and >10 cm in 17 (23%) patients. Median follow-up was for 12 months (range: 1–77 months). No significant postprocedure complications were encountered. Overall survival rate was 66%, 47%, and 36.4% at 1, 2, and 3 years, respectively. Tumor size emerged as an important predictor of survival. TACE offers a reasonable palliative therapy for HCC. Initial tumor size is an independent predictor of survival

A control study of TACE using high-dosed and routine-dosed iodized oil as a treatment of large hepatocellular carcinoma

International Nuclear Information System (INIS)

Zhou Junmin; Zhan Jincheng; Zhang Zhenming

2005-01-01

Objective: To investigate the side effects and curative effect in high-dosed lipiodol-transcatheter arterial chemoembolization as a treatment of large hepatocellular carcinoma. Methods: 79 patients with unresectable hepatocellular carcinoma were treated by TACE, and divided into 2 groups. In group A, 39 patients with the tumor sized 7-18cm in diameter, routine-dosed, 10-20ml lipiodol was given in TACE. 40 patients were enrolled in the high-dosed group B, who were given more than 20ml iodized oil in TACE. Results: The First to third year survival rate of group A was 66.7%, 33.3%, 0% respectively,while in group B it was 75%, 45%, 7.5% respectively. The effective rate was 71.7% in Group A and 87.5% in Group B. There was a significant difference between both groups. There was no significant difference of critical side effects and liver function damage between group A and B. Conclusion: High-dosed lipiodol chemoembolization as a treatment of unresectable hepatocellular carcinoma is superior to the routine TACE, especially when the tumor is large and the liver function reserve is good. (authors)

Petunia floral defensins with unique prodomains as novel candidates for development of fusarium wilt resistance in transgenic banana plants.

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Siddhesh B Ghag

Full Text Available Antimicrobial peptides are a potent group of defense active molecules that have been utilized in developing resistance against a multitude of plant pathogens. Floral defensins constitute a group of cysteine-rich peptides showing potent growth inhibition of pathogenic filamentous fungi especially Fusarium oxysporum in vitro. Full length genes coding for two Petunia floral defensins, PhDef1 and PhDef2 having unique C-terminal 31 and 27 amino acid long predicted prodomains, were overexpressed in transgenic banana plants using embryogenic cells as explants for Agrobacterium-mediated genetic transformation. High level constitutive expression of these defensins in elite banana cv. Rasthali led to significant resistance against infection of Fusarium oxysporum f. sp. cubense as shown by in vitro and ex vivo bioassay studies. Transgenic banana lines expressing either of the two defensins were clearly less chlorotic and had significantly less infestation and discoloration in the vital corm region of the plant as compared to untransformed controls. Transgenic banana plants expressing high level of full-length PhDef1 and PhDef2 were phenotypically normal and no stunting was observed. In conclusion, our results suggest that high-level constitutive expression of floral defensins having distinctive prodomains is an efficient strategy for development of fungal resistance in economically important fruit crops like banana.

Identification and targeting of a TACE-dependent autocrine loopwhich predicts poor prognosis in breast cancer

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Kenny, Paraic A.; Bissell, Mina J.

2005-06-15

The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop which provides an oncogenic stimulus in the absence of proto-oncogene mutation. Inhibition of this protease, TACE/ADAM17, reverts the malignant phenotype by preventing mobilization of two crucial growth factors, Amphiregulin and TGF{alpha}. We show further that the efficacy of EGFR inhibitors is overcome by physiological levels of growth factors and that successful EGFR inhibition is dependent on reducing ligand bioavailability. Using existing patient outcome data, we demonstrate a strong correlation between TACE and TGF{alpha} expression in human breast cancers that is predictive of poor prognosis.

Intraprocedural blood volume measurement using C-arm CT as a predictor for treatment response of malignant liver tumours undergoing repetitive transarterial chemoembolization (TACE)

International Nuclear Information System (INIS)

Vogl, Thomas J.; Schaefer, Patrik; Lehnert, Thomas; Mbalisike, Emmanuel; Hammerstingl, Renate; Eichler, Katrin; Zangos, Stephan; Nour-Eldin, Nour-Eldin A.; Ackermann, Hanns; Naguib, Nagy N.N.

2016-01-01

To evaluate feasibility of measuring parenchymal blood volume (PBV) of malignant hepatic tumours using C-arm CT, test the changes in PBV following repeated transarterial chemoembolization (TACE) and correlate these changes with the change in tumour size in MRI. 111 patients with liver malignancy were included. Patients underwent MRI and TACE in a 4- to 6-week interval. During intervention C-arm CT was performed. Images were post-processed to generate PBV maps. Blood volume data in C-arm CT and change in size in MRI were evaluated. The correlation between PBV and size was tested using Spearman rank test. Pre-interventional PBV maps showed a mean blood volume of 84.5 ml/1000 ml ± 62.0, follow-up PBV maps after multiple TACE demonstrated 61.1 ml/1000 ml ± 57.5. The change in PBV was statistically significant (p = 0.02). Patients with initial tumour blood volume >100 ml/1000 ml dropped 7.1 % in size and 47.2 % in blood volume; 50-100 ml/1000 ml dropped 4.6 % in size and 25.7 % in blood volume; and <50 ml/1000 ml decreased 2.8 % in size and increased 82.2 % in blood volume. PBV measurement of malignant liver tumours using C-arm CT is feasible. Following TACE PBV decreased significantly. Patients with low initial PBV show low local response rates and further increase in blood volume, whereas high initial tumour PBV showed better response to TACE. (orig.)

Highly Conserved Arg Residue of ERFNIN Motif of Pro-Domain is Important for pH-Induced Zymogen Activation Process in Cysteine Cathepsins K and L.

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Aich, Pulakesh; Biswas, Sampa

2018-06-01

Pro-domain of a cysteine cathepsin contains a highly conserved Ex 2 Rx 2 Fx 2 Nx 3 Ix 3 N (ERFNIN) motif. The zymogen structure of cathepsins revealed that the Arg(R) residue of the motif is a central residue of a salt-bridge/H-bond network, stabilizing the scaffold of the pro-domain. Importance of the arginine is also demonstrated in studies where a single mutation (Arg → Trp) in human lysosomal cathepsin K (hCTSK) is linked to a bone-related genetic disorder "Pycnodysostosis". In the present study, we have characterized in vitro Arg → Trp mutant of hCTSK and the same mutant of hCTSL. The R → W mutant of hCTSK revealed that this mutation leads to an unstable zymogen that is spontaneously activated and auto-proteolytically degraded rapidly. In contrast, the same mutant of hCTSL is sufficiently stable and has proteolytic activity almost like its wild-type counterpart; however it shows an altered zymogen activation condition in terms of pH, temperature and time. Far and near UV circular dichroism and intrinsic tryptophan fluorescence experiments have revealed that the mutation has minimal effect on structure of the protease hCTSL. Molecular modeling studies shows that the mutated Trp31 in hCTSL forms an aromatic cluster with Tyr23 and Trp30 leading to a local stabilization of pro-domain and supplements the loss of salt-bridge interaction mediated by Arg31 in wild-type. In hCTSK-R31W mutant, due to presence of a non-aromatic Ser30 residue such interaction is not possible and may be responsible for local instability. These differences may cause detrimental effects of R31W mutation on the regulation of hCTSK auto-activation process compared to altered activation process in hCTSL.

Evaluation of the malignant degree of primary hepatocellular carcinoma after endostar combined with transcatheter arterial chemoembolization ( TACE treatment

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Yong Zeng

2018-01-01

Full Text Available Objective: To analyze the malignant degree of primary hepatocellular carcinoma after endostar combined with transcatheter arterial chemoembolization (TACE treatment. Methods: A total of 68 cases of patients with primary hepatocellular carcinoma treated in our hospital from September 2011 to December 2014 were enrolled for study and divided into observation group 34 cases and control group 34 cases according to different treatment methods. Control group received transcatheter arterial chemoembolization (TACE treatment, observation group received endostar combined with TACE treatment, and then differences in serum amino acid levels, micro RNA levels, levels of GP73, GPC3, GS, etc as well as levels of ChE, TBA and AFP were compared between two groups after treatment. Results: Serum aspartic acid, leucine and arginine levels of observation group after treatment were higher than those of control group, and αα-aminoadipic acid, methionine, β-alanine and 3-methylhistidine levels were lower than those of control group; relative values of serum miR-106b, miR-222 and miR-21 expression of observation group after treatment were lower than those of control group, and relative values of miR-199a and miR-122 expression were higher than those of control group; GP73, IL-17, IL-6, GPC3, GS and HSP70 levels of observation group after treatment were lower than those of control group, and endostatin level was higher than that of control group; ChE level of observation group after treatment was higher than that of control group, and TBA and AFP levels were lower than those of control group. Conclusion: Endostar combined with TACE treatment for patients with primary hepatocellular carcinoma can effectively inhibit tumor proliferation, invasion and other malignant processes and improve liver function, and it has positive clinical significance.

Parametric response mapping of contrast-enhanced biphasic CT for evaluating tumour viability of hepatocellular carcinoma after TACE

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Hinrichs, Jan B.; Shin, Hoen-Oh; Kaercher, Daniel; Hasdemir, Davut; Kaireit, Till; Lutat, Carolin; Meyer, Bernhard C.; Wacker, Frank K.; Rodt, Thomas [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Hannover (Germany); Murray, Tim [Beaumont Hospital, Department of Diagnostic and Interventional Radiology, Dublin (Ireland); Vogel, Arndt [Hannover Medical School, Gastroenterology, Hepatology and Endocrinology, Hannover (Germany)

2016-10-15

To determine the feasibility and role of parametric response mapping (PRM) for quantitative assessment of regional contrast-enhancement patterns in hepatocellular carcinoma (HCC). Biphasic CT of 19 patients receiving repetitive conventional transarterial chemoembolisation (cTACE) for intermediate stage HCC were retrospectively analysed at baseline and follow-up at 3, 6, and 9 months. Voxel-based registration of arterial and porto-venous phases, with segmentation of the largest target lesion was performed. Frequency distribution plots of density-pairs of segmented voxels were generated. To differentiate necrotic, hypervascular and non-hypervascular tumour, and lipiodol/calcification, thresholds of 30, 100, and 300 HU were applied. Changes in density frequency plots over time were analysed and compared to response and assessment criteria (WHO, RECIST, EASL, mRECIST) and survival. PRM was feasible in all cases. Tumour volumes and hypervascular/non-hypervascular volume ratio showed significant longitudinal decrease (p < 0.05). Hypervascular volume at baseline was inversely correlated to survival (R = -0.57, p = 0.005). The only predictive parameter following cTACE to show significant survival difference was the change of the viable/non-viable ratio (p = 0.044), whereas common response assessment criteria showed no significant difference in survival. PRM allows a quantitative and more precise assessment of regional tumour vascularisation patterns and may be helpful for TACE treatment planning and response assessment. (orig.)

Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes.

Science.gov (United States)

Yong, Seok-Beom; Song, Yoonsung; Kim, Yong-Hee

2017-12-01

Obesity is an increasingly prevalent global health problem. Due to its close relations with metabolic diseases and cancer, new therapeutic approaches for treating obesity and obesity-induced metabolic diseases are required. Visceral white adipose tissue (WAT) has been closely associated with obesity-induced inflammation and adipose tissue macrophages (ATMs) are responsible for obesity-induced inflammation by releasing inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6. TNF-α converting enzyme (TACE) is a transmembrane enzyme that induces the enzymatic cleavage and release of inflammatory cytokines. In this study, we developed a nonviral gene delivery system consisting of an oligopeptide (ATS-9R) that can selectively target visceral ATMs. In here we shows visceral adipose tissue-dominant inflammatory gene over-expressions in obese mouse and our strategy enabled the preferential delivery of therapeutic genes to visceral ATMs and successfully achieved ATM-targeted gene silencing. Finally, ATS-9R-mediated TACE gene silencing in visceral ATMs alleviated visceral fat inflammation and improved type 2 diabetes by reducing whole body inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of TACE with endostatin on hemodynamics in hepatic implantation tumor using Doppler ultrasonography

International Nuclear Information System (INIS)

Zhou Guangli; Wu Yuanyuan; Wang Bin; Liu Yan; Zheng Chuanli; Sang Li; Liu Feng

2009-01-01

Objective: To investigate the hemodynamic changes in the rabbit liver and VX2 hepatic implantation tumor after treatment by transcatheter arterial chemoembolization (TACE)/endostatin using Doppler ultrasonography. Methods: Twenty rabbits with VX2 hepatic tumor were randomly distributed into the control group (n=10) and the anti- angiogenesis group (n=10). The rabbits were administered with endostatin and adriamycin-lipiodol in the anti-angiogenesis group and with 37℃ saline in the control group via hepatic artery. The hemodynamic changes of the tumors, hepatic artery, and portal vein were recorded with Doppler ultrasonography 1 week after the treatment. The results before and after the treatment were compared. Results: In the control group, the maximal hepatic artery blood flow velocity was significantly higher than that before the treatment (P<0.05). However, the resistance index and the portal vein blood flow velocities had no significantly change compared with those before the treatment (P>0.05). In the anti-angiogenesis group, the hepatic artery blood flow velocity was significantly lower than that before the treatment (P<0.05), and the resistance index was increased (P<0.05). However, the portal vein blood flow velocity had no significantly change (P>0.05). The blood flow signal in all tumors was rich before embolization. After TACE, the blood flow signal was significantly decreased, even partly disappeared in the anti-angiogenesis group. Conclusion: TACE with endostatin can effectively block the blood supplement of VX2 hepatic implantation tumor. Doppler ultrasonography can detected the blood flow changes and can be used in evaluating the therapeutic effect in hepatic implantation tumor. (authors)

Imaging follow-up in patients with unresectable cellular hepatocarcinoma treated with conventional TACE

International Nuclear Information System (INIS)

Dumitru, R.

2012-01-01

Full text: Background: Hepatocellular carcinoma (HCC) represents more than 5% of all neoplasms and is the most frequent cause of mortality in patients with cirrhosis. Although a number of therapeutic options are available, transarterial chemoembolisation is widely used in the treatment of unresectable HCC. Aim: Evaluation of the role of CT and MRI exams in the imaging followup of patients with unresectable hepatocellular carcinoma treated with conventional transarterial chemoembolisation (TACE). Materials and methods: We retrospectively reviewed 120 consecutive patients with the diagnosis of HCC, sent to the Department of Radiology, Medical Imaging and Interventional Radiology between january 2011 and april 2012 for TACE. The diagnosis of HCC was established using imaging criteria and elevated alfafetoprotein levels (higher than 400ng/ml) or histologic diagnosis. After the procedure, the imaging followup algorithm consisted in an ultrasound exam 24 hours after the procedure, a CT exam 1 month, a MRI exam 3 months later (if the previous CT showed no tumoral residues) and a CT exam 6 months later. The tumoral response was evaluated using the modified RECIST criteria (tumoral dimensions defined as the product of the 2 largest diameters), the visualisation of tumoral arterial enhancement and the presence of intratumoral lipiodol accumulation (defined as absent, homogenous or heterogenous). Results: At the CT exam performed 1 month after the procedure, 44 patients (37%) had homogenous intratumoral lipiodol accumulation, without any tumoral residues and with dimensional reduction. In patients with tumoral residue (n=76), the intratumoral lipiodol accumulation was homogenous (n=48) or heterogenous (n=28); in 5 cases, after the first TACE procedure, we had no lipiodol accumulation in the target lesion. Conclusion: CT exam is an essential tool in the postprocedural followup in patients with unresectable hepatocellular carcinoma treated with conventional transarterial

The clinical application of TACE together with RFA and 125I seed implantation in treating hepatocellular carcinoma

International Nuclear Information System (INIS)

Xie Xiaoxi; Lu Yinxiang; Zhang Hongxin; Zhang Shengchu; Zhou Jianwei; Zhang Guodong; Wang Xiaowei; Yang Liping

2011-01-01

Objective: to assess the clinical value of the combined treatment of transcatheter arterial chemoembolization (TACE), CT-guided radiofrequency ablation (RFA) and radioactive 125 I seed implantation for hepatocellular carcinoma (HCC). Methods: During the period from March 2008 to Dec. 2010, 15 patients with HCC were admitted to the hospital. A total of 25 hepatic lesions were detected with the size of 1-8 cm. TACE was carried out first, which was followed by CT-guided RFA and radioactive 125 I seed implantation. With the help of treat plan system (TPS), the radioactive 125 I seed implantation was conducted to make additional management for the same lesion when RFA was finished, or the radioactive 125 I seeds were directly implanted into the areas where RFA could not reach. The radioactive dose was 60-100 Gy. All the patients were followed up and were kept under observation for the signs of related complications. The therapeutic results were evaluated. Results: The combined treatment was successfully accomplished in all patients. All patients were followed up for 3-28 months (mean of 10.6 months). The complete necrosis rate of the tumor was 96%. No serious complications occurred except the immigration of 125 I seeds in 1 case. Conclusion: The combined treatment of TACE and CT-guided RFA together with 125 I seed implantation is a safe, reliable and effective therapy for HCC with excellent short-term result. (authors)

Comparação entre a frequência de positividade do questionário T-ACE entre mães de recém-nascidos de termo e prematuros

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Inês Maria Crespo Gutierrez Pardo

2013-12-01

Full Text Available Objetivos: os objetivos deste estudo foram verificar a frequência de positividade do T-ACE questionário durante a gravidez de mães de recém-nascidos prematuros comparados com as de termo, e avaliar a associação de álcool referido pelo teste com o tabagismo materno e paterno. Métodos: estudo tipo observacional, transversal, com recrutamento de forma sequencial de 142 puérperas de uma maternidade pública. Foram aplicados: entrevista para coleta de dados clínicos e sociodemográficos e T-ACE questionário. Os recém-nascidos de termo e prematuros destas mulheres foram avaliados em relação ao peso, comprimento e perímetro cefálico ao nascimento. Estudo aprovado pelo comitê de Ética local e a participação das mulheres foi mediante assinatura do termo de consentimento livre e esclarecido. A análise dos dados foi realizada usando o programa SPSS, sendo adotado nível de significância de 5%. Resultados: das puérperas entrevistadas 21,1% foram consideradas consumidoras de álcool pelo T-ACE questionário. Quando divididas entre puérperas de partos de termo e prematuros, encontraram-se 21% de positividade do T-ACE teste no grupo de termo e 21,3% no grupo dos prematuros (p = 0,98. Houve importante associação entre positividade do T-ACE questionário e tabagismo materno e paterno durante a gestação (p = 0,04. Conclusões: cerca de duas em cada dez gestantes apresentaram teste T-ACE positivo, sem diferença entre o grupo de parto de termo e prematuros. A associação encontrada entre o consumo de álcool e fumo durante a gravidez sugere a importância do rastreamento rotineiro do T-ACE questionário, tendo em vista que esses dois agentes potencializam efeitos adversos no feto.

A comparative study on the changes of serum fibrosis indicators after TACE with use of low-dose versus conventional-dose of anticancer drugs in hepatocellular carcinoma

International Nuclear Information System (INIS)

Lu Wei; Li Yanhao; He Xiaofeng; Chen Yong

2004-01-01

Objective: To study the changes of serum fibrosis indicators after transcatheter arterial chemo-embolization (TACE) with the use of low-dose vs conventional-dose of anticancer drugs in hepatocellular carcinoma (HCC). Methods: Forty patients with HCC were divided into two groups to receive superselective TACE. Patients in group A(n=20) received low-dose anticancer drug(s): 2-4 mg mitomycin C (MMC) with the tumor mass less than 5 cm in size; while MMC 4-6 mg and epirubicin (EPI) 10 mg were given with tumor size of 5-8 cm in diameter, and MMC 6-8 mg, EPI 10 mg, CBP 100 mg with tumors larger than 8 cm. Patients in group B (n=20) were given conventional-dose of anticancer drugs (MMC 10 mg, EPI 40 mg and CBP 300 mg). Lipiodol-anticancer drugs emulsion was injected into the feeding arteries of tumors and followed by gelatin sponge or PVA particles embolization participation. Four serum fibrosis indicators, including hyaluronate acid (HA), human procollagen type-III (hPC-III), laminin (LN), collagen type-IV (IV-C) were assessed before and 7 days after TACE. Results: There was no significant difference between the two groups concerning the four indicators before TACE, but the concentrations of the four serum indicators were increased significantly in group B (P 0.05). Conclusions: The formation of liver fibrosis after TACE in HCC is related to the dosage of anticancer drugs employed for chemoembolization. Therefore, low-dose anticancer drugs should be advocated. (authors)

Validation of the Risk Prediction Models STATE-Score and START-Strategy to Guide TACE Treatment in Patients with Hepatocellular Carcinoma.

Science.gov (United States)

Mähringer-Kunz, Aline; Kloeckner, Roman; Pitton, Michael B; Düber, Christoph; Schmidtmann, Irene; Galle, Peter R; Koch, Sandra; Weinmann, Arndt

2017-07-01

Several scoring systems that guide patients' treatment regimen for transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) have been introduced, but none have gained widespread acceptance in clinical practice. The purpose of this study is to externally validate the Selection for TrAnsarterial chemoembolization TrEatment (STATE)-score and START-strategy [i.e., sequential use of the STATE-score and Assessment for Retreatment with TACE (ART)-score]. From January 2000 to September 2015, 933 patients with HCC underwent TACE at our institution. All variables needed to calculate the STATE-score and implement the START-strategy were determined. STATE comprised serum albumin, up-to-seven criteria, and C-reactive protein (CRP). ART comprised an increase in aspartate aminotransferase, the Child-Pugh score, and a radiological tumor response. Overall survival was calculated, and multivariate analysis performed. In addition, the STATE-score and START-strategy were validated using the Harrell's C-index and integrated Brier score (IBS). The STATE-score was calculated in 228 patients. Low and high STATE-scores corresponded to median survival of 14.3 and 20.2 months, respectively. Harrell's C was 0.558 and IBS 0.133. For the STATE-score, significant predictors of survival were up-to-seven criteria (p = 0.006) and albumin (p = 0.022). CRP values were not predictive (p = 0.367). The ART-score was calculated in 207 patients. Combining the STATE-score and ART-score led to a Harrell's C of 0.580 and IBS of 0.132. The STATE-score was unable to reliably determine the suitability for initial TACE. The START-strategy only slightly improved the predictive ability compared to the ART-score alone. Therefore, neither the STATE-score nor START-strategy alone provides sufficient certainty for clear-cut clinical decisions.

Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-alpha converting enzyme (TACE): discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1' substituents.

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Lu, Zhonghui; Ott, Gregory R; Anand, Rajan; Liu, Rui-Qin; Covington, Maryanne B; Vaddi, Krishna; Qian, Mingxin; Newton, Robert C; Christ, David D; Trzaskos, James; Duan, James J-W

2008-03-15

Potent and selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC(50) value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F%>90%) in rat n-in-1 PK studies.

Activation of PKA, p38 MAPK and ERK1/2 by gonadotropins in cumulus cells is critical for induction of EGF-like factor and TACE/ADAM17 gene expression during in vitro maturation of porcine COCs

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Yamashita Yasuhisa

2009-12-01

Full Text Available Abstract Objectives During ovulation, it has been shown that LH stimulus induces the expression of numerous genes via PKA, p38 MAPK, PI3K and ERK1/2 in cumulus cells and granulosa cells. Our recent study showed that EGF-like factor and its protease (TACE/ADAM17 are required for the activation of EGF receptor (EGFR, cumulus expansion and oocyte maturation of porcine cumulus-oocyte complexes (COCs. In the present study, we investigated which signaling pathways are involved in the gene expression of EGF-like factor and in Tace/Adam17 expression in cumulus cells of porcine COC during in vitro maturation. Methods Areg, Ereg, Tace/Adam17, Has2, Tnfaip6 and Ptgs2 mRNA expressions were detected in cumulus cells of porcine COCs by RT-PCR. Protein level of ERK1/2 phosphorylation in cultured cumulus cells was analyzed by westernblotting. COCs were visualized using a phase-contrast microscope. Results When COCs were cultured with FSH and LH up to 2.5 h, Areg, Ereg and Tace/Adam17 mRNA were expressed in cumulus cells of COCs. Areg, Ereg and Tace/Adam17 gene expressions were not suppressed by PI3K inhibitor (LY294002, whereas PKA inhibitor (H89, p38 MAPK inhibitor (SB203580 and MEK inhibitor (U0126 significantly suppressed these gene expressions. Phosphorylation of ERK1/2, and the gene expression of Has2, Tnfaip6 and Ptgs2 were also suppressed by H89, SB203580 and U0126, however, these negative effects were overcome by the addition of EGF to the medium, but not in the U0126 treatment group. Conclusion The results showed that PKA, p38 MAPK and ERK1/2 positively controlled the expression of EGF-like factor and TACE/ADMA17, the latter of which impacts the cumulus expansion and oocyte maturation of porcine COCs via the EGFR-ERK1/2 pathway in cumulus cells.

The ACEII recombinant Trichoderma reesei QM9414 strains with enhanced xylanase production and its applications in production of xylitol from tree barks.

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Xiong, Lili; Kameshwar, Ayyappa Kumar Sista; Chen, Xi; Guo, Zhiyun; Mao, Canquan; Chen, Sanfeng; Qin, Wensheng

2016-12-28

ACEII transcription factor plays a significant role in regulating the expression of cellulase and hemicellulase encoding genes. Apart from ACEII, transcription factors such as XYR1, CRE1, HAP2/3/5 complex and ACEI function in a coordinated pattern for regulating the gene expression of cellulases and hemicellulases. Studies have demonstrated that ACEII gene deletion results in decreased total cellulase and xylanase activities with reduced transcript levels of lignocellulolytic enzymes. In this study, we have successfully transformed the ACEII transcription factor encoding gene in Trichoderma reesei to significantly improve its degrading abilities. Transformation experiments on parental strain T. reesei QM9414 has resulted in five genetically engineered strains T/Ace2-2, T/Ace2-5, T/Ace2-8, T/Ace5-4 and T/Ace10-1. Among which, T/Ace2-2 has exhibited significant increase in enzyme activity by twofolds, when compared to parental strain. The T/Ace2-2 was cultured on growth substrates containing 2% bark supplemented with (a) sugar free + MA medium (b) glucose + MA medium and (c) xylose + MA medium. The bark degradation efficiency of genetically modified T/Ace2-2 strain was assessed by analyzing the xylitol production yield using HPAEC. By 6th day, about 10.52 g/l of xylitol was produced through enzymatic conversion of bark (2% bark + MA + xylose) by the T/Ace2-2 strain and by 7th day the conversion rate was found to be 0.21 g/g. Obtained results confirmed that bark growth medium supplemented with D-xylose has profoundly increased the conversion rate of bark by T/Ace2-2 strain when compared to sugar free and glucose supplemented growth media. Results obtained from scanning electron microscopy has endorsed our current results. Bark samples inoculated with T/Ace2-2 strain has showed large number of degraded cells with clearly visible cavities and fractures, by exposing the microfibrillar interwoven complex. We propose a cost effective and ecofriendly method for

SU-D-BRB-07: Lipiodol Impact On Dose Distribution in Liver SBRT After TACE

International Nuclear Information System (INIS)

Kawahara, D; Ozawa, S; Hioki, K; Suzuki, T; Lin, Y; Okumura, T; Ochi, Y; Nakashima, T; Ohno, Y; Kimura, T; Murakami, Y; Nagata, Y

2015-01-01

Purpose: Stereotactic body radiotherapy (SBRT) combining transarterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study aims to evaluate the impact of Lipiodol on dose distribution by comparing the dosimetric performance of the Acuros XB (AXB) algorithm, anisotropic analytical algorithm (AAA), and Monte Carlo (MC) method using a virtual heterogeneous phantom and a treatment plan for liver SBRT after TACE. Methods: The dose distributions calculated using AAA and AXB algorithm, both in Eclipse (ver. 11; Varian Medical Systems, Palo Alto, CA), and EGSnrc-MC were compared. First, the inhomogeneity correction accuracy of the AXB algorithm and AAA was evaluated by comparing the percent depth dose (PDD) obtained from the algorithms with that from the MC calculations using a virtual inhomogeneity phantom, which included water and Lipiodol. Second, the dose distribution of a liver SBRT patient treatment plan was compared between the calculation algorithms. Results In the virtual phantom, compared with the MC calculations, AAA underestimated the doses just before and in the Lipiodol region by 5.1% and 9.5%, respectively, and overestimated the doses behind the region by 6.0%. Furthermore, compared with the MC calculations, the AXB algorithm underestimated the doses just before and in the Lipiodol region by 4.5% and 10.5%, respectively, and overestimated the doses behind the region by 4.2%. In the SBRT plan, the AAA and AXB algorithm underestimated the maximum doses in the Lipiodol region by 9.0% in comparison with the MC calculations. In clinical cases, the dose enhancement in the Lipiodol region can approximately 10% increases in tumor dose without increase of dose to normal tissue. Conclusion: The MC method demonstrated a larger increase in the dose in the Lipiodol region than the AAA and AXB algorithm. Notably, dose enhancement were observed in the tumor area; this may lead to a clinical benefit

SU-D-BRB-07: Lipiodol Impact On Dose Distribution in Liver SBRT After TACE

Energy Technology Data Exchange (ETDEWEB)

Kawahara, D; Ozawa, S; Hioki, K; Suzuki, T; Lin, Y; Okumura, T; Ochi, Y; Nakashima, T; Ohno, Y; Kimura, T; Murakami, Y; Nagata, Y [Hiroshima University, Hiroshima, Hiroshima (Japan)

2015-06-15

Purpose: Stereotactic body radiotherapy (SBRT) combining transarterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study aims to evaluate the impact of Lipiodol on dose distribution by comparing the dosimetric performance of the Acuros XB (AXB) algorithm, anisotropic analytical algorithm (AAA), and Monte Carlo (MC) method using a virtual heterogeneous phantom and a treatment plan for liver SBRT after TACE. Methods: The dose distributions calculated using AAA and AXB algorithm, both in Eclipse (ver. 11; Varian Medical Systems, Palo Alto, CA), and EGSnrc-MC were compared. First, the inhomogeneity correction accuracy of the AXB algorithm and AAA was evaluated by comparing the percent depth dose (PDD) obtained from the algorithms with that from the MC calculations using a virtual inhomogeneity phantom, which included water and Lipiodol. Second, the dose distribution of a liver SBRT patient treatment plan was compared between the calculation algorithms. Results In the virtual phantom, compared with the MC calculations, AAA underestimated the doses just before and in the Lipiodol region by 5.1% and 9.5%, respectively, and overestimated the doses behind the region by 6.0%. Furthermore, compared with the MC calculations, the AXB algorithm underestimated the doses just before and in the Lipiodol region by 4.5% and 10.5%, respectively, and overestimated the doses behind the region by 4.2%. In the SBRT plan, the AAA and AXB algorithm underestimated the maximum doses in the Lipiodol region by 9.0% in comparison with the MC calculations. In clinical cases, the dose enhancement in the Lipiodol region can approximately 10% increases in tumor dose without increase of dose to normal tissue. Conclusion: The MC method demonstrated a larger increase in the dose in the Lipiodol region than the AAA and AXB algorithm. Notably, dose enhancement were observed in the tumor area; this may lead to a clinical benefit.

Discovery and process development of a novel TACE inhibitor for the topical treatment of psoriasis.

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Boiteau, Jean-Guy; Ouvry, Gilles; Arlabosse, Jean-Marie; Astri, Stéphanie; Beillard, Audrey; Bhurruth-Alcor, Yushma; Bonnary, Laetitia; Bouix-Peter, Claire; Bouquet, Karine; Bourotte, Marilyne; Cardinaud, Isabelle; Comino, Catherine; Deprez, Benoît; Duvert, Denis; Féret, Angélique; Hacini-Rachinel, Feriel; Harris, Craig S; Luzy, Anne-Pascale; Mathieu, Arnaud; Millois, Corinne; Orsini, Nicolas; Pascau, Jonathan; Pinto, Artur; Piwnica, David; Polge, Gaëlle; Reitz, Arnaud; Reversé, Kevin; Rodeville, Nicolas; Rossio, Patricia; Spiesse, Delphine; Tabet, Samuel; Taquet, Nathalie; Tomas, Loïc; Vial, Emmanuel; Hennequin, Laurent F

2018-02-15

Targeting the TNFα pathway is a validated approach to the treatment of psoriasis. In this pathway, TACE stands out as a druggable target and has been the focus of in-house research programs. In this article, we present the discovery of clinical candidate 26a. Starting from hits plagued with poor solubility or genotoxicity, 26a was identified through thorough multiparameter optimisation. Showing robust in vivo activity in an oxazolone-mediated inflammation model, the compound was selected for development. Following a polymorph screen, the hydrochloride salt was selected and the synthesis was efficiently developed to yield the API in 47% overall yield. Copyright © 2017. Published by Elsevier Ltd.

[Value of quantitative iodine-based material decomposition images with gemstone spectral CT imaging in the follow-up of patients with hepatocellular carcinoma after TACE treatment].

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Xing, Gusheng; Wang, Shuang; Li, Chenrui; Zhao, Xinming; Zhou, Chunwu

2015-03-01

To investigate the value of quantitative iodine-based material decomposition images with gemstone spectral CT imaging in the follow-up of patients with hepatocellular carcinoma (HCC) after transcatheter arterial chemoebolization (TACE). Consecutive 32 HCC patients with previous TACE treatment were included in this study. For the follow-up, arterial phase (AP) and venous phase (VP) dual-phase CT scans were performed with a single-source dual-energy CT scanner (Discovery CT 750HD, GE Healthcare). Iodine concentrations were derived from iodine-based material-decomposition images in the liver parenchyma, tumors and coagulation necrosis (CN) areas. The iodine concentration difference (ICD) between the arterial-phase (AP) and venal-phase (VP) were quantitatively evaluated in different tissues.The lesion-to-normal parenchyma iodine concentration ratio (LNR) was calculated. ROC analysis was performed for the qualitative evaluation, and the area under ROC (Az) was calculated to represent the diagnostic ability of ICD and LNR. In all the 32 HCC patients, the region of interesting (ROI) for iodine concentrations included liver parenchyma (n=42), tumors (n=28) and coagulation necrosis (n=24). During the AP the iodine concentration of CNs (median value 0.088 µg/mm(3)) appeared significantly higher than that of the tumors (0.064 µg/mm(3), P=0.022) and liver parenchyma (0.048 µg/mm(3), P=0.005). But it showed no significant difference between liver parenchyma and tumors (P=0.454). During the VP the iodine concentration in hepatic parenchyma (median value 0.181 µg/mm(3)) was significantly higher than that in CNs (0.140 µg/mm(3), P=0.042). There was no significant difference between liver parenchyma and tumors, CNs and tumors (both P>0.05). The median value of ICD in CNs was 0.006 µg/mm(3), significantly lower than that of the HCC (0.201 µg/mm(3), Piodine-based material decomposition images with gemstone spectral CT imaging can improve the diagnostic efficacy of CT imaging

Chemoembolization with drug-eluting microspheres (DEM-TACE for hepatocellular carcinoma: single-center review of safety and efficacy

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Bishay VL

2014-11-01

Full Text Available VL Bishay,1 K Maglione,1 R Khanna,2 KM Lee,1 AM Fischman,1 RA Lookstein,1 E Kim1 1Department of Radiology, Icahn School of Medicine at the Mount Sinai Hospital, New York, NY, USA; 2Department of Radiology, Queens Hospital Center, Jamaica, NY, USA Purpose: This study examines the safety and efficacy of transarterial chemoembolization using doxorubicin-loaded 30–60 µm QuadraSphere microspheres (DEM-TACE for the treatment of hepatocellular carcinoma. Materials and methods: Over 10 weeks, patients with hepatocellular carcinoma. (Child–Pugh A/B: 65%/35% were embolized with 30–60 µm QuadraSphere microspheres. Excluded patients had previous locoregional therapy, macrovascular invasion, extrahepatic disease, Child–Pugh score >B7, ECOG performance status >0, and total bilirubin >3 mg/dL. Technical success, minor and major complications, 30-day hospital readmission rate, and 30-day mortality were assessed. α-Fetoprotein levels before and after treatment were compared. Local response was evaluated by radiologic tumor response per modified Response Evaluation Criteria in Solid Tumors 1 month after treatment. Results: Thirty tumors (mean size, 2.3 cm; range, 1.0–4.9 cm were treated in 20 patients (16 male and 4 female; mean age, 64.7 years. There were no major complications. Thirty-day mortality was 0%. Minor complications included postembolization syndrome in 16.7% of cases and transient rise in liver enzymes requiring no therapy. Mean a-fetoprotein levels trended down following treatment (71.8±201.9 ng/mL vs 53.4±116.7 ng/mL, but were not statistically significant. Complete response was achieved in 30% of patients, partial response in 35%, stable disease in 30%, and progression of disease in 5%. Overall objective response was 65%. Mean follow-up was 10.4 months (range, 2–16.4 months. Conclusion: DEM-TACE with doxorubicin-loaded 30–60 µm QuadraSpheres is feasible, well tolerated, and associated with promising tumor response in early and

Recombinant Programming

OpenAIRE

Pawlak , Renaud; Cuesta , Carlos; Younessi , Houman

2004-01-01

This research report presents a promising new approach to computation called Recombinant Programming. The novelty of our approach is that it separates the program into two layers of computation: the recombination and the interpretation layer. The recombination layer takes sequences as inputs and allows the programmer to recombine these sequences through the definition of cohesive code units called extensions. The output of such recombination is a mesh that can be used by the interpretation la...

Recombiner

International Nuclear Information System (INIS)

Kikuchi, Nobuo.

1983-01-01

Purpose: To shorten the pre-heating time for a recombiner and obtain a uniform temperature distribution for the charged catalyst layer in a BWR type reactor. Constitution: A pre-heating heater is disposed to the outer periphery of a vessel for a recombiner packed with catalysts for recombining hydrogen and oxygen in gases flowing through a radioactive gaseous wastes processing system. Heat pipes for transmitting the heat applied to said container to the catalyst are disposed vertically and horizontally within the container. Different length of the heat pipes are combined. In this way, pre-heating time for the recombiner before the operation start and before the system switching can be shortened and the uniform pre-heating for the inside of the recombiner is also made possible. Further, heater control in the pre-heating can be carried out effectively and with ease. (Moriyama, K.)

Photoionization and Recombination

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Nahar, Sultana N.

2000-01-01

Theoretically self-consistent calculations for photoionization and (e + ion) recombination are described. The same eigenfunction expansion for the ion is employed in coupled channel calculations for both processes, thus ensuring consistency between cross sections and rates. The theoretical treatment of (e + ion) recombination subsumes both the non-resonant recombination ("radiative recombination"), and the resonant recombination ("di-electronic recombination") processes in a unified scheme. In addition to the total, unified recombination rates, level-specific recombination rates and photoionization cross sections are obtained for a large number of atomic levels. Both relativistic Breit-Pauli, and non-relativistic LS coupling, calculations are carried out in the close coupling approximation using the R-matrix method. Although the calculations are computationally intensive, they yield nearly all photoionization and recombination parameters needed for astrophysical photoionization models with higher precision than hitherto possible, estimated at about 10-20% from comparison with experimentally available data (including experimentally derived DR rates). Results are electronically available for over 40 atoms and ions. Photoionization and recombination of He-, and Li-like C and Fe are described for X-ray modeling. The unified method yields total and complete (e+ion) recombination rate coefficients, that can not otherwise be obtained theoretically or experimentally.

Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

Science.gov (United States)

da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

2016-01-01

The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. PMID:26645686

Recombiner

International Nuclear Information System (INIS)

Osumi, Morimichi.

1979-01-01

Purpose: To provide a recombiner which is capable of converting hydrogen gas into water by use of high-frequency heating at comparatively low temperatures and is safe and cheap in cost. Constitution: Hydrogen gas is introduced from an outer pipeline to the main structure of a recombiner, and when it passes through the vicinity of the central part of the recombiner, it is reacted with copper oxide (CuO 2 ) heated to a temperature more than 300 0 C by a high-frequency heater, and converted gently into water by reduction operation (2H 2 + CuO 2 → Cu + 2H 2 O). The thus prepared water is exhausted through the outer pipeline to a suppression pool. A part of hydrogen gas which has not been converted completely into water by the reaction and is remaining as hydrogen is recovered through exhaust nozzles and again introduced into the main structure of the recombiner. (Yoshino, Y.)

Repetitive transarterial chemoembolization (TACE) of liver metastases from gastric cancer: Local control and survival results

Energy Technology Data Exchange (ETDEWEB)

Vogl, Thomas J., E-mail: T.Vogl@em.uni-frankfurt.de [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Gruber-Rouh, Tatjana; Eichler, Katrin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Nour-Eldin, Nour-Eldin A. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Radiology, Faculty of Medicine, Cairo University, Cairo (Egypt); Trojan, Jörg [Department of Internal Medicine I, Johann Wolfgang Goethe-University Frankfurt (Germany); Zangos, Stephan [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Radiology Department, Faculty of Medicine, Alexandria University, Alexandria (Egypt)

2013-02-15

Objective: To evaluate the local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of patients with liver metastases of gastric cancer. Materials and methods: The study was retrospectively performed. 56 patients (mean age, 52.4) with unresectable liver metastases of gastric cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. In total, 310 chemoembolization procedures were performed (mean, 5.5 sessions per patient). The local chemotherapy protocol consisted of mitomycin alone (30.4%), mitomycin and gemcitabine (33.9%), or mitomycin, gemcitabine and cisplatin (35.7%). Embolization was performed with lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST. Survival data from first chemoembolization were calculated according to the Kaplan–Meier method. Results: The local tumor control was: complete response in 1.8% (n = 1), partial response in 1.8% (n = 1), stable disease in 51.8% (n = 29) and progressive disease in 44.6% (n = 25) of patients. The 1-, 2-, and 3-year survival rate from the start of chemoembolization were 58%, 38%, and 23% respectively. The median and mean survival times were 13 and 27.1 months. A Statistically significant difference between patients treated with different chemotherapy protocols was noted (ρ = 0.045) with the best survival time in the mitomycin, gemcitabine and cisplatin group. Conclusion: Transarterial chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with gastric cancer.

Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P).

Science.gov (United States)

da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

2016-01-29

The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Genome-wide recombination rate variation in a recombination map of cotton.

Science.gov (United States)

Shen, Chao; Li, Ximei; Zhang, Ruiting; Lin, Zhongxu

2017-01-01

Recombination is crucial for genetic evolution, which not only provides new allele combinations but also influences the biological evolution and efficacy of natural selection. However, recombination variation is not well understood outside of the complex species' genomes, and it is particularly unclear in Gossypium. Cotton is the most important natural fibre crop and the second largest oil-seed crop. Here, we found that the genetic and physical maps distances did not have a simple linear relationship. Recombination rates were unevenly distributed throughout the cotton genome, which showed marked changes along the chromosome lengths and recombination was completely suppressed in the centromeric regions. Recombination rates significantly varied between A-subgenome (At) (range = 1.60 to 3.26 centimorgan/megabase [cM/Mb]) and D-subgenome (Dt) (range = 2.17 to 4.97 cM/Mb), which explained why the genetic maps of At and Dt are similar but the physical map of Dt is only half that of At. The translocation regions between A02 and A03 and between A04 and A05, and the inversion regions on A10, D10, A07 and D07 indicated relatively high recombination rates in the distal regions of the chromosomes. Recombination rates were positively correlated with the densities of genes, markers and the distance from the centromere, and negatively correlated with transposable elements (TEs). The gene ontology (GO) categories showed that genes in high recombination regions may tend to response to environmental stimuli, and genes in low recombination regions are related to mitosis and meiosis, which suggested that they may provide the primary driving force in adaptive evolution and assure the stability of basic cell cycle in a rapidly changing environment. Global knowledge of recombination rates will facilitate genetics and breeding in cotton.

Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study

International Nuclear Information System (INIS)

Britten, Carolyn D; Gomes, Antoinette S; Wainberg, Zev A; Elashoff, David; Amado, Rafael; Xin, Yan; Busuttil, Ronald W; Slamon, Dennis J; Finn, Richard S

2012-01-01

Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE. 30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab. Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE. IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation

Fine-Scale Recombination Maps of Fungal Plant Pathogens Reveal Dynamic Recombination Landscapes and Intragenic Hotspots.

Science.gov (United States)

Stukenbrock, Eva H; Dutheil, Julien Y

2018-03-01

Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation, and rates of adaptation. In many organisms, recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate and positions of recombination hotspot can be studied using population genomics data and statistical methods. In this study, we conducted population genomics analyses to address the evolution of recombination in two closely related fungal plant pathogens: the prominent wheat pathogen Zymoseptoria tritici and a sister species infecting wild grasses Z. ardabiliae We specifically addressed whether recombination landscapes, including hotspot positions, are conserved in the two recently diverged species and if recombination contributes to rapid evolution of pathogenicity traits. We conducted a detailed simulation analysis to assess the performance of methods of recombination rate estimation based on patterns of linkage disequilibrium, in particular in the context of high nucleotide diversity. Our analyses reveal overall high recombination rates, a lack of suppressed recombination in centromeres, and significantly lower recombination rates on chromosomes that are known to be accessory. The comparison of the recombination landscapes of the two species reveals a strong correlation of recombination rate at the megabase scale, but little correlation at smaller scales. The recombination landscapes in both pathogen species are dominated by frequent recombination hotspots across the genome including coding regions, suggesting a strong impact of recombination on gene evolution. A significant but small fraction of these hotspots colocalize between the two species, suggesting that hotspot dynamics contribute to the overall pattern of fast evolving recombination in these species. Copyright © 2018 Stukenbrock and Dutheil.

Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion

Energy Technology Data Exchange (ETDEWEB)

Monier, Arnaud; Duran, Rafael; Bize, Pierre; Dunet, Vincent; Denys, Alban [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Guiu, Boris [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Montpellier University Hospital, Department of Diagnostic and Interventional Radiology, Montpellier (France); Aho, Serge [University Hospital, Department of Epidemiology, Dijon (France); Deltenre, Pierre [Lausanne University Hospital, Department of Gastroenterology, Lausanne (Switzerland)

2017-04-15

To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma. In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model. Biliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE (p < 0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p < 0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p < 0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p < 0.01), and between the dose of chemotherapy and intrahepatic biloma (p = 0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE (p = 0.025). DEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis. (orig.)

Genetic Recombination

Science.gov (United States)

Whitehouse, H. L. K.

1973-01-01

Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

BDNF pro-peptide: a novel synaptic modulator generated as an N-terminal fragment from the BDNF precursor by proteolytic processing

Directory of Open Access Journals (Sweden)

Toshiyuki Mizui

2017-01-01

Full Text Available Most growth factors are initially synthesized as precursors and it was cleaved into bioactive mature domain and pro-domain. However, compared with the expression and function of bioactive mature domain, the biological role of the pro-domain is poorly understood. Unexpectedly, we found that the pro-domain (or pro-peptide of brain-derived neurotrophic factor (BDNF, which is well-known neurotrophic factor in brain, has a potential ability to facilitate hippocampal long-term depression. Furthermore, a BDNF polymorphism Val66Met, which substitute valine into methionine at 66 amino acid, impacted the biological activity of the BDNF pro-peptide. We lastly discuss the possible roles of BDNF and its pro-peptide in the generation of neural stem cells and progress of ischemia.

Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila

Science.gov (United States)

Smukowski Heil, Caiti S.; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A.F.

2015-01-01

Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human–chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. PMID:26430062

Laser-induced electron--ion recombination used to study enhanced spontaneous recombination during electron cooling

International Nuclear Information System (INIS)

Schramm, U.; Wolf, A.; Schuess ler, T.; Habs, D.; Schwalm, D.; Uwira, O.; Linkemann, J.; Mueller, A.

1997-01-01

Spontaneous recombination of highly charged ions with free electrons in merged velocity matched electron and ion beams has been observed in earlier experiments to occur at rates significantly higher than predicted by theoretical estimates. To study this enhanced spontaneous recombination, laser induced recombination spectra were measured both in velocity matched beams and in beams with well defined relative velocities, corresponding to relative electron-ion detuning energies ranging from 1 meV up to 6.5 meV where the spontaneous recombination enhancement was found to be strongly reduced. Based on a comparison with simplified calculations, the development of the recombination spectra for decreasing detuning energies indicates additional contributions at matched velocities which could be related to the energy distribution of electrons causing the spontaneous recombination rate enhancement

Effects of nuclear mutations for recombination and repair functions and of caffeine on mitochondrial recombination

International Nuclear Information System (INIS)

Fraenkel, A.H.M.

1974-01-01

Studies of both prokaryotic and eukaryotic organisms indicate that pathways governing repair of damage to nuclear DNA caused by x-ray or ultraviolet irradiation overlap with those controlling recombination. Fourteen nuclear mutants of Saccharomyces cerevisiae were tested in order to determine whether these mutant genes affected mitochondrial recombination. None of the mutations studied significantly affected mitochondrial recombination. The nuclear recombination and repair pathways studied do not overlap with the nuclear pathway which controls recombination of mitochondrial DNA. A second set of experiments was designed to test the effect of caffeine on both nuclear and mitochondrial recombination in Saccharomyces cerevisiae. (U.S.)

Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila.

Science.gov (United States)

Smukowski Heil, Caiti S; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A F

2015-10-01

Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human-chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Therapeutic Recombinant Monoclonal Antibodies

Science.gov (United States)

Bakhtiar, Ray

2012-01-01

During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients

Directory of Open Access Journals (Sweden)

Abeer Hassan

2015-01-01

Full Text Available Transarterial chemoembolization (TACE is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P<0.01. Conversely, the control group reported a significant CP score deterioration at 1 week (P<0.05 and 12 weeks after TACE (P<0.05. L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P<0.05 and 4 weeks after TACE (P<0.05. L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P<0.05, and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P<0.05. The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE.

Survival benefit of chemoembolization plus Iodine125 seed implantation in unresectable hepatitis B-related hepatocellular carcinoma with PVTT: a retrospective matched cohort study

Energy Technology Data Exchange (ETDEWEB)

Huang, Mingsheng; Wang, Haofan; Chen, Junwei; Bai, Mingjun; Wang, Long; Zhu, Kangshun; Jiang, Zaibo; Guan, Shouhai; Li, Zhengran; Qian, Jiesheng; Li, Mingan; Pang, Pengfei; Shan, Hong [Sun Yat-sen University, Department of Radiology, the Third Affiliated Hospital, Guangzhou (China); Sun Yat-Sen University, Department of Interventional Radiology, Ling-nan Hospital, Guangzhou (China); Sun Yat-sen University, Interventional Radiology Institute, Guangzhou (China); Lin, Qu [Sun Yat-sen University, Department of Oncology, the Third Affiliated Hospital, Guangzhou (China)

2016-10-15

To investigate the survival benefit of transarterial chemoembolization (TACE) plus Iodine125 seed implantation (TACE-Iodine125) in hepatitis B-related HCC patients with portal vein tumour thrombus (PVTT) and the underlying prognostic factors. A retrospective matched cohort study was performed on consecutive HCC patients with PVTT from January 2011 to June 2014. Seventy patients (TACE-Iodine125 group) who underwent TACE-Iodine125 were compared with a historical case-matched control group of 140 patients (TACE group) who received TACE alone. The survival of patients and the underlying prognostic factors were analysed. The median survival times of the TACE-Iodine125 and TACE groups were 11.0 and 7.5 months, respectively (p < 0.001). The survival probability at 12, 24, and 36 months was 50 %, 14.5 %, and 14.5 % vs. 25 %, 9 %, and 5 % in the TACE-Iodine125 and TACE groups, respectively (p < 0.001). The PVTT responders had better survival than the PVTT non-responders (p < 0.001). For the PVTT non-responders, there were no differences in the survival curves between the groups (p = 0.353). Multivariate analysis showed that type III PVTT (p < 0.001) and APS (p < 0.001) were independent predictors of poor prognosis. In contrast, the treatment modality of TACE-Iodine125 (p < 0.001) and PVTT response (p = 0.001) were favourable prognostic features. TACE combined with Iodine125 seed implantation may be a good choice for selected HB-HCC patients with PVTT. (orig.)

Switching the Loaded Agent from Epirubicin to Cisplatin: Salvage Transcatheter Arterial Chemoembolization with Drug-eluting Microspheres for Unresectable Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Seki, Akihiko; Hori, Shinich

2012-01-01

Purpose: There is no consensus on switching anticancer agents loaded onto drug carriers in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and clinical outcomes of TACE with cisplatin-loaded microspheres (CLM-TACE) in HCC patients refractory to TACE with epirubicin-loaded microspheres (ELM-TACE). Methods: Between February 2008 and June 2010, 85 patients with unresectable HCC refractory to ELM-TACE were enrolled to undergo CLM-TACE. The number of ELM-TACE sessions until judgment of resistance ranged from 1 to 4 (median, 2.1). CLM-TACE was performed using 50–100-μm superabsorbent polymer microspheres loaded with 1 mg cisplatin/1 mg microspheres together with hepatic arterial infusion of 25 mg cisplatin and 500 mg 5-fluorouracil per patient. Tumor responses were evaluated by computed tomography according to the European Association for the Study of the Liver criteria. Results: The median number of CLM-TACE treatment sessions was 1.8 (range, 1–5), and the mean total dose of cisplatin per session was 42.8 mg (range, 30.0–59.0). After 6 months, 3 (3.5%) patients achieved complete response, 31 (36.5%) had partial response, 15 (17.6%) had stable disease, and 36 (42.4%) had progressive disease. The median overall survival and time to treatment failure after initial CLM-TACE were 13.3 and 7.2 months, respectively. Overall, 9.4% of patients experienced grade 3/4 adverse events. Conclusions: witching the loaded agent from epirubicin to cisplatin is a safe, well-tolerated, and efficacious treatment strategy for salvage TACE with drug-eluting microspheres in HCC patients refractory to ELM-TACE.

Efficacy and Safety of Transarterial Radioembolization Versus Chemoembolization in Patients With Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Moreno-Luna, Laura E.; Yang, Ju Dong; Sanchez, William; Paz-Fumagalli, Ricardo; Harnois, Denise M.; Mettler, Teresa A.; Gansen, Denise N.; Groen, Piet C. de; Lazaridis, Konstantinos N.; Narayanan Menon, K. V.; LaRusso, Nicholas F.; Alberts, Steven R.; Gores, Gregory J.; Fleming, Chad J.; Slettedahl, Seth W.; Harmsen, William S.; Therneau, Terry M.; Wiseman, Gregory A.; Andrews, James C.; Roberts, Lewis R.

2013-01-01

Purpose. Intermediate-stage hepatocellular carcinoma (HCC) is usually treated with locoregional therapy using transarterial chemoembolization (TACE). Transarterial radioembolization (TARE) using β-emitting yttrium-90 integral to the glass matrix of the microspheres is an alternative to TACE. This retrospective case-control study compared the outcomes and safety of TARE versus TACE in patients with unresectable HCC. Materials and Methods. Patients with unresectable HCC without portal vein thrombosis treated with TARE between 2005 and 2008 (n = 61) were retrospectively frequency-matched by age, sex, and liver dysfunction with TACE-treated patients (n = 55) in the Mayo Clinic Hepatobiliary Neoplasia Registry. Imaging studies were reviewed, and clinical and safety outcomes were abstracted from the medical records. Results. Complete tumor response was more common after TARE (12 %) than after TACE (4 %) (p = 0.17). When complete response was combined with partial response and stable disease, there was no difference between TARE and TACE. Median survival did not differ between the two groups (15.0 months for TARE and 14.4 months for TACE; p = 0.47). Two-year survival rates were 30 % for TARE and 24 % for TACE. TARE patients received fewer treatments (p < 0.001). Fifty-nine (97 %) TARE patients received outpatient treatment. In contrast, 53 (98 %) TACE patients were hospitalized for ≥1 day (p < 0.001). Compared with TACE, TARE was more likely to induce fatigue (p = 0.003) but less likely to cause fever (p = 0.02). Conclusion. There was no significant difference in efficacy between TARE and TACE. TARE patients reported more fatigue but had less fever than TACE patients. Treatment with TARE required less hospitalization than treatment with TACE. These findings require confirmation in randomized trials.

Recombination every day: abundant recombination in a virus during a single multi-cellular host infection.

Directory of Open Access Journals (Sweden)

Remy Froissart

2005-03-01

Full Text Available Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment-based on data on the timing of coat protein detection-the per base and replication cycle recombination rate was on the order of 2 x 10(-5 to 4 x 10(-5. This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.

Regulation of Meiotic Recombination

Energy Technology Data Exchange (ETDEWEB)

Gregory p. Copenhaver

2011-11-09

Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

Recombination of cluster ions

Science.gov (United States)

Johnsen, Rainer

1993-01-01

Some of our recent work on molecular band emissions from recombination of molecular dimer ions (N4(+) and CO(+) CO) is discussed. Much of the experimental work was done by Y. S. Cao; the results on N4(+) recombination have been published. A brief progress report is given on our ongoing measurements of neutral products of recombination using the flowing-afterglow Langmuir-probe technique in conjunction with laser-induced fluorescence.

In vivo production of recombinant proteins using occluded recombinant AcMNPV-derived baculovirus vectors.

Science.gov (United States)

Guijarro-Pardo, Eva; Gómez-Sebastián, Silvia; Escribano, José M

2017-12-01

Trichoplusia ni insect larvae infected with vectors derived from the Autographa californica multiple nucleopolyhedrovirus (AcMNPV), are an excellent alternative to insect cells cultured in conventional bioreactors to produce recombinant proteins because productivity and cost-efficiency reasons. However, there is still a lot of work to do to reduce the manual procedures commonly required in this production platform that limit its scalability. To increase the scalability of this platform technology, a current bottleneck to be circumvented in the future is the need of injection for the inoculation of larvae with polyhedrin negative baculovirus vectors (Polh-) because of the lack of oral infectivity of these viruses, which are commonly used for production in insect cell cultures. In this work we have developed a straightforward alternative to obtain orally infective vectors derived from AcMNPV and expressing recombinant proteins that can be administered to the insect larvae (Trichoplusia ni) by feeding, formulated in the insect diet. The approach developed was based on the use of a recombinant polyhedrin protein expressed by a recombinant vector (Polh+), able to co-occlude any recombinant Polh- baculovirus vector expressing a recombinant protein. A second alternative was developed by the generation of a dual vector co-expressing the recombinant polyhedrin protein and the foreign gene of interest to obtain the occluded viruses. Additionally, by the incorporation of a reporter gene into the helper Polh+ vector, it was possible the follow-up visualization of the co-occluded viruses infection in insect larvae and will help to homogenize infection conditions. By using these methodologies, the production of recombinant proteins in per os infected larvae, without manual infection procedures, was very similar in yield to that obtained by manual injection of recombinant Polh- AcMNPV-based vectors expressing the same proteins. However, further analyses will be required for a

Recombination pattern reanalysis of some HIV-1 circulating recombination forms suggest the necessity and difficulty of revision.

Directory of Open Access Journals (Sweden)

Lei Jia

Full Text Available Recombination is one of the major mechanisms underlying the generation of HIV-1 variability. Currently 61 circulating recombinant forms of HIV-1 have been identified. With the development of recombination detection techniques and accumulation of HIV-1 reference stains, more accurate mosaic structures of circulating recombinant forms (CRFs, like CRF04 and CRF06, have undergone repeated analysis and upgrades. Such revisions may also be necessary for other CRFs. Unlike previous studies, whose results are based primarily on a single recombination detection program, the current study was based on multiple recombination analysis, which may have produced more impartial results.Representative references of 3 categories of intersubtype recombinants were selected, including BC recombinants (CRF07 and CRF08, BG recombinants (CRF23 and CRF24, and BF recombinants (CRF38 and CRF44. They were reanalyzed in detail using both the jumping profile hidden Markov model and RDP3.The results indicate that revisions and upgrades are very necessary and the entire re-analysis suggested 2 types of revision: (i length of inserted fragments; and (ii number of inserted fragments. The reanalysis also indicated that determination of small regions of about 200 bases or fewer should be performed with more caution.Results indicated that the involvement of multiple recombination detection programs is very necessary. Additionally, results suggested two major challenges, one involving the difficulty of accurately determining the locations of breakpoints and the second involving identification of small regions of about 200 bases or fewer with greater caution. Both indicate the complexity of HIV-1 recombination. The resolution would depend critically on development of a recombination analysis algorithm, accumulation of HIV-1 stains, and a higher sequencing quality. With the changes in recombination pattern, phylogenetic relationships of some CRFs may also change. All these results may

Electron-ion recombination in merged beams

International Nuclear Information System (INIS)

Wolf, A.; Habs, D.; Lampert, A.; Neumann, R.; Schramm, U.; Schuessler, T.; Schwalm, D.

1993-01-01

Detailed studies of recombination processes between electrons and highly charged ions have become possible by recent improvements of merged-beams experiments. We discuss in particular measurements with stored cooled ion beams at the Test Storage Ring (TSR) in Heidelberg. The cross section of dielectronic recombination was measured with high energy resolution for few-electron systems up to the nuclear charge of Cu at a relative energy up to 2.6 keV. At low energy (∼0.1 eV) total recombination rates of several ions were measured and compared with calculated radiative recombination rates. Laser-stimulated recombination of protons and of C 6+ ions was investigated as a function of the photon energy using visible radiation. Both the total recombination rates and the stimulated recombination spectra indicate that in spite of the short interaction time in merged beams, also collisional capture of electrons into weakly bound levels (related to three-body recombination) could be important

Multiple barriers to recombination between divergent HIV-1 variants revealed by a dual-marker recombination assay

DEFF Research Database (Denmark)

Nikolaitchik, Olga A; Galli, Andrea; Moore, Michael D

2011-01-01

Recombination is a major force for generating human immunodeficiency virus type 1 (HIV-1) diversity and produces numerous recombinants circulating in the human population. We previously established a cell-based system using green fluorescent protein gene (gfp) as a reporter to study the mechanisms...... of HIV-1 recombination. We now report an improved system capable of detecting recombination using authentic viral sequences. Frameshift mutations were introduced into the gag gene so that parental viruses do not express full-length Gag; however, recombination can generate a progeny virus that expresses...

Oxygen-hydrogen recombination system

International Nuclear Information System (INIS)

Sato, Shuichiro; Takejima, Masaki.

1981-01-01

Purpose: To avoid reduction in the performance of catalyst used for an oxygen-hydrogen recombiner in the off gas processing system of a nuclear reactor. Constitution: A thermometer is provided for the detection of temperature in an oxygen-hydrogen recombiner. A cooling pipe is provided in the recombiner and cooling medium is introduced externally. The cooling medium may be water or air. In accordance with the detection value from the thermometer, ON-OFF control is carried out for a valve to control the flow rate of the cooling medium thereby rendering the temperature in the recombiner to a predetermined value. This can prevent the catalyst from being exposed to high temperature and avoid the reduction in the performance of the catalyst. (Ikeda, J.)

Combination of Transarterial Chemoembolization and Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma With Inferior Vena Cava Tumor Thrombus

International Nuclear Information System (INIS)

Koo, Ja Eun; Kim, Jong Hoon; Lim, Young-Suk

2010-01-01

Purpose: To evaluate the effects of transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (CRT) in patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT). Methods and Materials: A total of 42 consecutive patients who underwent TACE and CRT (TACE+CRT group) for the treatment of HCC with IVCTT were prospectively enrolled from July 2004 to October 2006. As historical controls, 29 HCC patients with IVCTT who received TACE alone (TACE group) between July 2003 and June 2004 were included. CRT was designed to target only the IVCTT and to deliver a median total dose of 45 Gy (range, 28-50 Gy). Results: Most baseline characteristics of the two groups were similar (p > 0.05). The response and progression-free rates of IVCTT were significantly higher in the TACE+CRT group than in the TACE group (42.9% and 71.4% vs. 13.8% and 37.9%, respectively; p < 0.01 for both rates). Overall, patient survival was significantly higher in the TACE+CRT group than in the TACE group (p < 0.01), with a median survival time of 11.7 months and 4.7 months, respectively. Treatment with TACE+CRT (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20-0.71), progression of IVCTT (HR = 4.05; 95% CI, 2.00-8.21), Child-Pugh class B (HR = 3.44; 95% CI, 1.79-6.61), and portal vein invasion (HR = 2.31; 95% CI, 1.19-4.50) were identified as independent predictors of mortality by multivariable analysis. Conclusions: The combination of TACE and CRT is more effective in the control of IVCTT associated with HCC and improves patient survival compared with TACE alone.

Conditional inactivation of TNFα-converting enzyme in chondrocytes results in an elongated growth plate and shorter long bones.

Directory of Open Access Journals (Sweden)

Kenta Saito

Full Text Available TNFα-converting enzyme (TACE is a membrane-bound proteolytic enzyme with essential roles in the functional regulation of TNFα and epidermal growth factor receptor (EGFR ligands. Previous studies have demonstrated critical roles for TACE in vivo, including epidermal development, immune response, and pathological neoangiogenesis, among others. However, the potential contribution of TACE to skeletal development is still unclear. In the present study, we generated a Tace mutant mouse in which Tace is conditionally disrupted in chondrocytes under the control of the Col2a1 promoter. These mutant mice were fertile and viable but all exhibited long bones that were approximately 10% shorter compared to those of wild-type animals. Histological analyses revealed that Tace mutant mice exhibited a longer hypertrophic zone in the growth plate, and there were fewer osteoclasts at the chondro-osseous junction in the Tace mutant mice than in their wild-type littermates. Of note, we found an increase in osteoprotegerin transcripts and a reduction in Rankl and Mmp-13 transcripts in the TACE-deficient cartilage, indicating that dysregulation of these genes is causally related to the skeletal defects in the Tace mutant mice. Furthermore, we also found that phosphorylation of EGFR was significantly reduced in the cartilage tissue lacking TACE, and that suppression of EGFR signaling increases osteoprotegerin transcripts and reduces Rankl and Mmp-13 transcripts in primary chondrocytes. In accordance, chondrocyte-specific abrogation of Egfr in vivo resulted in skeletal defects nearly identical to those observed in the Tace mutant mice. Taken together, these data suggest that TACE-EGFR signaling in chondrocytes is involved in the turnover of the growth plate during postnatal development via the transcriptional regulation of osteoprotegerin, Rankl, and Mmp-13.

Combination of transcatheter arterial chemoembolization and interrupted dosing sorafenib improves patient survival in early–intermediate stage hepatocellular carcinoma

Science.gov (United States)

Lee, Teng-Yu; Lin, Chen-Chun; Chen, Chiung-Yu; Wang, Tsang-En; Lo, Gin-Ho; Chang, Chi-Sen; Chao, Yee

2017-01-01

Abstract Background/Objective: The survival benefit of treatment for unresectable hepatocellular carcinoma (HCC) with transcatheter arterial chemoembolization (TACE) combined with sorafenib remains uncertain. We compared the survival of patients treated with TACE and sorafenib with that of patients treated with TACE alone. Methods: This was a post hoc analysis of the Study in Asia of the Combination of TACE with Sorafenib in Patients with HCC (START) trial. All patients who received TACE and interrupted dosing of sorafenib for early or intermediate-stage HCC in Taiwan from 2009 to 2010 were recruited into the TACE and sorafenib group. They were randomly matched 1:1 by age, sex, Child–Pugh score, tumor size, tumor number, and tumor stage with patients from Taichung Veterans General Hospital in Taiwan who received TACE alone and who fulfilled the selection criteria of the START trial during the same time period (control group). Patient survival [cumulative incidence and hazard ratio (HR)] of the 2 groups were analyzed and compared. Results: The baseline characteristics of the 36 patients in each group were similar. Tumor response rates were significantly better in the TACE and sorafenib group (P < .04). Overall survival of the TACE and sorafenib group was also significantly better than that of the control (TACE alone) group over the 2 years [78%, 95% confidence interval (95% CI) 64–91 vs 49, 95% CI 32–66; P = .012]. In the multivariate regression analysis, TACE and sorafenib was found to be independently associated with a decreased risk of mortality (HR 0.33, 95% CI 0.12–0.89; P = .015). Multivariate stratified analyses verified this association in each patient subgroup (all HR < 1.0). Conclusion: With a high patient tolerance to an interrupted sorafenib dosing schedule, the combination of TACE with sorafenib was associated with improved overall survival in early–intermediate stage HCC when compared with treatment with TACE alone. PMID

Hydrogen recombiner development at AECL

International Nuclear Information System (INIS)

Dewit, W.A.; Koroll, G.W.; Loesel Sitar, J.; Graham, W.R.C.

1997-01-01

Catalytic recombiners have been developed at AECL for the purpose of hydrogen removal in post-accident nuclear containment buildings. The recombiners are based on a particular catalyst designed by AECL which has extraordinary resistance to fouling from water and water vapour and a large thermodynamic range of operation. The catalysts were developed, originally, for the purpose of heavy water manufacturing by way of a catalytic exchange process. Application of these catalyst materials in recombiners for containment applications began in the late 1980's. The first application was a passive recombiner, qualified for use in control of radiolytic hydrogen in the headspace of a pool-type experimental reactor of AECL design in 1988. The passive, or natural convection recombiner concept has continued development to commercial stage for application in power reactor containments. This paper reviews the AECL recombiner development, describes the current model and shows results from tests of full-scale recombiners in the Large Scale Vented Combustion Test Facility at AECL-WL. The AECL recombiner is designed for compactness and ease of engineering into containment. The design is a simple, open-ended rectangular enclosure with catalyst elements arranged inside to promote optimum convective flow driven by heat of recombination at the catalyst surface. Self start, as evidenced by catalyst heating and initiation of flow, is achieved in less than 1% hydrogen, with available oxygen, at room temperature and 100% relative humidity. This low temperature start-up in condensing atmospheres is viewed as the most challenging condition for wet-proofing effectiveness. Cold start-up is a vital performance requirement in containments, such as CANDU, where engineered air-cooling systems are operating and where long-term hydrogen control is required, after containment atmospheres have cooled. Once started, the removal capacity scales linearly with the inlet cross-section area and the partial

Multivariate Analysis of the Predictors of Survival for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Focusing on Superselective Chemoembolization

International Nuclear Information System (INIS)

Ji, Suk Kyeong; Cho, Yun Ku; Ahn, Yong Sik; Kim, Mi Young; Park, Yoon Ok; Kim, Jae Kyun; Kim, Wan Tae

2008-01-01

While the prognostic factors of survival for patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE) are well known, the clinical significance of performing selective TACE for HCC patients has not been clearly documented. We tried to analyze the potential factors of disease-free survival for these patients, including the performance of selective TACE. A total of 151 patients with HCC who underwent TACE were retrospectively analyzed for their disease-free survival (a median follow- up of 23 months, range: 1-88 months). Univariate and multivariate analyses were performed for 20 potential factors by using the Cox proportional hazard model, including 19 baseline factors and one procedure-related factor (conventional versus selective TACE). The parameters that proved to be significant on the univariate analysis were subsequently tested with the multivariate model. Conventional or selective TACE was performed for 40 and 111 patients, respectively. Univariate and multivariate analyses revealed that tumor multiplicity, venous tumor thrombosis and selective TACE were the only three independent significant prognostic factors of disease-free survival (p = 0.002, 0.015 and 0.019, respectively). In our study, selective TACE was a favorable prognostic factor for the disease-free survival of patients with HCC who underwent TACE

On the relict recombination lines

International Nuclear Information System (INIS)

Bershtejn, I.N.; Bernshtejn, D.N.; Dubrovich, V.K.

1977-01-01

Accurate numerical calculation of intensities and profiles of hydrogen recombination lines of cosmological origin is made. Relie radiation distortions stipulated by recombination quantum release at the irrevocable recombination are investigated. Mean number calculation is given for guantums educing for one irrevocably-lost electron. The account is taken of the educed quantums interraction with matter. The main quantum-matter interrraction mechanisms are considered: electronic blow broadening; free-free, free-bound, bound-bound absorptions Recombination dynamics is investigated depending on hydrogen density and total density of all the matter kinds in the Universe

Late replicating domains are highly recombining in females but have low male recombination rates: implications for isochore evolution.

Directory of Open Access Journals (Sweden)

Catherine J Pink

Full Text Available In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in

Prospective Randomized Study of Doxorubicin-Eluting-Bead Embolization in the Treatment of Hepatocellular Carcinoma: Results of the PRECISION V Study

International Nuclear Information System (INIS)

Lammer, Johannes; Malagari, Katarina; Vogl, Thomas; Pilleul, Frank; Denys, Alban; Watkinson, Anthony; Pitton, Michael; Sergent, Geraldine; Pfammatter, Thomas; Terraz, Sylvain; Benhamou, Yves; Avajon, Yves; Gruenberger, Thomas; Pomoni, Maria; Langenberger, Herbert; Schuchmann, Marcus; Dumortier, Jerome; Mueller, Christian; Chevallier, Patrick; Lencioni, Riccardo

2010-01-01

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

Evaluation of hepatic atrophy after transcatheter arterial embolization

International Nuclear Information System (INIS)

Chung, Hwan Hoon; Lee, Mee Ran; Oh, Min Cheol; Park, Chul Min; Seol, Hae Young; Cha, In Ho

1995-01-01

Hepatic atrophy has been recognized as a complication of hepatic and biliary disease but we have often found it in follow up CT after transcatheter arterial embolization (TACE). The purpose of this study is to evaluate the characteristics of hepatic atrophy after TACE. Of 53 patients who had TACE. We evaluated the relationship between the incidence of hepatic atrophy and the number of TACE, and also evaluated the average number of TACE in patients with hepatic atrophy. Of 20 patients who had received more than average number of TACE for development of hepatic atrophy (2 times with portal vein obstruction, 2.7 times without portal vein obstruction in this study), we evaluated the relationship between the lipiodol uptake pattern of tumor and the incidence of hepatic atrophy. There were 8 cases of hepatic atrophy (3 with portal vein obstruction, 5 without portal vein obstruction), average number for development of hepatic atrophy were 2.5 times. As the number of TACE were increased, the incidence of hepatic atrophy were also increased. Of 20 patients who received more than average number of TACE for development of hepatic atrophy, we noted 6 cases of hepatic atrophy in 11 patients with dense homogenous lipiodol uptake pattern of tumor and noted only 1 case of hepatic atrophy in 9 patient with inhomogenous lipiodol uptake pattern. Hepatic atrophy was one of the CT findings after TACE even without portal vein obstruction. Average number of TACE was 2.5 times and risk factors for development of hepatic atrophy were portal vein obstruction, increased number of TACE, and dense homogenous lipiodol uptake pattern of tumor

Auger recombination in sodium iodide

Science.gov (United States)

McAllister, Andrew; Kioupakis, Emmanouil; Åberg, Daniel; Schleife, André

2014-03-01

Scintillators are an important tool used to detect high energy radiation - both in the interest of national security and in medicine. However, scintillator detectors currently suffer from lower energy resolutions than expected from basic counting statistics. This has been attributed to non-proportional light yield compared to incoming radiation, but the specific mechanism for this non-proportionality has not been identified. Auger recombination is a non-radiative process that could be contributing to the non-proportionality of scintillating materials. Auger recombination comes in two types - direct and phonon-assisted. We have used first-principles calculations to study Auger recombination in sodium iodide, a well characterized scintillating material. Our findings indicate that phonon-assisted Auger recombination is stronger in sodium iodide than direct Auger recombination. Computational resources provided by LLNL and NERSC. Funding provided by NA-22.

Regulation of homologous recombination in eukaryotes

OpenAIRE

Heyer, Wolf-Dietrich; Ehmsen, Kirk T.; Liu, Jie

2010-01-01

Homologous recombination is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage including DNA double-stranded breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks enabling the evolution of larger genomes/replicons. Defects in recombination lead to genomic instability and ...

Recombination coefficients in extrinsic n-InSb

International Nuclear Information System (INIS)

Schneider, W.; Groh, H.; Huebner, K.

1976-01-01

The bulk recombination coefficients for linear recombination via recombination centers as well as for direct recombination have been determined measuring the conductivity decay after two-photon absorption with a CO 2 laser. The Suhl effect was applied to measure the surface recombination velocity. The corresponding literature is discussed and compared with our results. We conclude that two different kinds of recombination centers are possible in n-InSb, with energy levels (0.1-0.12)eV above the valence band, or (0.14-0.2)eV respectively. (orig.) [de

CT-guided interstitial brachytherapy of hepatocellular carcinoma before liver transplantation: an equivalent alternative to transarterial chemoembolization?

International Nuclear Information System (INIS)

Denecke, Timm; Stelter, Lars; Schnapauff, Dirk; Steffen, Ingo; Gebauer, Bernhard; Lopez Haenninen, Enrique; Wust, Peter; Sinn, Bruno; Schott, Eckart; Seidensticker, Ricarda; Puhl, Gero; Neuhaus, Peter; Seehofer, Daniel

2015-01-01

Transarterial chemoembolization (TACE) is established as bridging therapy of HCC listed for transplantation (LT). CT-guided brachytherapy (CTB) has not been evaluated as a bridging concept. We compared CTB and TACE for bridging before LT in HCC patients. Twelve patients with HCC received LT after CTB (minimal tumour dose, 15-20 Gy). Patients were matched (CTB:TACE, 1:2) by sex, age, number and size of lesions, and underlying liver disease with patients who received TACE before transplantation. Study endpoints were extent of necrosis at histopathology and recurrence rate after OLT. There were no significant differences between the CTB and TACE groups regarding Child-Pugh category (p = 0.732), AFP (0.765), time on waiting list (p = 0.659), number (p = 0.698) and size (p = 0.853) of HCC lesions, fulfilment of Milan-criteria (p = 0.638), or previous liver-specific treatments. CTB achieved higher tumour necrosis rates than TACE (p = 0.018). The 1- and 3-year recurrence rate in the CTB group was 10 and 10 % vs. TACE, 14 and 30 % (p = 0.292). Our data show comparable or even better response and post-LT recurrence rates of CTB compared to TACE for treating HCC in patients prior to LT. CTB should be further evaluated as an alternative bridging modality, especially for patients not suited for TACE. (orig.)

CT-guided interstitial brachytherapy of hepatocellular carcinoma before liver transplantation: an equivalent alternative to transarterial chemoembolization?

Energy Technology Data Exchange (ETDEWEB)

Denecke, Timm; Stelter, Lars; Schnapauff, Dirk; Steffen, Ingo; Gebauer, Bernhard; Lopez Haenninen, Enrique; Wust, Peter [Universitaetsmedizin Berlin, Klinik fuer Radiologie, Charite, Berlin (Germany); Sinn, Bruno [Charite - Universitaetsmedizin Berlin, Institut fuer Pathologie, Berlin (Germany); Schott, Eckart [Charite 2 - Universitaetsmedizin Berlin, Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Berlin (Germany); Seidensticker, Ricarda [Universitaetsklinikum der Otto-v.-Gericke-Universitaet, Klinik fuer Radiologie und Nuklearmedizin, Magdeburg (Germany); Puhl, Gero; Neuhaus, Peter; Seehofer, Daniel [Charite - Universitaetsmedizin Berlin, Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie, Berlin (Germany)

2015-09-15

Transarterial chemoembolization (TACE) is established as bridging therapy of HCC listed for transplantation (LT). CT-guided brachytherapy (CTB) has not been evaluated as a bridging concept. We compared CTB and TACE for bridging before LT in HCC patients. Twelve patients with HCC received LT after CTB (minimal tumour dose, 15-20 Gy). Patients were matched (CTB:TACE, 1:2) by sex, age, number and size of lesions, and underlying liver disease with patients who received TACE before transplantation. Study endpoints were extent of necrosis at histopathology and recurrence rate after OLT. There were no significant differences between the CTB and TACE groups regarding Child-Pugh category (p = 0.732), AFP (0.765), time on waiting list (p = 0.659), number (p = 0.698) and size (p = 0.853) of HCC lesions, fulfilment of Milan-criteria (p = 0.638), or previous liver-specific treatments. CTB achieved higher tumour necrosis rates than TACE (p = 0.018). The 1- and 3-year recurrence rate in the CTB group was 10 and 10 % vs. TACE, 14 and 30 % (p = 0.292). Our data show comparable or even better response and post-LT recurrence rates of CTB compared to TACE for treating HCC in patients prior to LT. CTB should be further evaluated as an alternative bridging modality, especially for patients not suited for TACE. (orig.)

Electron-ion recombination rates for merged-beams experiments

International Nuclear Information System (INIS)

Pajek, M.

1994-01-01

Energy dependence of the electron-ion recombination rates are studied for different recombination processes (radiative recombination, three-body recombination, dissociative recombination) for Maxwellian relative velocity distribution of arbitrary asymmetry. The results are discussed in context of the electron-ion merged beams experiments in cooling ion storage rings. The question of indication of a possible contribution of the three-body recombination to the measured recombination rates versus relative energy is particularly addressed. Its influence on the electron beam temperature derived from the energy dependence of recombination rate is discussed

Electron-ion recombination at low energy

International Nuclear Information System (INIS)

Andersen, L.H.

1993-01-01

The work is based on results obtained with a merged-beams experiment. A beam of electronics with a well characterized density and energy distribution was merged with a fast, monoenergetic ion beam. Results have been obtained for radiative recombination and dielectronic recombination at low relative energies (0 to ∼70eV). The obtained energy resolution was improved by about a factor of 30. High vacuum technology was used to suppress interactions with electrons from the environments. The velocity distribution of the electron beam was determined. State-selective dielectronic-recombination measurements were performable. Recombination processes were studied. The theoretical background for radiative recombination and Kramers' theory are reviewed. The quantum mechanical result and its relation to the semiclassical theory is discussed. Radiative recombination was also measured with several different non-bare ions, and the applicability of the semiclassical theory to non-bare ions was investigated. The use of an effective charge is discussed. For dielectronic recombination, the standard theoretical approach in the isolated resonance and independent-processes approximation is debated. The applicability of this method was tested. The theory was able to reproduce most of the experimental data except when the recombination process was sensitive to couplings between different electronic configurations. The influence of external perturbing electrostatic fields is discussed. (AB) (31 refs.)

Recombinant Innovation and Endogenous Transitions

OpenAIRE

Koen Frenken; Luis R. Izquierdo; Paolo Zeppini

2012-01-01

We propose a model of technological transitions based on two different types of innovations. Branching innovations refer to technological improvements along a particular path, while recombinant innovations represent fusions of multiple paths. Recombinant innovations create “short-cuts” which reduce switching costs allowing agents to escape a technological lock-in. As a result, recombinant innovations speed up technological progress allowing transitions that are impossible with only branching ...

Interface recombination influence on carrier transport

International Nuclear Information System (INIS)

Konin, A

2013-01-01

A theory of interface recombination in the semiconductor–semiconductor junction is developed. The interface recombination rate dependence on the nonequilibrium carrier densities is derived on the basis of a model in which the interface recombination occurs through the mechanism of trapping. The general relation between the interface recombination parameters at small carrier density deviation from the equilibrium ones is obtained. The validity of this relation is proved considering the generation of the Hall electric field in the extrinsic semiconductor sample. The anomalous Hall electromotive force in a weak magnetic field was investigated and interpreted by means of a new interface recombination model. The experimental data corroborate the developed theory. (paper)

Caenorhabditis briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination.

Directory of Open Access Journals (Sweden)

Joseph A Ross

2011-07-01

Full Text Available The nematode Caenorhabditis briggsae is an emerging model organism that allows evolutionary comparisons with C. elegans and exploration of its own unique biological attributes. To produce a high-resolution C. briggsae recombination map, recombinant inbred lines were generated from reciprocal crosses between two strains and genotyped at over 1,000 loci. A second set of recombinant inbred lines involving a third strain was also genotyped at lower resolution. The resulting recombination maps exhibit discrete domains of high and low recombination, as in C. elegans, indicating these are a general feature of Caenorhabditis species. The proportion of a chromosome's physical size occupied by the central, low-recombination domain is highly correlated between species. However, the C. briggsae intra-species comparison reveals striking variation in the distribution of recombination between domains. Hybrid lines made with the more divergent pair of strains also exhibit pervasive marker transmission ratio distortion, evidence of selection acting on hybrid genotypes. The strongest effect, on chromosome III, is explained by a developmental delay phenotype exhibited by some hybrid F2 animals. In addition, on chromosomes IV and V, cross direction-specific biases towards one parental genotype suggest the existence of cytonuclear epistatic interactions. These interactions are discussed in relation to surprising mitochondrial genome polymorphism in C. briggsae, evidence that the two strains diverged in allopatry, the potential for local adaptation, and the evolution of Dobzhansky-Muller incompatibilities. The genetic and genomic resources resulting from this work will support future efforts to understand inter-strain divergence as well as facilitate studies of gene function, natural variation, and the evolution of recombination in Caenorhabditis nematodes.

Molecular requirements for radiation-activated recombination

International Nuclear Information System (INIS)

Stevens, Craig W.; Zeng Ming; Stamato, Thomas; Cerniglia, George

1997-01-01

Purpose/Objective: The major stumbling block to successful gene therapy today is poor gene transfer. We hypothesized that ionizing radiation might activate cellular recombination, and so improve stable gene transfer. We further hypothesized that known DNA-damage-repair proteins might also be important in radiation-activated recombination. Materials and Methods: The effect of irradiation on stable gene transfer efficiency was determined in human (A549 and 39F) and rodent (NIH/3T3) cell lines. Continuous low dose rate and multiple radiation fractions were also tested. Nuclear extracts were made and the effect of irradiation on inter-plasmid recombination/ligation determined. Multiple DNA damage-repair deficient cell lines were tested for radiation-activated recombination. Results: A significant radiation dose-dependent improvement in stable plasmid transfection (by as much as 1300 fold) is demonstrated in neoplastic and primary cells. An improvement in transient plasmid transfection is also seen, with as much as 85% of cells transiently expressing b-galactosidase (20-50 fold improvement). Stable transfection is only improved for linearized or nicked plasmids. Cells have improved gene transfer for at least 96 hours after irradiation. Both fractionated and continuous low dose rate irradiation are effective at improving stable gene transfer in mammalian cells, thus making relatively high radiation dose delivery clinically feasible. Inter-plasmid recombination is radiation dose dependent in nuclear extract assays, and the type of overhang (3', 5' or blunt end) significantly affects recombination efficiency and the type of product. The most common end-joining activity involves filling-in of the overhang followed by blunt end ligation. Adenovirus is a linear, double stranded DNA virus. We demonstrate that adenoviral infection efficiency is increased by irradiation. The duration of transgene expression is lengthened because the virus integrates with high efficiency (∼10

Recombinant pinoresinol/lariciresinol reductase, recombinant dirigent protein, and methods of use

Science.gov (United States)

Lewis, Norman G.; Davin, Laurence B.; Dinkova-Kostova, Albena T.; Fujita, Masayuki; Gang, David R.; Sarkanen, Simo; Ford, Joshua D.

2001-04-03

Dirigent proteins and pinoresinol/lariciresinol reductases have been isolated, together with cDNAs encoding dirigent proteins and pinoresinol/lariciresinol reductases. Accordingly, isolated DNA sequences are provided which code for the expression of dirigent proteins and pinoresinol/lariciresinol reductases. In other aspects, replicable recombinant cloning vehicles are provided which code for dirigent proteins or pinoresinol/lariciresinol reductases or for a base sequence sufficiently complementary to at least a portion of dirigent protein or pinoresinol/lariciresinol reductase DNA or RNA to enable hybridization therewith. In yet other aspects, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding dirigent protein or pinoresinol/lariciresinol reductase. Thus, systems and methods are provided for the recombinant expression of dirigent proteins and/or pinoresinol/lariciresinol reductases.

Population inversion in recombining hydrogen plasma

International Nuclear Information System (INIS)

Furukane, Utaro; Yokota, Toshiaki; Oda, Toshiatsu.

1978-11-01

The collisional-radiative model is applied to a recombining hydrogen plasma in order to investigate the plasma condition in which the population inversion between the energy levels of hydrogen can be generated. The population inversion is expected in a plasma where the three body recombination has a large contribution to the recombining processes and the effective recombination rate is beyond a certain value for a given electron density and temperature. Calculated results are presented in figures and tables. (author)

Consequences of recombination on traditional phylogenetic analysis

DEFF Research Database (Denmark)

Schierup, M H; Hein, J

2000-01-01

We investigate the shape of a phylogenetic tree reconstructed from sequences evolving under the coalescent with recombination. The motivation is that evolutionary inferences are often made from phylogenetic trees reconstructed from population data even though recombination may well occur (mt......DNA or viral sequences) or does occur (nuclear sequences). We investigate the size and direction of biases when a single tree is reconstructed ignoring recombination. Standard software (PHYLIP) was used to construct the best phylogenetic tree from sequences simulated under the coalescent with recombination....... With recombination present, the length of terminal branches and the total branch length are larger, and the time to the most recent common ancestor smaller, than for a tree reconstructed from sequences evolving with no recombination. The effects are pronounced even for small levels of recombination that may...

Extrahepatic Blood Supply to Hepatocellular Carcinoma: Angiographic Demonstration and Transcatheter Arterial Chemoembolization

International Nuclear Information System (INIS)

Miyayama, Shiro; Matsui, Osamu; Taki, Keiichi; Minami, Tetsuya; Ryu, Yasuji; Ito, Chiharu; Nakamura, Koichi; Inoue, Dai; Notsumata, Kazuo; Toya, Daisyu; Tanaka, Nobuyoshi; Mitsui, Takeshi

2006-01-01

Purpose. To evaluate the incidence of each extrahepatic collateral pathway to hepatocellular carcinoma (HCC) and to assess technical success rates and complications of transcatheter arterial chemoembolization (TACE) through each collateral. Methods. We retrospective evaluated extrahepatic collateral pathways to HCC on angiography in 386 procedures on 181 consecutive patients. One hundred and seventy patients had previously undergone TACE. TACE through extrahepatic collaterals using iodized oil and gelatin sponge particles was performed when a catheter was advanced into the tumor-feeding branch to avoid nontarget embolization. Results. A single collateral was revealed in 275 TACE procedures, two were revealed in 74, and three or more were revealed in 34. Incidences of collateral source to HCC were 83% from the right inferior phrenic artery (IPA), 24% from the cystic artery, 13% from the omental artery, 12% from the right renal capsular artery (RCA) and left IPA, 8% from the right internal mammary artery (IMA) and right intercostal artery (ICA), and 7% from the right inferior adrenal artery (IAA). Technical success rates of TACE were 53% in the right ICA, 70% in the cystic artery, 74% in the omental artery, 93% in the left IPA, 96% in the right IPA, and 100% in the right RCA, right IMA, and right IAA. Complications included skin necrosis after TACE through the right IMA (n = 1), cholecystitis after TACE through the cystic artery (n = 1), and ulcer formation after TACE through the right gastric artery (n = 1), in addition to pleural effusion and basal atelectasis after TACE through the IPA and IMA. Conclusion. Our study suggests that TACE through extrahepatic collaterals is possible with high success rates, and is also relatively safe

Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus 90Y-radioembolization for hepatocellular carcinoma

International Nuclear Information System (INIS)

Ludwig, Johannes M.; Xing, Minzhi; Zhang, Di; Kim, Hyun S.

2017-01-01

To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 ( 90 Y)-radioembolization for hepatocellular carcinoma (HCC). Studies comparing conventional (c)TACE versus 90 Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus 90 Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger's and Begg's tests. Fourteen studies comparing DEB-TACE or 90 Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over 90 Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. DEB-TACE and 90 Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to 90 Y-radioembolization but direct comparison is warranted for further evaluation. (orig.)

Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus {sup 90}Y-radioembolization for hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Ludwig, Johannes M.; Xing, Minzhi [Yale School of Medicine, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Zhang, Di [University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (United States); Kim, Hyun S. [Yale School of Medicine, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Yale School of Medicine, Yale Cancer Center, New Haven, CT (United States)

2017-05-15

To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 ({sup 90}Y)-radioembolization for hepatocellular carcinoma (HCC). Studies comparing conventional (c)TACE versus {sup 90}Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus {sup 90}Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger's and Begg's tests. Fourteen studies comparing DEB-TACE or {sup 90}Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over {sup 90}Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. DEB-TACE and {sup 90}Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to {sup 90}Y-radioembolization but direct comparison is warranted for further evaluation. (orig.)

Sustained multiple organ ischaemia after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

Science.gov (United States)

Kim, Young Woon; Kwon, Jung Hyun; Nam, Soon Woo; Jang, Jeong Won; Jung, Hyun Suk; Shin, Yu Ri; Park, Eun Su; Shim, Dong Jae

2018-02-01

Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers. The pathology specimens of the duodenum contained DC beads that had passed through small vessels in the connective tissue. The patient's condition appeared to improve after 2 weeks of antibiotic treatment and supportive care, but new multifocal liver and spleen infarction subsequently developed. After 2 months, he was well enough to be discharged. His HCC partially responded to the TACE with DC beads but eventually progressed and he died after 11 months. The present case report highlights unexpected ongoing multiple organ ischaemia in a 66-year-old man treated for HCC using TACE with DC beads. The use of TACE with DC beads should be carefully considered in patients with vascular strictures or aberrant blood supply.

Cryotherapy combined with chemoembolization for the treatment of advanced hepatic carcinoma: a clinical study

International Nuclear Information System (INIS)

Zhou Yiting; Cao Jianming; Xu Jian; Hu Xiaobo; Shi Donghong; Kong Weidong; Gao Dazhi

2009-01-01

Objective: To discuss the technique, efficacy and clinical significance of cryoablation combined with transcatheter arterial chemoembolization(TACE) for the treatment of advanced hepatic carcinoma. Methods: One hundred and ninety-two patients, who accorded with the selected criterion, were divided into TACE group (n=100) and combination group (cryotherapy combined with TACE, n=92). Pre-and post-treatment AFP level, recurrence rate and life span between two groups were compared. Results: The complete necrosis rate of the tumor and the recurrence rate in TACE group were 29% and 42%, which were 88.04% and 24% in combination group, respectively. The serum AFP level was significantly decreased after treatment in both groups (P<0.05), and the reduction in AFP level was significantly greater in combination group than that in TACE group (P<0.05). During a follow-up of 30 months the survival rate at each evaluation period of combination group was higher than that of TACE group without exception. Conclusion: As an effective and safe technique, cryoablation combined with chemoembolization is far superior to simple TACE in treating advanced hepatic carcinoma. (authors)

Density dependence of dielectronic recombination in selenium

International Nuclear Information System (INIS)

Hagelstein, P.L.; Rosen, M.D.; Jacobs, V.L.

1986-01-01

Dielectronic recombination has been found to be the dominant recombination process in the determination of the ionization balance of selenium near the Ne-like sequence under conditions relevant to the exploding-foil EUV laser plasmas. The dielectronic recombination process tends to populate excited levels, and these levels in turn are more susceptible to subsequent excitation and ionization than are the ground-state ions. If one defines an effective recombination rate which includes, in addition to the primary recombination, the subsequent excitation and ionization of the additional excited-state population due to the primary recombination, then this effective recombination rate can be density-sensitive at relatively low electron density. We present results for this effective dielectronic recombination rate at an electron density of 3 x 10/sup 20/ electrons/cm 3 for recombination from Ne-like to Na-like selenium and from F-like to Ne-like selenium. In the former case, the effective recombination rate coefficient is found to be 1.8 x 10/sup -11/ cm 3 /sec at 1.0 keV, which is to be compared with the zero-density value of 2.8 x 10/sup -11/ cm 3 /sec. In the latter case (F-like to Ne-like), the effective recombination rate coefficient is found to be 1.3 x 10/sup -11/ cm 3 /sec, which is substantially reduced from the zero-density result of 3.3 x 10/sup -11/ cm 3 /sec. We have examined the effects of dielectronic recombination on the laser gain of the dominant Ne-like 3p-3s transitions and have compared our results with those presented by Whitten et al. [Phys. Rev. A 33, 2171 (1986)

SequenceLDhot: detecting recombination hotspots.

Science.gov (United States)

Fearnhead, Paul

2006-12-15

There is much local variation in recombination rates across the human genome--with the majority of recombination occurring in recombination hotspots--short regions of around approximately 2 kb in length that have much higher recombination rates than neighbouring regions. Knowledge of this local variation is important, e.g. in the design and analysis of association studies for disease genes. Population genetic data, such as that generated by the HapMap project, can be used to infer the location of these hotspots. We present a new, efficient and powerful method for detecting recombination hotspots from population data. We compare our method with four current methods for detecting hotspots. It is orders of magnitude quicker, and has greater power, than two related approaches. It appears to be more powerful than HotspotFisher, though less accurate at inferring the precise positions of the hotspot. It was also more powerful than LDhot in some situations: particularly for weaker hotspots (10-40 times the background rate) when SNP density is lower (maths.lancs.ac.uk/~fearnhea/Hotspot.

Experimental evolution across different thermal regimes yields genetic divergence in recombination fraction but no divergence in temperature associated plastic recombination.

Science.gov (United States)

Kohl, Kathryn P; Singh, Nadia D

2018-04-01

Phenotypic plasticity is pervasive in nature. One mechanism underlying the evolution and maintenance of such plasticity is environmental heterogeneity. Indeed, theory indicates that both spatial and temporal variation in the environment should favor the evolution of phenotypic plasticity under a variety of conditions. Cyclical environmental conditions have also been shown to yield evolved increases in recombination frequency. Here, we use a panel of replicated experimental evolution populations of D. melanogaster to test whether variable environments favor enhanced plasticity in recombination rate and/or increased recombination rate in response to temperature. In contrast to expectation, we find no evidence for either enhanced plasticity in recombination or increased rates of recombination in the variable environment lines. Our data confirm a role of temperature in mediating recombination fraction in D. melanogaster, and indicate that recombination is genetically and plastically depressed under lower temperatures. Our data further suggest that the genetic architectures underlying plastic recombination and population-level variation in recombination rate are likely to be distinct. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

The extent and importance of intragenic recombination

Directory of Open Access Journals (Sweden)

de Silva Eric

2004-11-01

Full Text Available Abstract We have studied the recombination rate behaviour of a set of 140 genes which were investigated for their potential importance in inflammatory disease. Each gene was extensively sequenced in 24 individuals of African descent and 23 individuals of European descent, and the recombination process was studied separately in the two population samples. The results obtained from the two populations were highly correlated, suggesting that demographic bias does not affect our population genetic estimation procedure. We found evidence that levels of recombination correlate with levels of nucleotide diversity. High marker density allowed us to study recombination rate variation on a very fine spatial scale. We found that about 40 per cent of genes showed evidence of uniform recombination, while approximately 12 per cent of genes carried distinct signatures of recombination hotspots. On studying the locations of these hotspots, we found that they are not always confined to introns but can also stretch across exons. An investigation of the protein products of these genes suggested that recombination hotspots can sometimes separate exons belonging to different protein domains; however, this occurs much less frequently than might be expected based on evolutionary studies into the origins of recombination. This suggests that evolutionary analysis of the recombination process is greatly aided by considering nucleotide sequences and protein products jointly.

Involvement of TNF-α converting enzyme in the development of psoriasis-like lesions in a mouse model.

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Kenji Sato

Full Text Available TNF-α plays a crucial role in psoriasis; therefore, TNF inhibition has become a gold standard for the treatment of psoriasis. TNF-α is processed from a membrane-bound form by TNF-α converting enzyme (TACE to soluble form, which exerts a number of biological activities. EGF receptor (EGFR ligands, including heparin-binding EGF-like growth factor (HB-EGF, amphiregulin and transforming growth factor (TGF-α are also TACE substrates and are psoriasis-associated growth factors. Vascular endothelial growth factor (VEGF, one of the downstream molecules of EGFR and TNF signaling, plays a key role in angiogenesis for developing psoriasis. In the present study, to assess the possible role of TACE in the pathogenesis of psoriasis, we investigated the involvement of TACE in TPA-induced psoriasis-like lesions in K5.Stat3C mice, which represent a mouse model of psoriasis. In this mouse model, TNF-α, amphiregulin, HB-EGF and TGF-α were significantly up-regulated in the skin lesions, similar to human psoriasis. Treatment of K5.Stat3C mice with TNF-α or EGFR inhibitors attenuated the skin lesions, suggesting the roles of TACE substrates in psoriasis. Furthermore, the skin lesions of K5.Stat3C mice showed down-regulation of tissue inhibitor of metalloproteinase-3, an endogenous inhibitor of TACE, and an increase in soluble TNF-α. A TACE inhibitor abrogated EGFR ligand-dependent keratinocyte proliferation and VEGF production in vitro, suggesting that TACE was involved in both epidermal hyperplasia and angiogenesis during psoriasis development. These results strongly suggest that TACE contributes to the development of psoriatic lesions through releasing two kinds of psoriasis mediators, TNF-α and EGFR ligands. Therefore, TACE could be a potential therapeutic target for the treatment of psoriasis.

Recombination epoch revisited

International Nuclear Information System (INIS)

Krolik, J.H.

1989-01-01

Previous studies of cosmological recombination have shown that this process produces as a by-product a highly superthermal population of Ly-alpha photons which retard completion of recombination. Cosmological redshifting was thought to determine the frequency distribution of the photons, while two-photon decay of hydrogen's 2s state was thought to control their numbers. It is shown here that frequency diffusion due to photon scattering dominate the cosmological redshift in the frequency range near line center which fixes the ratio of ground state to excited state population, while incoherent scattering into the far-red damping wing effectively destroys Ly-alpha photons as a rate which is competitive with two-photon decay. The former effect tends to hold back recombination, while the latter tends to accelerate it; the net results depends on cosmological parameters, particularly the combination Omega(b) h/sq rt (2q0), where Omega(b) is the fraction of the critical density provided by baryons. 18 references

Recombination of Globally Circulating Varicella-Zoster Virus

Science.gov (United States)

Depledge, Daniel P.; Kundu, Samit; Atkinson, Claire; Brown, Julianne; Haque, Tanzina; Hussaini, Yusuf; MacMahon, Eithne; Molyneaux, Pamela; Papaevangelou, Vassiliki; Sengupta, Nitu; Koay, Evelyn S. C.; Tang, Julian W.; Underhill, Gillian S.; Grahn, Anna; Studahl, Marie; Breuer, Judith; Bergström, Tomas

2015-01-01

ABSTRACT Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the

Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

Energy Technology Data Exchange (ETDEWEB)

Joskin, Julien, E-mail: j.joskin@gmail.com; Baere, Thierry de, E-mail: Thierry.DEBAERE@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France); Auperin, Anne, E-mail: Anne.AUPERIN@igr.fr [Institut Gustave Roussy, Department of Epidemiology (France); Tselikas, Lambros, E-mail: lambros.tselikas@gmail.com; Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Farouil, Geoffroy, E-mail: g.farouil@gmail.com [Institut Gustave Roussy, Department of Interventional Radiology (France); Boige, Valérie, E-mail: boige@igr.fr; Malka, David, E-mail: david.malka@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Leboulleux, Sophie, E-mail: sophie.leboulleux@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Ducreux, Michel, E-mail: ducreux@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Baudin, Eric, E-mail: baudin@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Deschamps, Frédéric, E-mail: frederic.deschamps@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France)

2015-04-15

PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.

Reduction in non-protein respiratory quotient is related to overall survival after hepatocellular carcinoma treatment.

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Masaya Saito

Full Text Available BACKGROUND: Transcatheter arterial chemoembolization (TACE is an effective treatment for hepatocellular carcinoma (HCC that can occasionally lead to the shortening of life expectancy. We aimed to make a new and more accurate prognostic model taking into account the course of disease after TACE. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. Time-dependent and time-fixed factors associated with 1-year mortality after TACE were assessed by multivariate analyses. A predictive model of 1-year mortality was established by the combination of odds ratios of these factors. Multivariate analyses showed that the ratio of non-protein respiratory quotient (npRQ (7 days after/before TACE and Cancer of Liver Italian Program (CLIP score were independent factors of 1-year mortality after TACE (p = 0.014 and 0.013, respectively. Patient-specific 1-year mortality risk scores can be calculated by summarizing the individual risk scores and looking up the patient-specific risk on the graph. CONCLUSIONS: The short-term reduction of npRQ was a time-dependent prognostic factor associated with overall survival in HCC patients undergoing TACE. CLIP score was a time-fixed prognostic factor associated with overall survival. Using the prediction model, which consists of the combination of time-dependent (npRQ ratio and time-fixed (CLIP score prognostic factors, 1-year mortality risk after TACE would be better estimated by taking into account changes during the course of disease.

Transcatheter arterial chemoembolization of colorectal liver metastases using degradable starch microspheres (Spherex registered). Own investigations and review to the literature

International Nuclear Information System (INIS)

Wasser, K.; Landwehr, P.

2005-01-01

Since two decades transarterial chemoembolization (TACE) of liver metastases has been investigated in numerous studies. However, no standardized therapeutic procedure exists so far. The present study retrospectively investigated survival, response and side effects after TACE of liver metastases in 21 patients with colorectal cancer and results are compared with previous literature. A total of 68 TACE procedures were performed. A suspension of degradable starch microspheres (DSM, Spherex registered ) and Mitomycin C was applied selectively into hepatic arteries via a transfemoral approach. DSM effect a temporary arterial occlusion. Follow-up studies were performed by contrast enhanced spiral computed tomography (CT). The median survival was 13.8 months. Therapeutic response (according to WHO) was observed only in three patients. The progression free interval was 5.8 months. Patients developed a postembolization-syndrome (abdominal pain, fever, nausea) and increased transaminases in 27-43% of all interventions. A gastric ulcer occurred after four, cholecystitis after two TACE. As already shown in most previous studies, regardless of the used agents, also this investigation underlines the moderate therapeutic effect of TACE on colorectal liver metastases. So far, no significant survival benefit has been shown in the literature and the response rates are rather limited. In general, complications of TACE seem to be rare, but should not to be underestimated. Compared to TACE with long or permanent arterial occlusion, postembolization syndrome seems to be less pronounced using DSM. As TACE is rather a palliative therapeutic approach, DSM therefore might be more suited. Further studies on TACE of liver metastases should focus on to the patients' quality of life. (orig.) [de

BIOTECHNOLOGY OF RECOMBINANT HORMONES IN DOPING

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Biljana Vitošević

2011-09-01

Full Text Available Recombinant DNA technology has allowed rapid progress in creating biosynthetic gene products for the treatment of many diseases. In this way it can produce large amounts of hormone, which is intended for the treatment of many pathological conditions. Recombinant hormones that are commonly used are insulin, growth hormone and erythropoietin. Precisely because of the availability of these recombinant hormones, it started their abuse by athletes. Experiments in animal models confirmed the potential effects of some of these hormones in increasing physical abilities, which attracted the attention of athletes who push the limits of their competitive capability by such manipulation. The risks of the use of recombinant hormones in doping include serious consequences for the health of athletes. Methods of detection of endogenous hormones from recombined based on the use of a monoclonal antibodies, capillary zone electrophoresis and protein biomarkers

Delayed recombination and cosmic parameters

International Nuclear Information System (INIS)

Galli, Silvia; Melchiorri, Alessandro; Bean, Rachel; Silk, Joseph

2008-01-01

Current cosmological constraints from cosmic microwave background anisotropies are typically derived assuming a standard recombination scheme, however additional resonance and ionizing radiation sources can delay recombination, altering the cosmic ionization history and the cosmological inferences drawn from the cosmic microwave background data. We show that for recent observations of the cosmic microwave background anisotropy, from the Wilkinson microwave anisotropy probe satellite mission (WMAP) 5-year survey and from the arcminute cosmology bolometer array receiver experiment, additional resonance radiation is nearly degenerate with variations in the spectral index, n s , and has a marked effect on uncertainties in constraints on the Hubble constant, age of the universe, curvature and the upper bound on the neutrino mass. When a modified recombination scheme is considered, the redshift of recombination is constrained to z * =1078±11, with uncertainties in the measurement weaker by 1 order of magnitude than those obtained under the assumption of standard recombination while constraints on the shift parameter are shifted by 1σ to R=1.734±0.028. From the WMAP5 data we obtain the following constraints on the resonance and ionization sources parameters: ε α i <0.058 at 95% c.l.. Although delayed recombination limits the precision of parameter estimation from the WMAP satellite, we demonstrate that this should not be the case for future, smaller angular scales measurements, such as those by the Planck satellite mission.

Meiotic recombination in human oocytes.

Directory of Open Access Journals (Sweden)

Edith Y Cheng

2009-09-01

Full Text Available Studies of human trisomies indicate a remarkable relationship between abnormal meiotic recombination and subsequent nondisjunction at maternal meiosis I or II. Specifically, failure to recombine or recombination events located either too near to or too far from the centromere have been linked to the origin of human trisomies. It should be possible to identify these abnormal crossover configurations by using immunofluorescence methodology to directly examine the meiotic recombination process in the human female. Accordingly, we initiated studies of crossover-associated proteins (e.g., MLH1 in human fetal oocytes to analyze their number and distribution on nondisjunction-prone human chromosomes and, more generally, to characterize genome-wide levels of recombination in the human female. Our analyses indicate that the number of MLH1 foci is lower than predicted from genetic linkage analysis, but its localization pattern conforms to that expected for a crossover-associated protein. In studies of individual chromosomes, our observations provide evidence for the presence of "vulnerable" crossover configurations in the fetal oocyte, consistent with the idea that these are subsequently translated into nondisjunctional events in the adult oocyte.

Electron - ion recombination processes - an overview

International Nuclear Information System (INIS)

Hahn, Yukap

1997-01-01

Extensive theoretical and experimental studies have been carried out for the past 20 years on electron - ion recombination processes, as they are applied to the analysis of astrophysical and laboratory plasmas. We review the basic understanding gained through these efforts, with emphasis on some of the more recent progress made in recombination theory as the recombining system is affected by time-dependent electric fields and plasma particles at low temperature. Together with collisional ionization and excitation processes, recombination is important in determining ionization balance and excited-state population in non-equilibrium plasmas. The radiation emitted by plasmas is usually the principal medium with which to study the plasma condition, as it is produced mainly during the recombination and decay of excited states of ions inside the plasma. This is especially true when the plasma under study is not readily accessible by direct probes, as in astrophysical plasmas. Moreover, external probes may sometimes cause undesirable disturbances of the plasma. Electron-ion recombination proceeds in several different modes. The direct modes include three-body recombination (TBR) and one-step radiative recombination (RR), all to the ground- and singly-excited states of the target ions. By contrast, the indirect resonant mode is a two-step dielectronic recombination (DR), which proceeds first with the formation of doubly-excited states by radiationless excitation/capture. The resonant states thus formed may relax by autoionization and/or radiative cascades. For more exotic modes of recombination, we consider off-shell dielectronic recombination (radiative DR = RDR), in which an electron capture is accompanied by simultaneous radiative emission and excitation of the target ion. Some discussion on attachment of electrons to neutral atoms, resulting in the formation of negative ions, is also given. When resonance states involve one or more electrons in high Rydberg states

Controlled Release from Recombinant Polymers

Science.gov (United States)

Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

2014-01-01

Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

Live recombinant BHV/BRSV vaccine

NARCIS (Netherlands)

Keil, G.M.; Rijsewijk, F.A.M.

1998-01-01

The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the

First-principles study of Frenkel pair recombination in tungsten

International Nuclear Information System (INIS)

Qin, Shi-Yao; Jin, Shuo; Li, Yu-Hao; Zhou, Hong-Bo; Zhang, Ying; Lu, Guang-Hong

2017-01-01

The recombination of one Frenkel pair in tungsten has been investigated through first-principles simulation. Two different recombination types have been identified: instantaneous and thermally activated. The small recombination barriers for thermally activated recombination cases indicate that recombination can occur easily with a slightly increased temperature. For both of the two recombination types, recombination occurs through the self-interstitial atom moving towards the vacancy. The recombination process can be direct or through replacement sequences, depending on the vertical distance between the vacancy and the 〈1 1 1〉 line of self-interstitial atom pair.

Containment air circulation for optimal hydrogen recombination

International Nuclear Information System (INIS)

Spinks, N.; Krause, M.

1997-01-01

An accepted first-line defense for hydrogen mitigation is to design for the hydrogen to be rapidly mixed with the containment atmosphere and diluted to below flammability concentrations. Then, as hydrogen continues to be produced in the longer term, recombiners can be used to remove hydrogen: recombiners can be located in forced-air ducts or passive recombiners can be distributed within containment and the heat of recombination used to promote local air circulation. However, this principle does not eliminate the possibility of high hydrogen concentrations at locations removed from the recombiners. An improvement on this strategy is to arrange for a specific, buoyancy-driven, overall circulation of the containment atmosphere such that the recombiners can be located within the recirculation flow, immediately downstream of the hydrogen source. This would make the mixing process more predictable and solve the mass-transfer problem associated with distributed recombiners. Ideally, the recombiners would be located just above the hydrogen source so that the heat of recombination would assist the overall circulation. In this way, the hydrogen would be removed as close as possible to the source, thereby minimizing the amount of hydrogen immediately downstream of the source and reducing the hydrogen concentration to acceptable levels at other locations. Such a strategy requires the containment volume to be divided into an upflow path, past the hydrogen source and the recombiner, and a downflow path to complete the circuit. The flow could be generated actively using fans or passively using buoyancy forces arising from the difference in density of gases in the upfiow and downflow paths; the gases in the downflow path being cooled at an elevated heat sink. (author)

Recombination properties of dislocations in GaN

Science.gov (United States)

Yakimov, Eugene B.; Polyakov, Alexander Y.; Lee, In-Hwan; Pearton, Stephen J.

2018-04-01

The recombination activity of threading dislocations in n-GaN with different dislocation densities and different doping levels was studied using electron beam induced current (EBIC). The recombination velocity on a dislocation, also known as the dislocation recombination strength, was calculated. The results suggest that dislocations in n-GaN giving contrast in EBIC are charged and surrounded by a space charge region, as evidenced by the observed dependence of dislocation recombination strength on dopant concentration. For moderate (below ˜108 cm-2) dislocation densities, these defects do not primarily determine the average diffusion length of nonequilibrium charge carriers, although locally, dislocations are efficient recombination sites. In general, it is observed that the effect of the growth method [standard metalorganic chemical vapor deposition (MOCVD), epitaxial lateral overgrowth versions of MOCVD, and hydride vapor phase epitaxy] on the recombination activity of dislocations is not very pronounced, although the average diffusion lengths can widely differ for various samples. The glide of basal plane dislocations at room temperature promoted by low energy electron irradiation does not significantly change the recombination properties of dislocations.

Oligonucleotide recombination enabled site-specific mutagenesis in bacteria

Science.gov (United States)

Recombineering refers to a strategy for engineering DNA sequences using a specialized mode of homologous recombination. This technology can be used for rapidly constructing precise changes in bacterial genome sequences in vivo. Oligo recombination is one type of recombineering that uses ssDNA olig...

Recombination: the good, the bad and the variable.

Science.gov (United States)

Stapley, Jessica; Feulner, Philine G D; Johnston, Susan E; Santure, Anna W; Smadja, Carole M

2017-12-19

Recombination, the process by which DNA strands are broken and repaired, producing new combinations of alleles, occurs in nearly all multicellular organisms and has important implications for many evolutionary processes. The effects of recombination can be good , as it can facilitate adaptation, but also bad when it breaks apart beneficial combinations of alleles, and recombination is highly variable between taxa, species, individuals and across the genome. Understanding how and why recombination rate varies is a major challenge in biology. Most theoretical and empirical work has been devoted to understanding the role of recombination in the evolution of sex-comparing between sexual and asexual species or populations. How recombination rate evolves and what impact this has on evolutionary processes within sexually reproducing organisms has received much less attention. This Theme Issue focusses on how and why recombination rate varies in sexual species, and aims to coalesce knowledge of the molecular mechanisms governing recombination with our understanding of the evolutionary processes driving variation in recombination within and between species. By integrating these fields, we can identify important knowledge gaps and areas for future research, and pave the way for a more comprehensive understanding of how and why recombination rate varies. © 2017 The Authors.

Evaluation of the therapeutic effect of hepatic arterial chemoembolization combined with portal chemoembolization for advanced hepatic carcinomas

International Nuclear Information System (INIS)

He Hongde; He Jing; Luo Zhonghua; Xu Jian; Sun Lijun; Li Jingbang; Zhang Xuexin

2010-01-01

Objective: To evaluate the effect of transcatheter arterial chemoembolization (TACE) together with portal vein chemoembolization (PVCE) for the treatment of advanced liver carcinomas. Methods: Forty-eight patients with liver carcinoma were randomly divided into two groups. Patients in study group (n = 22) were treated with TACE together with PVCE, and patients in control group (n = 26) were treated with TACE alone. Results: Based on the postoperative CT findings and AFP levels, the effective rate of the study group was markedly higher than that of control group and the difference between two groups was statistically significant (P < 0.05). The volume of un-embolized liver tissue in the patients of study group was obviously increased after treatment. Conclusion: TACE together with PVCE is superior to TACE alone in treating advanced hepatic carcinomas. The combination of TACE and PVCE can effectively increase the successful rate of surgical resection for the advanced hepatic carcinomas. (authors)

Genetic recombination of the hepatitis C virus: clinical implications.

Science.gov (United States)

Morel, V; Fournier, C; François, C; Brochot, E; Helle, F; Duverlie, G; Castelain, S

2011-02-01

Genetic recombination is a well-known feature of RNA viruses that plays a significant role in their evolution. Although recombination is well documented for Flaviviridae family viruses, the first natural recombinant strain of hepatitis C virus (HCV) was identified as recently as 2002. Since then, a few other natural inter-genotypic, intra-genotypic and intra-subtype recombinant HCV strains have been described. However, the frequency of recombination may have been underestimated because not all known HCV recombinants are screened for in routine practice. Furthermore, the choice of treatment regimen and its predictive outcome remain problematic as the therapeutic strategy for HCV infection is genotype dependent. HCV recombination also raises many questions concerning its mechanisms and effects on the epidemiological and physiopathological features of the virus. This review provides an update on recombinant HCV strains, the process that gives rise to recombinants and clinical implications of recombination. © 2010 Blackwell Publishing Ltd.

Cell biology of mitotic recombination

DEFF Research Database (Denmark)

Lisby, Michael; Rothstein, Rodney

2015-01-01

Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as w...

Test tube systems with cutting/recombination operations

Energy Technology Data Exchange (ETDEWEB)

Freund, R. [Technische Universitaet Wien (Austria); Csuhaj-Varju, E. [Computer and Automation Institute, Budapest (Hungary); Wachtler, F. [Universitaet Wien (Austria)

1996-12-31

We introduce test tube systems based on operations that are closely related to the splicing operations, i.e. we consider the operations of cutting a string at a specific site into two pieces with marking them at the cut ends and of recombining two strings with specifically marked endings. Whereas in the splicing of two strings these strings are cut at specific sites and the cut pieces are recombined immediately in a crosswise way, in CR(cutting/recombination)-schemes cutting can happen independently from recombining the cut pieces. Test tube systems based on these operations of cutting and recombination turn out to have maximal generative power even if only very restricted types of input filters for the test tubes are used for the redistribution of the contents of the test tubes after a period of cuttings and recombinations in the test tubes. 10 refs.

Atomic excitation and recombination in external fields

International Nuclear Information System (INIS)

Nayfeh, M.H.; Clark, C.W.

1985-01-01

This volume offers a timely look at Rydberg states of atoms in external fields and dielectronic recombination. Each topic provides authoritative coverage, presents a fresh account of a flourishing field of current atomic physics and introduces new opportunities for discovery and development. Topics considered include electron-atom scattering in external fields; observations of regular and irregular motion as exemplified by the quadratic zeeman effect and other systems; Rydberg atoms in external fields and the Coulomb geometry; crossed-field effects in the absorption spectrum of lithium in a magnetic field; precise studies of static electric field ionization; widths and shapes of stark resonances in sodium above the saddle point; studies of electric field effects and barium autoionizing resonances; autoionization and dielectronic recombination in plasma electric microfields; dielectronic recombination measurements on multicharged ions; merged beam studies of dielectronic recombination; Rydberg atoms and dielectronic recombination in astrophysics; and observations on dielectronic recombination

Genetic evidence for inducibility of recombination competence in yeast

International Nuclear Information System (INIS)

Fabre, F.; Roman, H.

1977-01-01

Recombination between unirradiated chromosomes was induced by UV or x-ray irradiation of haploids followed by a mating with heteroallelic diploids of Saccharomyces cerevisiae. The selected event of intragenic recombination did not involve the participation of the irradiated chromosome and apparently was not caused by lesions introduced into the unirradiated chromosomes by some indirect process. The results favor the idea that recombination is repressed in the majority of vegetative cells and that one effect of radiation is the release of some factor(s) necessary for recombination. Consequently, the proportion of competent cells (i.e., cells able to recombine) in the population increases. This competent state seems necessary not only for the recombinational repair of radiation-induced lesions but also, since recombinants are produced in the absence of such lesions, for spontaneous recombination. Photoreactivation of the UV-irradiated haploids led to a decrease in the production of recombinants. Hence, lesions in the DNA appear to be responsible for the induction of the recombinational ability

Three-body recombination of cold fermionic atoms

International Nuclear Information System (INIS)

Suno, H; Esry, B D; Greene, Chris H

2003-01-01

Recombination of identical, spin-polarized fermions in cold three-body collisions is investigated. We parametrize the mechanisms for recombination in terms of the 'scattering volume' V p and another length scale r 0 . Model two-body interactions were used within the framework of the adiabatic hyperspherical representation. We examine the recombination rate K 3 as a function of the collision energy E for various values of V p . Not only do we consider the dominant J Π = 1 + case, but also the next-leading order contributions from J Π = 1 - and 3 - . We discuss the behaviour near a two-body resonance and the expected universality of fermionic recombination. Comparisons with boson recombination are considered in detail

Recombination Modulates How Selection Affects Linked Sites in Drosophila

Science.gov (United States)

McGaugh, Suzanne E.; Heil, Caiti S. S.; Manzano-Winkler, Brenda; Loewe, Laurence; Goldstein, Steve; Himmel, Tiffany L.; Noor, Mohamed A. F.

2012-01-01

One of the most influential observations in molecular evolution has been a strong association between local recombination rate and nucleotide polymorphisms across the genome. This is interpreted as evidence for ubiquitous natural selection. The alternative explanation, that recombination is mutagenic, has been rejected by the absence of a similar association between local recombination rate and nucleotide divergence between species. However, many recent studies show that recombination rates are often very different even in closely related species, questioning whether an association between recombination rate and divergence between species has been tested satisfactorily. To circumvent this problem, we directly surveyed recombination across approximately 43% of the D. pseudoobscura physical genome in two separate recombination maps and 31% of the D. miranda physical genome, and we identified both global and local differences in recombination rate between these two closely related species. Using only regions with conserved recombination rates between and within species and accounting for multiple covariates, our data support the conclusion that recombination is positively related to diversity because recombination modulates Hill–Robertson effects in the genome and not because recombination is predominately mutagenic. Finally, we find evidence for dips in diversity around nonsynonymous substitutions. We infer that at least some of this reduction in diversity resulted from selective sweeps and examine these dips in the context of recombination rate. PMID:23152720

Recombinational repair: workshop summary

International Nuclear Information System (INIS)

Howard-Flanders, P.

1983-01-01

Recombinational repair may or may not be synonymous with postreplication repair. Considerable progress has been made in the study of the relevant enzymes, particularly those from bacteria. In this workshop we focus on the recombination enzyme RecA protein. What structural changes take place in the protein and in DNA during repair. How does homologous pairing take place. How is ATP hydrolysis coupled to the stand exchange reaction and the formation of heteroduplx DNA. Turning to another enzyme needed for certain kinds of bacterial recombination, we will ask whether the purified recB protein and recC protein complement each other and are sufficient for exonuclease V activity. In higher cells, we would like to know whether sister exchanges, which occur in bacteria after uv irradiation, are also seen in animal cells

Comparison of post-embolization syndrome in the treatment of patients with unresectable hepatocellular carcinoma: Trans-catheter arterial chemo-embolization versus Yttrium-90 glass microspheres

International Nuclear Information System (INIS)

Goin, J.E.; Roberts, C.A.; Dancey, J.E.; Sickles, C.J.; Leung, D.A.; Soulen, M.C.

2004-01-01

Post-embolization syndrome (PES) occurs in most patients who undergo trans-catheter arterial chemoembolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). Intra-hepatic arterial administration of TheraSphere, yttrium-90 glass microspheres, is an alternative treatment for unresectable HCC that does not require embolization of major vessels and may have a more favorable toxicity profile than TACE. This paper compares the incidence of PES after TACE vs. TheraSphere treatment in unresectable HCC patients. Data for 29 TACE-treated and 34 TheraSphere-treated patients were evaluated for PES. PES toxicities (i.e., nausea, vomiting, fever in the absence of infection, and abdominal pain) were scored according to Southwest Oncology Group (SWOG) toxicity criteria. PES was defined as a total score for the four toxicities of 2 or greater. Survival was defined from the date of treatment to the date of death. TACE patients underwent one to seven treatment procedures; TheraSphere patients underwent one to two treatment procedures. The incidence of PES was 3.8-times (95% confidence interval 1.6-16.3) higher after TACE [20/29(69%)] than after TheraSphere [6/34 (18%)] treatment; this difference was statistically significant (p=.003). Median survival was similar for TheraSphere (N=20; 378 days, CI 209-719) and TACE (N=29; 343 days, CI 217-511) patients. It was concluded that treatment of unresectable HCC with TheraSphere results in a much lower incidence of PES compared to TACE. Since TheraSphere is a pure beta emitter; it can potentially be administered safely on an outpatient basis, and appears to be at least as efficacious as TACE on survival with fewer treatments per patient. (author)

Transarterial ablation of hepatocellular carcinoma. Status and developments

International Nuclear Information System (INIS)

Radeleff, B.A.; Stampfl, U.; Sommer, C.M.; Bellemann, N.; Kauczor, H.U.; Hoffmann, K.; Ganten, T.; Ehehalt, R.

2012-01-01

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and represents the main cause of death among European patients with liver cirrhosis. Only 30-40% of patients diagnosed with HCC are candidates for curative treatment options (e.g. surgical resection, liver transplantation or ablation). The remaining majority of patients must undergo local regional and palliative therapies. Transvascular ablation of HCC takes advantage of the fact that the hypervascularized HCC receives most of its blood supply from the hepatic artery. In this context transvascular ablation describes different therapy regimens which can be assigned to four groups: cTACE (conventional transarterial chemoembolization), bland embolization (transarterial embolization TAE), DEB-TACE (TACE with drug-eluting beads, DEB) and SIRT (selective internal radiation therapy, radioembolization). Conventional TACE is the most common type of transvascular ablation and represents a combination of intra-arterial chemotherapy and embolization with occlusion of the arterial blood supply. However, there is no standardized regimen with respect to the chemotherapeutic drug, the embolic agent, the usage of lipiodol and the interval between the TACE procedures. Even the exact course of a cTACE procedure (order of chemotherapy or embolization) is not standardized. It remains unclear whether or not intra-arterial chemotherapy is definitely required as bland embolization using very small, tightly calibrated spherical particles (without intra-arterial administration of a chemotherapeutic drug) shows tumor necrosis comparable to cTACE. For DEB-TACE microparticles loaded with a chemotherapeutic drug combine the advantages of cTACE and bland embolization. Thereby, a continuing chemotherapeutic effect within the tumor might cause a further increase in intratumoral cytotoxicity and at the same time a decrease in systemic toxicity. (orig.) [de

Recombinant vaccines: experimental and applied aspects

DEFF Research Database (Denmark)

Lorenzen, Niels

1999-01-01

Development of vaccines for aquaculture fish represent an important applied functional aspect of fish immunology research. Particularly in the case of recombinant vaccines, where a single antigen is usually expected to induce immunity to a specific pathogen, knowledge of mechanisms involved...... in induction of a protective immune response may become vital. The few recombinant vaccines licensd so far, despite much research during the last decade, illustrate that this is not a straightforward matter. However, as vaccine technology as well as our knowledge of the fish immune system is steadily improved......, these fields will open up a number of interesting research objectives of mutual benefit. Recent aspects of recombinant protein vaccines, live recombinant vaccines and DNA vaccines are discussed....

Mitigating Mitochondrial Genome Erosion Without Recombination.

Science.gov (United States)

Radzvilavicius, Arunas L; Kokko, Hanna; Christie, Joshua R

2017-11-01

Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller's ratchet. How mitochondria escape this irreversible defect accumulation is a fundamental unsolved question. Occasional paternal leakage could in principle promote recombination, but it would also compromise the purifying selection benefits of uniparental inheritance. We assess this tradeoff using a stochastic population-genetic model. In the absence of recombination, uniparental inheritance of freely-segregating genomes mitigates mutational erosion, while paternal leakage exacerbates the ratchet effect. Mitochondrial fusion-fission cycles ensure independent genome segregation, improving purifying selection. Paternal leakage provides opportunity for recombination to slow down the mutation accumulation, but always at a cost of increased steady-state mutation load. Our findings indicate that random segregation of mitochondrial genomes under uniparental inheritance can effectively combat the mutational meltdown, and that homologous recombination under paternal leakage might not be needed. Copyright © 2017 by the Genetics Society of America.

Transarterial chemoembolization using gelatin sponges or microspheres plus lipiodol-doxorubicin versus doxorubicin-loaded beads for the treatment of hepatocellular carcinoma

International Nuclear Information System (INIS)

Liu, Yi Sheng; Ou, Ming Ching; Tsai, Yi Shan; Lin, Xi Zhang; Wang, Chien Kuo; Tsai, Hong Ming; Chuang, Ming Tsung

2015-01-01

To retrospectively compare treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) using gelatin sponges or microspheres plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB). A total of 158 patients with HCC received TACE from November 2010 to November 2011 were enrolled in this study, including 64 (40.5%) received TACE with lipiodol-doxorubicin and gelatin sponges (group A), 41 (25.9%) received TACE with lipiodol-doxorubicin and microspheres (group B), and 53 (33.5%) received TACE with doxorubicin-loaded DEB (group C). Tumor response and adverse events (AEs) were evaluated. No significant difference was found at baseline among the three groups. The doxorubicin dosage in group C was significantly (p < 0.001) higher compared to the dose used in groups A or B (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in group C achieved complete response compared to those in groups A or B (32.1% vs. 6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs were more common in groups A and B compared to group C, with rates of 54.7%, 34.1%, and 5.7%, respectively. In patients with HCC, TACE with DEB offers better safety and efficacy profiles compared to either TACE with gelatin sponges or TACE with microspheres.

A comparison of chemoembolization endpoints using angiographic versus transcatheter intraarterial perfusion/MR imaging monitoring.

Science.gov (United States)

Lewandowski, Robert J; Wang, Dingxin; Gehl, James; Atassi, Bassel; Ryu, Robert K; Sato, Kent; Nemcek, Albert A; Miller, Frank H; Mulcahy, Mary F; Kulik, Laura; Larson, Andrew C; Salem, Riad; Omary, Reed A

2007-10-01

Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable liver cancer. This study was conducted to test the hypothesis that angiographic endpoints during TACE are measurable and reproducible by comparing subjective angiographic versus objective magnetic resonance (MR) endpoints of TACE. The study included 12 consecutive patients who presented for TACE for surgically unresectable HCC or progressive hepatic metastases despite chemotherapy. All procedures were performed with a dedicated imaging system. Angiographic series before and after TACE were reviewed independently by three board-certified interventional radiologists. A subjective angiographic chemoembolization endpoint (SACE) classification scheme, modified from an established angiographic grading system in the cardiology literature, was designed to assist in reproducibly classifying angiographic endpoints. Reproducibility in SACE classification level was compared among operators, and MR imaging perfusion reduction was compared with SACE levels for each observer. Twelve patients successfully underwent 15 separate TACE sessions. SACE levels ranged from I through IV. There was moderate agreement in SACE classification (kappa = 0.46 +/- 0.12). There was no correlation between SACE level and MR perfusion reduction (r = 0.16 for one operator and 0.02 for the other two). Angiographic endpoints during TACE vary widely, have moderate reproducibility among operators, and do not correlate with functional MR imaging perfusion endpoints. Future research should aim to determine ideal angiographic and functional MR imaging endpoints for TACE according to outcome measures such as imaging response, pathologic response, and survival.

The effect of a single recombination event

DEFF Research Database (Denmark)

Schierup, Mikkel Heide; Jensen, Thomas Mailund; Wiuf, Carsten

We investigate the variance in how visible a single recombination event is in a SNP data set as a function of the type of recombination event and its age. Data is simulated under the coalescent with recombination and inference is by the popular composite likelihood methods. The major determinant...

Preoperative Chemoembolization in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation: Influence of Emergent Versus Elective Procedures on Patient Survival and Tumor Recurrence Rate

International Nuclear Information System (INIS)

Stockland, A. H.; Walser, E. M.; Paz-Fumagalli, R.; McKinney, J. M.; May, G. R.

2007-01-01

Our purpose was to compare the recurrence rate and survival in patients with hepatocellular carcinoma (HCC) who had elective transarterial chemoembolization (TACE), immediate preoperative TACE, or no treatment prior to orthotopic liver transplantation (OLT). A total of 132 patients with HCC had TACE prior to OLT. Eighteen patients had no TACE before OLT and functioned as a control group. The urgent group included 35 patients embolized less than 24 h before OLT and the elective group included 97 patients embolized greater than 1 day before transplantation. These groups were compared with regard to tumor staging, hepatic synthetic function, and post-TACE tumor necrosis and survival and recurrence rates.Patients were followed for a mean of 780 days post OLT (1-2912 days). The tumor staging was similar between groups but the Childs-Pugh score in the urgent and untreated group was significantly higher than that of the other groups. The degree of necrosis at explant was also significantly different between the two treated groups, with an average 35% necrosis in the patients embolized less than 24 h before OLT vs 77% in the elective group (p < 0.002). Recurrence rate in the urgent group was 8 of 35 (23%) in a median of 580 days, 20 of 97 (21%) in a median of 539 days in the elective group, and 2 of 18 (11%) in a median of 331 days in the no-TACE group. Survival at 1, 3, and 5 years was 91%, 80%, and 72% in the elective group, 79%, 58%, and 39% in the urgent group, and 69%, 61%, and 41% in the no-TACE group, respectively. The urgent and no-TACE groups had significantly worse survival compared with the other groups; however, the tumor recurrence rates were statistically the same among all three groups. TACE within 24 h of OLT causes an average of 35% necrosis and elective TACE increases necrosis further to 77%. Despite this difference, the tumor recurrence rate in the three groups is equivalent and no different from that in the group that received no treatment before OLT

[Hepatobronchial Fistula and Lung Abscess after Transarterial Chemoembolization].

Science.gov (United States)

Lee, Kwanjoo; Song, Jeong Eun; Jeong, Hyang Sook; Kim, Do Young

2017-05-25

Transarterial chemoembolization (TACE) is a common treatment modality to locally manage hepatocellular carcinoma. Liver abscess and bile duct injury are common complications of TACE. However, hepatobronchial fistula is a rare complication. Herein, we report a case of lung abscess due to hepatobronchial fistula after TACE. A 67-year-old man, who had underwent TACE 6 months ago, presented cough and bile-colored sputum. He was diagnosed with lung abscess and hepatobronchial fistula. We performed endoscopic retrograde cholangiopancreatography; however, there was no improvement in his symptoms. Thereafter, partial hepatectomy and repair of fistula were successively conducted.

Recombination rate plasticity: revealing mechanisms by design

Science.gov (United States)

Sefick, Stephen; Rushton, Chase

2017-01-01

For over a century, scientists have known that meiotic recombination rates can vary considerably among individuals, and that environmental conditions can modify recombination rates relative to the background. A variety of external and intrinsic factors such as temperature, age, sex and starvation can elicit ‘plastic’ responses in recombination rate. The influence of recombination rate plasticity on genetic diversity of the next generation has interesting and important implications for how populations evolve. Further, many questions remain regarding the mechanisms and molecular processes that contribute to recombination rate plasticity. Here, we review 100 years of experimental work on recombination rate plasticity conducted in Drosophila melanogaster. We categorize this work into four major classes of experimental designs, which we describe via classic studies in D. melanogaster. Based on these studies, we highlight molecular mechanisms that are supported by experimental results and relate these findings to studies in other systems. We synthesize lessons learned from this model system into experimental guidelines for using recent advances in genotyping technologies, to study recombination rate plasticity in non-model organisms. Specifically, we recommend (1) using fine-scale genome-wide markers, (2) collecting time-course data, (3) including crossover distribution measurements, and (4) using mixed effects models to analyse results. To illustrate this approach, we present an application adhering to these guidelines from empirical work we conducted in Drosophila pseudoobscura. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’. PMID:29109222

Arterial blood supply to the caudate lobe of the liver from the proximal branches of the right inferior phrenic artery in patients with recurrent hepatocellular carcinoma after chemoembolization

International Nuclear Information System (INIS)

Miyayama, Shiro; Yamashiro, Masashi; Shibata, Yoshihiro; Hashimoto, Masahiro; Yoshida, Miki; Tsuji, Kazunobu; Toshima, Fumihito; Matsui, Osamu

2012-01-01

The purpose of this study was to evaluate the arterial blood supply to the caudate lobe of the liver from the proximal branches of the right inferior phrenic artery (RIPA) in patients with recurrent hepatocellular carcinoma after transcatheter arterial chemoembolization (TACE). Thirteen patients, including 10 who had a history of TACE of the caudate artery (A1), underwent TACE of the proximal RIPA branches. Iodized oil distribution was evaluated by computed tomography (CT) 1-week after TACE. Angiographic findings were also evaluated. Previously embolized A1 was occluded (n=15) or attenuated (n=2). In one of three patients without A1 TACE, A1 was also attenuated. TACE was performed at the first branch of the proximal RIPA (n=8), the first branch of the anterior branch (n=6), and the first branch of the posterior branch (n=1), respectively. Iodized oil was mainly distributed into the dorsal part of the Siegel lobe (SP) (n=10), the caudate process (n=1), and both (n=2). In three of seven patients who had undergone serial RIPA angiography, RIPA parasitization to SP was suspected before A1 TACE. The proximal RIPA branches mainly supply the SP when A1 is attenuated. (author)

Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis

Energy Technology Data Exchange (ETDEWEB)

Bush, David A., E-mail: dbush@llu.edu [Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Smith, Jason C. [Department of Diagnostic Radiology, Loma Linda University Medical Center, Loma Linda, California (United States); Slater, Jerry D. [Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Volk, Michael L. [Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California (United States); Reeves, Mark E. [VA Loma Linda Health Care System, Loma Linda, California (United States); Cheng, Jason [Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California (United States); Grove, Roger [Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Vera, Michael E. de [Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California (United States)

2016-05-01

Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC). Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractions over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization. Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group. Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are

WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments

Energy Technology Data Exchange (ETDEWEB)

Lin, M [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States); Saboury, B [University of Maryland School of Medicine, Baltimore, MD (United States)

2016-06-15

Purpose: Selective-internal-radiation-therapy (SIRT) and transarterial-chemoembolization (TACE) are commonly used for treatment of liver tumors. The use of TACE, which is macroembolic, prior to SIRT may cause hemodynamic changes in tumor vasculature that impair yttrium-90 (90Y) microsphere delivery to the targeted lesions. This work aims to quantify dosimetric tumor coverage using 90Y positron emission tomography (PET) dosimetry after SIRT alone compared to TACE followed by SIRT. Methods: A total of 40 consecutive hepatocellular carcinoma (HCC) SIRT patients who had a post-SIRT 90Y PET/CT scan were evaluated. The patient-specific-3D-dose was reconstructed from the PET images. Patients were categorized into two groups: patients received TACE prior SIRT procedure (n=18) and patient received SIRT alone (n=22). The lesions and liver were delineated by a senior radiologist. We evaluated both the lesion-specific dose-volume-histogram (DVH) and the selectivity index (SI) defined as the ratio of the average dose inside the total lesion(s) and the average dose of the normal liver. The SI values of patients were compared based on whether TACE was previously used. Results: A wide spectrum was observed in the lesion-specific DVH-evaluation and SI appeared to be suitable of evaluating the quality of each SIRT infusion. The average SI of the entire patient group was 3.0, i.e. targeted lesion receiving three times higher dose than normal liver. The average SI was 1.8 for patients who had prior TACE and 3.9 for patients who did not have prior TACE (p=0.008). 85% of the patients with prior TACE demonstrated poor 90Y-microsphere delivery (SI <2) while none demonstrated excellent delivery (SI >4). On the other hand, the incidence SI >4 among patients with no prior TACE was 37%. Conclusion: 3D dose evaluation using post-SIRT PET suggests that 90Y microsphere delivery to liver tumors is impaired among patients who received prior TACE compared to those who receive SIRT alone.

Recombination analysis based on the complete genome of bocavirus

Directory of Open Access Journals (Sweden)

Chen Shengxia

2011-04-01

Full Text Available Abstract Bocavirus include bovine parvovirus, minute virus of canine, porcine bocavirus, gorilla bocavirus, and Human bocaviruses 1-4 (HBoVs. Although recent reports showed that recombination happened in bocavirus, no systematical study investigated the recombination of bocavirus. The present study performed the phylogenetic and recombination analysis of bocavirus over the complete genomes available in GenBank. Results confirmed that recombination existed among bocavirus, including the likely inter-genotype recombination between HBoV1 and HBoV4, and intra-genotype recombination among HBoV2 variants. Moreover, it is the first report revealing the recombination that occurred between minute viruses of canine.

FASEB Summer Research Conference. Genetic Recombination and Chromosome Rearrangements

Energy Technology Data Exchange (ETDEWEB)

Jinks-Robertson, Sue

2002-02-01

The 2001 meeting entitled ''Genetic Recombination and Genome Rearrangements'' was held July 21-26 in Snowmass, Colorado. The goal of the meeting was to bring together scientists using diverse approaches to study all aspects of genetic recombination. This goal was achieved by integrating talks covering the genetics, biochemistry and structural biology of homologous recombination, site-specific recombination, and nonhomologous recombination. The format of the meeting consisted of a keynote address on the opening evening, two formal plenary sessions on each of the four full meeting days, a single afternoon workshop consisting of short talks chosen from among submitted abstracts, and afternoon poster sessions on each of the four full meeting days. The eight plenary session were entitled: (1) Recombination Mechanisms, (2) Prokaryotic Recombination, (3) Repair and Recombination, (4) Site-specific Recombination and Transposition, (5) Eukaryotic Recombination I, (6) Genome Rearrangements, (7) Meiosis, and (8) Eukaryotic Recombination II. Each session included a mix of genetic, biochemical and structural talks; talks were limited to 20 minutes, followed by 10 minutes of very lively, general discussion. Much of the data presented in the plenary sessions was unpublished, thus providing attendees with the most up-to-date knowledge of this rapidly-moving field.

Hadron Correlations and Parton Recombination

Energy Technology Data Exchange (ETDEWEB)

Fries, R.J. [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)]. E-mail: rjfries@comp.tamu.edu

2007-02-15

Parton recombination has been found to be an extremely useful model to understand hadron production at the Relativistic Heavy Ion Collider. It is particularly important to explore its connections with hard processes. This article reviews some of the aspects of the quark recombination model and places particular emphasis on hadron correlations.

The tumble occurred after transcatheter arterial chemoembolization: an investigation and analysis of its causes

International Nuclear Information System (INIS)

Xiao Shuping; Li Xiaofang; Zheng Chuansheng

2012-01-01

Objective: To investigate and analyze the cause of the tumble which occurs after transcatheter arterial chemoembolization (TACE), and to discuss its related factors. Methods: During the period from January 2003 to February 2010 in the Department of Interventional Radiology of Union Hospital (Wuhan city), post-TACE tumble occurred in 28 patients. The causes of the tumble were investigated and analyzed. Results: (1) The total number of the tumble occurrence after TACE was declining with the year. (2) Certain relationship existed between the occurrence of post-TACE tumble and the patient's age, drugs used in surgery, unit environment, nurse's shift, etc. Conclusion: Based on the patient's individual condition, intentionally enhancing the perioperative nursing care and adjusting the nurse's shift are very important measures to prevent the occurrence of post-TACE tumble. (authors)

Transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma: its research progress

International Nuclear Information System (INIS)

Zhao Yan; Han Guohong; Bai Wei; Fan Daiming

2012-01-01

Transarterial chemoembolization (TACE) has been the main treatment for patients with intermediate-stage hepatocellular carcinoma (HCC). However, the clinical application of TACE is limited due to the technical deficiencies, such as uncontrolled local drug delivery and systemic toxicity. Recently, the new drug-eluting beads (DEB), loading with doxorubicin, have be used in the TACE procedures. This new technique can not only maintain the local drug level for quite a long time and thus get a higher objective response, but also decrease the systemic toxicity. Transarterial chemoembolization with drug-eluting beads (DEB-TACE) have already been widely used abroad, and more related clinical trials are underway to clarify its advantages. This paper aims to make a comprehensive review in the respects of its characteristics and the latest research progress in DEB-TACE. (authors)

Exceptionally high levels of recombination across the honey bee genome.

Science.gov (United States)

Beye, Martin; Gattermeier, Irene; Hasselmann, Martin; Gempe, Tanja; Schioett, Morten; Baines, John F; Schlipalius, David; Mougel, Florence; Emore, Christine; Rueppell, Olav; Sirviö, Anu; Guzmán-Novoa, Ernesto; Hunt, Greg; Solignac, Michel; Page, Robert E

2006-11-01

The first draft of the honey bee genome sequence and improved genetic maps are utilized to analyze a genome displaying 10 times higher levels of recombination (19 cM/Mb) than previously analyzed genomes of higher eukaryotes. The exceptionally high recombination rate is distributed genome-wide, but varies by two orders of magnitude. Analysis of chromosome, sequence, and gene parameters with respect to recombination showed that local recombination rate is associated with distance to the telomere, GC content, and the number of simple repeats as described for low-recombining genomes. Recombination rate does not decrease with chromosome size. On average 5.7 recombination events per chromosome pair per meiosis are found in the honey bee genome. This contrasts with a wide range of taxa that have a uniform recombination frequency of about 1.6 per chromosome pair. The excess of recombination activity does not support a mechanistic role of recombination in stabilizing pairs of homologous chromosome during chromosome pairing. Recombination rate is associated with gene size, suggesting that introns are larger in regions of low recombination and may improve the efficacy of selection in these regions. Very few transposons and no retrotransposons are present in the high-recombining genome. We propose evolutionary explanations for the exceptionally high genome-wide recombination rate.

Three-particle recombination at low temperature: QED approach

International Nuclear Information System (INIS)

Bhattacharyya, S.; Roy, A.

2001-01-01

A theoretical study of three-body recombination of proton in presence of a spectator electron with electronic beam at near-zero temperature is presented using field theory and invariant Lorentz gauge. Contributions from the Feynman diagrams of different orders give an insight into the physics of the phenomena. Recombination rate coefficient is obtained for low lying principal quantum number n = 1 to 10. At a fixed ion beam temperature (300 K) recombination rate coefficient is found to increase in general with n, having a flat and a sharp peak at quantum states 3 to 5, respectively. In absence of any theoretical and experimental results for low temperature formation of H-atom by three-body recombination at low lying quantum states, we have presented the theoretical results of Stevefelt and group for three-body recombination of deuteron with electron along with the present results. Three-body recombination of antihydrogen in antiproton-positron plasma is expected to yield similar result as that for three-body recombination of hydrogen formation in proton-electron plasma. The necessity for experimental investigation of low temperature three-body recombination at low quantum states is stressed. (author)

Stereotactic Body Radiation Therapy as an Alternative to Transarterial Chemoembolization for Hepatocellular Carcinoma.

Science.gov (United States)

Sapir, Eli; Tao, Yebin; Schipper, Matthew J; Bazzi, Latifa; Novelli, Paula M; Devlin, Pauline; Owen, Dawn; Cuneo, Kyle C; Lawrence, Theodore S; Parikh, Neehar D; Feng, Mary

2018-01-01

To conduct a large single-institution comparison of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) outcomes in similar groups of patients with hepatocellular carcinoma (HCC). From 2006 to 2014, 209 patients with 1 to 2 tumors underwent TACE (n=84) to 114 tumors or image guided SBRT (n=125) to 173 tumors. Propensity score analysis with inverse probability of treatment weighting was used to compare outcomes between treatments while adjusting for imbalances in treatment assignment. Local control (LC), toxicity, and overall survival (OS) were retrospectively analyzed. The TACE and SBRT groups were similar with respect to the number of tumors treated per patient, underlying liver disease, and baseline liver function. Patients treated with SBRT were older (65 vs 61 years, P=.01), had smaller tumors (2.3 vs 2.9 cm, P<.001), and less frequently underwent liver transplantation (8% vs 18%, P=.01). The 1- and 2-year LC favored SBRT: 97% and 91%, respectively, for SBRT and 47% and 23% for TACE (hazard ratio 66.5, P<.001). For patients treated with TACE, higher alpha-fetoprotein (hazard ratio 1.11 per doubling, P=.008) and segmental portal vein thrombosis (hazard ratio 9.9, P<.001) were associated with worse LC. Predictors associated with LC after SBRT were not identified. Grade 3+ toxicity occurred after 13% and 8% of TACE and SBRT treatments, respectively (P=.05). There was no difference in OS between patients treated with TACE or SBRT. Stereotactic body radiation therapy is a safe alternative to TACE for 1 to 2 tumors and provides better LC, with no observed difference in OS. Prospective comparative trials of TACE and SBRT are warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

The correlation between psychological intervention and heart rate,systolic pressure in patients of cervical cancer treated with interventional chemoembolization

International Nuclear Information System (INIS)

Qiao Cuiyun; Lan Guiyun; Liu Shuang; Chen Bao'e; Liu Yali; Wang Zhujun

2010-01-01

Objective: To discuss the effect of psychological intervention on the heart rate, systolic pressure of the patients with cervical cancer who are treated with interventional chemoembolization. Methods: Eighty patients with cervical cancer were randomly and equally divided into two groups. Transcatheter arterial chemoembolization (TACE) was performed in all cases. Patients in study group (n=10) received systemic psychological intervention 30 minutes before TACE. The heart rate and systolic pressure of the patients were measured when TACE started. The results were compared with that obtained at the time of admission. Patients in control group (n=10) did not receive systemic psychological intervention before TACE and their heart rate and systolic pressure were measured in the same way as in study group. Results: At the time TACE started the heart rate and systolic pressure of the patients in study group were significantly lower than that in control group (P < 0.05). Conclusion: Preoperative psychological intervention is very helpful for reducing psychological stress and mental tension,in stabilizing heart rate and systolic pressure of the patients with cervical cancer who are treated with TACE. (authors)

Pulmonary Lipiodol Accumulation after Transarterial Chemoembolization: CT Findings and Its Radiologic Outcomes

Energy Technology Data Exchange (ETDEWEB)

Youn, In Young; Chong, Se Min; Kwak, Byung Kook; Shin, Hyung Jin; Seo, Gi Young; Seo, Jae Seung; Kim, Jae Kyun [Dept. of Radiology, Chung Ang University Medical Center, Chung Ang University College of Medicine, Seoul (Korea, Republic of)

2011-12-15

To evaluate CT findings and radiologic outcomes of pulmonary lipiodol accumulation (PLA) after transarterial chemoembolization (TACE). This retrospective study involved 488 TACEs for hepatocellular carcinoma (HCC) (n = 160) and hepatic metastasis for non-hepatic malignancies (n = 7) in 167 patients. We reviewed the patient clinicoradiologic findings before and after TACE and calculated the incidence of PLA and PLA resolution time after initial CT and after TACE. Lipiodol accumulation in the lungs was seen under CT after TACE in seven patients (M : F = 6 : 1, mean age 61 years). The incidence of PLA at CT was 4.1% (7/167 patients). In five patients, associated intrathoracic abnormalities including pleural effusion with (n 3) or without consolidation (n = 2) were revealed at CT scans. The CT resolution time and PLA recovery time were 56 {+-} 54 days and 66 {+-} 52 days, respectively. The recovery time for lipiodol accumulation was 66 days. It is believed that the clinical and radiologic outcome of PLA without respiratory failure is promising, and conservative treatment will suffice when lipiodol accumulation in the lungs is seen in CT images after TACE.

Activated recombinant adenovirus proteinases

Science.gov (United States)

Anderson, Carl W.; Mangel, Walter F.

1999-08-10

This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

Hadron correlations from recombination

Energy Technology Data Exchange (ETDEWEB)

Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

2005-01-01

Quark recombination is a successful model to describe the hadronization of a deconfined quark gluon plasma. Jet-like dihadron correlations measured at RHIC provide a challenge for this picture. We discuss how correlations between hadrons can arise from correlations between partons before hadronization. An enhancement of correlations through the recombination process, similar to the enhancement of elliptic flow is found. Hot spots from completely or partially quenched jets are a likely source of such parton correlations.

X-ray- and TEM-induced mitotic recombination in Drosophila melanogaster: Unequal and sister-strand recombination

International Nuclear Information System (INIS)

Becker, H.J.

1975-01-01

Twin mosaic spots of dark-apricot and light-apricot ommatidia were found in the eyes of wsup(a)/wsup(a) females, of wsup(a) males, of females homozygous for In(1)sc 4 , wsup(a) and of attached-X females homozygous for wsup(a). The flies were raised from larvae which had been treated with 1,630 R of X-rays at the age of 48-52 hours. An additional group of wsup(a)/wsup(a) females and wsup(a) males came from larvae that had been fed with triethylene melamine (TEM) at the age of 22-24 hours. The twin spots apparently were the result of induced unequal mitotic recombination, i.e. from unequal sister-strand recombination in the males and from unequal sister-strand recombination as well as, possibly, unequal recombination between homologous strands in the females. That is, a duplication resulted in wsup(a)Dpwsup(a)/wsup(a) dark-apricto ommatidia and the corresponding deficiency in an adjacent area of wsup(a)/Dfwsup(a) light-apricot ommatidia. In an additional experiment sister-strand mitotic recombination in the ring-X chromosome of ring-X/rod-X females heterozygous for w and wsup(co) is believed to be the cause for X-ray induced single mosaic spots that show the phenotype of the rod-X marker. (orig.) [de

Two novel porcine epidemic diarrhea virus (PEDV) recombinants from a natural recombinant and distinct subtypes of PEDV variants.

Science.gov (United States)

Chen, Nanhua; Li, Shuangjie; Zhou, Rongyun; Zhu, Meiqin; He, Shan; Ye, Mengxue; Huang, Yucheng; Li, Shuai; Zhu, Cong; Xia, Pengpeng; Zhu, Jianzhong

2017-10-15

Porcine epidemic diarrhea virus (PEDV) causes devastating impact on global pig-breeding industry and current vaccines have become not effective against the circulating PEDV variants since 2011. During the up-to-date investigation of PEDV prevalence in Fujian China 2016, PEDV was identified in vaccinated pig farms suffering severe diarrhea while other common diarrhea-associated pathogens were not detected. Complete genomes of two PEDV representatives (XM1-2 and XM2-4) were determined. Genomic comparison showed that these two viruses share the highest nucleotide identities (99.10% and 98.79%) with the 2011 ZMDZY strain, but only 96.65% and 96.50% nucleotide identities with the attenuated CV777 strain. Amino acid alignment of spike (S) proteins indicated that they have the similar mutation, insertion and deletion pattern as other Chinese PEDV variants but also contain several unique substitutions. Phylogenetic analysis showed that 2016 PEDV variants belong to the cluster of recombination strains but form a new branch. Recombination detection suggested that both XM1-2 and XM2-4 are inter-subgroup recombinants with breakpoints within ORF1b. Remarkably, the natural recombinant HNQX-3 isolate serves as a parental virus for both natural recombinants identified in this study. This up-to-date investigation provides the direct evidence that natural recombinants may serve as parental viruses to generate recombined PEDV progenies that are probably associated with the vaccination failure. Copyright © 2017. Published by Elsevier B.V.

Rapid generation of markerless recombinant MVA vaccines by en passant recombineering of a self-excising bacterial artificial chromosome.

Science.gov (United States)

Cottingham, Matthew G; Gilbert, Sarah C

2010-09-01

The non-replicating poxviral vector modified vaccinia virus Ankara (MVA) is currently a leading candidate for development of novel recombinant vaccines against globally important diseases. The 1980s technology for making recombinant MVA (and other poxviruses) is powerful and robust, but relies on rare recombination events in poxviral-infected cells. In the 21st century, it has become possible to apply bacterial artificial chromosome (BAC) technology to poxviruses, as first demonstrated by B. Moss' lab in 2002 for vaccinia virus. A similar BAC clone of MVA was subsequently derived, but while recombination-mediated genetic engineering for rapid production was used of deletion mutants, an alternative method was required for efficient insertion of transgenes. Furthermore "markerless" viruses, which carry no trace of the selectable marker used for their isolation, are increasingly required for clinical trials, and the viruses derived via the new method contained the BAC sequence in their genomic DNA. Two methods are adapted to MVA-BAC to provide more rapid generation of markerless recombinants in weeks rather than months. "En passant" recombineering is applied to the insertion of a transgene expression cassette and the removal of the selectable marker in bacteria; and a self-excising variant of MVA-BAC is constructed, in which the BAC cassette region is rapidly and efficiently lost from the viral genome following rescue of the BAC into infectious virus. These methods greatly facilitate and accelerate production of recombinant MVA, including markerless constructs. Copyright 2010 Elsevier B.V. All rights reserved.

Mechanisms and factors that influence high frequency retroviral recombination

DEFF Research Database (Denmark)

Delviks-Frankenberry, Krista; Galli, Andrea; Nikolaitchik, Olga

2011-01-01

With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse...... transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity...... of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. Specifically, the high mutation rates and high recombination frequencies of HIV-1 will be analyzed for their roles in influencing HIV-1 global diversity, as well as HIV-1 diagnosis, drug treatment...

Induction of homologous recombination in Saccharomyces cerevisiae.

Science.gov (United States)

Simon, J R; Moore, P D

1988-09-01

We have investigated the effects of UV irradiation of Saccharomyces cerevisiae in order to distinguish whether UV-induced recombination results from the induction of enzymes required for homologous recombination, or the production of substrate sites for recombination containing regions of DNA damage. We utilized split-dose experiments to investigate the induction of proteins required for survival, gene conversion, and mutation in a diploid strain of S. cerevisiae. We demonstrate that inducing doses of UV irradiation followed by a 6 h period of incubation render the cells resistant to challenge doses of UV irradiation. The effects of inducing and challenge doses of UV irradiation upon interchromosomal gene conversion and mutation are strictly additive. Using the yeast URA3 gene cloned in non-replicating single- and double-stranded plasmid vectors that integrate into chromosomal genes upon transformation, we show that UV irradiation of haploid yeast cells and homologous plasmid DNA sequences each stimulate homologous recombination approximately two-fold, and that these effects are additive. Non-specific DNA damage has little effect on the stimulation of homologous recombination, as shown by studies in which UV-irradiated heterologous DNA was included in transformation/recombination experiments. We further demonstrate that the effect of competing single- and double-stranded heterologous DNA sequences differs in UV-irradiated and unirradiated cells, suggesting an induction of recombinational machinery in UV-irradiated S. cerevisiae cells.

Spectrum Recombination.

Science.gov (United States)

Greenslade, Thomas B., Jr.

1984-01-01

Describes several methods of executing lecture demonstrations involving the recombination of the spectrum. Groups the techniques into two general classes: bringing selected portions of the spectrum together using lenses or mirrors and blurring the colors by rapid movement or foreshortening. (JM)

Genetic analysis of variation in human meiotic recombination.

Directory of Open Access Journals (Sweden)

Reshmi Chowdhury

2009-09-01

Full Text Available The number of recombination events per meiosis varies extensively among individuals. This recombination phenotype differs between female and male, and also among individuals of each gender. In this study, we used high-density SNP genotypes of over 2,300 individuals and their offspring in two datasets to characterize recombination landscape and to map the genetic variants that contribute to variation in recombination phenotypes. We found six genetic loci that are associated with recombination phenotypes. Two of these (RNF212 and an inversion on chromosome 17q21.31 were previously reported in the Icelandic population, and this is the first replication in any other population. Of the four newly identified loci (KIAA1462, PDZK1, UGCG, NUB1, results from expression studies provide support for their roles in meiosis. Each of the variants that we identified explains only a small fraction of the individual variation in recombination. Notably, we found different sequence variants associated with female and male recombination phenotypes, suggesting that they are regulated by different genes. Characterization of genetic variants that influence natural variation in meiotic recombination will lead to a better understanding of normal meiotic events as well as of non-disjunction, the primary cause of pregnancy loss.

Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus

Directory of Open Access Journals (Sweden)

Mark W. Jackwood

2011-09-01

Full Text Available Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus.

The unconventional xer recombination machinery of Streptococci/Lactococci

NARCIS (Netherlands)

Le Bourgeois, Pascal; Bugarel, Marie; Campo, Nathalie; Daveran-Mingot, Marie-Line; Labonte, Jessica; Lanfranchi, Daniel; Lautier, Thomas; Pages, Carine; Ritzenthaler, Paul

Homologous recombination between circular sister chromosomes during DNA replication in bacteria can generate chromosome dimers that must be resolved into monomers prior to cell division. In Escherichia coli, dimer resolution is achieved by site-specific recombination, Xer recombination, involving

The effect of different methods of transarterial chemoembolization on the angiogenesis of hepatocellular carcinoma

International Nuclear Information System (INIS)

Guo Dong; Xiao Enhua

2007-01-01

Objective: To investigate the effect of different methods of transarterial chemoembolisation (TACE) on the angiogenesis of hepatocellular carcinoma (HCC). Methods: One hundred and thirty-six HCC specimens from 136 patients were collected. Fifty-seven tumors came from patients who were treated only by surgery (group A), 11 tumors from patients who were treated by transarterial chemoperfusion before surgery (group B), 68 tumors from patients who were treated by TACE before surgery (group TACE ), respectively. And the TACE group was classified into 3 sub-groups: iodinated oil + chemotherapeutics for 33 cases (group C), iodinated oil + chemotherapeutics + gelatin sponge for 23 cases (group D), iodinated oil + chemotherapeutics + gelatin sponge + absolute alcohol for 12 cases (group E), respectively. Also, the tumors of TACE were divided into 4 groups according to an elapse between the last TACE therapy and the surgery. They were group ≤30 days (n=24), group 31- 60 days (n=25), group 61-90 days (n=13), group > 90 days (n=6), respectively. The pathological sections were stained by immunohistochemical method. The microvessels were marked by CD31. And the stained cells were counted under the light microscope. Results: The mean of microvessels density (MVD) were (44±18), (48±23), (55±22), respectively. The mean of MVD in group TACE was significantly higher than that in group A (t=-2.897, P 0.05). The mean of MVD in group C, group D and group E were (56 ± 22), (54 ± 24), (52 ± 19), respectively. The differences of the mean of MVD were not statistically significant among the three groups. (F=0.152, P>0.05). The mean of MVD in group ≤ 30 days, group 31-60 days, group 61-90 days, group >90 days were (50 ± 19), (55 ± 24), (62 ± 29), (53 ± 10), respectively. The mean of MVD of group A was significantly lower than those of 4 groups( group A was served as a control group as they were supposed as treated by TACE after 0 day) (P>0.05). There was significant differences

Graded Recombination Layers for Multijunction Photovoltaics

KAUST Repository

Koleilat, Ghada I.; Wang, Xihua; Sargent, Edward H.

2012-01-01

it to achieve multicolor and spectrally tunable behavior. In series-connected current-matched multijunction devices, the recombination layers must allow the hole current from one cell to recombine, with high efficiency and low voltage loss, with the electron

V(D)J recombination frequency is affected by the sequence interposed between a pair of recombination signals: sequence comparison reveals a putative recombinational enhancer element

DEFF Research Database (Denmark)

Roch, F A; Hobi, R; Berchtold, M W

1997-01-01

respectively, can markedly affect the frequency of V(D)J recombination. We report that the entire Emu, the Emu core as well as its flanking 5' and 3' matrix associated regions (5' and 3' MARs) upregulate V(D)J recombination while the downstream section of the 3' MAR of Emu does not. Also, prokaryotic sequences...

Bio-equivalent doses of recombinent HCG and recombinent LH during ovarian stimulation result in similar oestradiol output

DEFF Research Database (Denmark)

Alsbjerg, Birgit; Elbaek, Helle Olesen; Laursen, Rita Jakubcionyte

2017-01-01

In nature, HCG is secreted by the implanting embryo from peri-implantation and onwards. In contrast, LH is mandatory for steroidogenesis and follicular development during the follicular phase, working in synergy with FSH. Moreover, LH is mandatory for the function of the corpus luteum. Although LH...... and HCG bind to the same receptor, significant molecular, structural and functional differences exist, inducing differences in bioactivity. This randomized controlled study compared the effect of recombinant FSH stimulation combined with daily either micro-dose recombinant HCG or recombinant LH...

Mechanisms and Factors that Influence High Frequency Retroviral Recombination

Science.gov (United States)

Delviks-Frankenberry, Krista; Galli, Andrea; Nikolaitchik, Olga; Mens, Helene; Pathak, Vinay K.; Hu, Wei-Shau

2011-01-01

With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. Specifically, the high mutation rates and high recombination frequencies of HIV-1 will be analyzed for their roles in influencing HIV-1 global diversity, as well as HIV-1 diagnosis, drug treatment, and vaccine development. PMID:21994801

Recombinant innovation and endogenous technological transitions

NARCIS (Netherlands)

Frenken, K.; Izquierdo, L.R.; Zeppini, P.

2012-01-01

We propose a model of technological transitions based on two different types of innovations. Branching innovations refer to technological improvements along a particular path, while recombinant innovations represent fusions of multiple paths. Recombinant innovations create "short-cuts" which reduce

Treatment Outcome Following Transarterial Chemoembolization in Advanced Bone and Soft Tissue Sarcomas

Energy Technology Data Exchange (ETDEWEB)

Jiang, Chunyu; Wang, Jianbo, E-mail: a602131499@163.com [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of Radiology (China); Wang, Yonggang [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of Oncology (China); Zhao, Jungong; Zhu, Yueqi; Ma, Xu; Zhou, Jia [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of Radiology (China); Yan, Xuebing [Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Department of General Surgery (China)

2016-10-15

PurposeTransarterial chemoembolization (TACE) is used to treat unresectable bone and soft tissue sarcoma (STS) and as a pre-surgical adjuvant treatment. However, its efficiency for advanced STS is undetermined. This study evaluated TACE’s efficiency in treating advanced STS and prognostic factors for patient survival.Materials and MethodsWe enrolled 39 patients with unresectable STS who underwent TACE as an alternative treatment during 2010–2014, with overall survival (OS) as the primary end point. Cancer pain was evaluated by visual analogue scores (VAS) before and after TACE procedures. Factors that affect survival were evaluated by multivariate analyses (Cox proportional hazard model).ResultsMean OS after TACE was 23.7 ± 2.1 months, with 1-year OS 71.5 %, 2-year OS 45.8 %, and 3-year OS 32.5 %. Lesion number and tumor stage were key predictors of survival. TACE was found to decrease cancer pain VAS and increase relapse interval. Size of polyvinyl alcohol (PVA) particle diameter (P = 0.03) and imaging response (P = 0.044) were also found to affect relapse interval.ConclusionTACE was an effective treatment for advanced STS, with a 32.5 % 3-year OS rate, and led to lower cancer pain VAS and longer relapse intervals than chemoinfusion only. Smaller PVA particles are preferable during the TACE procedure.

A Meta-Analysis of Arsenic Trioxide Combined with Transcatheter Arterial Chemoembolization for Treatment of Primary Hepatic Carcinoma

Directory of Open Access Journals (Sweden)

Ling He

2016-01-01

Full Text Available Primary hepatic carcinoma (PHC is one of the most common malignant tumours in the world. More and more research has shown that As2O3 combined with TACE has a good curative effect in treating PHC. The objectives of this study were to evaluate the therapeutic efficacy and safety of As2O3 combined with TACE in treating PHC. The CNKI, VIP, Wanfang, PubMed, and Cochrane databases were searched from their inception until December 2015. Randomized controlled trials (RCTs comparing As2O3 combined with TACE versus TACE alone in treating PHC were identified. Stata SE 12.0 was used for data analysis. 17 RCTs with 1055 patients were included. Meta-analysis showed that, compared with TACE alone, As2O3 combined with TACE showed significant effects in improving the clinical efficacy rate (P<0.01, decreasing the value of alpha-fetoprotein (P<0.01, increasing the one-year survival rate (P<0.01, and improving the quality of life of PHC patients (P<0.01. Fifteen studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, As2O3 combined with TACE therapy appears to be potentially effective in treating PHC and is generally safe. However, further studies with rigorous designs trials and multiregional cooperation trials are needed.

Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model

Energy Technology Data Exchange (ETDEWEB)

Sato, Takeshi; Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp; Nishiofuku, Hideyuki; Fukuoka, Yasushi [IVR CenterNara Medical University, Department of Radiology (Japan); Sakaguchi, Hiroshi [South Nara General Medical Center, Department of Radiology (Japan); Masada, Tetsuya; Tatsumoto, Shota [IVR CenterNara Medical University, Department of Radiology (Japan); Marugami, Nagaaki [Diagnostic Imaging Center, Department of Radiology (Japan); Takano, Masato [Nara Medical University, Department of Diagnostic Pathology (Japan); Yamato, Ichiro; Sho, Masayuki [Nara Medical University, Department of Surgery (Japan); Ohbayashi, Chiho [Nara Medical University, Department of Diagnostic Pathology (Japan); Hirai, Toshiko [Diagnostic Imaging Center, Department of Radiology (Japan); Kichikawa, Kimihiko [IVR CenterNara Medical University, Department of Radiology (Japan)

2017-03-15

PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.

Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model

International Nuclear Information System (INIS)

Sato, Takeshi; Tanaka, Toshihiro; Nishiofuku, Hideyuki; Fukuoka, Yasushi; Sakaguchi, Hiroshi; Masada, Tetsuya; Tatsumoto, Shota; Marugami, Nagaaki; Takano, Masato; Yamato, Ichiro; Sho, Masayuki; Ohbayashi, Chiho; Hirai, Toshiko; Kichikawa, Kimihiko

2017-01-01

PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.

Bimolecular recombination in ambipolar organic field effect transistors

NARCIS (Netherlands)

Charrier, D. S. H.; de Vries, T.; Mathijssen, S. G. J.; Geluk, E. -J.; Smits, E. C. P.; Kemerink, M.; Janssen, R. A. J.

In ambipolar organic field effect transistors (OFET) the shape of the channel potential is intimately related to the recombination zone width W, and hence to the electron-hole recombination strength. Experimentally, the recombination profile can be assessed by scanning Kelvin probe microscopy

Bimolecular recombination in ambipolar organic field effect transistors

NARCIS (Netherlands)

Charrier, D.S.H.; Vries, T. de; Mathijssen, S.G.J.; Geluk, E.-J.; Smits, E.C.P.; Kemerink, M.; Janssen, R.A.J.

2009-01-01

In ambipolar organic field effect transistors (OFET) the shape of the channel potential is intimately related to the recombination zone width W, and hence to the electron–hole recombination strength. Experimentally, the recombination profile can be assessed by scanning Kelvin probe microscopy

Genome-wide variation in recombination rate in Eucalyptus.

Science.gov (United States)

Gion, Jean-Marc; Hudson, Corey J; Lesur, Isabelle; Vaillancourt, René E; Potts, Brad M; Freeman, Jules S

2016-08-09

Meiotic recombination is a fundamental evolutionary process. It not only generates diversity, but influences the efficacy of natural selection and genome evolution. There can be significant heterogeneity in recombination rates within and between species, however this variation is not well understood outside of a few model taxa, particularly in forest trees. Eucalypts are forest trees of global economic importance, and dominate many Australian ecosystems. We studied recombination rate in Eucalyptus globulus using genetic linkage maps constructed in 10 unrelated individuals, and markers anchored to the Eucalyptus reference genome. This experimental design provided the replication to study whether recombination rate varied between individuals and chromosomes, and allowed us to study the genomic attributes and population genetic parameters correlated with this variation. Recombination rate varied significantly between individuals (range = 2.71 to 3.51 centimorgans/megabase [cM/Mb]), but was not significantly influenced by sex or cross type (F1 vs. F2). Significant differences in recombination rate between chromosomes were also evident (range = 1.98 to 3.81 cM/Mb), beyond those which were due to variation in chromosome size. Variation in chromosomal recombination rate was significantly correlated with gene density (r = 0.94), GC content (r = 0.90), and the number of tandem duplicated genes (r = -0.72) per chromosome. Notably, chromosome level recombination rate was also negatively correlated with the average genetic diversity across six species from an independent set of samples (r = -0.75). The correlations with genomic attributes are consistent with findings in other taxa, however, the direction of the correlation between diversity and recombination rate is opposite to that commonly observed. We argue this is likely to reflect the interaction of selection and specific genome architecture of Eucalyptus. Interestingly, the differences amongst

Induction of intrachromosomal homologous recombination in whole plants

International Nuclear Information System (INIS)

Puchta, H.; Swoboda, P.; Hohn, B.

1995-01-01

The influence of different factors on frequencies of intrachromosomal homologous recombination in whole Arabidopsis thaliana and tobacco plants was analyzed using a disrupted β-glucuronidase marker gene. Recombination frequencies were enhanced several fold by DNA damaging agents like UV-light or MMS (methyl methanesulfonate). Applying 3-methoxybenzamide (3-MB), an inhibitor of poly(ADP)ribose polymerase (PARP), an enzyme that is postulated to be involved in DNA repair, enhanced homologous recombination frequencies strongly. These findings indicate that homologous recombination is involved in DNA repair and can (at least partially) compensate for other DNA repair pathways. Indications that recombination in plants can be induced by environmental stress factors that are not likely to be involved in DNA metabolism were also found; Arabidopsis plants growing in a medium containing 0.1 M NaCl exhibited elevated recombination frequencies. The possible general effects of ‘environmental’ challenges on genome flexibility are discussed. (author)

Metal binding proteins, recombinant host cells and methods

Science.gov (United States)

Summers, Anne O.; Caguiat, Jonathan J.

2004-06-15

The present disclosure provides artificial heavy metal binding proteins termed chelons by the inventors. These chelons bind cadmium and/or mercuric ions with relatively high affinity. Also disclosed are coding sequences, recombinant DNA molecules and recombinant host cells comprising those recombinant DNA molecules for expression of the chelon proteins. In the recombinant host cells or transgenic plants, the chelons can be used to bind heavy metals taken up from contaminated soil, groundwater or irrigation water and to concentrate and sequester those ions. Recombinant enteric bacteria can be used within the gastrointestinal tracts of animals or humans exposed to toxic metal ions such as mercury and/or cadmium, where the chelon recombinantly expressed in chosen in accordance with the ion to be rededicated. Alternatively, the chelons can be immobilized to solid supports to bind and concentrate heavy metals from a contaminated aqueous medium including biological fluids.

Electric hydrogen recombiner special tests

International Nuclear Information System (INIS)

Wilson, J.F.

1975-12-01

Westinghouse has produced an electric hydrogen recombiner to control hydrogen levels in reactor containments following a postulated loss-of-coolant accident. The recombiner underwent extensive testing for NRC qualification (see WCAP 7709-L and Supplements 1, 2, 3, 4). As a result, WCAP 7709-L and Supplements 1, 2, 3, and 4 have been accepted by the NRC for reference in applications not committed to IEEE-323-1974. Supplement 5 and the next supplement will demonstrate conformance to IEEE-323-1974. This supplement describes additional tests, beyond those necessary to qualify the system, which will be referenced in supplement 6. Each test has demonstrated a considerable margin of safety over required performance. Concurrently, the test results increased the fund of technical information on the electric hydrogen recombiner

Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

Directory of Open Access Journals (Sweden)

Ireen E Kiwelu

Full Text Available The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR of 38 (28-50 sequences per subject. Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84% subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60% subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69% to 36 (82% over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design.

Construction and characterization of a recombinant invertebrate iridovirus.

Science.gov (United States)

Ozgen, Arzu; Muratoglu, Hacer; Demirbag, Zihni; Vlak, Just M; van Oers, Monique M; Nalcacioglu, Remziye

2014-08-30

Chilo iridescent virus (CIV), officially named Insect iridescent virus 6 (IIV6), is the type species of the genus Iridovirus (family Iridoviridae). In this paper we constructed a recombinant CIV, encoding the green fluorescent protein (GFP). This recombinant can be used to investigate viral replication dynamics. We showed that homologous recombination is a valid method to make CIV gene knockouts and to insert foreign genes. The CIV 157L gene, putatively encoding a non-functional inhibitor of apoptosis (IAP), was chosen as target for foreign gene insertion. The gfp open reading frame preceded by the viral mcp promoter was inserted into the 157L locus by homologous recombination in Anthonomus grandis BRL-AG-3A cells. Recombinant virus (rCIV-Δ157L-gfp) was purified by successive rounds of plaque purification. All plaques produced by the purified recombinant virus emitted green fluorescence due to the presence of GFP. One-step growth curves for recombinant and wild-type CIV were similar and the recombinant was fully infectious in vivo. Hence, CIV157L can be inactivated without altering the replication kinetics of the virus. Consequently, the CIV 157L locus can be used as a site for insertion of foreign DNA, e.g. to modify viral properties for insect biocontrol. Copyright © 2014 Elsevier B.V. All rights reserved.

Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance

Science.gov (United States)

Kempf, Brian J.; Peersen, Olve B.

2016-01-01

ABSTRACT RNA recombination is important in the formation of picornavirus species groups and the ongoing evolution of viruses within species groups. In this study, we examined the structure and function of poliovirus polymerase, 3Dpol, as it relates to RNA recombination. Recombination occurs when nascent RNA products exchange one viral RNA template for another during RNA replication. Because recombination is a natural aspect of picornavirus replication, we hypothesized that some features of 3Dpol may exist, in part, to facilitate RNA recombination. Furthermore, we reasoned that alanine substitution mutations that disrupt 3Dpol-RNA interactions within the polymerase elongation complex might increase and/or decrease the magnitudes of recombination. We found that an L420A mutation in 3Dpol decreased the frequency of RNA recombination, whereas alanine substitutions at other sites in 3Dpol increased the frequency of recombination. The 3Dpol Leu420 side chain interacts with a ribose in the nascent RNA product 3 nucleotides from the active site of the polymerase. Notably, the L420A mutation that reduced recombination also rendered the virus more susceptible to inhibition by ribavirin, coincident with the accumulation of ribavirin-induced G→A and C→U mutations in viral RNA. We conclude that 3Dpol Leu420 is critically important for RNA recombination and that RNA recombination contributes to ribavirin resistance. IMPORTANCE Recombination contributes to the formation of picornavirus species groups and the emergence of circulating vaccine-derived polioviruses (cVDPVs). The recombinant viruses that arise in nature are occasionally more fit than either parental strain, especially when the two partners in recombination are closely related, i.e., members of characteristic species groups, such as enterovirus species groups A to H or rhinovirus species groups A to C. Our study shows that RNA recombination requires conserved features of the viral polymerase. Furthermore, a

Genome-wide recombination dynamics are associated with phenotypic variation in maize.

Science.gov (United States)

Pan, Qingchun; Li, Lin; Yang, Xiaohong; Tong, Hao; Xu, Shutu; Li, Zhigang; Li, Weiya; Muehlbauer, Gary J; Li, Jiansheng; Yan, Jianbing

2016-05-01

Meiotic recombination is a major driver of genetic diversity, species evolution, and agricultural improvement. Thus, an understanding of the genetic recombination landscape across the maize (Zea mays) genome will provide insight and tools for further study of maize evolution and improvement. Here, we used c. 50 000 single nucleotide polymorphisms to precisely map recombination events in 12 artificial maize segregating populations. We observed substantial variation in the recombination frequency and distribution along the ten maize chromosomes among the 12 populations and identified 143 recombination hot regions. Recombination breakpoints were partitioned into intragenic and intergenic events. Interestingly, an increase in the number of genes containing recombination events was accompanied by a decrease in the number of recombination events per gene. This kept the overall number of intragenic recombination events nearly invariable in a given population, suggesting that the recombination variation observed among populations was largely attributed to intergenic recombination. However, significant associations between intragenic recombination events and variation in gene expression and agronomic traits were observed, suggesting potential roles for intragenic recombination in plant phenotypic diversity. Our results provide a comprehensive view of the maize recombination landscape, and show an association between recombination, gene expression and phenotypic variation, which may enhance crop genetic improvement. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

RNAi and heterochromatin repress centromeric meiotic recombination

DEFF Research Database (Denmark)

Ellermeier, Chad; Higuchi, Emily C; Phadnis, Naina

2010-01-01

During meiosis, the formation of viable haploid gametes from diploid precursors requires that each homologous chromosome pair be properly segregated to produce an exact haploid set of chromosomes. Genetic recombination, which provides a physical connection between homologous chromosomes, is essen......During meiosis, the formation of viable haploid gametes from diploid precursors requires that each homologous chromosome pair be properly segregated to produce an exact haploid set of chromosomes. Genetic recombination, which provides a physical connection between homologous chromosomes....... Surprisingly, one mutant derepressed for recombination in the heterochromatic mating-type region during meiosis and several mutants derepressed for centromeric gene expression during mitotic growth are not derepressed for centromeric recombination during meiosis. These results reveal a complex relation between...... types of repression by heterochromatin. Our results also reveal a previously undemonstrated role for RNAi and heterochromatin in the repression of meiotic centromeric recombination and, potentially, in the prevention of birth defects by maintenance of proper chromosome segregation during meiosis....

Effects of UV radiation on genetic recombination

International Nuclear Information System (INIS)

Vlahovic, K.; Zahradka, D.; Petranovic, M.; Petranovic, D.

1996-01-01

We have used the model consisting of Escherichia coli cells and l phage to study the effects of UV radiation on genetic recombination. We found two radiation induced processes that reduce or inhibit genetic recombination. One such process leads to the inability of prophage to excise itself from the irradiated bacterial chromosome by the site-specific recombination. The other process was shown to inhibit a type of general recombination by which the prophage transfers one of its genetic markers to the infecting homologous phage. Loss of the prophage ability to take part in both site-specific and general recombination was shown to develop in recB + but not in recB cells. From this we infer that the loss of prophage recombinogenicity in irradiated cells is a consequence of one process in which RecBCD enzyme (the product of recB, recC and recD genes) plays an essential role. (author)

Temporally-controlled site-specific recombination in zebrafish.

Directory of Open Access Journals (Sweden)

Stefan Hans

Full Text Available Conventional use of the site-specific recombinase Cre is a powerful technology in mouse, but almost absent in other vertebrate model organisms. In zebrafish, Cre-mediated recombination efficiency was previously very low. Here we show that using transposon-mediated transgenesis, Cre is in fact highly efficient in this organism. Furthermore, temporal control of recombination can be achieved by using the ligand-inducible CreER(T2. Site-specific recombination only occurs upon administration of the drug tamoxifen (TAM or its active metabolite, 4-hydroxy-tamoxifen (4-OHT. Cre-mediated recombination is detectable already 4 or 2 hours after administration of TAM or 4-OHT, demonstrating fast recombination kinetics. In addition, low doses of TAM allow mosaic labeling of single cells. Combined, our results show that conditional Cre/lox will be a valuable tool for both, embryonic and adult zebrafish studies. Furthermore, single copy insertion transgenesis of Cre/lox constructs suggest a strategy suitable also for other organisms.

Algae-based oral recombinant vaccines

Science.gov (United States)

Specht, Elizabeth A.; Mayfield, Stephen P.

2014-01-01

Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for “molecular pharming” in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae could be poised to become the next candidate in recombinant subunit vaccine production, as they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and systemic immune reactivity. PMID:24596570

Recombination in hepatitis C virus.

Science.gov (United States)

González-Candelas, Fernando; López-Labrador, F Xavier; Bracho, María Alma

2011-10-01

Hepatitis C virus (HCV) is a Flavivirus with a positive-sense, single-stranded RNA genome of about 9,600 nucleotides. It is a major cause of liver disease, infecting almost 200 million people all over the world. Similarly to most RNA viruses, HCV displays very high levels of genetic diversity which have been used to differentiate six major genotypes and about 80 subtypes. Although the different genotypes and subtypes share basic biological and pathogenic features they differ in clinical outcomes, response to treatment and epidemiology. The first HCV recombinant strain, in which different genome segments derived from parentals of different genotypes, was described in St. Petersburg (Russia) in 2002. Since then, there have been only a few more than a dozen reports including descriptions of HCV recombinants at all levels: between genotypes, between subtypes of the same genotype and even between strains of the same subtype. Here, we review the literature considering the reasons underlying the difficulties for unequivocally establishing recombination in this virus along with the analytical methods necessary to do it. Finally, we analyze the potential consequences, especially in clinical practice, of HCV recombination in light of the coming new therapeutic approaches against this virus.

Algae-based oral recombinant vaccines

Directory of Open Access Journals (Sweden)

Elizabeth A Specht

2014-02-01

Full Text Available Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for molecular pharming in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae are poised to become the next candidate in recombinant subunit vaccine production, and they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally-delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and system immune reactivity.

Enhanced defects recombination in ion irradiated SiC

International Nuclear Information System (INIS)

Izzo, G.; Litrico, G.; Grassia, F.; Calcagno, L.; Foti, G.

2010-01-01

Point defects induced in SiC by ion irradiation show a recombination at temperatures as low as 320 K and this process is enhanced after running current density ranging from 80 to 120 A/cm 2 . Ion irradiation induces in SiC the formation of different defect levels and low-temperature annealing changes their concentration. Some levels (S 0 , S x and S 2 ) show a recombination and simultaneously a new level (S 1 ) is formed. An enhanced recombination of defects is besides observed after running current in the diode at room temperature. The carriers introduction reduces the S 2 trap concentration, while the remaining levels are not modified. The recombination is negligible up to a current density of 50 A/cm 2 and increases at higher current density. The enhanced recombination of the S 2 trap occurs at 300 K, which otherwise requires a 400 K annealing temperature. The process can be related to the electron-hole recombination at the associated defect.

Complications after transcatheter arterial chemoembolization via the inferior phrenic arteries: incidence, risk factors, and prophylaxis

International Nuclear Information System (INIS)

Wang Maoqiang; Liu Fengyong; Guan Jun; Gu Xiaofang; Lin Hanying; Wang Zhiqiang

2004-01-01

Objective: To investigate the frequency, patterns of the angiographic findings and risk factors for development of complications after transcatheter arterial chemoembolization (TACE) via the inferior phrenic artery (IPA). Methods: One hundred and sixty eight patients with hepatic tumor fed by the IPA underwent a total of 226 procedures of TACE of the IPA, with combined routine TACEO (88.7%) or without (11.3%) the combination of routine TACE of the hepatic artery. TACE of the malignancy was performed with an emulsion of iodized oil and anti-cancer agents and then followed by gelatin sponge particle injection. The complications were assessed on clinical observation, laboratory tests, and computed tomographic (CT) images after TACE of the IPA; and finally were correlated with the angiographic findings of the IPA. Results: The tumor supplied by IPA was noted at initial TACE in 25 (14.9%), at successive TACE in 97 (57.8%), after percutaneous tumor ablation guided by ultrasound in 28 (16.7%), and after hepatic surgery in 18 (10.7%) cases. The abnormal findings on arteriography showed enlargement of the IPA with tumor staining in all cases, dense non-tumor staining in 61 (36.3%), artery-to-artery anastomosis in 62(36.9%), arteriovenous shunts in 12(7.1%) cases. 96.4% of these patients complained of shoulder pain during TACE of the IPA. The cumulative complication rate after the procedure was 8.9%, including hiccup in 13 cases (5.8%), chest pain with cough and mild hemoptysis in 9 (4.0%), phrenoparalysis in 8 (3.5%), angina with abnormal ECG in 4 (1.8%), increasing of CPK, AST, and ALT significantly in 6 (2.7%), transient myeloparalysis in 2 (0.9%), and subphrenic abscess in 2 cases (0.9%). Two patients with the subphrenic abscess were successfully treated with percutaneous catheter drainage and antibiotics. The symptoms of these mild complications subsided with symptomatic treatment. Conclusions: Complications of TACE via the IPA occur in about 9% of the patients and

PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS

Energy Technology Data Exchange (ETDEWEB)

Moriya, Takashi J., E-mail: takashi.moriya@ipmu.jp [Kavli Institute for the Physics and Mathematics of the Universe, Todai Institutes for Advanced Study, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8583 (Japan)

2012-05-01

Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with ionization temperature higher than the electron temperature, has been recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.

Dissociation of recombinant prion autocatalysis from infectivity.

Science.gov (United States)

Noble, Geoffrey P; Supattapone, Surachai

2015-01-01

Within the mammalian prion field, the existence of recombinant prion protein (PrP) conformers with self-replicating (ie. autocatalytic) activity in vitro but little to no infectious activity in vivo challenges a key prediction of the protein-only hypothesis of prion replication--that autocatalytic PrP conformers should be infectious. To understand this dissociation of autocatalysis from infectivity, we recently performed a structural and functional comparison between a highly infectious and non-infectious pair of autocatalytic recombinant PrP conformers derived from the same initial prion strain. (1) We identified restricted, C-terminal structural differences between these 2 conformers and provided evidence that these relatively subtle differences prevent the non-infectious conformer from templating the conversion of native PrP(C) substrates containing a glycosylphosphatidylinositol (GPI) anchor. (1) In this article we discuss a model, consistent with these findings, in which recombinant PrP, lacking post-translational modifications and associated folding constraints, is capable of adopting a wide variety of autocatalytic conformations. Only a subset of these recombinant conformers can be adopted by post-translationally modified native PrP(C), and this subset represents the recombinant conformers with high specific infectivity. We examine this model's implications for the generation of highly infectious recombinant prions and the protein-only hypothesis of prion replication.

Hepatocellular carcinoma: treatment with transcatheter arterial chemoembolization

International Nuclear Information System (INIS)

Acunas, Buelent; Rozanes, Izzet

1999-01-01

This article presents a review of the literature regarding the use of transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). There have been two different approaches to the treatment: (a) percutaneous tumor ablation methods which can be divided into injectable and thermal methods; percutaneous ethanol injection (PEI) is the most widely used method, and (b) TACE. PEI is the treatment of choice for single HCCs smaller or equal to 3 cm in size. For patients with large HCCs combined TACE and PEI is probably the most effective nonsurgical treatment. In the presence of multiple HCC nodules, TACE remains the treatment of choice

Recombiner

International Nuclear Information System (INIS)

Saalfrank, H.

1985-01-01

Air containing hydrogen can be oxidized by heating in a container called a recombiner, in order to avoid the collection of hydrogen. The container is long and a large number of straight heating bars are arranged in parallel in it and they are flanged to a lid. The heating bars are surrounded by tubes, in order to obtain good heat transfer by a narrow annular gap. (orig.) [de

Anti-proliferative activity of recombinant melittin expressed in ...

African Journals Online (AJOL)

Recombinant melittin was then successfully expressed in Escherichia coli. The activity of affinity-purified recombinant melittin was determined in human leukemic U937 cells. Results show that the recombinant melittin had the same anti-proliferative activity in human leukemic U937 cells in vitro as natural one. This shows the ...

[Clinical features and risk factors of biloma formation after transcatheter arterial chemoembolization].

Science.gov (United States)

Zhaolin, Zeng; Xuelian, Liu; Wensou, Huang; Mingyue, Cai; Haofan, Wang; Ming'an, Li; Hong, Shan; Zhu, Kangshun

2015-04-07

To explore the risk factors, treatment and outcomes of biloma after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). A total of 481 patients with a diagnosis of HCC underwent TACE at our hospital from January 2011 to December 2013. Biloma was tracked by the follow-ups of computed tomography or magnetic resonance imaging (CT/ MRI) . Retrospective analyses were conducted for their clinical features, treatments and prognosis. The statistically significant factors for univariate analysis were introduced into Logistic regression models for multivariate analysis to obtain the risk factors of biloma post-TACE. There were 43 cases of complicated biloma after TACE. And 38 patients (88.4% ) developed biloma at 0.5-3 months post-TACE while another 5 (9.7%) did so at 3-5 months. The multivariate analysis showed that bile duct dilation, a history of hepatectomy prior to TACE, use of polyvinyl alcohol (PVA) particles and nonsuperselective embolization were the risk factors of biloma formation after TACE. Among 9 symptomatics, there were jaundice (n =2) and fever (n =7). The diameter of bilomas was (8.07 ± 3.53) cm for 9 symptomatics and (2.81 ± 1.26) cm for 35 asymptomatics. And the difference was statistically significant (P <0. 01). Nine symptomatic patients underwent percutaneous drainage with tube and biloma diminished (n = 7) and even vanished (n = 2). Only conservative treatment was offered for 35 asymptomatics. During the follow-ups, it showed no change (n = 24) , diminishing (n = 8) and disappearance (n = 2). One case died from a greatly enlarged biloma due to hepatic failure and septic shock via a rupture into abdominal cavity and choleperitonitis. The risk factors of biloma formation after TACE for HCC are bile duct dilation, a history of hepatectomy before TACE, use of PVA particles and nonsuperselective embolization. For symptomatics, drainage must be performed timely and the prognosis is fair. For asymptomatics, regular imaging

Clinical application of argon-helium cryotherapy system in the treatment of hepatocellular carcinoma

International Nuclear Information System (INIS)

Guo Zhi Xin Wenge; Liu Fang; Yu Haipeng; Li Baoguo; Guo Xiuying; Zhang Sheng; Fu Li; Xing Jizhong; Zhang Junyi; Wang Youju; Gong Bing

2005-01-01

Objective: To explore the efficacy of Argon-Helium cryotherapy system (AHCS) after transarterial chemoembolization (TACE) in treating the large hepatocellular carcinoma (HCC) with diameter over 10 cm. Methods: Forty-eight HCC patients were randomly divided into therapy group (n=26) and control group (n=22), and patients in the therapy group were treated with AHCS [(Cryocare) TM Surgical System] 4 weeks after TACE. Tumor size ranged from 10 to 13 cm. All tumors were hypervascular with Child A in 38 cases and Child B in 10 cases. AFP was positive in 40 cases and negative in 8. Reexamination included pathology, tumor marker, T-lymphocyte subgroup, ultrasound, CT, or MRI. Necrosis rate was calculated with Cavalieri theory. Numerical rating scale (NRS) for pain evaluation and EORTC QLQ-C30 for life quality evaluation were performed. Results: Technical success rate was 100%. Follow-up time varied from 6 to 14 months, and follow-up rate was 100%. Average neoplasm necrosis rate was 8.07% after TACE, and 28.65% after AHCS. Tumor marker significantly deceased after AHCS. The necrosis after AHCS was more significant than that after TACE alone. AST and ALT deteriorated for 2 weeks after TACE and for 1 week after AHCS. Local pain 48 hours after AHCS was the only more serious side effect than after TACE. Immunological function was significantly suppressed after TACE. CD 3 + , CD 4 + , and NK increased after AHCS, and abnormal distribution was corrected. Coagulative necrosis was founded in the tumor target area pathologically. Quality of life increased according EORTC QLQ-C30 results after AHCS. No severe complication occurred. Conclusion: AHCS after TACE can reduce tumor load in short term, and it can improve cellular immunity, ameliorate the liver function, increase the quality of life, and make satisfactory effect in the near future. The key point to increase therapeutic efficacy is the embolization of blood vessel and control of heat sink effect by TACE. Interventional

Site directed recombination

Science.gov (United States)

Jurka, Jerzy W.

1997-01-01

Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.

Recombination and dissociative recombination of H2+ and H3+ ions on surfaces with application to hydrogen negative ion sources

International Nuclear Information System (INIS)

Hiskes, J.R.; Karo, A.M.

1988-12-01

A four-step model for recombination and dissociative recombination of H 2 + and H 3 + ions on metal surfaces is discussed. Vibrationally excited molecules, H 2 (v''), from H 3 + recombination are produced in a broad spectrum that enhances the excited level distribution. The application of this latter process to hydrogen negative ion discharges is discussed. 5 refs., 3 figs., 1 tab

Recombination rate variation in mice from an isolated island.

Science.gov (United States)

Wang, Richard J; Gray, Melissa M; Parmenter, Michelle D; Broman, Karl W; Payseur, Bret A

2017-01-01

Recombination rate is a heritable trait that varies among individuals. Despite the major impact of recombination rate on patterns of genetic diversity and the efficacy of selection, natural variation in this phenotype remains poorly characterized. We present a comparison of genetic maps, sampling 1212 meioses, from a unique population of wild house mice (Mus musculus domesticus) that recently colonized remote Gough Island. Crosses to a mainland reference strain (WSB/EiJ) reveal pervasive variation in recombination rate among Gough Island mice, including subchromosomal intervals spanning up to 28% of the genome. In spite of this high level of polymorphism, the genomewide recombination rate does not significantly vary. In general, we find that recombination rate varies more when measured in smaller genomic intervals. Using the current standard genetic map of the laboratory mouse to polarize intervals with divergent recombination rates, we infer that the majority of evolutionary change occurred in one of the two tested lines of Gough Island mice. Our results confirm that natural populations harbour a high level of recombination rate polymorphism and highlight the disparities in recombination rate evolution across genomic scales. © 2016 John Wiley & Sons Ltd.

Live recombinant BHV/BRSV vaccine

OpenAIRE

Keil, G.M.; Rijsewijk, F.A.M.

1998-01-01

The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the protection of cattle against both Bovine herpesvirus infection and against Bovine Respiratory Syncytium virus infection. Also the invention relates to methods for the preparation of such live attenuated r...

Recombinant snake venom prothrombin activators

OpenAIRE

L?vgren, Ann

2012-01-01

Three prothrombin activators; ecarin, which was originally isolated from the venom of the saw-scaled viper Echis carinatus, trocarin from the rough-scaled snake Tropidechis carinatus, and oscutarin from the Taipan snake Oxyuranus scutellatus, were expressed in mammalian cells with the purpose to obtain recombinant prothrombin activators that could be used to convert prothrombin to thrombin. We have previously reported that recombinant ecarin can efficiently generate thrombin without the need ...

Electronic recombination in some physics problems

International Nuclear Information System (INIS)

Guzman, O.

1988-01-01

This work is related to calculations of electronic recombination rates, as a function of electronic density, electronic temperature, and ion nuclear charge. Recombination times can be calculated and compared to cooling time, in cooling processes of ion beans by electrons from storage rings. (A.C.A.S.) [pt

Expression and purification of recombinant hemoglobin in Escherichia coli.

Directory of Open Access Journals (Sweden)

Chandrasekhar Natarajan

Full Text Available Recombinant DNA technologies have played a pivotal role in the elucidation of structure-function relationships in hemoglobin (Hb and other globin proteins. Here we describe the development of a plasmid expression system to synthesize recombinant Hbs in Escherichia coli, and we describe a protocol for expressing Hbs with low intrinsic solubilities. Since the α- and β-chain Hbs of different species span a broad range of solubilities, experimental protocols that have been optimized for expressing recombinant human HbA may often prove unsuitable for the recombinant expression of wildtype and mutant Hbs of other species.As a test case for our expression system, we produced recombinant Hbs of the deer mouse (Peromyscus maniculatus, a species that has been the subject of research on mechanisms of Hb adaptation to hypoxia. By experimentally assessing the combined effects of induction temperature, induction time and E. coli expression strain on the solubility of recombinant deer mouse Hbs, we identified combinations of expression conditions that greatly enhanced the yield of recombinant protein and which also increased the efficiency of post-translational modifications.Our protocol should prove useful for the experimental study of recombinant Hbs in many non-human animals. One of the chief advantages of our protocol is that we can express soluble recombinant Hb without co-expressing molecular chaperones, and without the need for additional reconstitution or heme-incorporation steps. Moreover, our plasmid construct contains a combination of unique restriction sites that allows us to produce recombinant Hbs with different α- and β-chain subunit combinations by means of cassette mutagenesis.

Expression and purification of recombinant hemoglobin in Escherichia coli.

Science.gov (United States)

Natarajan, Chandrasekhar; Jiang, Xiaoben; Fago, Angela; Weber, Roy E; Moriyama, Hideaki; Storz, Jay F

2011-01-01

Recombinant DNA technologies have played a pivotal role in the elucidation of structure-function relationships in hemoglobin (Hb) and other globin proteins. Here we describe the development of a plasmid expression system to synthesize recombinant Hbs in Escherichia coli, and we describe a protocol for expressing Hbs with low intrinsic solubilities. Since the α- and β-chain Hbs of different species span a broad range of solubilities, experimental protocols that have been optimized for expressing recombinant human HbA may often prove unsuitable for the recombinant expression of wildtype and mutant Hbs of other species. As a test case for our expression system, we produced recombinant Hbs of the deer mouse (Peromyscus maniculatus), a species that has been the subject of research on mechanisms of Hb adaptation to hypoxia. By experimentally assessing the combined effects of induction temperature, induction time and E. coli expression strain on the solubility of recombinant deer mouse Hbs, we identified combinations of expression conditions that greatly enhanced the yield of recombinant protein and which also increased the efficiency of post-translational modifications. Our protocol should prove useful for the experimental study of recombinant Hbs in many non-human animals. One of the chief advantages of our protocol is that we can express soluble recombinant Hb without co-expressing molecular chaperones, and without the need for additional reconstitution or heme-incorporation steps. Moreover, our plasmid construct contains a combination of unique restriction sites that allows us to produce recombinant Hbs with different α- and β-chain subunit combinations by means of cassette mutagenesis.

Expression and purification of recombinant hemoglobin in Escherichia coli

DEFF Research Database (Denmark)

Natarajan, Chandrasekhar; Jiang, Xiaoben; Fago, Angela

2011-01-01

BACKGROUND: Recombinant DNA technologies have played a pivotal role in the elucidation of structure-function relationships in hemoglobin (Hb) and other globin proteins. Here we describe the development of a plasmid expression system to synthesize recombinant Hbs in Escherichia coli, and we describe...... a protocol for expressing Hbs with low intrinsic solubilities. Since the alpha- and beta-chain Hbs of different species span a broad range of solubilities, experimental protocols that have been optimized for expressing recombinant human HbA may often prove unsuitable for the recombinant expression......-translational modifications. CONCLUSION/SIGNIFICANCE: Our protocol should prove useful for the experimental study of recombinant Hbs in many non-human animals. One of the chief advantages of our protocol is that we can express soluble recombinant Hb without co-expressing molecular chaperones, and without the need...

Bayesian inference of shared recombination hotspots between humans and chimpanzees.

Science.gov (United States)

Wang, Ying; Rannala, Bruce

2014-12-01

Recombination generates variation and facilitates evolution. Recombination (or lack thereof) also contributes to human genetic disease. Methods for mapping genes influencing complex genetic diseases via association rely on linkage disequilibrium (LD) in human populations, which is influenced by rates of recombination across the genome. Comparative population genomic analyses of recombination using related primate species can identify factors influencing rates of recombination in humans. Such studies can indicate how variable hotspots for recombination may be both among individuals (or populations) and over evolutionary timescales. Previous studies have suggested that locations of recombination hotspots are not conserved between humans and chimpanzees. We made use of the data sets from recent resequencing projects and applied a Bayesian method for identifying hotspots and estimating recombination rates. We also reanalyzed SNP data sets for regions with known hotspots in humans using samples from the human and chimpanzee. The Bayes factors (BF) of shared recombination hotspots between human and chimpanzee across regions were obtained. Based on the analysis of the aligned regions of human chromosome 21, locations where the two species show evidence of shared recombination hotspots (with high BFs) were identified. Interestingly, previous comparative studies of human and chimpanzee that focused on the known human recombination hotspots within the β-globin and HLA regions did not find overlapping of hotspots. Our results show high BFs of shared hotspots at locations within both regions, and the estimated locations of shared hotspots overlap with the locations of human recombination hotspots obtained from sperm-typing studies. Copyright © 2014 by the Genetics Society of America.

Effects of the rad52 gene on recombination in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Prakash, S.; Prakash, L.; Burke, W.; Montelone, B.A.

1979-01-01

Effects of the rad52 mutation in Saccharomyces cerevisiae on meiotic, γ-ray-induced, uv-induced, and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Intra- and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the hisl-1/hisl-315 and trp5-2/trp5-48 heteroalleles. Gene-centromere recombination was also not observed in rad52/rad52 diploids. No γ-ray-induced intragenic mitotic recombination is seen in rad52/rad52 diploids and uv-induced intragenic recombination is greatly reduced. However, spontaneous mitotic recombination is not similarly affected. The RAD52 gene thus functions in recombination in meiosis and in γ-ray and uv-induced mitotic recombination but not in spontaneous mitotic recombination

Heterogeneous recombination among Hepatitis B virus genotypes.

Science.gov (United States)

Castelhano, Nadine; Araujo, Natalia M; Arenas, Miguel

2017-10-01

The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the latter, it is known that recombination played a major role in the emergence and genetic diversification of novel genotypes. In this regard, the quantification of viral recombination in each genotype can provide relevant information to devise expectations about the evolutionary trends of the epidemic. Here we measured the amount of this evolutionary force by estimating global and local recombination rates in >4700 HBV complete genome sequences corresponding to nine (A to I) HBV genotypes. Counterintuitively, we found that genotype E presents extremely high levels of recombination, followed by genotypes B and C. On the other hand, genotype G presents the lowest level, where recombination is almost negligible. We discuss these findings in the light of known characteristics of these genotypes. Additionally, we present a phylogenetic network to depict the evolutionary history of the studied HBV genotypes. This network clearly classified all genotypes into specific groups and indicated that diverse pairs of genotypes are derived from a common ancestor (i.e., C-I, D-E and, F-H) although still the origin of this virus presented large uncertainty. Altogether we conclude that the amount of observed recombination is heterogeneous among HBV genotypes and that this heterogeneity can influence on the future expansion of the epidemic. Copyright © 2017 Elsevier B.V. All rights reserved.

Graded Recombination Layers for Multijunction Photovoltaics

KAUST Repository

Koleilat, Ghada I.

2012-06-13

Multijunction devices consist of a stack of semiconductor junctions having bandgaps tuned across a broad spectrum. In solar cells this concept is used to increase the efficiency of photovoltaic harvesting, while light emitters and detectors use it to achieve multicolor and spectrally tunable behavior. In series-connected current-matched multijunction devices, the recombination layers must allow the hole current from one cell to recombine, with high efficiency and low voltage loss, with the electron current from the next cell. We recently reported a tandem solar cell in which the recombination layer was implemented using a progression of n-type oxides whose doping densities and work functions serve to connect, with negligible resistive loss at solar current densities, the constituent cells. Here we present the generalized conditions for design of efficient graded recombination layer solar devices. We report the number of interlayers and the requirements on work function and doping of each interlayer, to bridge an work function difference as high as 1.6 eV. We also find solutions that minimize the doping required of the interlayers in order to minimize optical absorption due to free carriers in the graded recombination layer (GRL). We demonstrate a family of new GRL designs experimentally and highlight the benefits of the progression of dopings and work functions in the interlayers. © 2012 American Chemical Society.

Review of Parton Recombination Models

International Nuclear Information System (INIS)

Bass, Steffen A

2006-01-01

Parton recombination models have been very successful in explaining data taken at RHIC on hadron spectra and emission patterns in Au+Au collisions at transverse momenta above 2 GeV/c, which have exhibited features which could not be understood in the framework of basic perturbative QCD. In this article I will review the current status on recombination models and outline which future challenges need to be addressed by this class of models

The model of recombination process in TlBr

International Nuclear Information System (INIS)

Grigorjeva, L.; Millers, D.

2002-01-01

The time-resolved luminescence was used as a tool in the study of recombination process in several undoped TlBr crystals. The spectra and decay kinetics observed under electron beam excitation were investigated. Observation of several luminescence bands with different decay rates shows that more than one recombination center is involved and the recombination process is quite complicated. The band at ∼2.5 eV is dominant under 10 ns excitation pulse (electron beam or nitrogen laser pulses). The results of short-lived absorption and luminescence are used for analysis of possible mechanisms of recombination processes in TlBr

Response evaluation of malignant liver lesions after TACE/SIRT. Comparison of manual and semi-automatic measurement of different response criteria in multislice CT

International Nuclear Information System (INIS)

Hoeink, Anna Janina

2017-01-01

To compare measurement precision and interobserver variability in the evaluation of hepatocellular carcinoma (HCC) and liver metastases in MSCT before and after transarterial local ablative therapies. Retrospective study of 72 patients with malignant liver lesions (42 metastases; 30 HCCs) before and after therapy (43 SIRT procedures; 29 TACE procedures). Established (LAD; SAD; WHO) and vitality-based parameters (mRECIST; mLAD; mSAD; EASL) were assessed manually and semi-automatically by two readers. The relative interobserver difference (RID) and intraclass correlation coefficient (ICC) were calculated. The median RID for vitality-based parameters was lower from semi-automatic than from manual measurement of mLAD (manual 12.5 %; semi-automatic 3.4 %), mSAD (manual 12.7 %; semi-automatic 5.7 %) and EASL (manual 10.4 %; semi-automatic 1.8 %). The difference in established parameters was not statistically noticeable (p > 0.05). The ICCs of LAD (manual 0.984; semi-automatic 0.982), SAD (manual 0.975; semi-automatic 0.958) and WHO (manual 0.984; semi-automatic 0.978) are high, both in manual and semi-automatic measurements. The ICCs of manual measurements of mLAD (0.897), mSAD (0.844) and EASL (0.875) are lower. This decrease cannot be found in semi-automatic measurements of mLAD (0.997), mSAD (0.992) and EASL (0.998). Conclusion Vitality-based tumor measurements of HCC and metastases after transarterial local therapies should be performed semi-automatically due to greater measurement precision, thus increasing the reproducibility and in turn the reliability of therapeutic decisions.

Response evaluation of malignant liver lesions after TACE/SIRT. Comparison of manual and semi-automatic measurement of different response criteria in multislice CT

Energy Technology Data Exchange (ETDEWEB)

Hoeink, Anna Janina [Univ. Hospital Cologne (Germany). Diagnostic and Interventional Radiology; Schuelke, Christoph; Loehnert, Annika; Kammerer, Sara; Fortkamp, Rasmus; Heindel, Walter; Buerke, Boris [Univ. Hospital Muenster (UKM), Muenster (Germany). Dept. of Clinical Radiology; Koch, Raphael [Univ. Hospital Muenster (UKM), Muenster (Germany). Inst. of Biostatistics and Clinical Research (IBKF)

2017-11-15

To compare measurement precision and interobserver variability in the evaluation of hepatocellular carcinoma (HCC) and liver metastases in MSCT before and after transarterial local ablative therapies. Retrospective study of 72 patients with malignant liver lesions (42 metastases; 30 HCCs) before and after therapy (43 SIRT procedures; 29 TACE procedures). Established (LAD; SAD; WHO) and vitality-based parameters (mRECIST; mLAD; mSAD; EASL) were assessed manually and semi-automatically by two readers. The relative interobserver difference (RID) and intraclass correlation coefficient (ICC) were calculated. The median RID for vitality-based parameters was lower from semi-automatic than from manual measurement of mLAD (manual 12.5 %; semi-automatic 3.4 %), mSAD (manual 12.7 %; semi-automatic 5.7 %) and EASL (manual 10.4 %; semi-automatic 1.8 %). The difference in established parameters was not statistically noticeable (p > 0.05). The ICCs of LAD (manual 0.984; semi-automatic 0.982), SAD (manual 0.975; semi-automatic 0.958) and WHO (manual 0.984; semi-automatic 0.978) are high, both in manual and semi-automatic measurements. The ICCs of manual measurements of mLAD (0.897), mSAD (0.844) and EASL (0.875) are lower. This decrease cannot be found in semi-automatic measurements of mLAD (0.997), mSAD (0.992) and EASL (0.998). Conclusion Vitality-based tumor measurements of HCC and metastases after transarterial local therapies should be performed semi-automatically due to greater measurement precision, thus increasing the reproducibility and in turn the reliability of therapeutic decisions.

Affinity purification of recombinant human plasminogen activator ...

African Journals Online (AJOL)

Affinity purification of recombinant human plasminogen activator from ... Screening antibody was performed using rhPA milk in an ELISA-elution assay. ... useful for purifying other tPA mutants or other novel recombinant milkderived proteins.

Recombinant human bone morphogenetic protein induces bone formation

International Nuclear Information System (INIS)

Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M.

1990-01-01

The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy.

Science.gov (United States)

Lahrsow, Maximilian; Albrecht, Moritz H; Bickford, Matthew W; Vogl, Thomas J

2017-06-01

To use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment. Fifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions. One month after initial cTACE, seven lesions showed early response. There was no significant difference in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10 -3  mm 2 /s) and no response (median 1.30 × 10 -3  mm 2 /s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC. In patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.

Inference of Ancestral Recombination Graphs through Topological Data Analysis

Science.gov (United States)

Cámara, Pablo G.; Levine, Arnold J.; Rabadán, Raúl

2016-01-01

The recent explosion of genomic data has underscored the need for interpretable and comprehensive analyses that can capture complex phylogenetic relationships within and across species. Recombination, reassortment and horizontal gene transfer constitute examples of pervasive biological phenomena that cannot be captured by tree-like representations. Starting from hundreds of genomes, we are interested in the reconstruction of potential evolutionary histories leading to the observed data. Ancestral recombination graphs represent potential histories that explicitly accommodate recombination and mutation events across orthologous genomes. However, they are computationally costly to reconstruct, usually being infeasible for more than few tens of genomes. Recently, Topological Data Analysis (TDA) methods have been proposed as robust and scalable methods that can capture the genetic scale and frequency of recombination. We build upon previous TDA developments for detecting and quantifying recombination, and present a novel framework that can be applied to hundreds of genomes and can be interpreted in terms of minimal histories of mutation and recombination events, quantifying the scales and identifying the genomic locations of recombinations. We implement this framework in a software package, called TARGet, and apply it to several examples, including small migration between different populations, human recombination, and horizontal evolution in finches inhabiting the Galápagos Islands. PMID:27532298

Retroviral Vectors for Analysis of Viral Mutagenesis and Recombination

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Jonathan M.O. Rawson

2014-09-01

Full Text Available Retrovirus population diversity within infected hosts is commonly high due in part to elevated rates of replication, mutation, and recombination. This high genetic diversity often complicates the development of effective diagnostics, vaccines, and antiviral drugs. This review highlights the diverse vectors and approaches that have been used to examine mutation and recombination in retroviruses. Retroviral vectors for these purposes can broadly be divided into two categories: those that utilize reporter genes as mutation or recombination targets and those that utilize viral genes as targets of mutation or recombination. Reporter gene vectors greatly facilitate the detection, quantification, and characterization of mutants and/or recombinants, but may not fully recapitulate the patterns of mutagenesis or recombination observed in native viral gene sequences. In contrast, the detection of mutations or recombination events directly in viral genes is more biologically relevant but also typically more challenging and inefficient. We will highlight the advantages and disadvantages of the various vectors and approaches used as well as propose ways in which they could be improved.

Hadron production at RHIC: recombination of quarks

Energy Technology Data Exchange (ETDEWEB)

Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

2005-01-01

We discuss quark recombination applied to the hadronization of a quark gluon plasma. It has been shown that the quark recombination model can explain essential features of hadron production measured in high energy heavy ion collisions.

Catalytic hydrogen recombination for nuclear containments

International Nuclear Information System (INIS)

Koroll, G.W.; Lau, D.W.P.; Dewit, W.A.; Graham, W.R.C.

1994-01-01

Catalytic recombiners appear to be a credible option for hydrogen mitigation in nuclear containments. The passive operation, versatility and ease of back fitting are appealing for existing stations and new designs. Recently, a generation of wet-proofed catalyst materials have been developed at AECL which are highly specific to H 2 -O 2 , are active at ambient temperatures and are being evaluated for containment applications. Two types of catalytic recombiners were evaluated for hydrogen removal in containments based on the AECL catalyst. The first is a catalytic combustor for application in existing air streams such as provided by fans or ventilation systems. The second is an autocatalytic recombiner which uses the enthalpy of reaction to produce natural convective flow over the catalyst elements. Intermediate-scale results obtained in 6 m 3 and 10 m 3 spherical and cylindrical vessels are given to demonstrate self-starting limits, operating limits, removal capacity, scaling parameters, flow resistance, mixing behaviour in the vicinity of an operating recombiner and sensitivity to poisoning, fouling and radiation. (author). 13 refs., 10 figs

Recombination Processes and Nonlinear Markov Chains.

Science.gov (United States)

Pirogov, Sergey; Rybko, Alexander; Kalinina, Anastasia; Gelfand, Mikhail

2016-09-01

Bacteria are known to exchange genetic information by horizontal gene transfer. Since the frequency of homologous recombination depends on the similarity between the recombining segments, several studies examined whether this could lead to the emergence of subspecies. Most of them simulated fixed-size Wright-Fisher populations, in which the genetic drift should be taken into account. Here, we use nonlinear Markov processes to describe a bacterial population evolving under mutation and recombination. We consider a population structure as a probability measure on the space of genomes. This approach implies the infinite population size limit, and thus, the genetic drift is not assumed. We prove that under these conditions, the emergence of subspecies is impossible.

[Construction and expression of a recombinant adenovirus with LZP3].

Science.gov (United States)

Chen, Bang-dang; Zhang, Fu-chun; Sun, Mei-yu; Li, Yi-jie; Ma, Zheng-hai

2007-08-01

To explore a new immunocontraceptive vaccine and construct an attenuated recombinant adenoviral vaccine against Lagurus lagurus zona pellucida 3(LZP3). LZP3 gene was subcloned into the shuttle vector pShuttle-CMV, and then a two-step transformation procedure was employed to construct a recombinant adenoviral plasmid with LZP3, which was digested with Pac I and transfected into HEK293 cells to package recombinant adenovirus particles. Finally, HeLa cells were infected by the recombinant adenovirus. LZP3 gene was detected from the recombinant virus by PCR, and its transcription and expression were analyzed by RT-PCR and Western blot. Recombinant adenovirus vector pAd-LZP3 with LZP3 gene was constructed by homologous recombination in E.coli, and a recombinant adenovirus was obtained by transfecting HEK293 cells with pAd-LZP3. PCR test indicated that LZP3 gene was successfully integrated into the adenoviral genome, and the titer of the recombinant adenovirus reached 1.2x10(10) pfu/L. The transcription and expression of LZP3 gene in the infected HeLa cells were confirmed by RT-PCR and Western blot. The recombinant adenovirus RAd-LZP3 can be successfully expressed in the infected HeLa cells, which lays the foundation for further researches into immunizing animals with RAd-LZP3.

Genetic characterization of somatic recombination in Trichoderma pseudokoningii

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Barcellos Fernando Gomes

2003-01-01

Full Text Available Crossing experiments via hyphal anastomosis between two strains contrasting for auxotrophic markers of Trichoderma pseudokoningii were conducted to characterize the somatic recombination process in this specie. Four crossings were made and a total of 1052 colonies obtained from conidial suspensions of the heterokaryotic colonies were analyzed. Sixty-eight recombinant colonies, from four growing generations, were analyzed for the auxotrophic markers. Of the 68 colonies analyzed, 58 were stable after four generations and the remainders were unstable, reverting to one of the parentals. Most of the recombinant colonies were unstable through subculture and after four growing generations they showed the leu ino met markers (auxotrophic for leucin, inositol and metionin respectively. The unstable recombinant colonies showed irregular growing borders, sparse sporulation and frequent sector formation. The results suggest the occurrence of recombination mechanisms in the heterokaryon (somatic recombination, different from those described for the parasexual cycle or parameiosis. Therefore, we proposed the ocurrence of nuclei degradation from one parental (non prevalent parental in the heterokaryon and that the resulting chromosomal fragments may be incorporated into whole nuclei of the another parental (prevalent parental. However the parameiosis as originally described cannot be excluded.

Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors

International Nuclear Information System (INIS)

Roche, Alain; Girish, Baragur V.; de Baere, Thierry; Baudin, Eric; Schlumberger, Martin; Boige, Valerie; Ducreux, Michel; Elias, Dominique; Lasser, Philippe

2003-01-01

Our objective was to report the outcome in patients with liver metastasis from endocrine tumors who underwent transarterial chemoembolization (TACE) as first-line non-surgical treatment. From January 1990 to December 2000, 14 patients with progressive unresectable liver metastases from digestive neuroendocrine tumor were treated with TACE (mean of 3.6 sessions) before any non-surgical treatment (somatostatin analogue, chemotherapy or interferon). Liver involvement was less than 50% in 11 patients. Size of the largest lesion ranged from 1.5 to 10 cm. Ten patients presented with carcinoid symptoms. The TACE was performed with Doxorubicin emulsified in Lipiodol and gelatin sponge particles. Symptomatic response upon flushes and/or diarrhea was complete in 7 of 10 cases and partial in 2 of 10 cases. An objective morphologic response was noted in 12 of 14 cases. The 5- and 10-year survival rate from diagnosis was 83 and 56%, respectively. Six patients were alive at the end of the study after 27-100 months from first TACE and 38-142 months from diagnosis. Three of them were successfully palliated for 55, 69, and 100 months with only TACE as treatment. Long-term palliation is possible in unresectable liver metastases from digestive neuroendocrine tumors with a few sessions of TACE as first-line and eventually exclusive treatment. (orig.)

Variation in Recombination Rate and Its Genetic Determinism in Sheep Populations.

Science.gov (United States)

Petit, Morgane; Astruc, Jean-Michel; Sarry, Julien; Drouilhet, Laurence; Fabre, Stéphane; Moreno, Carole R; Servin, Bertrand

2017-10-01

Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and data sets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified ∼50,000 crossover hotspots on the genome, and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting interindividual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly two other loci of smaller effects including the KCNJ15 and FSHR genes. The comparison of these new results to those obtained previously in a distantly related population of domestic sheep (the Soay) revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome. The two data sets were thus combined to create more precise male meiotic recombination maps in Sheep. However, despite their similar recombination maps, Soay and Lacaune males were found to exhibit different heritabilities and QTL effects for interindividual variation in genome-wide recombination rates. This highlights the robustness of recombination patterns to underlying variation in their genetic determinism. Copyright © 2017 by the Genetics Society

Evolution of recombination in eutherian mammals: insights into mechanisms that affect recombination rates and crossover interference

OpenAIRE

Segura, Joana; Ferretti, Luca; Ramos-Onsins, Sebastián; Capilla, Laia; Farré, Marta; Reis, Fernanda; Oliver-Bonet, Maria; Fernández-Bellón, Hugo; Garcia, Francisca; Garcia-Caldés, Montserrat; Robinson, Terence J.; Ruiz-Herrera, Aurora

2013-01-01

Recombination allows faithful chromosomal segregation during meiosis and contributes to the production of new heritable allelic variants that are essential for the maintenance of genetic diversity. Therefore, an appreciation of how this variation is created and maintained is of critical importance to our understanding of biodiversity and evolutionary change. Here, we analysed the recombination features from species representing the major eutherian taxonomic groups Afrotheria, Rodentia, Primat...

In vitro V(D)J recombination: signal joint formation.

Science.gov (United States)

Cortes, P; Weis-Garcia, F; Misulovin, Z; Nussenzweig, A; Lai, J S; Li, G; Nussenzweig, M C; Baltimore, D

1996-11-26

The first step of V(D)J recombination, specific cleavage at the recombination signal sequence (RSS), can be carried out by the recombination activating proteins RAG1 and RAG2. In vivo, the cleaved coding and signal ends must be rejoined to generate functional antigen receptors and maintain chromosomal integrity. We have investigated signal joint formation using deletion and inversion substrates in a cell free system. RAG1 and RAG2 alone or in combination were unable to generate signal joints. However, RAG1 and RAG2 complemented with nuclear extracts were able to recombine an extrachromosomal substrate and form precise signal joints. The in vitro reaction resembled authentic V(D)J recombination in being Ku-antigen-dependent.

Recombinant DNA production of spider silk proteins.

Science.gov (United States)

Tokareva, Olena; Michalczechen-Lacerda, Valquíria A; Rech, Elíbio L; Kaplan, David L

2013-11-01

Spider dragline silk is considered to be the toughest biopolymer on Earth due to an extraordinary combination of strength and elasticity. Moreover, silks are biocompatible and biodegradable protein-based materials. Recent advances in genetic engineering make it possible to produce recombinant silks in heterologous hosts, opening up opportunities for large-scale production of recombinant silks for various biomedical and material science applications. We review the current strategies to produce recombinant spider silks. © 2013 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Recombination-Driven Genome Evolution and Stability of Bacterial Species.

Science.gov (United States)

Dixit, Purushottam D; Pang, Tin Yau; Maslov, Sergei

2017-09-01

While bacteria divide clonally, horizontal gene transfer followed by homologous recombination is now recognized as an important contributor to their evolution. However, the details of how the competition between clonality and recombination shapes genome diversity remains poorly understood. Using a computational model, we find two principal regimes in bacterial evolution and identify two composite parameters that dictate the evolutionary fate of bacterial species. In the divergent regime, characterized by either a low recombination frequency or strict barriers to recombination, cohesion due to recombination is not sufficient to overcome the mutational drift. As a consequence, the divergence between pairs of genomes in the population steadily increases in the course of their evolution. The species lacks genetic coherence with sexually isolated clonal subpopulations continuously formed and dissolved. In contrast, in the metastable regime, characterized by a high recombination frequency combined with low barriers to recombination, genomes continuously recombine with the rest of the population. The population remains genetically cohesive and temporally stable. Notably, the transition between these two regimes can be affected by relatively small changes in evolutionary parameters. Using the Multi Locus Sequence Typing (MLST) data, we classify a number of bacterial species to be either the divergent or the metastable type. Generalizations of our framework to include selection, ecologically structured populations, and horizontal gene transfer of nonhomologous regions are discussed as well. Copyright © 2017 by the Genetics Society of America.

Genetic recombination of tick-borne flaviviruses among wild-type strains.

Science.gov (United States)

Norberg, Peter; Roth, Anette; Bergström, Tomas

2013-06-05

Genetic recombination has been suggested to occur in mosquito-borne flaviviruses. In contrast, tick-borne flaviviruses have been thought to evolve in a clonal manner, although recent studies suggest that recombination occurs also for these viruses. We re-analyzed the data and found that previous conclusions on wild type recombination were probably falsely drawn due to misalignments of nucleotide sequences, ambiguities in GenBank sequences, or different laboratory culture histories suggestive of recombination events in laboratory. To evaluate if reliable predictions of wild type recombination of tick-borne flaviviruses can be made, we analyzed viral strains sequenced exclusively for this study, and other flavivirus sequences retrieved from GenBank. We detected genetic signals supporting recombination between viruses within the three clades of TBEV-Eu, TBEV-Sib and TBEV-Fe, respectively. Our results suggest that the tick-borne encephalitis viruses may undergo recombination under natural conditions, but that geographic barriers restrict most recombination events to involve only closely genetically related viruses. Copyright © 2013 Elsevier Inc. All rights reserved.

The influence of recombination on human genetic diversity.

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Chris C A Spencer

2006-09-01

Full Text Available In humans, the rate of recombination, as measured on the megabase scale, is positively associated with the level of genetic variation, as measured at the genic scale. Despite considerable debate, it is not clear whether these factors are causally linked or, if they are, whether this is driven by the repeated action of adaptive evolution or molecular processes such as double-strand break formation and mismatch repair. We introduce three innovations to the analysis of recombination and diversity: fine-scale genetic maps estimated from genotype experiments that identify recombination hotspots at the kilobase scale, analysis of an entire human chromosome, and the use of wavelet techniques to identify correlations acting at different scales. We show that recombination influences genetic diversity only at the level of recombination hotspots. Hotspots are also associated with local increases in GC content and the relative frequency of GC-increasing mutations but have no effect on substitution rates. Broad-scale association between recombination and diversity is explained through covariance of both factors with base composition. To our knowledge, these results are the first evidence of a direct and local influence of recombination hotspots on genetic variation and the fate of individual mutations. However, that hotspots have no influence on substitution rates suggests that they are too ephemeral on an evolutionary time scale to have a strong influence on broader scale patterns of base composition and long-term molecular evolution.

Triplet formation in the ion recombination in irradiated liquids

International Nuclear Information System (INIS)

Bartczak, W.M.; Tachiya, M.; Hummel, A.

1990-01-01

The formation of singlet and triplet excited stages in the ion recombination in groups of oppositely charged ions (or positive ions and electrons) in nonpolar liquids, as occurs in the tracks of high energy electrons, is considered. Theoretical studies on triplet formation in groups of ion pairs have thus far concentrated on the case where recombination of the negative ions with any of the positive ions in the group is equally probable (random recombination). In this paper the probability for geminate recombination (electron and parent positive ion) vs cross-recombination (an electron with a positive ion other than its parent ion) in multiple ion pair groups is calculated by computer simulation and the effect of the initial spatial configuration of the charged species is investigated. It is also shown explicitly that the probability for singlet formation as a result of cross recombination is equal to 1/4, when spin relaxation by magnetic interaction with the medium and by exchange interaction can be neglected. The effect of the preferential recombination on the singlet formation probability is illustrated and recent experimental results on singlet to triplet ratios are discussed. (author)

Damage-induced ectopic recombination in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Kupiec, M; Steinlauf, R

1997-06-09

Mitotic recombination in the yeast Saccharomyces cerevisiae is induced when cells are irradiated with UV or X-rays, reflecting the efficient repair of damage by recombinational repair mechanisms. We have used multiply marked haploid strains that allow the simultaneous detection of several types of ectopic recombination events. We show that inter-chromosomal ectopic conversion of lys2 heteroalleles and, to a lesser extent, direct repeat recombination (DRR) between non-tandem repeats, are increased by DNA-damaging agents; in contrast, ectopic recombination of the naturally occurring Ty element is not induced. We have tested several hypotheses that could explain the preferential lack of induction of Ty recombination by DNA-damaging agents. We have found that the lack of induction cannot be explained by a cell cycle control or by an effect of the mating-type genes. We also found no role for the flanking long terminal repeats (LTRs) of the Ty in preventing the induction. Ectopic conversion, DRR, and forward mutation of artificial repeats show different kinetics of induction at various positions of the cell cycle, reflecting different mechanisms of recombination. We discuss the mechanistic and evolutionary aspects of these results.

A Glance at Recombination Hotspots in the Domestic Cat.

Directory of Open Access Journals (Sweden)

Hasan Alhaddad

Full Text Available Recombination has essential roles in increasing genetic variability within a population and in ensuring successful meiotic events. The objective of this study is to (i infer the population-scaled recombination rate (ρ, and (ii identify and characterize regions of increased recombination rate for the domestic cat, Felis silvestris catus. SNPs (n = 701 were genotyped in twenty-two East Asian feral cats (random bred. The SNPs covered ten different chromosomal regions (A1, A2, B3, C2, D1, D2, D4, E2, F2, X with an average region size of 850 Kb and an average SNP density of 70 SNPs/region. The Bayesian method in the program inferRho was used to infer regional population recombination rates and hotspots localities. The regions exhibited variable population recombination rates and four decisive recombination hotspots were identified on cat chromosome A2, D1, and E2 regions. As a description of the identified hotspots, no correlation was detected between the GC content and the locality of recombination spots, and the hotspots enclosed L2 LINE elements and MIR and tRNA-Lys SINE elements.

Risk factors for the leakage of chemotherapeutic agents into systemic circulation after transcatheter arterial chemoembolization of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Ming-Yen Hsieh

2011-10-01

Full Text Available This prospective study was to investigate the possible risk factors for the leakage of chemotherapeutic agent into the systemic circulation after transcatheter arterial chemoembolization (TACE of hepatocellular carcinoma (HCC. Peripheral plasma concentrations of chemotherapeutic agents were determined at 1 hour and 72 hours after TACE by high-performance liquid chromatography in 53 patients. HCC were divided into three types namely single nodule (<5 cm, multiple nodules (all <5 cm, and main nodule measuring 5 cm or more. Forty-four patients (83% showed detectable chemotherapeutic concentrations within 72 hours after TACE. Patients with single nodular-type HCC had lower incidence of detectable plasma chemotherapeutic agents after TACE than the other two groups (all p<0.05. The injected doses of lipiodol, epirubicin, and mitomycin C were lower in patients without detection than in patients with detectable chemotherapeutic agents (all p<0.05. Multivariate logistic regression showed that tumor type and injected dose of lipiodol were two independent risk factors for the leakage of mitomycin C at 1 hour after TACE (all p<0.05, and the injected dose of mitomycin C was the risk factor for the leakage of epirubicin at 1 hour after TACE (p<0.05. In conclusion, multiple nodular type and large nodule measuring 5 cm or more have a risk of leakage of mitomycin C after TACE. Injected dose of lipiodol and mitomycin C as risk factor for the leakage of mitomycin C and epirubicin respectively may be because of competition of their injected volume within the limited space of target.

Dielectronic recombination theory

International Nuclear Information System (INIS)

LaGattuta, K.J.

1991-01-01

A theory now in wide use for the calculation of dielectronic recombination cross sections (σ DR ) and rate coefficients (α DR ) was one introduced originally by Feshbach for nuclear physics applications, and then later adapted for atomic scattering problems by Hahn. In the following, we briefly review this theory in a very general form, which allows one to account for the effects of overlapping and interacting resonances, as well as continuum-continuum coupling. An extension of our notation will then also allow for the inclusion of the effects of direct radiative recombination, along with a treatment of the interference between radiative and dielectronic recombination. Other approaches to the calculation of σ DR have been described by Fano and by Seaton. We will not consider those theories here. Calculations of α DR have progressed considerably over the last 25 years, since the early work of Burgess. Advances in the reliability of theoretical predictions have also been promoted recently b a variety of direct laboratory measurements of σ DR . While the measurements of σ DR for δn ≠ 0 excitations have tended to agree very well with calculations, the case of δn = 0 has been much problematic. However, by invoking a mechanism originally proposed by Jacobs, which takes into account the effect of stray electric fields on high Rydberg states (HRS) participating in the DR process, new calculations have improved the agreement between theory and experiment for these cases. Nevertheless, certain discrepancies still remain

Scrambling Eggs: Meiotic Drive and the Evolution of Female Recombination Rates

Science.gov (United States)

Brandvain, Yaniv; Coop, Graham

2012-01-01

Theories to explain the prevalence of sex and recombination have long been a central theme of evolutionary biology. Yet despite decades of attention dedicated to the evolution of sex and recombination, the widespread pattern of sex differences in the recombination rate is not well understood and has received relatively little theoretical attention. Here, we argue that female meiotic drivers—alleles that increase in frequency by exploiting the asymmetric cell division of oogenesis—present a potent selective pressure favoring the modification of the female recombination rate. Because recombination plays a central role in shaping patterns of variation within and among dyads, modifiers of the female recombination rate can function as potent suppressors or enhancers of female meiotic drive. We show that when female recombination modifiers are unlinked to female drivers, recombination modifiers that suppress harmful female drive can spread. By contrast, a recombination modifier tightly linked to a driver can increase in frequency by enhancing female drive. Our results predict that rapidly evolving female recombination rates, particularly around centromeres, should be a common outcome of meiotic drive. We discuss how selection to modify the efficacy of meiotic drive may contribute to commonly observed patterns of sex differences in recombination. PMID:22143919

Recombinant expression systems: the obstacle to helminth vaccines?

Science.gov (United States)

Geldhof, Peter; De Maere, Veerle; Vercruysse, Jozef; Claerebout, Edwin

2007-11-01

The need for alternative ways to control helminth parasites has in recent years led to a boost in vaccination experiments with recombinant antigens. Despite the use of different expression systems, only a few recombinants induced high levels of protection against helminths. This is often attributed to the limitations of the current expression systems. Therefore, the need for new systems that can modify and glycosylate the expressed antigens has been advocated. However, analysis of over 100 published vaccine trials with recombinant helminth antigens indicates that it is often not known whether the native parasite antigen itself can induce protection or, if it does, which epitopes are important. This information is vital for a well-thought-out strategy for recombinant production. So, in addition to testing more expression systems, it should be considered that prior evaluation and characterization of the native antigens might help the development of recombinant vaccines against helminths in the long term.

A study on the hydrogen recombination rates of catalytic recombiners and deliberate ignition

International Nuclear Information System (INIS)

Fineschi, F.; Bazzichi, M.; Carcassi, M.

1994-01-01

A study is being carried out by the Department of Nuclear and Mechanical Constructions (DCMN) at the University of Pisa on catalytic recombiners and on deliberately induced weak deflagration. The recombination rates of different types of catalytic devices were obtained from a thorough analysis of published experimental data. The main parameter that affects the effectiveness of these devices seems to be the molar density of the deficiency reactant rather than its volumetric concentration. The recombination rate of weak deflagrations in vented compartments has been assessed with experimental tests carried out in a small scale glass vessel. Through a computerized system of analysis of video recordings of the deflagrations, the flame surface and the burned gas volume were obtained as functions of time. Although approximations are inevitable, the method adopted to identify the position of the flame during propagation is more reliable than other non-visual methods (thermocouples and ion-probes). It can only easily be applied to vented weak deflagrations, i.e. when the hydrogen concentration is far from stoichiometric conditions and near to flammability limits, because the pressurization has to be limited due to the low mechanical resistance of the glass. The values of flame surface and burned gas volume were used as inputs for a computer code to calculate the recombining rate, the burning velocity and the pressure transient in the experimental test. The code is being validated with a methodology principally based on a comparison of the measurements of pressure with the calculated values. The research gave some very interesting results on a small scale which should in the future be compared with large scale data

TACE with Ar-He Cryosurgery Combined Minimal Invasive Technique for the Treatment of Primary NSCLC in 139 Cases

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Yunzhi ZHOU

2010-01-01

Full Text Available Background and objective TACE, Ar-He target cryosurgery and radioactive seeds implantation are the mainly micro-invasive methods in the treatment of lung cancer. This article summarizes the survival quality after treatment, the clinical efficiency and survival period, and analyzes the advantages and shortcomings of each methods so as to evaluate the clinical effect of non-small cell lung cancer with multiple minimally invasive treatment. Methods All the 139 cases were nonsmall cell lung cancer patients confirmed by pathology and with follow up from July 2006 to July 2009 retrospectively, and all of them lost operative chance by comprehensive evaluation. Different combination of multiple minimally invasive treatments were selected according to the blood supply, size and location of the lesion. Among the 139 cases, 102 cases of primary and 37 cases of metastasis to mediastinum, lung and chest wall, 71 cases of abundant blood supply used the combination of superselective target artery chemotherapy, Ar-He target cryoablation and radiochemotherapy with seeds implantation; 48 cases of poor blood supply use single Ar-He target cryoablation; 20 cases of poor blood supply use the combination of Ar-He target cryoablation and radiochemotheraoy with seeds implantation. And then the pre- and post-treatment KPS score, imaging data and the result of follow up were analyzed. Results The KPS score increased 20.01 meanly after the treatment. Follow up 3 years, 44 cases of CR, 87 cases of PR, 3 cases of NC and 5 cases of PD, and the efficiency was 94.2%. Ninety-nine cases of 1 year survival (71.2%, 43 cases of 2 years survival (30.2%, 4 cases with over 3 years survival and the median survival was 19 months. Average survival was (16±1.5months. There was no severe complications, such as spinal cord injury, vessel and pericardial aspiration. Conclusion Minimally invasive technique is a highly successful, micro-invasive and effective method with mild complications

Photoionization and electron-ion recombination of Cr I

International Nuclear Information System (INIS)

Nahar, Sultana N.

2009-01-01

Using the unified method, the inverse processes of photoionization and electron-ion recombination are studied in detail for neutral chromium, (CrI+hν↔CrII+e), for the ground and excited states. The unified method based on close-coupling approximation and R-matrix method (i) subsumes both the radiative recombination (RR) and dielectronic recombination (DR) for the total rate and (ii) provides self-consistent sets of photoionization cross sections σ PI and recombination rates α RC . The present results show in total photoionization of the ground and excited states an enhancement in the background at the first excited threshold, 3d 4 4s 5 D state of the core. One prominent phot-excitation-of-core (PEC) resonance due to one dipole allowed transition ( 6 S- 6 P o ) in the core is found in the photoionization cross sections of most of the valence electron excited states. Structures in the total and partial photoionization, for ionization into various excited core states and ground state only, respectively, are demonstrated. Results are presented for the septet and quintet states with n≤10 and l≤9 of Cr I. These states couple to the core ground state 6 S and contribute to the recombination rates. State-specific recombination rates are also presented for these states and their features are illustrated. The total recombination rate shows two DR peaks, one at a relatively low temperature, at 630 K, and the other around 40,000 K. This can explain existence of neutral Cr in interstellar medium. Calculations were carried out in LS coupling using a close-coupling wave function expansion of 40 core states. The results illustrate the features in the radiative processes of Cr I and provide photoionization cross sections and recombination rates with good approximation for this astrophysically important ion.

Workshop on Radio Recombination Lines

CERN Document Server

1980-01-01

Since their first detection 15 years ago, radio recombination lines from several elements have been observed in a wide variety of objects including HII regions, planetary nebulae, molecular clouds, the diffuse interstellar medium, and recently, other galaxies. The observations span almost the entire range from 0.1 to 100 GHz, and employ both single­ djsh and aperture synthesis techniques. The theory of radio recombination lines has also advanced strongly, to the point where it is perhaps one of the best-understood in astro­ physics. In a parallel development, it has become possible over the last decade to study these same highly-excited atoms in the laboratory; this work provides further confirmation of the theoretical framework. However there has been continuing controversy over the astrophysical interpre­ tation of radio recombination line observations, especially regarding the role of stimulated emission. A workshop was held in Ottawa on 24-25 August, 1979, bringing together many of the active scientist...

Determination of recombination in Mycoplasma hominis

DEFF Research Database (Denmark)

Jacobsen, Iben Søgaard; Boesen, Thomas; Mygind, Tina

2002-01-01

disequilibrium and distance between the segregating sites, by the homoplasy ratio (H ratio), and by compatibility matrices. The gap gene showed well-supported evidence for high levels of recombination, whereas recombination was less frequent and not significant within the other genes. The analysis revealed......B-hitL, excinuclease ABC subunit A (uvrA) and glyceraldehyde-3-phosphate dehydrogenase (gap) genes. The level of variability of these M. hominis genes was low compared with the housekeeping genes from Helicobacter pylori and Neisseria meningitidis, but only few M. hominis isolates had identical sequences in all genes...... intergenic and intragenic recombination in M. hominis and this may explain the high intraspecies variability. The results obtained in the present study may be of importance for future population studies of Mycoplasma species....

Radiative and three-body recombination in the Alcator C-Mod divertor

International Nuclear Information System (INIS)

Lumma, D.; Terry, J.L.; Lipschultz, B.

1997-01-01

Significant recombination of the majority ion species has been observed in the divertor region of Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] under detached conditions. This determination is made by analysis of the visible spectrum from the divertor, in particular the Balmer series line emission and the observed recombination continuum, including an apparent recombination edge at ∼375 nm. The analysis shows that the electron temperature in the recombining plasma is 0.8 endash 1.5 eV. The measured volume recombination rate is comparable to the rate of ion collection at the divertor plates. The dominant recombination mechanism is three-body recombination into excited states (e+e+D + Right-arrow D 0 +e), although radiative recombination (e+D + Right-arrow D 0 +hν) contributes ∼5% to the total rate. Analysis of the Balmer series line intensities (from n upper =3 through 10) shows that the upper levels of these transitions are populated primarily by recombination. Thus the brightnesses of the Balmer series (and Lyman series) are directly related to the recombination rate. copyright 1997 American Institute of Physics

Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

Science.gov (United States)

Weller, Sandra K.; Sawitzke, James A.

2015-01-01

The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096

A New Metazoan Recombination Rate Record and Consistently High Recombination Rates in the Honey Bee Genus Apis Accompanied by Frequent Inversions but Not Translocations

Science.gov (United States)

Kuster, Ryan; Miller, Katelyn; Fouks, Bertrand; Rubio Correa, Sara; Collazo, Juan; Phaincharoen, Mananya; Tingek, Salim; Koeniger, Nikolaus

2016-01-01

Abstract Western honey bees (Apis mellifera) far exceed the commonly observed 1–2 meiotic recombination events per chromosome and exhibit the highest Metazoan recombination rate (20 cM/Mb) described thus far. However, the reasons for this exceptional rate of recombination are not sufficiently understood. In a comparative study, we report on the newly constructed genomic linkage maps of Apis florea and Apis dorsata that represent the two honey bee lineages without recombination rate estimates so far. Each linkage map was generated de novo, based on SNP genotypes of haploid male offspring of a single female. The A. florea map spans 4,782 cM with 1,279 markers in 16 linkage groups. The A. dorsata map is 5,762 cM long and contains 1,189 markers in 16 linkage groups. Respectively, these map sizes result in average recombination rate estimates of 20.8 and 25.1 cM/Mb. Synteny analyses indicate that frequent intra-chromosomal rearrangements but no translocations among chromosomes accompany the high rates of recombination during the independent evolution of the three major honey bee lineages. Our results imply a common cause for the evolution of very high recombination rates in Apis. Our findings also suggest that frequent homologous recombination during meiosis might increase ectopic recombination and rearrangements within but not between chromosomes. It remains to be investigated whether the resulting inversions may have been important in the evolutionary differentiation between honey bee species. PMID:28173114

Analysis of chickens for recombination within the MHC (B-complex)

DEFF Research Database (Denmark)

Skjødt, K; Koch, C; Crone, M

1985-01-01

In an attempt to further map the chicken MHC (the B complex), a systematic search for genetic recombinants within the B complex was performed by serotyping the progeny from F2 crosses of chickens by means of specific anti-class I, anti-class II, and anti-class IV alloantisera. Two recombinant B......-haplotypes (B21r and B15r) were found by analysing 2,656 F2 chickens representing 5,312 informative typings. In either case, the B-G (class IV) allele was recombined with both the B-F and B-L alleles of the opposite haplotype. MLC typings, tests for direct compatibility by GVH reactions, and absorption analyses...... confirmed the original serological typing of the two recombinant B haplotypes. No recombination between B-F (class I) and B-L (class II) loci was found. This very low frequency of recombination within the B complex as compared with recombination frequencies found in mammalian MHC's is discussed...

Meiotic recombination hotspots - a comparative view.

Science.gov (United States)

Choi, Kyuha; Henderson, Ian R

2015-07-01

During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double-stranded breaks that are processed to form single-stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Clinical implications of bile duct injury after transcatheter arterial chemoembolization

International Nuclear Information System (INIS)

Wang Maoqiang; Tang Wenjie; Lin Hanying; Ye Huiyi; Dai Guanghai; Wang Zhiqiang

2005-01-01

Objective: To evaluate the incidence, risk factors , and clinical course of bile duct injury after transcatheter arterial chemoembolization (TACE) for treatment of hepatic malignancy. Methods: A total of 1240 consecutive patients with hepatic malignancies underwent 2680 TACE procedures. None of these patients were found to have any radiographic evidence of biliary abnormalities pre-TACE. Eighteen patients developed bile duct injuries at 3 weeks to 3 months after TACE. A retrospective review of medical records and imaging studies were carried out to evaluate the occurrence of TACE-induced bile duct injury, the clinical outcome, and the statistical significance of potential predisposing factors. Results: The TACE-induced bile duct injuries occurred in 13 of 148 patients with liver metastatic tumors (8.8%), 5 of 1092 patients with HCC (0.5%). Biliary injuries, including focal (n=4) and multiple intrahepatic bile duct dilatation (n=8), and cystic lesion or biloma (n=6), were identified on the follow-up imaging studies after TACE. Three patients with multiple bile duct injuries had mild jaundice at the presentation, two of them responded well to the conservative treatment, one died of irreversible deterioration of liver function at 2 weeks after the onset of jaundice. Four patients with a large biloma had associated serious bacterial infections; 3 of which were treated with percutaneous catheter drainage and antibiotics, 2 of them died of purulent peritonitis due to rupture of the cystic lesions and 1 cured with antibiotic. The remaining 11 patients were asymptomatic. The mortality related to the biliary injury occurred in 3 patients (16.7%). The incidences of bile duct injury were higher in patients with metastatic tumors in non-cirrhotic livers than in patients with hepatocellular carcinoma associated with cirrhosis (P<0.01), higher in patient with hypovascular lesions (P<0.01), and higher in patients using an emulsion of lipiodol-platinum for selective embolization

Cell biology of homologous recombination in yeast

DEFF Research Database (Denmark)

Eckert-Boulet, Nadine Valerie; Rothstein, Rodney; Lisby, Michael

2011-01-01

Homologous recombination is an important pathway for error-free repair of DNA lesions, such as single- and double-strand breaks, and for rescue of collapsed replication forks. Here, we describe protocols for live cell imaging of single-lesion recombination events in the yeast Saccharomyces...

Recombination Parameters for Antimonide-Based Semiconductors using RF Photoreflection Techniques

International Nuclear Information System (INIS)

Kumar, R.J.; Borrego, J.M.; Dutta, P.S.; Gutmann, R.J.; Wang, C.A.; Martinelli, R.U.; Nichols, G.

2002-01-01

RF photoreflection measurements and PC-1D simulations have been used to evaluate bulk and surface recombination parameters in antimonide-based materials. PC-1D is used to simulate the photoconductivity response of antimonide-based substrates and doubly-capped epitaxial layers and also to determine how to extract the recombination parameters using experimental results. Excellent agreement has been obtained with a first-order model and test structure simulation when Shockley-Reed-Hall (SRH) recombination is the bulk recombination process. When radiative, Auger and surface recombination are included, the simulation results show good agreement with the model. RF photoreflection measurements and simulations using PC-1D are compatible with a radiative recombination coefficient (B) of approximately 5 x 10 -11 cm 3 /s, Auger coefficient (C) ∼ 1.0 x 10 -28 cm 6 /s and surface recombination velocity (SRV) ∼ 600 cm/s for 0.50-0.55 eV doubly-capped InGaAsSb material with GaSb capping layers using the experimentally determined active layer doping of 2 x 10 17 cm -3 . Photon recycling, neglected in the analysis and simulations presented, will affect the extracted recombination parameters to some extent

Effects of the rad52 gene on recombination in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Prakash, S.; Prakash, L.; Burke, W.; Montelone, B.A.

1980-01-01

Effects of the rad 52 mutation in Saccharomyces cerevisiae on meiotic, γ-ray-induced, uv-induced and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Both intra and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the his1-1/his1-315 and trp-5-2/trp5-48 heteroalleles. Gene-centromere recombination also was not observed in rad/52/rad52 diploids. No γ-ray- or uv-induced intragenic mitotic recombination is seen in rad52/rad52 diploids. The rate of spontaneous mitotic recombination is lowered five-fold at the his1-1/his1-315 and leu1-c/leu1-12 heteroalleles. Spontaneous reversion rates of both his1-1 and his1-315 were elevated 10 to 20 fold in rad52/rad52 diploids. The RAD52 gene function is required for spontaneous mitotic recombination, uv- and γ-ray-induced mitotic recombination and mitotic recombination

Phylogenetic and recombination analysis of tomato spotted wilt virus.

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Sen Lian

Full Text Available Tomato spotted wilt virus (TSWV severely damages and reduces the yield of many economically important plants worldwide. In this study, we determined the whole-genome sequences of 10 TSWV isolates recently identified from various regions and hosts in Korea. Phylogenetic analysis of these 10 isolates as well as the three previously sequenced isolates indicated that the 13 Korean TSWV isolates could be divided into two groups reflecting either two different origins or divergences of Korean TSWV isolates. In addition, the complete nucleotide sequences for the 13 Korean TSWV isolates along with previously sequenced TSWV RNA segments from Korea and other countries were subjected to phylogenetic and recombination analysis. The phylogenetic analysis indicated that both the RNA L and RNA M segments of most Korean isolates might have originated in Western Europe and North America but that the RNA S segments for all Korean isolates might have originated in China and Japan. Recombination analysis identified a total of 12 recombination events among all isolates and segments and five recombination events among the 13 Korea isolates; among the five recombinants from Korea, three contained the whole RNA L segment, suggesting reassortment rather than recombination. Our analyses provide evidence that both recombination and reassortment have contributed to the molecular diversity of TSWV.

Effect of interface roughness on Auger recombination in semiconductor quantum wells

Science.gov (United States)

Tan, Chee-Keong; Sun, Wei; Wierer, Jonathan J.; Tansu, Nelson

2017-03-01

Auger recombination in a semiconductor is a three-carrier process, wherein the energy from the recombination of an electron and hole pair promotes a third carrier to a higher energy state. In semiconductor quantum wells with increased carrier densities, the Auger recombination becomes an appreciable fraction of the total recombination rate and degrades luminescence efficiency. Gaining insight into the variables that influence Auger recombination in semiconductor quantum wells could lead to further advances in optoelectronic and electronic devices. Here we demonstrate the important role that interface roughness has on Auger recombination within quantum wells. Our computational studies find that as the ratio of interface roughness to quantum well thickness is increased, Auger recombination is significantly enhanced. Specifically, when considering a realistic interface roughness for an InGaN quantum well, the enhancement in Auger recombination rate over a quantum well with perfect heterointerfaces can be approximately four orders of magnitude.

Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

International Nuclear Information System (INIS)

Chapiro, Julius; Savic, Lynn Jeanette; Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois; Lin, MingDe; Lesage, David

2015-01-01

This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

Energy Technology Data Exchange (ETDEWEB)

Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

2015-07-15

This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

Total and partial recombination cross sections for F6+

International Nuclear Information System (INIS)

Mitnik, D.M.; Pindzola, M.S.; Badnell, N.R.

1999-01-01

Total and partial recombination cross sections for F 6+ are calculated using close-coupling and distorted-wave theory. For total cross sections, close-coupling and distorted-wave results, which include interference between the radiative and dielectronic pathways, are found to be in good agreement with distorted-wave results based on a sum of independent processes. Total cross sections near zero energy are dominated by contributions from low-energy dielectronic recombination resonances. For partial cross sections, the close-coupling and distorted-wave theories predict strong interference for recombination into the final recombined ground state 1s 2 2s 21 S 0 of F 5+ , but only weak interference for recombination into the levels of the 1s 2 2s2p configuration. copyright 1999 The American Physical Society

B chromosomes are associated with redistribution of genetic recombination towards lower recombination chromosomal regions in perennial ryegrass.

Science.gov (United States)

Harper, John; Phillips, Dylan; Thomas, Ann; Gasior, Dagmara; Evans, Caron; Powell, Wayne; King, Julie; King, Ian; Jenkins, Glyn; Armstead, Ian

2018-04-09

Supernumerary 'B' chromosomes are non-essential components of the genome present in a range of plant and animal species-including many grasses. Within diploid and polyploid ryegrass and fescue species, including the forage grass perennial ryegrass (Lolium perenne L.), the presence of B chromosomes has been reported as influencing both chromosome pairing and chiasma frequencies. In this study, the effects of the presence/absence of B chromosomes on genetic recombination has been investigated through generating DArT (Diversity Arrays Technology) marker genetic maps for six perennial ryegrass diploid populations, the pollen parents of which contained either two B or zero B chromosomes. Through genetic and cytological analyses of these progeny and their parents, we have identified that, while overall cytological estimates of chiasma frequencies were significantly lower in pollen mother cells with two B chromosomes as compared with zero B chromosomes, the recombination frequencies within some marker intervals were actually increased, particularly for marker intervals in lower recombination regions of chromosomes, namely pericentromeric regions. Thus, in perennial ryegrass, the presence of two B chromosomes redistributed patterns of meiotic recombination in pollen mother cells in ways which could increase the range of allelic variation available to plant breeders.

Analysis of intermolecular RNA-RNA recombination by rubella virus

International Nuclear Information System (INIS)

Adams, Sandra D.; Tzeng, W.-P.; Chen, M.-H.; Frey, Teryl K.

2003-01-01

To investigate whether rubella virus (RUB) undergoes intermolecular RNA-RNA recombination, cells were cotransfected with pairs of in vitro transcripts from genomic cDNA plasmid vectors engineered to contain nonoverlapping deletions: the replicative transcript maintained the 5'-proximal nonstructural (NS) ORF (which contained the replicase, making it RNA replication competent), had a deletion in the 3'-proximal structural protein (SP) ORF, and maintained the 3' end of the genome, including the putative 3' cis-acting elements (CSE), while the nonreplicative transcript consisted of the 3' half of the genome including the SP-ORF and 3' CSE. Cotransfection yielded plaque-forming virus that synthesized the standard genomic and subgenomic RNAs and thus was generated by RNA-RNA recombination. Using transcripts tagged with a 3'-terminal deletion, it was found that recombinants contained the 3' end derived from the replicative strand, indicating a cis-preference for initiation of negative-strand synthesis. In cotransfections in which the replicative transcript lacked the 3' CSE, recombination occurred, albeit at lower efficiency, indicating that initiation in trans from the NS-ORF can occur. The 3' CSE was sufficient as a nonreplicative transcript, showing that it can serve as a promoter for negative-strand RNA synthesis. While deletion mutagenesis showed that the presence of the junction untranslated region (J-UTR) between the ORFs appeared to be necessary on both transcripts for recombination in this region of the genome, analysis with transcripts tagged with restriction sites showed that the J-UTR was not a hot spot for recombination compared to neighboring regions in both ORFs. Sequence analysis of recombinants revealed that both precise (homologous) and imprecise recombination (aberrant, homologous resulting in duplications) occurred; however, imprecise recombination only involved the J-UTR or the 3' end of the NS-ORF and the J-UTR (maintaining the NS-ORF), indicating

Intrinsic and experimental quasiparticle recombination times in superconducting films

International Nuclear Information System (INIS)

Eisenmenger, W.; Lassmann, K.; Trumpp, H.J.; Krauss, R.

1977-01-01

Experimental quasiparticle recombination lifetime data for superconducting Al, Sn, and Pb films are compared with calculations based on a ray acoustic model taking account of the film thickness dependence of the reabsorption of recombination phonons. Information on the true or intrinsic quasiparticle recombination lifetime obtained from these and other data is discussed. (orig.) [de

Generation of Modified Pestiviruses by Targeted Recombination

DEFF Research Database (Denmark)

Rasmussen, Thomas Bruun; Friis, Martin Barfred; Risager, Peter Christian

involves targeted modification of viral cDNA genomes, cloned within BACs, by Red/ET recombination-mediated mutagenesis in E.coli DH10B cells. Using recombination-mediated mutagenesis for the targeted design, the work can be expedited and focused in principal on any sequence within the viral genome...

Effect of surgical resection combined with transcatheter arterial chemoembolization on postoperative serum tumor marker levels and stem cell characteristics during tumor recurrence

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Sen Yang

2017-05-01

Full Text Available Objective: To study the effect of surgical resection combined with transcatheter arterial chemoembolization (TACE on postoperative serum tumor marker levels and stem cell characteristics during tumor recurrence. Methods: A total of 98 patients with liver cancer who received radical resection in our hospital between May 2013 and July 2015 were reviewed and divided into TACE group and control group according to whether they received TACE within two months after surgical resection. Serum levels of tumor markers were detected 4 weeks after operation; the tumor recurrence was followed up within 3 years after operation, and the expression of stem cell marker molecules and cell proliferation molecules in recurrent lesions were detected. Results: 4 weeks after radical hepatectomy, serum AFP, AFP-L3, GP73 and GPC3 levels in TACE group were significantly lower than those in control group; Nanog, CD133, EpCAM, PICK1, CyclinD1, C-myc and Survivin expression in surgically removed lesions of TACE group were not different from those of control group while Nanog, CD133, EpCAM, PICK1, CyclinD1, C-myc and Survivin expression in recurrent lesions were significantly lower than those of control group. Conclusion: Surgical resection combined with TACE can more effectively remove liver cancer lesions, reduce the tumor marker levels and inhibit the tumor stem cell characteristics and cell proliferation activity in recurrent lesions.

[Comparison liver resection with transarterial chemoembolization for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma patients on long-term survival after SPSS propensity score matching].

Science.gov (United States)

Ke, Yang; Zhong, Jianhong; Guo, Zhe; Liang, Yongrong; Li, Lequn; Xiang, Bangde

2014-03-18

To compare the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) undergoing either liver resection or transarterial chemoembolization (TACE) after propensity score matching (PSM). One hundred sixty-seven and 70 BCLC-B HCC patients undergoing liver resection and TACE were retrospectively collected. PSM function of SPSS software was conducted to reduce confounding bias between the groups. And then survival analysis was performed for the matched data. Fifty-three pairs of patients were successfully matched. And then survival analysis showed that the median survival periods and their 95% confidence intervals were 35.0 (26.3-43.7)months in the liver resection group versus 20.0(15.0-25.0) months in the TACE group. The 1, 3, 5 and 7-year survival rates were 91.0%, 49.0%, 30.0% and 17.0% in the liver resection group versus 73.0%, 25.0%, 8.0% and 5.0% respectively in the TACE group (P = 0.001). Cox regression analysis revealed that TACE, total bilirubin ≥ 34.2 µmol/L, alpha fetoprotein ≥ 400 ng/ml and tumor number ≥ 3 were independent risk factors of survival (hazard ratio >1, P < 0.05). The balance of covariates may be achieved through PSM. And for patients with BCLC-B HCC, liver resection provides better long-term overall survival than TACE.

Hepatocellular carcinomas 2–3 cm in diameter: Transarterial chemoembolization plus radiofrequency ablation vs. radiofrequency ablation alone

International Nuclear Information System (INIS)

Kim, Jong Woo; Kim, Jin Hyoung; Won, Hyung Jin; Shin, Yong Moon; Yoon, Hyun-Ki; Sung, Kyu-Bo; Kim, Pyo Nyun

2012-01-01

Objective: There is debate whether transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) is more effective than RFA alone in the treatment of patients with small hepatocellular carcinoma (HCC). We therefore retrospectively compared these treatments in patients with HCCs of diameter 2–3 cm. Materials and methods: Outcomes, including tumor progression, survival rates, and major complications, were compared in 83 patients (83 tumors) treated with combined TACE and RFA and in 231 patients (231 tumors) treated with RFA alone. Results: Median follow-up periods were similar in the TACE + RFA and RFA alone groups (37 vs. 38 months). During follow-up, local tumor progression was observed in 16% and 41% of tumors, respectively. The 1, 3, and 5 year local tumor progression-free survival rates were significantly higher in the TACE + RFA group (95%, 86%, and 83%, respectively) than in the RFA-alone group (78%, 61%, and 53%, respectively; P < 0.001). The 1, 3, and 5 year overall survival rates, however, were similar in the TACE + RFA (93%, 72%, and 63%, respectively) and RFA (93%, 73%, and 53%, respectively) groups (P = 0.545), as were the rates of major complications (1.2% vs. 0.4%). Conclusions: Combined TACE and RFA was safe and provided better local tumor control than RFA alone in the treatment of 2- to 3-cm sized HCCs, although survival rates were similar.

Polarity of recombination in transformation of Streptococcus pneumoniae.

Science.gov (United States)

Pasta, F; Sicard, M A

1999-03-16

In transformation of Streptococcus pneumoniae DNA enters the cell as single-strand fragments and integrates into the chromosome by homologous recombination. Deletions and insertions of a few hundred base pairs frequently stop the recombination process of a donor strand. In this work we took advantage of such interruptions of recombination to compare the transformation efficiencies of the segments 5'- and 3'-ward from a deletion. The deletion was created in the center of a fragment of the ami locus, and sites around the deletion were labeled by a frameshift generating a restriction site. Heteroduplexes were constructed containing two restriction sites on one strand and two different ones on the complementary strand. ami+ bacteria were transformed with such heteroduplexes. ami- transformants were isolated and individually underwent amplification of the transformed ami region. We have obtained two kinds of amplification products: short when the deletion was integrated, long when recombination stops at the deletion. Each long fragment was tested by the four restriction enzymes to detect which strand and which side of the deletion had recombined. We found that 80% of the cuts were located 5' to the deletion, showing that, in vivo, the 5' side is strongly favored by recombination. Further results suggest that exchanges occurring from 5' to 3' relative to the donor strand are more efficient than in the opposite direction, thus accounting for the 5' preference.

Recombinant activated factor VII in cardiac surgery: single-center experience.

Science.gov (United States)

Singh, Sarvesh Pal; Chauhan, Sandeep; Choudhury, Minati; Malik, Vishwas; Choudhary, Shiv Kumar

2014-02-01

The widespread off-label use of recombinant activated factor VII for the control of refractory postoperative hemorrhage continues despite a warning from the Food and Drug Administration. Although effective in reducing the need for transfusion of blood and blood products, safety concerns still prevail. To compare the dosing and efficacy of recombinant activated factor VII between pediatric and adult patients, and in the operating room and intensive care unit. The records of 69 patients (33 children and 36 adults) who underwent cardiovascular surgery and received recombinant activated factor VII were reviewed retrospectively. The dose of recombinant activated factor VII, mediastinal drainage, use of blood and blood products, incidence of thrombosis, and 28-day mortality were studied. the efficacy of recombinant activated factor VII was comparable in adults and children, despite the lower dose in adults. Prophylactic use of recombinant activated factor VII decreased the incidence of mediastinal exploration and the duration of intensive care unit stay. A 4.3% incidence of thrombotic complications was observed in this study. The efficacious dose of recombinant activated factor VII is much less in adults compared to children. Prophylactic use of recombinant activated factor VII decreases the dose required, the incidence of mediastinal exploration, and intensive care unit stay, with no survival benefit.

Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

International Nuclear Information System (INIS)

Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis; Matsaidonis, Dimitrios

2010-01-01

The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% ± 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% ± 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

Diffusion-weighted MR imaging for liver cancer follow-up after transcatheter arterial chemoembolization

International Nuclear Information System (INIS)

Yuan Zheng; Xiao Xiangsheng; Liu Shiyuan; Dong Sheng; Dong Weihua; Jia Ningyang; Sun Zhichao; Ye Xiaodan; Yan Bing

2007-01-01

Objective: To investigate prospectively the apparent diffusion coefficient (ADC)in evaluating the capability of diffusion-weighted imaging (DWI) technique for detecting viable tumor tissue after transarterial chemoembolization (TACE) of liver cancer. Methods: Institutional review board approval was obtained, and all patients were provided with informed consent. DWI, enhanced CT and DSA examinations were performed in 16 patients with liver cancer after TACE. Qualitative evaluations of the capability for detecting the remaining or recurrent viable tumor with DWI were performed by comparing enhanced-CT and DSA. ADCs and maximum CT enhancement value(HU) were measured(in 14 of the 16 patients)for lesions after TACE. And their relationships were investigated by comprehension correlative analysis. Results: Liver cancer after TACE presented variable signal intensities on DWI. The homogeneous accumulation of iodized oil observed on CT in 2 of 16 patients with liver cancer after TACE showed no tumor stain observed on DSA but with corresponding homogeneous hypointensity on DWI. The partial defects shown in accumulation of iodized oil in 2 of 16 patients represented the tumor stain on DSA corresponding to hyperintensities on DWI. None or faint accumulation of iodized oil areas in 12 of all patients, showed striking tumor stains corresponding to hyperintensities on DWI, and tumor necrosis had none or sight tumor stain on DSA, corresponding to hypointensities on DWI. A correlation between ADCs and maximum CT enhancement value (HU) of lesions after TACE was found (r=-0.76490, <0.05). Conclusion: Diffusion MRI is an useful method for detecting tumor remnant or recurrence of liver cancer after TACE, and can be used for the follow-up. (authors)

Superselective transarterial chemoembolization vs hepatic resection for resectable early-stage hepatocellular carcinoma in patients with Child-Pugh class a liver function

International Nuclear Information System (INIS)

Hsu, Kuo-Feng; Chu, Chi-Hung; Chan, De-Chuan; Yu, Jyh-Cherng; Shih, Ming-Lang; Hsieh, Huan-Fa; Hsieh, Tsai-Yuan; Yu, Chih-Yung; Hsieh, Chung-Bao

2012-01-01

Purpose: In contrast to hepatic resection (HR) for resectable early-stage HCC, the efficacy of transarterial chemoembolization (TACE) is controversial. This study is designed to compare the long-term outcome of TACE using superselective technique with hepatic resection for the treating resectable early-stage HCC and Child-Pugh class A liver function. Methods: In total, 185 consecutive patients with resectable early-stage HCC and Child-Pugh class A liver function were included: 73 patients received superselective TACE (group I) and 112 patients underwent HR (group II). We evaluated the therapy-related recurrence and long-term outcome and in both groups. The risk factors of recurrence and mortality were assessed by Cox's model. Results: The mean survival time of group 1 patient was similar to that of group 2 patient (40.8 ± 19.8 vs 46.7 ± 24.6 months respectively, p = 0.91). The 1-, 3-, and 5-year overall survival rates after TACE (group I)and HR (group II) were 91%, 66%, and 52% and 93%, 71%, and 57%, respectively (p = 0.239). The 1-, 3-, and 5-year recurrence-free survival rates in groups 1 and 2 were 68%, 28%, and 17% and 78%, 55%, and 35%, respectively (p < 0.0001). Serum albumin, tumour size, tumour number and recurrence interval were independent risk factors for mortality. Serum albumin level, tumour size, tumour number, and treatment modality of TACE or HR could predict HCC recurrence. Conclusion: TACE is an efficient and safe treatment for resectable early-stage HCC with overall survival rates similar to that of HR. Thus, TACE is indicated in selected patients with resectable early-stage HCC.

Homologous Recombination as a Replication Fork Escort: Fork-Protection and Recovery

Directory of Open Access Journals (Sweden)

Audrey Costes

2012-12-01

Full Text Available Homologous recombination is a universal mechanism that allows DNA repair and ensures the efficiency of DNA replication. The substrate initiating the process of homologous recombination is a single-stranded DNA that promotes a strand exchange reaction resulting in a genetic exchange that promotes genetic diversity and DNA repair. The molecular mechanisms by which homologous recombination repairs a double-strand break have been extensively studied and are now well characterized. However, the mechanisms by which homologous recombination contribute to DNA replication in eukaryotes remains poorly understood. Studies in bacteria have identified multiple roles for the machinery of homologous recombination at replication forks. Here, we review our understanding of the molecular pathways involving the homologous recombination machinery to support the robustness of DNA replication. In addition to its role in fork-recovery and in rebuilding a functional replication fork apparatus, homologous recombination may also act as a fork-protection mechanism. We discuss that some of the fork-escort functions of homologous recombination might be achieved by loading of the recombination machinery at inactivated forks without a need for a strand exchange step; as well as the consequence of such a model for the stability of eukaryotic genomes.

Low-temperature radiative recombination of electrons with bare nuclei

International Nuclear Information System (INIS)

Omidvar, K.

1993-01-01

Aside from empirical formulas, the radiative-recombination cross section and coefficient are usually given in tabulated forms instead of analytic formulas. Here, we give analytic expressions in the form of expansions for the recombination cross section as a function of the electron energy E for low E, and for the recombination coefficient as a function of the temperature T for low T. The expansion coefficients are combinations of confluent hypergeometric functions, and are tabulated for a large number of the final principal and angular-momentum quantum numbers n and l. It is shown that the recombination cross section for arbitrary nuclear charge number Z is independent of Z, while the recombination coefficient for T/Z 2 much-lt 1.58x10 5 K increases as Z 2 . Excellent agreement is found with the published tabulated values

PRODUCTION OF RECOMBINANT HIGH pI-BARLEY α-GLUCOSIDASE

DEFF Research Database (Denmark)

Næsted, Henrik; Svensson, Birte

plantlet [1]. Recently, expression and characterization of the recombinant full length, fully functional barley high pI α-glucosidase in Pichia pastoris has been achieved. To enable production of recombinant protein in mg amounts, a transformant harbouring a clone encoding the N-terminally hexa histidine...... tagged recombinant form of the enzyme was propagated using a high cell-density fermentation procedure. This system resulted in successful expression under the highly sensitive methanol utilization phase conducting the fermentation process using a BiostatB 5 L reactor. The recombinant high pI α...... glycosylation of the recombinant α-glucosidase. The enzyme activity was highly stable during the 5 day long fermentation. Characterisation of the enzymatic properties confirmed the specific activity actually to be superior to that of the native enzyme purified from malt [2]. The kinetic parameters Km, Vmax...

High-Resolution Patterns of Meiotic Recombination across the Human Major Histocompatibility Complex

Science.gov (United States)

Cullen, Michael; Perfetto, Stephen P.; Klitz, William; Nelson, George; Carrington, Mary

2002-01-01

Definitive characteristics of meiotic recombination events over large (i.e., >1 Mb) segments of the human genome remain obscure, yet they are essential for establishing the haplotypic structure of the genome and for efficient mapping of complex traits. We present a high-resolution map of recombination at the kilobase level across a 3.3-Mb interval encompassing the major histocompatibility complex (MHC). Genotyping of 20,031 single sperm from 12 individuals resulted in the identification and fine mapping of 325 recombinant chromosomes within genomic intervals as small as 7 kb. Several principal characteristics of recombination in this region were observed: (1) rates of recombination can differ significantly between individuals; (2) intense hot spots of recombination occur at least every 0.8 Mb but are not necessarily evenly spaced; (3) distribution in the location of recombination events can differ significantly among individuals; (4) between hot spots, low levels of recombination occur fairly evenly across 100-kb segments, suggesting the presence of warm spots of recombination; and (5) specific sequence motifs associate significantly with recombination distribution. These data provide a plausible model for recombination patterns of the human genome overall. PMID:12297984

Intermediate bands versus levels in non-radiative recombination

International Nuclear Information System (INIS)

Luque, Antonio; Marti, Antonio; Antolin, Elisa; Tablero, Cesar

2006-01-01

There is a practical interest in developing semiconductors with levels situated within their band gap while preventing the non-radiative recombination that these levels promote. In this paper, the physical causes of this non-radiative recombination are analyzed and the increase in the density of the impurities responsible for the mid-gap levels to the point of forming bands is suggested as the means of suppressing the recombination. Simple models supporting this recommendation and helping in its quantification are presented

Correlation between pairing initiation sites, recombination nodules and meiotic recombination in Sordaria macrospora.

Science.gov (United States)

Zickler, D; Moreau, P J; Huynh, A D; Slezec, A M

1992-09-01

The decrease of meiotic exchanges (crossing over and conversion) in two mutants of Sordaria macrospora correlated strongly with a reduction of chiasmata and of both types of "recombination nodules." Serial section reconstruction electron microscopy was used to compare the synapsis pattern of meiotic prophase I in wild type and mutants. First, synapsis occurred but the number of synaptonemal complex initiation sites was reduced in both mutants. Second, this reduction was accompanied by, or resulted in, modifications of the pattern of synapsis. Genetic and synaptonemal complex maps were compared in three regions along one chromosome arm divided into well marked intervals. Reciprocal exchange frequencies and number of recombination nodules correlated in wild type in the three analyzed intervals, but disparity was found between the location of recombination nodules and exchanges in the mutants. Despite the twofold exchange decrease, sections of the genome such as the short arm of chromosome 2 and telomere regions were sheltered from nodule decrease and from pairing modifications. This indicated a certain amount of diversity in the control of these features and suggested that exchange frequency was dependent not only on the amount of effective pairing but also on the localization of the pairing sites, as revealed by the synaptonemal complex progression in the mutants.

The value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

Energy Technology Data Exchange (ETDEWEB)

Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Vienna (Austria); Peck-Radosavljevic, Markus; Pinter, Matthias [Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Vienna (Austria); Wang, Hao [Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing (China); Nanoff, Christian [Medical University of Vienna, Institute of Pharmacology, Vienna (Austria); Kaczirek, Klaus [Medical University of Vienna, Department of Surgery, Vienna (Austria)

2017-09-15

This prospective study was to investigate the value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [{sup 11}C]-acetate PET, [{sup 18}F]-FDG PET, and combined [{sup 11}C]-acetate and [{sup 18}F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [{sup 11}C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [{sup 18}F]-FDG with [{sup 11}C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

International Nuclear Information System (INIS)

Lahrsow, Maximilian; Albrecht, Moritz H.; Bickford, Matthew W.; Vogl, Thomas J.

2017-01-01

PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant difference in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10 −3  mm 2 /s) and no response (median 1.30 × 10 −3  mm 2 /s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.

Effectiveness of transarterial chemoembolization in hepatoblastoma: a preliminary study

International Nuclear Information System (INIS)

Park, Hark Hoon; Han, Young Min; Kang, Sung Soo; Kim, Jae Chun; Lee, Dong Geun; Hwang, Pyoung Han; Kim, Chong Soo; Lee, Jeong Min

1998-01-01

To evaluate the therapeutic effectiveness and useful as well as the ness, systemic effect and effectiveness, of preoperative TACE when used in patients with unresectable or high risk hepatoblastoma. We retrospectively evaluated four patients with pathologically proven hepatoblastoma. One was male and three were female, and they were aged between 8 and 27 (mean, 15) months. All underwent selective hepatic angiography and chemoembolization after superselection of tumor feeding vessels. Cisplatin 90mg/m 2 (50-80mg), adriamycine 40mg/m 2 (20mg) and lipiodol suspension 4cc ere used as chemotherapeutic agents. Embolization was then performed, gelfoam particles. TACE was repeated at intervals of 3 weeks, and after the second episode, all patients underwent hepatic resection. To evaluate changes in the size, volume, internal texture and margin of the mass, as well as the systemic toxicity of chemotherapeutic drugs, we performed con-trast-enhanced CT and checked AFP,CBC and GOT/GPT before and after TACE. In all patients, TACE was successfully performed and major problems related to the procedure and toxicity of chemotherapeutic agents used were not noted. The largest diameter and volume of tumors were reduced by 33% (from 8.3 to 5.6 cm) and 69% respectively. Tumor necrosis was evident in all patients. Lipiodol uptake by tumors was homogenous and tumors were well distingulished from normal parenchyma. Compared to pre-TACE, serum alpha-feto-protein was reduced from 994(range:615--1690 ng/ml) to 46 ng/ml(42-- 47ng/ml) after the second TACE, and six months after surgery was in the normal range(13ng/ml;3--23ng/ml). SGOT/SGPT levels were temporally elevated after TACE but normalized within a few weeks. TACE can be a useful technique for preoperative treatment of hepatoblestomas. In tomors which are high-risk or inoperable, the therapeutio agents involved were not shown to be toxic.=20

Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

Energy Technology Data Exchange (ETDEWEB)

Lahrsow, Maximilian, E-mail: mlahrsow@gmail.com; Albrecht, Moritz H. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Bickford, Matthew W. [Medical University of South Carolina, Department of Radiology and Radiological Science (United States); Vogl, Thomas J. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

2017-06-15

PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant difference in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10{sup −3} mm{sup 2}/s) and no response (median 1.30 × 10{sup −3} mm{sup 2}/s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.

The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

International Nuclear Information System (INIS)

Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus; Peck-Radosavljevic, Markus; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus

2017-01-01

This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab.

Science.gov (United States)

Li, Shuren; Peck-Radosavljevic, Markus; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus; Haug, Alexander; Hacker, Marcus

2017-09-01

This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization

Directory of Open Access Journals (Sweden)

Sun Hong Yoo

2016-12-01

Full Text Available Background/Aims Hepatic damage during transarterial chemoembolization (TACE is a critical complication in patients with hepatitis B virus (HBV-related hepatocellular carcinoma (HCC. Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. Methods This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. Results Of the 108 patients, 30 (27.8% patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1% patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008. In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013, hypoalbuminemia (HR=3.990, P=0.015, and absence of antiviral therapy (HR=7.597, P=0.006 were significantly associated with treatment-related hepatic decompensation. Conclusions Our findings suggest that

Sequence and recombination analyses of the geminivirus replication

Indian Academy of Sciences (India)

Prakash

2006-09-18

Sep 18, 2006 ... Recombination can provide selective advantage in the evolution of viruses .... Program (v 1.08): Recombination Detection Program (RDP). (Martin and Rybicki ..... Sweet potato leaf curl virus - [US:Louisiana:1994]. AF104036.

Recombinant zoster (shingles) vaccine, RZV - what you need to know

Science.gov (United States)

... year in the United States get shingles. Shingles vaccine (recombinant) Recombinant shingles vaccine was approved by FDA in 2017 for the ... life-threatening allergic reaction after a dose of recombinant shingles vaccine, or has a severe allergy to any component ...

Variation in recombination frequency and distribution across eukaryotes: patterns and processes

Science.gov (United States)

Feulner, Philine G. D.; Johnston, Susan E.; Santure, Anna W.; Smadja, Carole M.

2017-01-01

Recombination, the exchange of DNA between maternal and paternal chromosomes during meiosis, is an essential feature of sexual reproduction in nearly all multicellular organisms. While the role of recombination in the evolution of sex has received theoretical and empirical attention, less is known about how recombination rate itself evolves and what influence this has on evolutionary processes within sexually reproducing organisms. Here, we explore the patterns of, and processes governing recombination in eukaryotes. We summarize patterns of variation, integrating current knowledge with an analysis of linkage map data in 353 organisms. We then discuss proximate and ultimate processes governing recombination rate variation and consider how these influence evolutionary processes. Genome-wide recombination rates (cM/Mb) can vary more than tenfold across eukaryotes, and there is large variation in the distribution of recombination events across closely related taxa, populations and individuals. We discuss how variation in rate and distribution relates to genome architecture, genetic and epigenetic mechanisms, sex, environmental perturbations and variable selective pressures. There has been great progress in determining the molecular mechanisms governing recombination, and with the continued development of new modelling and empirical approaches, there is now also great opportunity to further our understanding of how and why recombination rate varies. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’. PMID:29109219

Lineage specific recombination rates and microevolution in Listeria monocytogenes

Directory of Open Access Journals (Sweden)

Nightingale Kendra K

2008-10-01

Full Text Available Abstract Background The bacterium Listeria monocytogenes is a saprotroph as well as an opportunistic human foodborne pathogen, which has previously been shown to consist of at least two widespread lineages (termed lineages I and II and an uncommon lineage (lineage III. While some L. monocytogenes strains show evidence for considerable diversification by homologous recombination, our understanding of the contribution of recombination to L. monocytogenes evolution is still limited. We therefore used STRUCTURE and ClonalFrame, two programs that model the effect of recombination, to make inferences about the population structure and different aspects of the recombination process in L. monocytogenes. Analyses were performed using sequences for seven loci (including the house-keeping genes gap, prs, purM and ribC, the stress response gene sigB, and the virulence genes actA and inlA for 195 L. monocytogenes isolates. Results Sequence analyses with ClonalFrame and the Sawyer's test showed that recombination is more prevalent in lineage II than lineage I and is most frequent in two house-keeping genes (ribC and purM and the two virulence genes (actA and inlA. The relative occurrence of recombination versus point mutation is about six times higher in lineage II than in lineage I, which causes a higher genetic variability in lineage II. Unlike lineage I, lineage II represents a genetically heterogeneous population with a relatively high proportion (30% average of genetic material imported from external sources. Phylograms, constructed with correcting for recombination, as well as Tajima's D data suggest that both lineages I and II have suffered a population bottleneck. Conclusion Our study shows that evolutionary lineages within a single bacterial species can differ considerably in the relative contributions of recombination to genetic diversification. Accounting for recombination in phylogenetic studies is critical, and new evolutionary models that

3D Quantitative tumour burden analysis in patients with hepatocellular carcinoma before TACE: comparing single-lesion vs. multi-lesion imaging biomarkers as predictors of patient survival

International Nuclear Information System (INIS)

Fleckenstein, Florian N.; Schernthaner, Ruediger E.; Duran, Rafael; Sohn, Jae Ho; Sahu, Sonia; Zhao, Yan; Hamm, Bernd; Gebauer, Bernhard; Lin, MingDe; Geschwind, Jean-Francois; Chapiro, Julius

2016-01-01

To compare the ability of single- vs. multi-lesion assessment on baseline MRI using 1D- and 3D-based measurements to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) before transarterial chemoembolization (TACE). This retrospective analysis included 122 patients. A quantitative 3D analysis was performed on baseline MRI to calculate enhancing tumour volume (ETV [cm 3 ]) and enhancing tumour burden (ETB [%]) (ratio between ETV [cm 3 ] and liver volume). Furthermore, enhancing and overall tumour diameters were measured. Patients were stratified into two groups using thresholds derived from the BCLC staging system. Statistical analysis included Kaplan-Meier plots, uni- and multivariate cox proportional hazard ratios (HR) and concordances. All methods achieved good separation of the survival curves (p < 0.05). Multivariate analysis showed an HR of 5.2 (95 % CI 3.1-8.8, p < 0.001) for ETV [cm 3 ] and HR 6.6 (95 % CI 3.7-11.5, p < 0.001) for ETB [%] vs. HR 2.6 (95 % CI 1.2-5.6, p = 0.012) for overall diameter and HR 3.0 (95 % CI 1.5-6.3, p = 0.003) for enhancing diameter. Concordances were highest for ETB [%], with no added predictive power for multi-lesion assessment (difference between concordances not significant). 3D quantitative assessment is a stronger predictor of survival as compared to diameter-based measurements. Assessing multiple lesions provides no substantial improvement in predicting OS than evaluating the dominant lesion alone. (orig.)

Regulation of Homologous Recombination by SUMOylation

DEFF Research Database (Denmark)

Pinela da Silva, Sonia Cristina

factors such as the homologous recombination (HR) machinery. HR constitutes the main DSB repair pathway in Saccharomyces cerevisiae and despite being largely considered an error-free process and essential for genome stability, uncontrolled recombination can lead to loss of heterozygosity, translocations......, deletions, and genome rearrangements that can lead to cell death or cancer in humans. The post-translational modification by SUMO (small ubiquitinlike modifier) has proven to be an important regulator of HR and genome integrity, but the molecular mechanisms responsible for these roles are still unclear....... In this study I present new insights for the role of SUMOylation in regulating HR by dissecting the role of SUMO in the interaction between the central HR-mediator protein Rad52 and its paralogue Rad59 and the outcome of recombination. This data provides evidence for the importance of SUMO in promoting protein...

Study of volume recombination and radiation opacity effects in Alcator C-Mod

International Nuclear Information System (INIS)

Terry, J.L.; Lipschultz, B.; Pigarov, A.Y.; Boswell, C.; Krasheninnikov, S.I.; LaBombard, B.; Pappas, D.A.

1998-01-01

Observations of significant volume recombination within the Alcator C-Mod divertor plasma and in the edge plasma (MARFE) are described. The recombination occurs in regions where T e approx-lt 1 eV and n e approx-gt 1x10 21 m -3 . The determinations of the recombination rates are made by measuring the D 0 Lyman and/or Balmer spectra and by using a collisional radiative model describing the level populations, ionization and recombination of D 0 . In regions of strong recombination the upper levels (n approx-gt 4) populations are close to those determined by Saha-Boltzmann distribution and are independent of the ground state density. Thus the intensities of lines from these levels are related to the recombination rate, and curves determining the number of open-quote recombinations per photon close-quote are calculated. Ly β line emission is shown to be trapped in some cases, meaning that Ly α can be strongly trapped. Since opacity affects the recombination rates, the effects of the trapping of Ly α,β photons on the open-quote recombinations per photon close-quote curves are calculated and considered in the recombination rate determinations. Total recombination rates in the detached divertor plasma and in MARFEs located at the periphery of the main plasma are determined. Recombination can be a significant sink for ions. copyright 1998 American Institute of Physics

Evidence of recombination in intrapatient populations of hepatitis C virus.

Science.gov (United States)

Sentandreu, Vicente; Jiménez-Hernández, Nuria; Torres-Puente, Manuela; Bracho, María Alma; Valero, Ana; Gosalbes, María José; Ortega, Enrique; Moya, Andrés; González-Candelas, Fernando

2008-09-18

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. HCV is characterized by a high level of genetic heterogeneity. Although homologous recombination has been demonstrated in many members of the family Flaviviridae, to which HCV belongs, there are only a few studies reporting recombination on natural populations of HCV, suggesting that these events are rare in vivo. Furthermore, these few studies have focused on recombination between different HCV genotypes/subtypes but there are no reports on the extent of intra-genotype or intra-subtype recombination between viral strains infecting the same patient. Given the important implications of recombination for RNA virus evolution, our aim in this study has been to assess the existence and eventually the frequency of intragenic recombination on HCV. For this, we retrospectively have analyzed two regions of the HCV genome (NS5A and E1-E2) in samples from two different groups: (i) patients infected only with HCV (either treated with interferon plus ribavirin or treatment naïve), and (ii) HCV-HIV co-infected patients (with and without treatment against HIV). The complete data set comprised 17712 sequences from 136 serum samples derived from 111 patients. Recombination analyses were performed using 6 different methods implemented in the program RDP3. Recombination events were considered when detected by at least 3 of the 6 methods used and were identified in 10.7% of the amplified samples, distributed throughout all the groups described and the two genomic regions studied. The resulting recombination events were further verified by detailed phylogenetic analyses. The complete experimental procedure was applied to an artificial mixture of relatively closely viral populations and the ensuing analyses failed to reveal artifactual recombination. From these results we conclude that recombination should be considered as a potentially

Genome-Wide Fine-Scale Recombination Rate Variation in Drosophila melanogaster

Science.gov (United States)

Song, Yun S.

2012-01-01

Estimating fine-scale recombination maps of Drosophila from population genomic data is a challenging problem, in particular because of the high background recombination rate. In this paper, a new computational method is developed to address this challenge. Through an extensive simulation study, it is demonstrated that the method allows more accurate inference, and exhibits greater robustness to the effects of natural selection and noise, compared to a well-used previous method developed for studying fine-scale recombination rate variation in the human genome. As an application, a genome-wide analysis of genetic variation data is performed for two Drosophila melanogaster populations, one from North America (Raleigh, USA) and the other from Africa (Gikongoro, Rwanda). It is shown that fine-scale recombination rate variation is widespread throughout the D. melanogaster genome, across all chromosomes and in both populations. At the fine-scale, a conservative, systematic search for evidence of recombination hotspots suggests the existence of a handful of putative hotspots each with at least a tenfold increase in intensity over the background rate. A wavelet analysis is carried out to compare the estimated recombination maps in the two populations and to quantify the extent to which recombination rates are conserved. In general, similarity is observed at very broad scales, but substantial differences are seen at fine scales. The average recombination rate of the X chromosome appears to be higher than that of the autosomes in both populations, and this pattern is much more pronounced in the African population than the North American population. The correlation between various genomic features—including recombination rates, diversity, divergence, GC content, gene content, and sequence quality—is examined using the wavelet analysis, and it is shown that the most notable difference between D. melanogaster and humans is in the correlation between recombination and

Hadron correlations from recombination and fragmentation

Energy Technology Data Exchange (ETDEWEB)

Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

2005-04-01

We review the formalism of quark recombination applied to the hadronization of a quark-gluon plasma. Evidence in favour of the quark recombination model is outlined. Recent work on parton correlations, leading to detectable correlations between hadrons, is discussed. Hot spots from completely quenched jets are a likely source of such correlations which appear to be jet like. It will be discussed how such a picture compares with measurement of associated hadron yields at RHIC.

Feline immunodeficiency virus (FIV) env recombinants are common in natural infections.

Science.gov (United States)

Bęczkowski, Paweł M; Hughes, Joseph; Biek, Roman; Litster, Annette; Willett, Brian J; Hosie, Margaret J

2014-09-17

Recombination is a common feature of retroviral biology and one of the most important factors responsible for generating viral diversity at both the intra-host and the population levels. However, relatively little is known about rates and molecular processes of recombination for retroviruses other than HIV, including important model viruses such as feline immunodeficiency virus (FIV). We investigated recombination in complete FIV env gene sequences (n = 355) isolated from 43 naturally infected cats. We demonstrated that recombination is abundant in natural FIV infection, with over 41% of the cats being infected with viruses containing recombinant env genes. In addition, we identified shared recombination breakpoints; the most significant hotspot occurred between the leader/signal fragment and the remainder of env. Our results have identified the leader/signal fragment of env as an important site for recombination and highlight potential limitations of the current phylogenetic classification of FIV based on partial env sequences. Furthermore, the presence of abundant recombinant FIV in the USA poses a significant challenge for commercial diagnostic tests and should inform the development of the next generation of FIV vaccines.

Charge-carrier transport and recombination in heteroepitaxial CdTe

International Nuclear Information System (INIS)

Kuciauskas, Darius; Farrell, Stuart; Dippo, Pat; Moseley, John; Moutinho, Helio; Li, Jian V.; Allende Motz, A. M.; Kanevce, Ana; Zaunbrecher, Katherine; Gessert, Timothy A.; Levi, Dean H.; Metzger, Wyatt K.; Colegrove, Eric; Sivananthan, S.

2014-01-01

We analyze charge-carrier dynamics using time-resolved spectroscopy and varying epitaxial CdTe thickness in undoped heteroepitaxial CdTe/ZnTe/Si. By employing one-photon and nonlinear two-photon excitation, we assess surface, interface, and bulk recombination. Two-photon excitation with a focused laser beam enables characterization of recombination velocity at the buried epilayer/substrate interface, 17.5 μm from the sample surface. Measurements with a focused two-photon excitation beam also indicate a fast diffusion component, from which we estimate an electron mobility of 650 cm 2 (Vs) −1 and diffusion coefficient D of 17 cm 2  s −1 . We find limiting recombination at the epitaxial film surface (surface recombination velocity S surface  = (2.8 ± 0.3) × 10 5  cm s −1 ) and at the heteroepitaxial interface (interface recombination velocity S interface  = (4.8 ± 0.5) × 10 5  cm s −1 ). The results demonstrate that reducing surface and interface recombination velocity is critical for photovoltaic solar cells and electronic devices that employ epitaxial CdTe.

Regulation of homologous recombination at telomeres in budding yeast

DEFF Research Database (Denmark)

Eckert-Boulet, Nadine; Lisby, Michael

2010-01-01

Homologous recombination is suppressed at normal length telomere sequences. In contrast, telomere recombination is allowed when telomeres erode in the absence of telomerase activity or as a consequence of nucleolytic degradation or incomplete replication. Here, we review the mechanisms that contr...... that contribute to regulating mitotic homologous recombination at telomeres and the role of these mechanisms in signalling short telomeres in the budding yeast Saccharomyces cerevisiae....

Recombining overlapping BACs into a single larger BAC

Directory of Open Access Journals (Sweden)

Huxley Clare

2004-01-01

Full Text Available Abstract Background BAC clones containing entire mammalian genes including all the transcribed region and long range controlling elements are very useful for functional analysis. Sequenced BACs are available for most of the human and mouse genomes and in many cases these contain intact genes. However, large genes often span more than one BAC, and single BACs covering the entire region of interest are not available. Here we describe a system for linking two or more overlapping BACs into a single clone by homologous recombination. Results The method was used to link a 61-kb insert carrying the final 5 exons of the human CFTR gene onto a 160-kb BAC carrying the first 22 exons. Two rounds of homologous recombination were carried out in the EL350 strain of bacteria which can be induced for the Red genes. In the first round, the inserts of the two overlapping BACs were subcloned into modified BAC vectors using homologous recombination. In the second round, the BAC to be added was linearised with the very rare-cutting enzyme I-PpoI and electroporated into recombination efficient EL350 bacteria carrying the other BAC. Recombined BACs were identified by antibiotic selection and PCR screening and 10% of clones contained the correctly recombined 220-kb BAC. Conclusion The system can be used to link the inserts from any overlapping BAC or PAC clones. The original orientation of the inserts is not important and desired regions of the inserts can be selected. The size limit for the fragments recombined may be larger than the 61 kb used here and multiple BACs in a contig could be combined by alternating use of the two pBACLink vectors. This system should be of use to many investigators wishing to carry out functional analysis on large mammalian genes which are not available in single BAC clones.

Mitochondrial Recombination and Introgression during Speciation by Hybridization.

Science.gov (United States)

Leducq, Jean-Baptiste; Henault, Mathieu; Charron, Guillaume; Nielly-Thibault, Lou; Terrat, Yves; Fiumera, Heather L; Shapiro, B Jesse; Landry, Christian R

2017-08-01

Genome recombination is a major source of genotypic diversity and contributes to adaptation and speciation following interspecies hybridization. The contribution of recombination in these processes has been thought to be largely limited to the nuclear genome because organelles are mostly uniparentally inherited in animals and plants, which prevents recombination. Unicellular eukaryotes such as budding yeasts do, however, transmit mitochondria biparentally, suggesting that during hybridization, both parents could provide alleles that contribute to mitochondrial functions such as respiration and metabolism in hybrid populations or hybrid species. We examined the dynamics of mitochondrial genome transmission and evolution during speciation by hybridization in the natural budding yeast Saccharomyces paradoxus. Using population-scale mitochondrial genome sequencing in two endemic North American incipient species SpB and SpC and their hybrid species SpC*, we found that both parental species contributed to the hybrid mitochondrial genome through recombination. We support our findings by showing that mitochondrial recombination between parental types is frequent in experimental crosses that recreate the early step of this speciation event. In these artificial hybrids, we observed that mitochondrial genome recombination enhances phenotypic variation among diploid hybrids, suggesting that it could play a role in the phenotypic differentiation of hybrid species. Like the nuclear genome, the mitochondrial genome can, therefore, also play a role in hybrid speciation. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Trends in recombinant protein use in animal production.

Science.gov (United States)

Gifre, Laia; Arís, Anna; Bach, Àlex; Garcia-Fruitós, Elena

2017-03-04

Recombinant technologies have made possible the production of a broad catalogue of proteins of interest, including those used for animal production. The most widely studied proteins for the animal sector are those with an important role in reproduction, feed efficiency, and health. Nowadays, mammalian cells and fungi are the preferred choice for recombinant production of hormones for reproductive purposes and fibrolytic enzymes to enhance animal performance, respectively. However, the development of low-cost products is a priority, particularly in livestock. The study of cell factories such as yeast and bacteria has notably increased in the last decades to make the new developed reproductive hormones and fibrolytic enzymes a real alternative to the marketed ones. Important efforts have also been invested to developing new recombinant strategies for prevention and therapy, including passive immunization and modulation of the immune system. This offers the possibility to reduce the use of antibiotics by controlling physiological processes and improve the efficacy of preventing infections. Thus, nowadays different recombinant fibrolytic enzymes, hormones, and therapeutic molecules with optimized properties have been successfully produced through cost-effective processes using microbial cell factories. However, despite the important achievements for reducing protein production expenses, alternative strategies to further reduce these costs are still required. In this context, it is necessary to make a giant leap towards the use of novel strategies, such as nanotechnology, that combined with recombinant technology would make recombinant molecules affordable for animal industry.

Constraints from jet calculus on quark recombination

International Nuclear Information System (INIS)

Jones, L.M.; Lassila, K.E.; Willen, D.

1979-01-01

Within the QCD jet calculus formalism, we deduce an equation describing recombination of quarks and antiquarks into mesons within a quark or gluon jet. This equation relates the recombination function R(x 1 ,x 2 ,x) used in current literature to the fragmentation function for producing that same meson out of the parton initiating the jet. We submit currently used recombination functions to our consistency test, taking as input mainly the u-quark fragmentation data into π + mesons, but also s-quark fragmentation into K - mesons. The constraint is well satisfied at large Q 2 for large moments. Our results depend on one parameter, Q 0 2 , the constraint equation being satisfied for small values of this parameter

Experimental study of para- and ortho-H3+ recombination

International Nuclear Information System (INIS)

Plasil, R; Varju, J; Hejduk, M; Dohnal, P; KotrIk, T; Glosik, J

2011-01-01

Recombination of H 3 + with electrons is a key process for many plasmatic environments. Recent experiments on storage ring devices used ion sources producing H 3 + with enhanced populations of H 3 + ions in the para nuclear spin configuration to shed light on the theoretically predicted faster recombination of para states. Although increased recombination rates were observed, no in situ characterization of recombining ions was performed. We present a state selective recombination study of para- and ortho-H 3 + ions with electrons at 77 K in afterglow plasma in a He/Ar/H 2 gas-mixture. Both spin configurations of H 3 + have been observed in situ with a near infrared cavity ring down spectrometer (NIR-CRDS) using the two lowest energy levels of H 3 + . Using hydrogen with an enhanced population of H 2 molecules in para states allowed us to influence the [para-H 3 + ]/[ortho-H 3 + ] ratio in the discharge and in the afterglow. We observed an increase in the measured effective recombination rate coefficients with the increase of the fraction of para-H 3 + . Measurements with different fractions of para-H 3 + at otherwise identical conditions allowed us to determine the binary recombination rate coefficients for pure para-H 3 + p α bin (77 K) = (2.0±0.4)x10 -7 cm 3 s -1 and pure ortho-H 3 + o α bin (77 K) = (4±3)x10 -8 cm 3 s -1 .

Experimental study of para- and ortho-H3+ recombination

Science.gov (United States)

Plašil, R.; Varju, J.; Hejduk, M.; Dohnal, P.; Kotrík, T.; Glosík, J.

2011-07-01

Recombination of H3+ with electrons is a key process for many plasmatic environments. Recent experiments on storage ring devices used ion sources producing H3+ with enhanced populations of H3+ ions in the para nuclear spin configuration to shed light on the theoretically predicted faster recombination of para states. Although increased recombination rates were observed, no in situ characterization of recombining ions was performed. We present a state selective recombination study of para- and ortho-H3+ ions with electrons at 77 K in afterglow plasma in a He/Ar/H2 gas-mixture. Both spin configurations of H3+ have been observed in situ with a near infrared cavity ring down spectrometer (NIR-CRDS) using the two lowest energy levels of H3+. Using hydrogen with an enhanced population of H2 molecules in para states allowed us to influence the [para-H3+]/[ortho-H3+] ratio in the discharge and in the afterglow. We observed an increase in the measured effective recombination rate coefficients with the increase of the fraction of para-H3+. Measurements with different fractions of para-H3+ at otherwise identical conditions allowed us to determine the binary recombination rate coefficients for pure para-H3+ pαbin(77 K) = (2.0±0.4)×10-7 cm3s-1 and pure ortho-H3+ oαbin(77 K) = (4±3)×10-8 cm3s-1.

Characterization of recombination features and the genetic basis in multiple cattle breeds.

Science.gov (United States)

Shen, Botong; Jiang, Jicai; Seroussi, Eyal; Liu, George E; Ma, Li

2018-04-27

Crossover generated by meiotic recombination is a fundamental event that facilitates meiosis and sexual reproduction. Comparative studies have shown wide variation in recombination rate among species, but the characterization of recombination features between cattle breeds has not yet been performed. Cattle populations in North America count millions, and the dairy industry has genotyped millions of individuals with pedigree information that provide a unique opportunity to study breed-level variations in recombination. Based on large pedigrees of Jersey, Ayrshire and Brown Swiss cattle with genotype data, we identified over 3.4 million maternal and paternal crossover events from 161,309 three-generation families. We constructed six breed- and sex-specific genome-wide recombination maps using 58,982 autosomal SNPs for two sexes in the three dairy cattle breeds. A comparative analysis of the six recombination maps revealed similar global recombination patterns between cattle breeds but with significant differences between sexes. We confirmed that male recombination map is 10% longer than the female map in all three cattle breeds, consistent with previously reported results in Holstein cattle. When comparing recombination hotspot regions between cattle breeds, we found that 30% and 10% of the hotspots were shared between breeds in males and females, respectively, with each breed exhibiting some breed-specific hotspots. Finally, our multiple-breed GWAS found that SNPs in eight loci affected recombination rate and that the PRDM9 gene associated with hotspot usage in multiple cattle breeds, indicating a shared genetic basis for recombination across dairy cattle breeds. Collectively, our results generated breed- and sex-specific recombination maps for multiple cattle breeds, provided a comprehensive characterization and comparison of recombination patterns between breeds, and expanded our understanding of the breed-level variations in recombination features within an

Linkage disequilibrium in HLA cannot be explained by selective recombination.

Science.gov (United States)

Termijtelen, A; D'Amaro, J; van Rood, J J; Schreuder, G M

1995-11-01

Some combinations of HLA-A, -B and -DR antigens occur more frequently than would be expected from their gene frequencies in the population. This phenomenon, referred to as Linkage Disequilibrium (LD) has been the origin of many speculations. One hypothesis to explain LD is that some haplotypes are protected from recombination. A second hypothesis is that these HLA antigens preferentially recombine after cross-over to create an LD haplotype. We tested these 2 hypotheses: from a pool of over 10,000 families typed in our department, we analyzed 126 families in which HLA-A:B or B:DR recombinant offspring was documented. To overcome a possible bias in our material, we used the non-recombined haplotypes from the same 126 families as a control group. Our results show that the number of cross-overs through LD haplotypes is not significantly lower then would be expected if recombination occurred randomly. Also the number of LD haplotypes created upon recombination was not significantly increased.

Branching innovation, recombinant innovation, and endogenous technological transitions

NARCIS (Netherlands)

Frenken, K.; Izquierdo, L.; Zeppini, P.

2012-01-01

We propose a model of technological transitions based on two different types of innovations. Branching innovations refer to technological improvements along a particular path, while recombinant innovations represent fusions of multiple paths. Recombinant innovations create "short-cuts" which reduce

Quality of Life in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

Directory of Open Access Journals (Sweden)

Saleem Ahmed

2016-01-01

Full Text Available Hepatocellular carcinoma (HCC is one of the most commonly diagnosed cancers worldwide. Majority of patients with HCC are diagnosed in the advanced stages of disease and hence they are only suitable for palliative therapy. TACE (transarterial chemoembolization is the most commonly used treatment for unresectable HCC. It is however unclear if TACE improves the quality of life (QoL in patients with HCC. The aim of this review is to evaluate the impact of TACE on QoL of HCC patients.

Determination of the trap-assisted recombination strength in polymer light emitting diodes

NARCIS (Netherlands)

Kuik, Martijn; Nicolai, Herman T.; Lenes, Martijn; Wetzelaer, Gert-Jan A. H.; Lu, Mingtao; Blom, Paul W. M.

2011-01-01

The recombination processes in poly(p-phenylene vinylene) based polymer light-emitting diodes (PLEDs) are investigated. Photogenerated current measurements on PLED device structures reveal that next to the known Langevin recombination also trap-assisted recombination is an important recombination

Determination of the trap-assisted recombination strength in polymer light emitting diodes

NARCIS (Netherlands)

Kuik, M.; Nicolai, H.T.; Lenes, M.; Wetzelaer, G.-J.A.H.; Lu, M.; Blom, P.W.M.

2011-01-01

The recombination processes in poly(p -phenylene vinylene) based polymer light-emitting diodes (PLEDs) are investigated. Photogenerated current measurements on PLED device structures reveal that next to the known Langevin recombination also trap-assisted recombination is an important recombination

Recombination of a fast expanding plasma

International Nuclear Information System (INIS)

Salvat, M.

1979-05-01

The goal of the following calculations is to determine numerically the recombination of dense plasmas (for instance of laser-produced plasmas). The recombination is computed for plasmas with initial densities of 10 24 27 [m -3 ] and with initial temperatures >= 50 eV. The ionization of the plasma remains essentially constant during the early phase of expansion. The time for which the ionization is 'frozen-in' grows with decreasing initial density and with increasing initial temperature. (orig.) [de

Co-factor activated recombinant adenovirus proteinases

Science.gov (United States)

Anderson, Carl W.; Mangel, Walter F.

1996-08-06

This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

Mitochondrial recombination increases with age in Podospora anserina

NARCIS (Netherlands)

van Diepeningen, Anne D; Goedbloed, Daniël J; Slakhorst, S Marijke; Koopmanschap, A Bertha; Maas, Marc F P M; Hoekstra, Rolf F; Debets, Alfons J M

With uniparental inheritance of mitochondria, there seems little reason for homologous recombination in mitochondria, but the machinery for mitochondrial recombination is quite well-conserved in many eukaryote species. In fungi and yeasts heteroplasmons may be formed when strains fuse and transfer

The Λ0 polarization and the recombination mechanism

International Nuclear Information System (INIS)

Herrera, G.; Montano, L.M.

1997-01-01

We use the recombination and the Thomas Precession Model to obtain a prediction for the Λ 0 polarization in the p+p → Λ 0 + X reaction. We study the effect of the recombination function on the Λ 0 polarization. (author)

A simple negative selection method to identify adenovirus recombinants using colony PCR

Directory of Open Access Journals (Sweden)

Yongliang Zhao

2014-01-01

Conclusions: The negative selection method to identify AdEasy adenovirus recombinants by colony PCR can identify the recombined colony within a short time-period, and maximally avoid damage to the recombinant plasmid by limiting recombination time, resulting in improved adenovirus packaging.

The potential of shifting recombination hotspots to increase genetic gain in livestock breeding.

Science.gov (United States)

Gonen, Serap; Battagin, Mara; Johnston, Susan E; Gorjanc, Gregor; Hickey, John M

2017-07-04

This study uses simulation to explore and quantify the potential effect of shifting recombination hotspots on genetic gain in livestock breeding programs. We simulated three scenarios that differed in the locations of quantitative trait nucleotides (QTN) and recombination hotspots in the genome. In scenario 1, QTN were randomly distributed along the chromosomes and recombination was restricted to occur within specific genomic regions (i.e. recombination hotspots). In the other two scenarios, both QTN and recombination hotspots were located in specific regions, but differed in whether the QTN occurred outside of (scenario 2) or inside (scenario 3) recombination hotspots. We split each chromosome into 250, 500 or 1000 regions per chromosome of which 10% were recombination hotspots and/or contained QTN. The breeding program was run for 21 generations of selection, after which recombination hotspot regions were kept the same or were shifted to adjacent regions for a further 80 generations of selection. We evaluated the effect of shifting recombination hotspots on genetic gain, genetic variance and genic variance. Our results show that shifting recombination hotspots reduced the decline of genetic and genic variance by releasing standing allelic variation in the form of new allele combinations. This in turn resulted in larger increases in genetic gain. However, the benefit of shifting recombination hotspots for increased genetic gain was only observed when QTN were initially outside recombination hotspots. If QTN were initially inside recombination hotspots then shifting them decreased genetic gain. Shifting recombination hotspots to regions of the genome where recombination had not occurred for 21 generations of selection (i.e. recombination deserts) released more of the standing allelic variation available in each generation and thus increased genetic gain. However, whether and how much increase in genetic gain was achieved by shifting recombination hotspots depended

Polyploidization increases meiotic recombination frequency in Arabidopsis

Directory of Open Access Journals (Sweden)

Rehmsmeier Marc

2011-04-01

Full Text Available Abstract Background Polyploidization is the multiplication of the whole chromosome complement and has occurred frequently in vascular plants. Maintenance of stable polyploid state over generations requires special mechanisms to control pairing and distribution of more than two homologous chromosomes during meiosis. Since a minimal number of crossover events is essential for correct chromosome segregation, we investigated whether polyploidy has an influence on the frequency of meiotic recombination. Results Using two genetically linked transgenes providing seed-specific fluorescence, we compared a high number of progeny from diploid and tetraploid Arabidopsis plants. We show that rates of meiotic recombination in reciprocal crosses of genetically identical diploid and autotetraploid Arabidopsis plants were significantly higher in tetraploids compared to diploids. Although male and female gametogenesis differ substantially in meiotic recombination frequency, both rates were equally increased in tetraploids. To investigate whether multivalent formation in autotetraploids was responsible for the increased recombination rates, we also performed corresponding experiments with allotetraploid plants showing strict bivalent pairing. We found similarly increased rates in auto- and allotetraploids, suggesting that the ploidy effect is independent of chromosome pairing configurations. Conclusions The evolutionary success of polyploid plants in nature and under domestication has been attributed to buffering of mutations and sub- and neo-functionalization of duplicated genes. Should the data described here be representative for polyploid plants, enhanced meiotic recombination, and the resulting rapid creation of genetic diversity, could have also contributed to their prevalence.

Report of recombinant norovirus GII.g/GII.12 in Beijing, China.

Science.gov (United States)

Sang, Shaowei; Zhao, Zhongtang; Suo, Jijiang; Xing, Yubin; Jia, Ning; Gao, Yan; Xie, Lijun; Du, Mingmei; Liu, Bowei; Ren, Shiwang; Liu, Yunxi

2014-01-01

Norovirus (NoV) has been recognized as the most important cause of nonbacterial acute gastroenteritis affecting all age group people in the world. Genetic recombination is a common occurance in RNA viruses and many recombinant NoV strains have been described since it was first reported in 1997. However, the knowledge of recombinant NoV in China is extremely limited. A total of 685 stool specimens were tested for NoV infection from the acute gastroenteritis patients who visited one general hospital in Beijing from April 2009 to November 2011. The virus recombination was identified by constructing phylogenetic trees of two genes, further SimPlot and the maximum chi-square analysis. The overall positive rate was 9.6% (66/685). GII.4 New Orleans 2009 and GII.4 2006b variants were the dominant genotype. Four GII.g/GII.12 and one GII.12/GII.3 recombinant strains were confirmed, and all derived from adult outpatients. The predictive recombination point occurred at the open reading frame (ORF)1/ORF2 overlap. The GII.g ORF1/GII.12ORF2 recombinant has been reported in several countries and it was the first report of this recombinant in China.

Recombinational Cloning Using Gateway and In-Fusion Cloning Schemes

Science.gov (United States)

Throop, Andrea L.; LaBaer, Joshua

2015-01-01

The comprehensive study of protein structure and function, or proteomics, depends on the obtainability of full-length cDNAs in species-specific expression vectors and subsequent functional analysis of the expressed protein. Recombinational cloning is a universal cloning technique based on site-specific recombination that is independent of the insert DNA sequence of interest, which differentiates this method from the classical restriction enzyme-based cloning methods. Recombinational cloning enables rapid and efficient parallel transfer of DNA inserts into multiple expression systems. This unit summarizes strategies for generating expression-ready clones using the most popular recombinational cloning technologies, including the commercially available Gateway® (Life Technologies) and In-Fusion® (Clontech) cloning technologies. PMID:25827088

Productive Homologous and Non-homologous Recombination of Hepatitis C Virus in Cell Culture

Science.gov (United States)

Li, Yi-Ping; Mikkelsen, Lotte S.; Gottwein, Judith M.; Bukh, Jens

2013-01-01

Genetic recombination is an important mechanism for increasing diversity of RNA viruses, and constitutes a viral escape mechanism to host immune responses and to treatment with antiviral compounds. Although rare, epidemiologically important hepatitis C virus (HCV) recombinants have been reported. In addition, recombination is an important regulatory mechanism of cytopathogenicity for the related pestiviruses. Here we describe recombination of HCV RNA in cell culture leading to production of infectious virus. Initially, hepatoma cells were co-transfected with a replicating JFH1ΔE1E2 genome (genotype 2a) lacking functional envelope genes and strain J6 (2a), which has functional envelope genes but does not replicate in culture. After an initial decrease in the number of HCV positive cells, infection spread after 13–36 days. Sequencing of recovered viruses revealed non-homologous recombinants with J6 sequence from the 5′ end to the NS2–NS3 region followed by JFH1 sequence from Core to the 3′ end. These recombinants carried duplicated sequence of up to 2400 nucleotides. HCV replication was not required for recombination, as recombinants were observed in most experiments even when two replication incompetent genomes were co-transfected. Reverse genetic studies verified the viability of representative recombinants. After serial passage, subsequent recombination events reducing or eliminating the duplicated region were observed for some but not all recombinants. Furthermore, we found that inter-genotypic recombination could occur, but at a lower frequency than intra-genotypic recombination. Productive recombination of attenuated HCV genomes depended on expression of all HCV proteins and tolerated duplicated sequence. In general, no strong site specificity was observed. Non-homologous recombination was observed in most cases, while few homologous events were identified. A better understanding of HCV recombination could help identification of natural recombinants

Inhomogeneous bimolecular recombination in partially crystallised tri-methylphenyl diamine glasses

International Nuclear Information System (INIS)

Goldie, D.M.

2013-01-01

The rise and fall dynamics of transient photocurrents induced by exposure to ultraviolet radiation have been analysed for a series of glassy tri-methylphenyl diamine films that have been partially crystallised by ageing under ambient conditions following vapour deposition. An inhomogeneous bimolecular recombination model that uses coupled rate equations is found to provide a consistent fit for the observed photocurrent dynamics provided the recombination rate of holes in the crystallised regions of the films is lower compared to the amorphous regions. Parameters returned by the bimolecular model are investigated as a function of the film age but are observed to be highly sensitive to the initial experimental estimates that are supplied for the effective hole recombination time. The effective hole recombination time generated by the model is found to be relatively independent of film age, however, and has a value of around 0.16 s for a carrier generation rate of 7 × 10 14 cm −3 s −1 . The effective recombination time and steady-state photoconductivity magnitudes are found to be consistent with experimental hole mobility and photo-carrier generation efficiency values that are obtained using complementary time-of-flight and charge collection experiments. - Highlights: ► Transient photocurrents in evaporated diamine films have fast and slow components. ► Transient photocurrents are modelled using inhomogeneous bimolecular recombination. ► Recombination rates differ between crystallised and amorphous film regions. ► Recombination parameters evolve with film age as the films crystallise

Dielectronic recombination of highly ionized iron

International Nuclear Information System (INIS)

Griffin, D.C.; Pindzola, M.S.

1987-01-01

Dielectronic recombination of the iron ions Fe/sup 15+/, Fe/sup 23+/, and Fe/sup 25+/ has been studied in the isolated-resonance, distorted-wave approximation. The cross-section calculations include the dielec- tronic transitions associated with the 3s→3l and 3s→4l excitations in Fe/sup 15+/, the 2s→2p and 2s→3l excitations in Fe/sup 23+/, and the 1s→2l excitations in Fe/sup 25+/. The effects of external electric fields have been included by employing intermediate-coupled, field-mixed eigenvectors for the doubly excited Rydberg states, determined by diagonalizing a Hamiltonian matrix which includes the internal electrostatic and spin-orbit terms, as well as the Stark matrix elements. The field effects are found to be quite large in Fe/sup 15+/, relatively small in Fe/sup 23+/, and negligible in Fe/sup 25+/. The calculations indicate that there are large resonances near threshold in Fe/sup 23+/ that are unaffected by external fields and may be measurable in new experiments currently being designed. In addition, the contributions of radiative recombination and the possible interference between radiative and dielectronic recombination in low-lying resonances are considered. Even though the radiative recombination cross sections may be appreciable near threshold in Fe/sup 15+/ and Fe/sup 23+/, the interference between these processes appears to be completely negligible

Engineering N-terminal domain of tissue inhibitor of metalloproteinase (TIMP)-3 to be a better inhibitor against tumour necrosis factor-alpha-converting enzyme.

Science.gov (United States)

Lee, Meng-Huee; Verma, Vandana; Maskos, Klaus; Nath, Deepa; Knäuper, Vera; Dodds, Philippa; Amour, Augustin; Murphy, Gillian

2002-01-01

We previously reported that full-length tissue inhibitor of metalloproteinase-3 (TIMP-3) and its N-terminal domain form (N-TIMP-3) displayed equal binding affinity for tissue necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE). Based on the computer graphic of TACE docked with a TIMP-3 model, we created a number of N-TIMP-3 mutants that showed significant improvement in TACE inhibition. Our strategy was to select those N-TIMP-3 residues that were believed to be in actual contact with the active-site pockets of TACE and mutate them to amino acids of a better-fitting nature. The activities of these mutants were examined by measuring their binding affinities (K(app)(i)) and association rates (k(on)) against TACE. Nearly all mutants at position Thr-2 exhibited slightly impaired affinity as well as association rate constants. On the other hand, some Ser-4 mutants displayed a remarkable increase in their binding tightness with TACE. In fact, the binding affinities of several mutants were less than 60 pM, beyond the sensitivity limits of fluorimetric assays. Further studies on cell-based processing of pro-TNF-alpha demonstrated that wild-type N-TIMP-3 and one of its tight-binding mutants, Ser-4Met, were capable of inhibiting the proteolytic shedding of TNF-alpha. Furthermore, the Ser-4Met mutant was also significantly more active (P<0.05) than the wild-type N-TIMP-3 in its cellular inhibition. Comparison of N-TIMP-3 and full-length TIMP-3 revealed that, despite their identical TACE-interaction kinetics, the latter was nearly 10 times more efficient in the inhibition of TNF-alpha shedding, with concomitant implications for the importance of the TIMP-3 C-terminal domain in vivo. PMID:11988096

The ART score is not effective to select patients for transarterial chemoembolization retreatment in an Italian series.

Science.gov (United States)

Terzi, Eleonora; Terenzi, Laura; Venerandi, Laura; Croci, Luca; Renzulli, Matteo; Mosconi, Cristina; Allegretti, Giulia; Granito, Alessandro; Golfieri, Rita; Bolondi, Luigi; Piscaglia, Fabio

2014-01-01

The ART score (a point score for the assessment of retreatment with transarterial chemoembolization, TACE) has been recently developed in Austria to differentiate patients who may benefit from multiple sessions of TACE for hepatocellular carcinoma (HCC) treatment. The primary aim of the study was to test the validity of the ART score in an Italian study cohort. The secondary aims were to evaluate overall survival (OS) and clinical determinants of improved survival in patients treated with multiple TACE sessions. The ART score and the clinical outcome of 51 consecutive patients with HCC submitted to multiple TACE sessions from April 2002 to December 2009 were retrospectively analyzed. Median OS was 26.0 months (95% confidence interval 18.4-33.6) with 1-, 3- and 5-year survival rates of 75, 33 and 11%, respectively). Thirty-three patients had an ART score of 0-1.5 and in 18 it was ≥2.5, but in our patient series, the ART score was not found to be a predictor of survival (p = 0.173). At univariate analysis, tumor extent (uni- vs. bilobar: 34.0 vs. 9.0 months; p < 0.001), Child-Pugh score before the second TACE (A vs. B7 vs. B8-9: 26.0 vs. 16.0 vs. 5.0 months; p = 0.005) and Child-Pugh score increase between the first and second TACE (absent vs. + 1 point vs. + ≥2 points: 27.0 vs. 4.0 vs. 5.0 months; p < 0.001) were statistically related with survival. At multivariate analysis, only Child-Pugh score increase remained a significant predictor of worse survival (p = 0.001, hazard rate = 11.6). The ART score was not found to work as an objective tool to guide TACE retreatment in our Italian patient series, only the Child-Pugh score increase was an independent predictor of a shorter survival.

Transarterial Chemoembolization for Hepatocellular Carcinoma with a New Generation of Beads: Clinical–Radiological Outcomes and Safety Profile

Energy Technology Data Exchange (ETDEWEB)

Spreafico, Carlo, E-mail: carlo.spreafico@istitutotumori.mi.it; Cascella, Tommaso, E-mail: tommaso.cascella@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Facciorusso, Antonio, E-mail: antonio.facciorusso@istitutotumori.mi.it; Sposito, Carlo, E-mail: carlo.sposito@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy); Rodolfo, Lanocita, E-mail: rodolfo.lanocita@istitutotumori.mi.it; Morosi, Carlo, E-mail: carlo.morosi@istitutotumori.mi.it; Civelli, Enrico M., E-mail: enrico.civelli@istitutotumori.mi.it; Vaiani, Marta, E-mail: marta.vaiani@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Bhoori, Sherrie, E-mail: sherrie.bhoori@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy); Pellegrinelli, Alessandro, E-mail: alessandro.pellegrinelli@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Pathology (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Mazzaferro, Vincenzo, E-mail: vincenzo.mazzaferro@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy)

2015-02-15

PurposeTo evaluate the short-term safety and efficacy of the new generation of 70–150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT).MethodsForty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response.ResultsAll patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1–6) and 43 mm (range 10–190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2–4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures).ConclusionDEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

Expression of testicular angiotensin-converting enzyme in adult spontaneously hypertensive rats.

Directory of Open Access Journals (Sweden)

Genka Krasteva

2009-05-01

Full Text Available Recent studies demonstrated that one isoform of angiotensin-converting enzyme named testicular or germinal (tACE is localized in postmeiotic male germ cells and is essential for fertilizing ability of spermatozoa. Hypertension in spontaneously hypertensive rats (SHR is androgen-dependent and reduction in male gametes is reported in this experimental conditions. Expression of tACE was not studied under conditions of spontaneous hypertension. The aim of this work is to characterize immuno-expression of tACE in the testis of adult (16-week-old SHR rats in relation to the changes in blood pressure and serum testosterone level. In 82% of adult SHR, the immuno-expression of tACE followed the normal stage-specific pattern. Destructive testicular changes, germ cells depletion have been observed in 18% of 16-week-old SHR and stronger expression of tACE in stages 8-11 compared to controls was detected. As a result stage specificity in SHR was not as evident as in control. No reaction was found in germ cell depleted tubules in which elongated spermatids were absent. Degenerating germ cells exhibited strong immunostaining comparable to that in residual bodies. The blood pressure was significantly higher in SHR and testosterone levels were more than twice but non-significantly elevated. There was no clear correlation between testicular structural changes, blood pressure level values or serum testosterone levels. Expression of tACE in postmeiotic germ cells, specifically altered by SHR, suggested possible involvement of components of renin-angiotensin system in the process of spermiogenesis. Loss of enzyme expression we found in germ cell depleted tubules in SHR is due to absence of corresponding stages of spermatid differentiation. Therefore, tACE can be used as a marker for germ cell depletion due to hypertension and other pathological conditions.

Transarterial chemoembolization versus resection for intermediate-stage (BCLC B hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Jun Young Kim

2016-06-01

Full Text Available Background/Aims: Several studies have suggested that surgical resection (SR can provide a survival benefit over transarterial chemoembolization (TACE for hepatocellular carcinoma (HCC at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. Methods: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225 or SR (N=52 were analyzed. Results: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002. Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP level, and Child-Pugh score, and these were then simplified into four subgroups (B1–B4 based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo’ (2–4 nodules of intermediate size (5–10 cm when the AFP levels was <400 ng/ml, or ‘oligo’ (2–4 nodules of small to intermediate size (<10 cm plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014. The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3. Conclusion: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.

Measurements of EEDF in recombination dominated afterglow plasma

Science.gov (United States)

Plasil, R.; Korolov, I.; Kotrik, T.; Varju, J.; Dohnal, P.; Donko, Z.; Bano, G.; Glosik, J.

2009-11-01

Electron energy distribution functions (EEDF) have been measured in decaying plasma in Flowing Afterglow Langmuir Probe (FALP) experiment. The measurements have been carried out in diffusion and recombination governed plasmas used for studies of recombination of KrD+ and H3+ ions.

Measurements of EEDF in recombination dominated afterglow plasma

International Nuclear Information System (INIS)

Plasil, R; Korolov, I; Kotrik, T; Varju, J; Dohnal, P; Glosik, J; Donko, Z; Bano, G

2009-01-01

Electron energy distribution functions (EEDF) have been measured in decaying plasma in Flowing Afterglow Langmuir Probe (FALP) experiment. The measurements have been carried out in diffusion and recombination governed plasmas used for studies of recombination of KrD + and H 3 + ions.

The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster.

Science.gov (United States)

Hunter, Chad M; Huang, Wen; Mackay, Trudy F C; Singh, Nadia D

2016-04-01

Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait.

Effect of Preoperative Radiological Treatment of Hepatocellular Carcinoma Before Liver Transplantation: A Retrospective Study

International Nuclear Information System (INIS)

Veltri, Andrea; Grosso, Maurizio; Martina, Maria C.; Ciancio, Alessia; David, Ezio; Salizzoni, Mauro; Soldano, Umberto; Galli, Joseph; Fava, Cesare

1998-01-01

Purpose: To assess the results of radiological treatment of patients with hepatocellular carcinoma (HCC) performed before orthotopic liver transplantation (OLT). Methods: Sixty-two transplanted patients with a total of 89 HCC nodules were studied; 50 lesions in 38 patients had been treated prior to OLT with transcatheter arterial chemoembolization (TACE; n= 29), percutaneous ethanol injection (PEI; n= 10), or combined therapy (TACE + PEI; n= 11). The induced necrosis was pathologically evaluated. The recurrence rate after OLT in the treated group of patients (n= 38) was compared with that in the non-treated group (n= 24). Results: After TACE, necrosis was complete in 7 of 29 lesions (24.1%), partial in 11 of 29 (37.9%), and absent in 11 of 29 (37.9%). After PEI, necrosis was complete in 8 of 10 lesions (80%), and partial in 2 of 10 (20%). Using combined therapy, necrosis was complete in 11 of 11 lesions (100%). Four of 24 untreated and 4 of 38 treated patients did not survive OLT from causes not related to the HCC; 3 of 20 non-treated patients (15%) and 4 of 34 treated patients (11.8%) had post-OLT recurrence (these last four patients had undergone only TACE and did not have tumor necrosis at pathological examination). Conclusion: TACE of HCC prior to OLT had no influence on the recurrence rate. PEI and combined therapy (TACE + PEI) may be recommended in patients awaiting OLT

Quantitative assessment of angiographic perfusion reduction using color-coded digital subtraction angiography during transarterial chemoembolization.

Science.gov (United States)

Wang, Ji; Cheng, Jie-Jun; Huang, Kai-Yi; Zhuang, Zhi-Guo; Zhang, Xue-Bin; Chi, Jia-Chang; Hua, Xiao-Lan; Xu, Jian-Rong

2016-03-01

The aim of this study was to develop a quantitative measurement of perfusion reduction using color-coded digital subtraction angiography (ccDSA) to monitor intra-procedural arterial stasis during TACE. A total number of 35 patients with hepatocellular carcinoma who had undergone TACE were enrolled into the study. Pre- and post-two-dimensional digital subtraction angiography scans were conducted with same protocol and post-processed with ccDSA prototype software. Time-contrast-intensity (CI[t]) curve was obtained by region-of-interest (ROI) measurement on the generated ccDSA image. Quantitative 2D perfusion parameters time to peak, area under the curve (AUC), maximum upslope, and contrast intensity peak (CI-Peak) derived from the ROI-based CI[t] curve for pre- and post-TACE were evaluated to assess the reduction of antegrade blood flow and tumor blush. Relationships between 2D perfusion parameters, subjective angiographic chemoembolization endpoint (SACE) scale, and clinical outcomes were analyzed. Area normalized AUC and CI-Peak revealed significant reduction after the TACE (P SACE level III and a reduction ranging from 60% to 70% was equivalent to SACE level IV. For intermediate reduction (SACE level III), better tumor response was found after TACE rather than a higher reduction (SACE level IV). ccDSA application provides an objective approach to quantify the perfusion reduction and subjectively evaluate the arterial stasis of antegrade blood flow and tumor blush caused by TACE.

Recombination in feline immunodeficiency virus from feral and companion domestic cats

Directory of Open Access Journals (Sweden)

Rodrigo Allen G

2008-06-01

Full Text Available Abstract Background Recombination is a relatively common phenomenon in retroviruses. We investigated recombination in Feline Immunodeficiency Virus from naturally-infected New Zealand domestic cats (Felis catus by sequencing regions of the gag, pol and env genes. Results The occurrence of intragenic recombination was highest in env, with evidence of recombination in 6.4% (n = 156 of all cats. A further recombinant was identified in each of the gag (n = 48 and pol (n = 91 genes. Comparisons of phylogenetic trees across genes identified cases of incongruence, indicating intergenic recombination. Three (7.7%, n = 39 of these incongruencies were found to be significantly different using the Shimodaira-Hasegawa test. Surprisingly, our phylogenies from the gag and pol genes showed that no New Zealand sequences group with reference subtype C sequences within intrasubtype pairwise distances. Indeed, we find one and two distinct unknown subtype groups in gag and pol, respectively. These observations cause us to speculate that these New Zealand FIV strains have undergone several recombination events between subtype A parent strains and undefined unknown subtype strains, similar to the evolutionary history hypothesised for HIV-1 "subtype E". Endpoint dilution sequencing was used to confirm the consensus sequences of the putative recombinants and unknown subtype groups, providing evidence for the authenticity of these sequences. Endpoint dilution sequencing also resulted in the identification of a dual infection event in the env gene. In addition, an intrahost recombination event between variants of the same subtype in the pol gene was established. This is the first known example of naturally-occurring recombination in a cat with infection of the parent strains. Conclusion Evidence of intragenic recombination in the gag, pol and env regions, and complex intergenic recombination, of FIV from naturally-infected domestic cats in New Zealand was found. Strains

Recombination in feline immunodeficiency virus from feral and companion domestic cats.

Science.gov (United States)

Hayward, Jessica J; Rodrigo, Allen G

2008-06-17

Recombination is a relatively common phenomenon in retroviruses. We investigated recombination in Feline Immunodeficiency Virus from naturally-infected New Zealand domestic cats (Felis catus) by sequencing regions of the gag, pol and env genes. The occurrence of intragenic recombination was highest in env, with evidence of recombination in 6.4% (n = 156) of all cats. A further recombinant was identified in each of the gag (n = 48) and pol (n = 91) genes. Comparisons of phylogenetic trees across genes identified cases of incongruence, indicating intergenic recombination. Three (7.7%, n = 39) of these incongruencies were found to be significantly different using the Shimodaira-Hasegawa test.Surprisingly, our phylogenies from the gag and pol genes showed that no New Zealand sequences group with reference subtype C sequences within intrasubtype pairwise distances. Indeed, we find one and two distinct unknown subtype groups in gag and pol, respectively. These observations cause us to speculate that these New Zealand FIV strains have undergone several recombination events between subtype A parent strains and undefined unknown subtype strains, similar to the evolutionary history hypothesised for HIV-1 "subtype E".Endpoint dilution sequencing was used to confirm the consensus sequences of the putative recombinants and unknown subtype groups, providing evidence for the authenticity of these sequences. Endpoint dilution sequencing also resulted in the identification of a dual infection event in the env gene. In addition, an intrahost recombination event between variants of the same subtype in the pol gene was established. This is the first known example of naturally-occurring recombination in a cat with infection of the parent strains. Evidence of intragenic recombination in the gag, pol and env regions, and complex intergenic recombination, of FIV from naturally-infected domestic cats in New Zealand was found. Strains of unknown subtype were identified in all three gene

Expression and purification of recombinant nattokinase in Spodoptera frugiperda cells.

Science.gov (United States)

Li, Xiaoxiang; Wang, Xiaoli; Xiong, Shaoling; Zhang, Jing; Cai, Litao; Yang, Yanyan

2007-10-01

A recombinant baculovirus, rv-egfp-NK, containing a reporter gene encoding the enhanced green fluorescent protein (EGFP), was used to express nattokinase (NK), a fibrinolytic enzyme, in Spodoptera frugiperda (SF-9) cells. The recombinant protein also included a histidine tag for purification using Ni(2+) resins. The recombinant NK, approximately 30 kDa, retained fibrinolytic activity (60 U/ml). The integration of the EGFP expression cassette in the Bac-to-Bac system is thus an effective method for the expression and purification of recombinant NK protein in Spodoptera frugiperda insect cells.

Recombinant organisms for production of industrial products

OpenAIRE

Adrio, Jose-Luis; Demain, Arnold L

2009-01-01

A revolution in industrial microbiology was sparked by the discoveries of ther double-stranded structure of DNA and the development of recombinant DNA technology. Traditional industrial microbiology was merged with molecular biology to yield improved recombinant processes for the industrial production of primary and secondary metabolites, protein biopharmaceuticals and industrial enzymes. Novel genetic techniques such as metabolic engineering, combinatorial biosynthesis and molecular breeding...

Prognostic factors in transcatheter arterial chemoembolization of hepatocellular carcinoma : analysis of more than 3 year survivors

International Nuclear Information System (INIS)

Seo, Heung Suk

1999-01-01

To determine which prognostic factors contribute to long-term survival after transcatheter arterial chemoembolization(TACE) of hepatocellular carcinoma. In 100 patients who expired within one year and 84 who survived or have survived for more than 3 years after TACE, prognostic factors were retrospectively evaluated. TACE was accomplished by hepatic arterial infusion of a suspension of Lipiodol and anticancer drugs(Mitomycin-C and Adriamycin), either alone or followed by gelfoam embolization. Fisher's exact test of probability was used to determine which prognostic factors were statistically significant. Statistically significant prognostic factors were as follows : Child classification(p 0.05). The prognosis of patients with hepatocellular carcinoma treated by TACE was affected favorably by good liver function(Child classification A), low alpha-fetoprotein value, nodular or massive-type tumor, patent main and first-order portal vein, and hypervascular tumor

Modelling of the operational behaviour of passive autocatalytic recombiners

International Nuclear Information System (INIS)

Schwarz, Ulrich

2011-01-01

Due to severe accidents in nuclear power plants, a significant amount of hydrogen can be produced. In pressurized water reactors, a possible and wide-spread measurement is the use of auto-catalytic recombiners. There are numerous numerical models describing the operational behaviour of recombiners for containment codes. The numerical model REKO-DIREKT was developed at the Forschungszentrum Juelich. This model describes the chemical reaction on the catalytic sheets by a physical model, as opposed to the usual codes based on empirical correlations. Additionally, there have been experimental studies concerning the catalytic recombination of hydrogen since the 1990s. The aim of this work is the further development of the program REKO-DIREKT to an independent recombiner model for severe accident and containment codes. Therefore, the catalyst model already existed has been submitted by a parameter optimization with an experimental database expanded during this work. In addition, a chimney model has been implemented which allows the calculation of the free convection flow through the recombiner housing due to the exothermal reaction. This model has been tested by experimental data gained by a recently built test facility. The complete recombiner model REKO-DIREKT has been validated by data from literature. Another aim of this work is the derivation of the reaction kinetics for recombiner designs regarding future reactor concepts. Therefore, experimental studies both on single catalytic coated meshes as well as on two meshes installed in a row have been performed in laboratory scale. By means of the measured data, a theoretical approach for the determination of the reaction rate has been derived.

On the Fokker-Planck theory of electron three-body recombination

International Nuclear Information System (INIS)

Sayasov, Yu. S.

1977-01-01

The Fokker-Planck theory of electron three-body recombination based on the concept of electron diffusion along the energy scale in the excited hydrogen-like atoms formed in the recombining plasmas, is extended in several respects. 1) An universal formula for population distribution of the excited atoms in strongly ionized plasmas was found under a sole assumption, that the cross-sections for the inelastic atom-electron collisions are governed by the classical impulse approximation. 2) A general Fokker-Planck theory of the recombination in a slightly ionized, two-temperature plasmas was formulated. The recombination coefficients for such plasmas were shown to possess some peculiar properties in case the electronic temperature differs appreciable from the atomic one. A few limitations of the existing schemas for calculation of the recombination kinetics are briefly discussed. (orig.) [de

Novel canine circovirus strains from Thailand: Evidence for genetic recombination.

Science.gov (United States)

Piewbang, Chutchai; Jo, Wendy K; Puff, Christina; van der Vries, Erhard; Kesdangsakonwut, Sawang; Rungsipipat, Anudep; Kruppa, Jochen; Jung, Klaus; Baumgärtner, Wolfgang; Techangamsuwan, Somporn; Ludlow, Martin; Osterhaus, Albert D M E

2018-05-14

Canine circoviruses (CanineCV's), belonging to the genus Circovirus of the Circoviridae family, were detected by next generation sequencing in samples from Thai dogs with respiratory symptoms. Genetic characterization and phylogenetic analysis of nearly complete CanineCV genomes suggested that natural recombination had occurred among different lineages of CanineCV's. Similarity plot and bootscaning analyses indicated that American and Chinese viruses had served as major and minor parental viruses, respectively. Positions of recombination breakpoints were estimated using maximum-likelihood frameworks with statistical significant testing. The putative recombination event was located in the Replicase gene, intersecting with open reading frame-3. Analysis of nucleotide changes confirmed the origin of the recombination event. This is the first description of naturally occurring recombinant CanineCV's that have resulted in the circulation of newly emerging CanineCV lineages.

Charge carrier recombination dynamics in perovskite and polymer solar cells

Energy Technology Data Exchange (ETDEWEB)

Paulke, Andreas; Kniepert, Juliane; Kurpiers, Jona; Wolff, Christian M.; Schön, Natalie; Brenner, Thomas J. K.; Neher, Dieter [Institute of Physics and Astronomy, University of Potsdam, Karl-Liebknecht-Str. 24–25, 14476, Potsdam (Germany); Stranks, Samuel D. [Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom); Research Laboratory of Electronics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 (United States); Cavendish Laboratory, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Snaith, Henry J. [Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom)

2016-03-14

Time-delayed collection field experiments are applied to planar organometal halide perovskite (CH{sub 3}NH{sub 3}PbI{sub 3}) based solar cells to investigate charge carrier recombination in a fully working solar cell at the nanosecond to microsecond time scale. Recombination of mobile (extractable) charges is shown to follow second-order recombination dynamics for all fluences and time scales tested. Most importantly, the bimolecular recombination coefficient is found to be time-dependent, with an initial value of ca. 10{sup −9} cm{sup 3}/s and a progressive reduction within the first tens of nanoseconds. Comparison to the prototypical organic bulk heterojunction device PTB7:PC{sub 71}BM yields important differences with regard to the mechanism and time scale of free carrier recombination.

Construction and Characterization of a Recombinant Invertebrate Iridovirus

NARCIS (Netherlands)

Ozgen, A.; Muratoglu, H.; Demirbag, Z.; Vlak, J.M.; Oers, van M.M.; Nalcacioglu, R.

2014-01-01

Chilo iridescent virus (CIV), officially named Insect iridescent virus 6 (IIV6), is the type species of the genus Iridovirus (family Iridoviridae). In this paper we constructed a recombinant CIV, encoding the green fluorescent protein (GFP). This recombinant can be used to investigate viral

Measurements of EEDF in recombination dominated afterglow plasma

Energy Technology Data Exchange (ETDEWEB)

Plasil, R; Korolov, I; Kotrik, T; Varju, J; Dohnal, P; Glosik, J [Charles University, Faculty of Mathematics and Physics, Department of Surface and Plasma Science, Prague (Czech Republic); Donko, Z; Bano, G, E-mail: radek.plasil@mff.cuni.c [Research Institute for Solid State Physics and Optics, Hungarian Academy of Sciences, Budapest (Hungary)

2009-11-15

Electron energy distribution functions (EEDF) have been measured in decaying plasma in Flowing Afterglow Langmuir Probe (FALP) experiment. The measurements have been carried out in diffusion and recombination governed plasmas used for studies of recombination of KrD{sup +} and H{sub 3}{sup +} ions.

78 FR 16447 - Rehabilitation Continuing Education Program (RCEP) for the Technical Assistance and Continuing...

Science.gov (United States)

2013-03-15

... (RCEP) for the Technical Assistance and Continuing Education Centers (TACE Centers); Proposed Extension... (RCEP) for the Technical Assistance and Continuing Education Centers (TACE Centers), the Secretary... with disabilities through enhanced technical assistance (TA) and continuing education (CE) for State...

Recombination Phenotypes of Escherichia coli greA Mutants

Directory of Open Access Journals (Sweden)

Poteete Anthony R

2011-03-01

Full Text Available Abstract Background The elongation factor GreA binds to RNA polymerase and modulates transcriptional pausing. Some recent research suggests that the primary role of GreA may not be to regulate gene expression, but rather, to promote the progression of replication forks which collide with RNA polymerase, and which might otherwise collapse. Replication fork collapse is known to generate dsDNA breaks, which can be recombinogenic. It follows that GreA malfunction could have consequences affecting homologous recombination. Results Escherichia coli mutants bearing substitutions of the active site acidic residues of the transcription elongation factor GreA, D41N and E44K, were isolated as suppressors of growth inhibition by a toxic variant of the bacteriophage lambda Red-beta recombination protein. These mutants, as well as a D41A greA mutant and a greA deletion, were tested for proficiency in recombination events. The mutations were found to increase the efficiency of RecA-RecBCD-mediated and RecA-Red-mediated recombination, which are replication-independent, and to decrease the efficiency of replication-dependent Red-mediated recombination. Conclusion These observations provide new evidence for a role of GreA in resolving conflicts between replication and transcription.

The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Chad M Hunter

2016-04-01

Full Text Available Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait.

The Contribution of Genetic Recombination to CRISPR Array Evolution.

Science.gov (United States)

Kupczok, Anne; Landan, Giddy; Dagan, Tal

2015-06-16

CRISPR (clustered regularly interspaced short palindromic repeats) is a microbial immune system against foreign DNA. Recognition sequences (spacers) encoded within the CRISPR array mediate the immune reaction in a sequence-specific manner. The known mechanisms for the evolution of CRISPR arrays include spacer acquisition from foreign DNA elements at the time of invasion and array erosion through spacer deletion. Here, we consider the contribution of genetic recombination between homologous CRISPR arrays to the evolution of spacer repertoire. Acquisition of spacers from exogenic arrays via recombination may confer the recipient with immunity against unencountered antagonists. For this purpose, we develop a novel method for the detection of recombination in CRISPR arrays by modeling the spacer order in arrays from multiple strains from the same species. Because the evolutionary signal of spacer recombination may be similar to that of pervasive spacer deletions or independent spacer acquisition, our method entails a robustness analysis of the recombination inference by a statistical comparison to resampled and perturbed data sets. We analyze CRISPR data sets from four bacterial species: two Gammaproteobacteria species harboring CRISPR type I and two Streptococcus species harboring CRISPR type II loci. We find that CRISPR array evolution in Escherichia coli and Streptococcus agalactiae can be explained solely by vertical inheritance and differential spacer deletion. In Pseudomonas aeruginosa, we find an excess of single spacers potentially incorporated into the CRISPR locus during independent acquisition events. In Streptococcus thermophilus, evidence for spacer acquisition by recombination is present in 5 out of 70 strains. Genetic recombination has been proposed to accelerate adaptation by combining beneficial mutations that arose in independent lineages. However, for most species under study, we find that CRISPR evolution is shaped mainly by spacer acquisition and

The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.

Science.gov (United States)

Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice

2009-09-01

The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.

Genetic recombination is directed away from functional genomic elements in mice.

Science.gov (United States)

Brick, Kevin; Smagulova, Fatima; Khil, Pavel; Camerini-Otero, R Daniel; Petukhova, Galina V

2012-05-13

Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9), the product of the only known speciation-associated gene in mammals. PRDM9 is thought to determine the preferred recombination sites--recombination hotspots--through sequence-specific binding of its highly polymorphic multi-Zn-finger domain. Nevertheless, Prdm9 knockout mice are proficient at initiating recombination. Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F(1) hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)--the only area of the genome that undergoes recombination in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements.

Assembly and dynamics of the bacteriophage T4 homologous recombination machinery

Directory of Open Access Journals (Sweden)

Morrical Scott W

2010-12-01

Full Text Available Abstract Homologous recombination (HR, a process involving the physical exchange of strands between homologous or nearly homologous DNA molecules, is critical for maintaining the genetic diversity and genome stability of species. Bacteriophage T4 is one of the classic systems for studies of homologous recombination. T4 uses HR for high-frequency genetic exchanges, for homology-directed DNA repair (HDR processes including DNA double-strand break repair, and for the initiation of DNA replication (RDR. T4 recombination proteins are expressed at high levels during T4 infection in E. coli, and share strong sequence, structural, and/or functional conservation with their counterparts in cellular organisms. Biochemical studies of T4 recombination have provided key insights on DNA strand exchange mechanisms, on the structure and function of recombination proteins, and on the coordination of recombination and DNA synthesis activities during RDR and HDR. Recent years have seen the development of detailed biochemical models for the assembly and dynamics of presynaptic filaments in the T4 recombination system, for the atomic structure of T4 UvsX recombinase, and for the roles of DNA helicases in T4 recombination. The goal of this chapter is to review these recent advances and their implications for HR and HDR mechanisms in all organisms.

Report of recombinant norovirus GII.g/GII.12 in Beijing, China.

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Shaowei Sang

Full Text Available BACKGROUND: Norovirus (NoV has been recognized as the most important cause of nonbacterial acute gastroenteritis affecting all age group people in the world. Genetic recombination is a common occurance in RNA viruses and many recombinant NoV strains have been described since it was first reported in 1997. However, the knowledge of recombinant NoV in China is extremely limited. METHODS: A total of 685 stool specimens were tested for NoV infection from the acute gastroenteritis patients who visited one general hospital in Beijing from April 2009 to November 2011. The virus recombination was identified by constructing phylogenetic trees of two genes, further SimPlot and the maximum chi-square analysis. RESULTS: The overall positive rate was 9.6% (66/685. GII.4 New Orleans 2009 and GII.4 2006b variants were the dominant genotype. Four GII.g/GII.12 and one GII.12/GII.3 recombinant strains were confirmed, and all derived from adult outpatients. The predictive recombination point occurred at the open reading frame (ORF1/ORF2 overlap. CONCLUSIONS: The GII.g ORF1/GII.12ORF2 recombinant has been reported in several countries and it was the first report of this recombinant in China.

Epigenetic functions enriched in transcription factors binding to mouse recombination hotspots.

Science.gov (United States)

Wu, Min; Kwoh, Chee-Keong; Przytycka, Teresa M; Li, Jing; Zheng, Jie

2012-06-21

The regulatory mechanism of recombination is a fundamental problem in genomics, with wide applications in genome-wide association studies, birth-defect diseases, molecular evolution, cancer research, etc. In mammalian genomes, recombination events cluster into short genomic regions called "recombination hotspots". Recently, a 13-mer motif enriched in hotspots is identified as a candidate cis-regulatory element of human recombination hotspots; moreover, a zinc finger protein, PRDM9, binds to this motif and is associated with variation of recombination phenotype in human and mouse genomes, thus is a trans-acting regulator of recombination hotspots. However, this pair of cis and trans-regulators covers only a fraction of hotspots, thus other regulators of recombination hotspots remain to be discovered. In this paper, we propose an approach to predicting additional trans-regulators from DNA-binding proteins by comparing their enrichment of binding sites in hotspots. Applying this approach on newly mapped mouse hotspots genome-wide, we confirmed that PRDM9 is a major trans-regulator of hotspots. In addition, a list of top candidate trans-regulators of mouse hotspots is reported. Using GO analysis we observed that the top genes are enriched with function of histone modification, highlighting the epigenetic regulatory mechanisms of recombination hotspots.

Improved means and methods for expressing recombinant proteins

NARCIS (Netherlands)

Poolman, Berend; Martinez Linares, Daniel; Gul, Nadia

2014-01-01

The invention relates to the field of genetic engineering and the production of recombinant proteins in microbial host cells. Provided is a method for enhanced expression of a recombinant protein of interest in a microbial host cell, comprising providing a microbial host cell wherein the function of

In vitro V(D)J recombination: Signal joint formation

OpenAIRE

Cortes, Patricia; Weis-Garcia, Frances; Misulovin, Ziva; Nussenzweig, Andre; Lai, Jiann-Shiun; Li, Gloria; Nussenzweig, Michel C.; Baltimore, David

1996-01-01

The first step of V(D)J recombination, specific cleavage at the recombination signal sequence (RSS), can be carried out by the recombination activating proteins RAG1 and RAG2. In vivo, the cleaved coding and signal ends must be rejoined to generate functional antigen receptors and maintain chromosomal integrity. We have investigated signal joint formation using deletion and inversion substrates in a cell free system. RAG1 and RAG2 alone or in combination were unabl...

Some recent developments in the recombination model

International Nuclear Information System (INIS)

Hwa, R.C.

1979-01-01

A critical review of the recombination model for hadron production at low P/sub T/ is first given, emphasizing not so much the successes as unanswered questions that the model faces. A systematic program to answer some of the basic questions is then developed. The theoretical framework is quantum chromodynamics. First, in what may appear as a digression, the possibility of formation of valence quark clusters (called valons) in a nucleon due to gluon bremsstrahlung and quark-pair creation is considered. Evidences are found not only for the valons in neutrino scattering data, but also indications for their momentum distribution in a nucleon. When similar considerations are applied to a meson, the meaning of the recombination function is discussed and its normalization as well as its shape are determined. Next, the problem of quark decay in a hard scattering process (e.g., pion production in e + e - annihilation) is considered. The joint distribution of partons in a quark jet is determined in QCD. The quark decay function for pions in the recombination model is then obtained with excellent fit to the data. Similar investigation is applied to the problem of photoproduction of pions in the fragmentation region; again good agreement with data is achieved. The results indicate the reliability of the recombination model when the two-parton distributions can be calculated in QCD. Finally, hadron initiated reactions are considered. A duality between quark recombination and valon fragmentation is suggested. The picture is consistent with dual Regge model. A possible way to determine the inclusive distribution in the context of QCD is suggested

A molecular recombination map of Antirrhinum majus

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Hudson Andrew

2010-12-01

Full Text Available Abstract Background Genetic recombination maps provide important frameworks for comparative genomics, identifying gene functions, assembling genome sequences and for breeding. The molecular recombination map currently available for the model eudicot Antirrhinum majus is the result of a cross with Antirrhinum molle, limiting its usefulness within A. majus. Results We created a molecular linkage map of A. majus based on segregation of markers in the F2 population of two inbred lab strains of A. majus. The resulting map consisted of over 300 markers in eight linkage groups, which could be aligned with a classical recombination map and the A. majus karyotype. The distribution of recombination frequencies and distorted transmission of parental alleles differed from those of a previous inter-species hybrid. The differences varied in magnitude and direction between chromosomes, suggesting that they had multiple causes. The map, which covered an estimated of 95% of the genome with an average interval of 2 cM, was used to analyze the distribution of a newly discovered family of MITE transposons and tested for its utility in positioning seven mutations that affect aspects of plant size. Conclusions The current map has an estimated interval of 1.28 Mb between markers. It shows a lower level of transmission ratio distortion and a longer length than the previous inter-species map, making it potentially more useful. The molecular recombination map further indicates that the IDLE MITE transposons are distributed throughout the genome and are relatively stable. The map proved effective in mapping classical morphological mutations of A. majus.

Recombination facilitates neofunctionalization of duplicate genes via originalization

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Huang Ren

2010-06-01

Full Text Available Abstract Background Recently originalization was proposed to be an effective way of duplicate-gene preservation, in which recombination provokes the high frequency of original (or wild-type allele on both duplicated loci. Because the high frequency of wild-type allele might drive the arising and accumulating of advantageous mutation, it is hypothesized that recombination might enlarge the probability of neofunctionalization (Pneo of duplicate genes. In this article this hypothesis has been tested theoretically. Results Results show that through originalization recombination might not only shorten mean time to neofunctionalizaiton, but also enlarge Pneo. Conclusions Therefore, recombination might facilitate neofunctionalization via originalization. Several extensive applications of these results on genomic evolution have been discussed: 1. Time to nonfunctionalization can be much longer than a few million generations expected before; 2. Homogenization on duplicated loci results from not only gene conversion, but also originalization; 3. Although the rate of advantageous mutation is much small compared with that of degenerative mutation, Pneo cannot be expected to be small.

Measuring the Edge Recombination Velocity of Monolayer Semiconductors.

Science.gov (United States)

Zhao, Peida; Amani, Matin; Lien, Der-Hsien; Ahn, Geun Ho; Kiriya, Daisuke; Mastandrea, James P; Ager, Joel W; Yablonovitch, Eli; Chrzan, Daryl C; Javey, Ali

2017-09-13

Understanding edge effects and quantifying their impact on the carrier properties of two-dimensional (2D) semiconductors is an essential step toward utilizing this material for high performance electronic and optoelectronic devices. WS 2 monolayers patterned into disks of varying diameters are used to experimentally explore the influence of edges on the material's optical properties. Carrier lifetime measurements show a decrease in the effective lifetime, τ effective , as a function of decreasing diameter, suggesting that the edges are active sites for carrier recombination. Accordingly, we introduce a metric called edge recombination velocity (ERV) to characterize the impact of 2D material edges on nonradiative carrier recombination. The unpassivated WS 2 monolayer disks yield an ERV ∼ 4 × 10 4 cm/s. This work quantifies the nonradiative recombination edge effects in monolayer semiconductors, while simultaneously establishing a practical characterization approach that can be used to experimentally explore edge passivation methods for 2D materials.

Similarity of recombinant human perlecan domain 1 by alternative expression systems bioactive heterogenous recombinant human perlecan D1

DEFF Research Database (Denmark)

Ellis, April L; Pan, Wensheng; Yang, Guang

2010-01-01

BACKGROUND: Heparan sulfate glycosaminoglycans are diverse components of certain proteoglycans and are known to interact with growth factors as a co-receptor necessary to induce signalling and growth factor activity. In this report we characterize heterogeneously glycosylated recombinant human...... perlecan domain 1 (HSPG2 abbreviated as rhPln.D1) synthesized in either HEK 293 cells or HUVECs by transient gene delivery using either adenoviral or expression plasmid technology. RESULTS: By SDS-PAGE analysis following anion exchange chromatography, the recombinant proteoglycans appeared to possess...... glycosaminoglycan chains ranging, in total, from 6 kDa to >90 kDa per recombinant. Immunoblot analysis of enzyme-digested high Mr rhPln.D1 demonstrated that the rhPln.D1 was synthesized as either a chondroitin sulfate or heparan sulfate proteoglycan, in an approximately 2:1 ratio, with negligible hybrids. Secondary...

Recombinant Vaccinia Virus: Immunization against Multiple Pathogens

Science.gov (United States)

Perkus, Marion E.; Piccini, Antonia; Lipinskas, Bernard R.; Paoletti, Enzo

1985-09-01

The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

The Recombination Landscape in Wild House Mice Inferred Using Population Genomic Data.

Science.gov (United States)

Booker, Tom R; Ness, Rob W; Keightley, Peter D

2017-09-01

Characterizing variation in the rate of recombination across the genome is important for understanding several evolutionary processes. Previous analysis of the recombination landscape in laboratory mice has revealed that the different subspecies have different suites of recombination hotspots. It is unknown, however, whether hotspots identified in laboratory strains reflect the hotspot diversity of natural populations or whether broad-scale variation in the rate of recombination is conserved between subspecies. In this study, we constructed fine-scale recombination rate maps for a natural population of the Eastern house mouse, Mus musculus castaneus We performed simulations to assess the accuracy of recombination rate inference in the presence of phase errors, and we used a novel approach to quantify phase error. The spatial distribution of recombination events is strongly positively correlated between our castaneus map, and a map constructed using inbred lines derived predominantly from M. m. domesticus Recombination hotspots in wild castaneus show little overlap, however, with the locations of double-strand breaks in wild-derived house mouse strains. Finally, we also find that genetic diversity in M. m. castaneus is positively correlated with the rate of recombination, consistent with pervasive natural selection operating in the genome. Our study suggests that recombination rate variation is conserved at broad scales between house mouse subspecies, but it is not strongly conserved at fine scales. Copyright © 2017 by the Genetics Society of America.

Sex in a test tube: testing the benefits of in vitro recombination.

Science.gov (United States)

Pesce, Diego; Lehman, Niles; de Visser, J Arjan G M

2016-10-19

The origin and evolution of sex, and the associated role of recombination, present a major problem in biology. Sex typically involves recombination of closely related DNA or RNA sequences, which is fundamentally a random process that creates but also breaks up beneficial allele combinations. Directed evolution experiments, which combine in vitro mutation and recombination protocols with in vitro or in vivo selection, have proved to be an effective approach for improving functionality of nucleic acids and enzymes. As this approach allows extreme control over evolutionary conditions and parameters, it also facilitates the detection of small or position-specific recombination benefits and benefits associated with recombination between highly divergent genotypes. Yet, in vitro approaches have been largely exploratory and motivated by obtaining improved end products rather than testing hypotheses of recombination benefits. Here, we review the various experimental systems and approaches used by in vitro studies of recombination, discuss what they say about the evolutionary role of recombination, and sketch their potential for addressing extant questions about the evolutionary role of sex and recombination, in particular on complex fitness landscapes. We also review recent insights into the role of 'extracellular recombination' during the origin of life.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'. © 2016 The Author(s).

Interfacial recombination at /AlGa/As/GaAs heterojunction structures

Science.gov (United States)

Ettenberg, M.; Kressel, H.

1976-01-01

Experiments were conducted to determine the interfacial recombination velocity at Al0.25Ga0.75As/GaAs and Al0.5Ga0.5As/GaAs heterojunctions. The recombination velocity was derived from a study of the injected minority-carrier lifetime as a function of the junction spacing. It is found that for heterojunction spacings in excess of about 1 micron, the interfacial recombination can be characterized by a surface recombination velocity of 4,000 and 8,000 cm/sec for the two types of heterojunctions, respectively. For double-heterojunction spacings below 1 micron, the constancy of the minority-carrier lifetime suggests that the interfacial recombination velocity decreases effectively. This effect is technologically very important since it makes it possible to construct very low-threshold injection lasers. No such effect is observed in single-heterojunction diodes.

Genetic and evolutionary correlates of fine-scale recombination rate variation in Drosophila persimilis.

Science.gov (United States)

Stevison, Laurie S; Noor, Mohamed A F

2010-12-01

Recombination is fundamental to meiosis in many species and generates variation on which natural selection can act, yet fine-scale linkage maps are cumbersome to construct. We generated a fine-scale map of recombination rates across two major chromosomes in Drosophila persimilis using 181 SNP markers spanning two of five major chromosome arms. Using this map, we report significant fine-scale heterogeneity of local recombination rates. However, we also observed "recombinational neighborhoods," where adjacent intervals had similar recombination rates after excluding regions near the centromere and telomere. We further found significant positive associations of fine-scale recombination rate with repetitive element abundance and a 13-bp sequence motif known to associate with human recombination rates. We noted strong crossover interference extending 5-7 Mb from the initial crossover event. Further, we observed that fine-scale recombination rates in D. persimilis are strongly correlated with those obtained from a comparable study of its sister species, D. pseudoobscura. We documented a significant relationship between recombination rates and intron nucleotide sequence diversity within species, but no relationship between recombination rate and intron divergence between species. These results are consistent with selection models (hitchhiking and background selection) rather than mutagenic recombination models for explaining the relationship of recombination with nucleotide diversity within species. Finally, we found significant correlations between recombination rate and GC content, supporting both GC-biased gene conversion (BGC) models and selection-driven codon bias models. Overall, this genome-enabled map of fine-scale recombination rates allowed us to confirm findings of broader-scale studies and identify multiple novel features that merit further investigation.

Identifying recombinants in human and primate immunodeficiency virus sequence alignments using quartet scanning

Directory of Open Access Journals (Sweden)

Martin Darren P

2009-04-01

Full Text Available Abstract Background Recombination has a profound impact on the evolution of viruses, but characterizing recombination patterns in molecular sequences remains a challenging endeavor. Despite its importance in molecular evolutionary studies, identifying the sequences that exhibit such patterns has received comparatively less attention in the recombination detection framework. Here, we extend a quartet-mapping based recombination detection method to enable identification of recombinant sequences without prior specifications of either query and reference sequences. Through simulations we evaluate different recombinant identification statistics and significance tests. We compare the quartet approach with triplet-based methods that employ additional heuristic tests to identify parental and recombinant sequences. Results Analysis of phylogenetic simulations reveal that identifying the descendents of relatively old recombination events is a challenging task for all methods available, and that quartet scanning performs relatively well compared to the triplet based methods. The use of quartet scanning is further demonstrated by analyzing both well-established and putative HIV-1 recombinant strains. In agreement with recent findings, we provide evidence that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas the presumed parental lineage subtype G has a recombinant origin. We also demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in chimpanzees and further disentangle the recombinant history of SIV lineages in a primate immunodeficiency virus data set. Conclusion Quartet scanning makes a valuable addition to triplet-based methods for identifying recombinant sequences without prior specifications of either query and reference sequences. The new method is available in the VisRD v.3.0 package http://www.cmp.uea.ac.uk/~vlm/visrd.

RPA homologs and ssDNA processing during meiotic recombination.

Science.gov (United States)

Ribeiro, Jonathan; Abby, Emilie; Livera, Gabriel; Martini, Emmanuelle

2016-06-01

Meiotic homologous recombination is a specialized process that involves homologous chromosome pairing and strand exchange to guarantee proper chromosome segregation and genetic diversity. The formation and repair of DNA double-strand breaks (DSBs) during meiotic recombination differs from those during mitotic recombination in that the homologous chromosome rather than the sister chromatid is the preferred repair template. The processing of single-stranded DNA (ssDNA) formed on intermediate recombination structures is central to driving the specific outcomes of DSB repair during meiosis. Replication protein A (RPA) is the main ssDNA-binding protein complex involved in DNA metabolism. However, the existence of RPA orthologs in plants and the recent discovery of meiosis specific with OB domains (MEIOB), a widely conserved meiosis-specific RPA1 paralog, strongly suggest that multiple RPA complexes evolved and specialized to subdivide their roles during DNA metabolism. Here we review ssDNA formation and maturation during mitotic and meiotic recombination underlying the meiotic specific features. We describe and discuss the existence and properties of MEIOB and multiple RPA subunits in plants and highlight how they can provide meiosis-specific fates to ssDNA processing during homologous recombination. Understanding the functions of these RPA homologs and how they interact with the canonical RPA subunits is of major interest in the fields of meiosis and DNA repair.

Collision and recombination driven instabilities in variable charged ...

Indian Academy of Sciences (India)

The dust-acoustic instability driven by recombination of electrons and ions on the surface of charged and variably-charged dust grains as well as by collisions in dusty plasmas with significant pressure of background neutrals have been theoretically investigated. The recombination driven instability is shown to be dominant ...

Collisional-radiative model including recombination processes for W27+ ion★

Science.gov (United States)

Murakami, Izumi; Sasaki, Akira; Kato, Daiji; Koike, Fumihiro

2017-10-01

We have constructed a collisional-radiative (CR) model for W27+ ions including 226 configurations with n ≤ 9 and ł ≤ 5 for spectroscopic diagnostics. We newly include recombination processes in the model and this is the first result of extreme ultraviolet spectrum calculated for recombining plasma component. Calculated spectra in 40-70 Å range in ionizing and recombining plasma components show similar 3 strong lines and 1 line weak in recombining plasma component at 45-50 Å and many weak lines at 50-65 Å for both components. Recombination processes do not contribute much to the spectrum at around 60 Å for W27+ ion. Dielectronic satellite lines are also minor contribution to the spectrum of recombining plasma component. Dielectronic recombination (DR) rate coefficient from W28+ to W27+ ions is also calculated with the same atomic data in the CR model. We found that larger set of energy levels including many autoionizing states gave larger DR rate coefficients but our rate agree within factor 6 with other works at electron temperature around 1 keV in which W27+ and W28+ ions are usually observed in plasmas. Contribution to the Topical Issue "Atomic and Molecular Data and their Applications", edited by Gordon W.F. Drake, Jung-Sik Yoon, Daiji Kato, and Grzegorz Karwasz.

Insect Larvae: A New Platform to Produce Commercial Recombinant Proteins.

Science.gov (United States)

Targovnik, Alexandra M; Arregui, Mariana B; Bracco, Lautaro F; Urtasun, Nicolas; Baieli, Maria F; Segura, Maria M; Simonella, Maria A; Fogar, Mariela; Wolman, Federico J; Cascone, Osvaldo; Miranda, Maria V

2016-01-01

In Biotechnology, the expression of recombinant proteins is a constantly growing field and different hosts are used for this purpose. Some valuable proteins cannot be produced using traditional systems. Insects from the order Lepidoptera infected with recombinant baculovirus have appeared as a good choice to express high levels of proteins, especially those with post-translational modifications. Lepidopteran insects, which are extensively distributed in the world, can be used as small protein factories, the new biofactories. Species like Bombyx mori (silkworm) have been analyzed in Asian countries to produce a great number of recombinant proteins for use in basic and applied science and industry. Many proteins expressed in this larva have been commercialized. Several recombinant proteins produced in silkworms have already been commercialized. On the other hand, species like Spodoptera frugiperda, Heliothis virescens, Rachiplusia nu, Helicoverpa zea and Trichoplusia ni are widely distributed in both the occidental world and Europe. The expression of recombinant proteins in larvae has the advantage of its low cost in comparison with insect cell cultures. A wide variety of recombinant proteins, including enzymes, hormones and vaccines, have been efficiently expressed with intact biological activity. The expression of pharmaceutically proteins, using insect larvae or cocoons, has become very attractive. This review describes the use of insect larvae as an alternative to produce commercial recombinant proteins.

Multifaceted regulation of V(D)J recombination

Science.gov (United States)

Wang, Guannan

V(D)J recombination is responsible for generating an enormous repertoire of immunoglobulins and T cell receptors, therefore it is a centerpiece to the formation of the adaptive immune system. The V(D)J recombination process proceeds through two steps, site-specific cleavage at RSS (Recombination Signal Sequence) site mediated by the RAG recombinase (RAG1/2) and the subsequent imprecise resolution of the DNA ends, which is carried out by the ubiquitous non-homologous end joining pathway (NHEJ). The V(D)J recombination reaction is obliged to be tightly controlled under all circumstances, as it involves generations of DNA double strand breaks, which are considered the most dangerous lesion to a cell. Multifaceted regulatory mechanisms have been evolved to create great diversity of the antigen receptor repertoire while ensuring genome stability. The RAG-mediated cleavage reaction is stringently regulated at both the pre-cleavage stage and the post-cleavage stage. Specifically, RAG1/2 first forms a pre-cleavage complex assembled at the boarder of RSS and coding flank, which ensures the appropriate DNA targeting. Subsequently, this complex initiates site-specific cleavage, generating two types of double stranded DNA breaks, hairpin-ended coding ends (HP-CEs) and blunt signal ends (SEs). After the cleavage, RAG1/2 proteins bind and retain the recombination ends to form post-cleavage complexes (PCC), which collaborates with the NHEJ machinery for appropriate transfer of recombination ends to NHEJ for proper end resolution. However, little is known about the molecular basis of this collaboration, partly attributed to the lack of sensitive assays to reveal the interaction of PCC with HP-CEs. Here, for the first time, by using two complementary fluorescence-based techniques, fluorescence anisotropy and fluorescence resonance energy transfer (FRET), I managed to monitor the RAG1/2-catalyzed cleavage reaction in real time, from the pre-cleavage to the post-cleavage stages. By

Accelerated Recombination in Cold Dense Plasmas with Metastable Ions due to Resonant Deexcitation

International Nuclear Information System (INIS)

Ralchenko, Yu.V.; Maron, M.

2001-01-01

In a recombining plasma the metastable states are known to accumulate population thereby slowing down the recombination process. We show that a proper account of the doubly-excited autoionizing states, populated through collisional 3-body recombination of metastable ions, results in a significant acceleration of recombination. 3-body recombination followed by collisional (de)excitations and autoionization effectively produces deexcitation via the following chain of elementary events: A fully time-dependent collisional-radiative (CR) modeling for stripped ions of carbon recombining in a cold dense plasma demonstrates an order of magnitude faster recombination of He-like ions. The CR model used in calculations is discussed in details

Parton recombination model

International Nuclear Information System (INIS)

Hwa, R.C.

1978-08-01

Low P/sub T/ meson production in hadronic collisions is described in the framework of the parton model. The recombination of quark and antiquark is suggested as the dominant mechanism in the large x region. Phenomenological evidences for the mechanism are given. The application to meson initiated reactions yields the quark distribution in mesons. 21 references

Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis.

Science.gov (United States)

Ma, Li; O'Connell, Jeffrey R; VanRaden, Paul M; Shen, Botong; Padhi, Abinash; Sun, Chuanyu; Bickhart, Derek M; Cole, John B; Null, Daniel J; Liu, George E; Da, Yang; Wiggans, George R

2015-11-01

Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

Recombinant cells and organisms having persistent nonstandard amino acid dependence and methods of making them

Science.gov (United States)

Church, George M.; Mandell, Daniel J.; Lajoie, Marc J.

2017-12-05

Recombinant cells and recombinant organisms persistently expressing nonstandard amino acids (NSAAs) are provided. Methods of making recombinant cells and recombinant organisms dependent on persistently expressing NSAAs for survival are also provided. These methods may be used to make safe recombinant cells and recombinant organisms and/or to provide a selective pressure to maintain one or more reassigned codon functions in recombinant cells and recombinant organisms.

Trap-assisted and Langevin-type recombination in organic light-emitting diodes

Science.gov (United States)

Wetzelaer, G. A. H.; Kuik, M.; Nicolai, H. T.; Blom, P. W. M.

2011-04-01

Trapping of charges is known to play an important role in the charge transport of organic semiconductors, but the role of traps in the recombination process has not been addressed. Here we show that the ideality factor of the current of organic light-emitting diodes (OLEDs) in the diffusion-dominated regime has a temperature-independent value of 2, which reveals that nonradiative trap-assisted recombination dominates the current. In contrast, the ideality factor of the light output approaches unity, demonstrating that luminance is governed by recombination of the bimolecular Langevin type. This apparent contradiction can be resolved by measuring the current and luminance ideality factor for a white-emitting polymer, where both free and trapped charge carriers recombine radiatively. With increasing bias voltage, Langevin recombination becomes dominant over trap-assisted recombination due to its stronger dependence on carrier density, leading to an enhancement in OLED efficiency.

Main Bile Duct Stricture Occurring After Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Miyayama, Shiro; Yamashiro, Masashi; Okuda, Miho; Yoshie, Yuichi; Nakashima, Yoshiko; Ikeno, Hiroshi; Orito, Nobuaki; Notsumata, Kazuo; Watanabe, Hiroyuki; Toya, Daisyu; Tanaka, Nobuyoshi; Matsui, Osamu

2010-01-01

The purpose of this study was to evaluate the clinical course of main bile duct stricture at the hepatic hilum after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Among 446 consecutive patients with HCC treated by TACE, main bile duct stricture developed in 18 (4.0%). All imaging and laboratory data, treatment course, and outcomes were retrospectively analyzed. All patients had 1 to 2 tumors measuring 10 to 100 mm in diameter (mean ± SD 24.5 ± 5.4 mm) near the hepatic hilum fed by the caudate arterial branch (A1) and/or medial segmental artery (A4) of the liver. During the TACE procedure that caused bile duct injury, A1 was embolized in 8, A4 was embolized in 5, and both were embolized in 5 patients. Nine patients (50.0%) had a history of TACE in either A1 or A4. Iodized oil accumulation in the bile duct wall was seen in all patients on computed tomography obtained 1 week later. Bile duct dilatation caused by main bile duct stricture developed in both lobes (n = 9), in the right lobe (n = 3), in the left lobe (n = 4), in segment (S) 2 (n = 1), and in S3 (n = 1). Serum levels of alkaline phosphatase and γ-glutamyltranspeptidase increased in 13 patients. Biloma requiring drainage developed in 2 patients; jaundice developed in 4 patients; and metallic stents were placed in 3 patients. Complications after additional TACE sessions, including biloma (n = 3) and/or jaundice (n = 5), occurred in 7 patients and were treated by additional intervention, including metallic stent placement in 2 patients. After initial TACE of A1 and/or A4, 8 patients (44.4%), including 5 with uncontrollable jaundice or cholangitis, died at 37.9 ± 34.9 months after TACE, and 10 (55.6%) have survived for 38.4 ± 37.9 months. Selective TACE of A1 and/or A4 carries a risk of main bile duct stricture at the hepatic hilum. Biloma and jaundice are serious complications associated with bile duct strictures.

Comparison of poliovirus recombinants: accumulation of point mutations provides further advantages.

Science.gov (United States)

Savolainen-Kopra, Carita; Samoilovich, Elena; Kahelin, Heidi; Hiekka, Anna-Kaisa; Hovi, Tapani; Roivainen, Merja

2009-08-01

The roles of recombination and accumulation of point mutations in the origin of new poliovirus (PV) characteristics have been hypothesized, but it is not known which are essential to evolution. We studied phenotypic differences between recombinant PV strains isolated from successive stool specimens of an oral PV vaccine recipient. The studied strains included three PV2/PV1 recombinants with increasing numbers of mutations in the VP1 gene, two of the three with an amino acid change I-->T in the DE-loop of VP1, their putative PV1 parent and strains Sabin 1 and 2. Growth of these viruses was examined in three cell lines: colorectal adenocarcinoma, neuroblastoma and HeLa. The main observation was a higher growth rate between 4 and 6 h post-infection of the two recombinants with the I-->T substitution. All recombinants grew at a higher rate than parental strains in the exponential phase of the replication cycle. In a temperature sensitivity test, the I-->T-substituted recombinants replicated equally well at an elevated temperature. Complete genome sequencing of the three recombinants revealed 12 (3), 19 (3) and 27 (3) nucleotide (amino acid) differences from Sabin. Mutations were located in regions defining attenuation, temperature sensitivity, antigenicity and the cis-acting replicating element. The recombination site was in the 5' end of 3D. In a competition assay, the most mutated recombinant beat parental Sabin in all three cell lines, strongly suggesting that this virus has an advantage. Two independent intertypic recombinants, PV3/PV1 and PV3/PV2, also showed similar growth advantages, but they also contained several point mutations. Thus, our data defend the hypothesis that accumulation of certain advantageous mutations plays a key role in gaining increased fitness.

Serendipitous identification of natural intergenotypic recombinants of hepatitis C in Ireland.

LENUS (Irish Health Repository)

Moreau, Isabelle

2006-01-01

BACKGROUND: Recombination between hepatitis C single stranded RNA viruses is a rare event. Natural viable intragenotypic and intergenotypic recombinants between 1b-1a, 1a-1c and 2k-1b, 2i-6p, respectively, have been reported. Diagnostically recombinants represent an intriguing challenge. Hepatitis C genotype is defined by interrogation of the sequence composition of the 5\\' untranslated region [5\\'UTR]. Occasionally, ambiguous specimens require further investigation of the genome, usually by interrogation of the NS5B region. The original purpose of this study was to confirm the existence of a suspected mixed genotype infection of genotypes 2 and 4 by clonal analysis at the NS5B region of the genome in two specimens from two separate individuals. This initial identification of genotype was based on analysis of the 5\\'UTR of the genome by reverse line probe hybridisation [RLPH]. RESULTS: The original diagnosis of a mixed genotype infection was not confirmed by clonal analysis of the NS5B region of the genome. The phylogenetic analysis indicated that both specimens were natural intergenotypic recombinant forms of HCV. The recombination was between genotypes 2k and 1b for both specimens. The recombination break point was identified as occurring within the NS2 region of the genome. CONCLUSION: The viral recombinants identified here resemble the recombinant form originally identified in Russia. The RLPH pattern observed in this study may be a signature indicative of this particular type of intergenotype recombinant of hepatitis C meriting clonal analysis of NS2.

The recombination of a helium plasma

International Nuclear Information System (INIS)

Hollenstein, C.; Sayasov, Y.; Schneider, H.

1975-01-01

A helium plasma (Tsub(e) 15 cm -3 ) in the afterglow without magnetic field was investigated. The measurements of the electron density and temperature are presented. Laser interferometry and radiowave diagnostics were used. The measured exponential decay of the electron density and temperature was explained with the collisional-radiative recombination and the thermal conduction of the electrons towards the wall of the discharge vessel. The measured recombination coefficients were compared with measurements and calculations of other authors. The best agreement was found with the calculations by Drawin. (Auth.)

High-yield secretion of recombinant proteins from the microalga Chlamydomonas reinhardtii

DEFF Research Database (Denmark)

Ramos Martinez, Erick Miguel; Fimognari, Lorenzo; Sakuragi, Yumiko

2017-01-01

Microalga-based biomanufacturing of recombinant proteins is attracting growing attention due to its advantages in safety, metabolic diversity, scalability and sustainability. Secretion of recombinant proteins can accelerate the use of microalgal platforms by allowing post......-translational modifications and easy recovery of products from the culture media. However, currently, the yields of secreted recombinant proteins are low, which hampers the commercial application of this strategy. This study aimed at expanding the genetic tools for enhancing secretion of recombinant proteins in Chlamydomonas...... in the endoplasmic reticulum (ER). Taken together, the results demonstrate the utility of the gametolysin signal sequence and (SP)n glycomodule to promote a more efficient biomanufacturing of microalgae-based recombinant proteins....

Mechanisms of sister chromatid recombination

International Nuclear Information System (INIS)

Nakai, Sayaka; Machida, Isamu; Tsuji, Satsuki

1985-01-01

Studies using T948 as a model system have been carried out aimed at elucidating the mechanism of sister chromatid recombination (SCR). Characterization of U.V. light- and x-ray-induced SCR, the relationiship between SCR induction and DNA repair using rad mutations, and the relationship between SCR induction and the time of cell division using cdc mutations are presented. It has been supposed that SCR is induced at the phase of S-G 2 following DNA replication, that postreplication break of DNA strands is strongly involved in the induction of SCR, and that induction type of SCR, i.e., conversion type or recombination type, is dependent upon the type of molecular damage of DNA. (Namekawa, K.)

A novel mechanism of myostatin regulation by its alternative splicing variant during myogenesis in avian species.

Science.gov (United States)

Shin, Sangsu; Song, Yan; Ahn, Jinsoo; Kim, Eunsoo; Chen, Paula; Yang, Shujin; Suh, Yeunsu; Lee, Kichoon

2015-11-15

Myostatin (MSTN) is a key negative regulator of muscle growth and development, and an increase of muscle mass is achieved by inhibiting MSTN signaling. In the current study, five alternative splicing isoforms of MSTN mRNAs in avian species were identified in various tissues. Among these five, three truncated forms of myostatin, MSTN-B, -C, and -E created premature stop codons and produced partial MSTN prodomains encoded from exon 1. MSTN-B is the second dominant isoform following full-length MSTN-A, and their expression was dynamically regulated during muscle development of chicken, turkey, and quail in vivo and in vitro. To clarify the function of MSTN-B, two stable cell lines of quail myoblasts (QM7) were generated to overexpress MSTN-A or MSTN-B. Interestingly, MSTN-B promoted both cell proliferation and differentiation similar to the function of the MSTN prodomain to counteract the negative role of MSTN on myogenesis. The coimmunoprecipitation assay revealed that MSTN-B binds to MSTN-A and reduces the generation of mature MSTN. Furthermore, the current study demonstrated that the partial prodomain encoded from exon 1 is critical for binding of MSTN-B to MSTN-A. Altogether, these data imply that alternative splicing isoforms of MSTN could negatively regulate pro-myostatin processing in muscle cells and prevent MSTN-mediated inhibition of myogenesis in avian species. Copyright © 2015 the American Physiological Society.

The Time Scale of Recombination Rate Evolution in Great Apes

Science.gov (United States)

Stevison, Laurie S.; Woerner, August E.; Kidd, Jeffrey M.; Kelley, Joanna L.; Veeramah, Krishna R.; McManus, Kimberly F.; Bustamante, Carlos D.; Hammer, Michael F.; Wall, Jeffrey D.

2016-01-01

Abstract We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471–475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10–15 Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- and between-species genome-wide recombination rate variation in several close relatives. PMID:26671457

Genetic dependence of recombination in recD mutants of Escherichia coli

International Nuclear Information System (INIS)

Lovett, S.T.; Luisi-DeLuca, C.; Kolodner, R.D.

1988-01-01

RecBCD enzyme has multiple activities including helicase, exonuclease and endonuclease activities. Mutations in the genes recB or recC, encoding two subunits of the enzyme, reduce the frequency of many types of recombinational events. Mutations in recD, encoding the third subunit, do not reduce recombination even though most of the activities of the RecBCD enzyme are severely reduced. In this study, the genetic dependence of different types of recombination in recD mutants has been investigated. The effects of mutations in genes in the RecBCD pathway (recA and recC) as well as the genes specific for the RecF pathway (recF, recJ, recN, recO, recQ, ruv and lexA) were tested on conjugational, transductional and plasmid recombination, and on UV survival. recD mutants were hyper-recombinogenic for all the monitored recombination events, especially those involving plasmids, and all recombination events in recD strains required recA and recC. In addition, unlike recD+ strains, chromosomal recombination events and the repair of UV damage to DNA in recD strains were dependent on one RecF pathway gene, recJ. Only a subset of the tested recombination events were affected by ruv, recN, recQ, recO and lexA mutations

Polymer:Nonfullerene Bulk Heterojunction Solar Cells with Exceptionally Low Recombination Rates

KAUST Repository

Gasparini, Nicola; Salvador, Michael; Heumueller, Thomas; Richter, Moses; Classen, Andrej; Shrestha, Shreetu; Matt, Gebhard J.; Holliday, Sarah; Strohm, Sebastian; Egelhaaf, Hans-Joachim; Wadsworth, Andrew; Baran, Derya; McCulloch, Iain; Brabec, Christoph J.

2017-01-01

Organic semiconductors are in general known to have an inherently lower charge carrier mobility compared to their inorganic counterparts. Bimolecular recombination of holes and electrons is an important loss mechanism and can often be described by the Langevin recombination model. Here, the device physics of bulk heterojunction solar cells based on a nonfullerene acceptor (IDTBR) in combination with poly(3-hexylthiophene) (P3HT) are elucidated, showing an unprecedentedly low bimolecular recombination rate. The high fill factor observed (above 65%) is attributed to non-Langevin behavior with a Langevin prefactor (β/βL) of 1.9 × 10−4. The absence of parasitic recombination and high charge carrier lifetimes in P3HT:IDTBR solar cells inform an almost ideal bimolecular recombination behavior. This exceptional recombination behavior is explored to fabricate devices with layer thicknesses up to 450 nm without significant performance losses. The determination of the photoexcited carrier mobility by time-of-flight measurements reveals a long-lived and nonthermalized carrier transport as the origin for the exceptional transport physics. The crystalline microstructure arrangement of both components is suggested to be decisive for this slow recombination dynamics. Further, the thickness-independent power conversion efficiency is of utmost technological relevance for upscaling production and reiterates the importance of understanding material design in the context of low bimolecular recombination.

Polymer:Nonfullerene Bulk Heterojunction Solar Cells with Exceptionally Low Recombination Rates

KAUST Repository

Gasparini, Nicola

2017-09-01

Organic semiconductors are in general known to have an inherently lower charge carrier mobility compared to their inorganic counterparts. Bimolecular recombination of holes and electrons is an important loss mechanism and can often be described by the Langevin recombination model. Here, the device physics of bulk heterojunction solar cells based on a nonfullerene acceptor (IDTBR) in combination with poly(3-hexylthiophene) (P3HT) are elucidated, showing an unprecedentedly low bimolecular recombination rate. The high fill factor observed (above 65%) is attributed to non-Langevin behavior with a Langevin prefactor (β/βL) of 1.9 × 10−4. The absence of parasitic recombination and high charge carrier lifetimes in P3HT:IDTBR solar cells inform an almost ideal bimolecular recombination behavior. This exceptional recombination behavior is explored to fabricate devices with layer thicknesses up to 450 nm without significant performance losses. The determination of the photoexcited carrier mobility by time-of-flight measurements reveals a long-lived and nonthermalized carrier transport as the origin for the exceptional transport physics. The crystalline microstructure arrangement of both components is suggested to be decisive for this slow recombination dynamics. Further, the thickness-independent power conversion efficiency is of utmost technological relevance for upscaling production and reiterates the importance of understanding material design in the context of low bimolecular recombination.

Fine-scale maps of recombination rates and hotspots in the mouse genome.

Science.gov (United States)

Brunschwig, Hadassa; Levi, Liat; Ben-David, Eyal; Williams, Robert W; Yakir, Benjamin; Shifman, Sagiv

2012-07-01

Recombination events are not uniformly distributed and often cluster in narrow regions known as recombination hotspots. Several studies using different approaches have dramatically advanced our understanding of recombination hotspot regulation. Population genetic data have been used to map and quantify hotspots in the human genome. Genetic variation in recombination rates and hotspots usage have been explored in human pedigrees, mouse intercrosses, and by sperm typing. These studies pointed to the central role of the PRDM9 gene in hotspot modulation. In this study, we used single nucleotide polymorphisms (SNPs) from whole-genome resequencing and genotyping studies of mouse inbred strains to estimate recombination rates across the mouse genome and identified 47,068 historical hotspots--an average of over 2477 per chromosome. We show by simulation that inbred mouse strains can be used to identify positions of historical hotspots. Recombination hotspots were found to be enriched for the predicted binding sequences for different alleles of the PRDM9 protein. Recombination rates were on average lower near transcription start sites (TSS). Comparing the inferred historical recombination hotspots with the recent genome-wide mapping of double-strand breaks (DSBs) in mouse sperm revealed a significant overlap, especially toward the telomeres. Our results suggest that inbred strains can be used to characterize and study the dynamics of historical recombination hotspots. They also strengthen previous findings on mouse recombination hotspots, and specifically the impact of sequence variants in Prdm9.

Genetic recombination is targeted towards gene promoter regions in dogs.

Science.gov (United States)

Auton, Adam; Rui Li, Ying; Kidd, Jeffrey; Oliveira, Kyle; Nadel, Julie; Holloway, J Kim; Hayward, Jessica J; Cohen, Paula E; Greally, John M; Wang, Jun; Bustamante, Carlos D; Boyko, Adam R

2013-01-01

The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.

Parameters of mitotic recombination in minute mutants of Drosophila melanogaster

International Nuclear Information System (INIS)

Ferrus, A.

1975-01-01

A sample of 16 Minutes, representing 12 loci distributed over all the chromosome arms and including 3 pairs of alleles and 4 deficiencies, has been studied with respect to several developmental and recombinational parameters. Cell marker mutants located in most of the chromosome arms were used to assess (1) spontaneous and x-ray-induced mitotic recombination frequencies of each Minute, and (2) clone sizes of the different cell marker clones. These parameters were analyzed both in the wing disc and in the abdominal histoblasts. Whereas spontaneous frequencies are not affected by the presence of the Minutes studied, the different Minutes characteristically increase the frequency of recombination clones arising after x irradiation. The recombinant clones which are M + /M + are significantly larger than clones in the same fly which retain the M + /M condition. This is particularly striking in clones in the wing disc, slightly so in clones in the tergites. The occurrence of mitotic recombination in the fourth chromosome is reported for the first time. Chaeta length and developmental delay correlates with the recombinational parameters in different ways. Possible causal interrelationships of the different traits of the Minute syndrome are discussed. (U.S.)

Theory of surface recombination of spin-polarized hydrogen

International Nuclear Information System (INIS)

Christou, C.T.; Haftel, M.I.

1989-01-01

A theory is presented, based on the Faddeev equations, for direct two-body recombination of hydrogen atoms on a liquid helium surface. The equations developed are applicable to hydrogen or deuterium atoms in any spin state, but are applied in particular to dipolar recombination of b state hydrogen atoms. The equations yield terms corresponding to one- and two-step processes. These terms are calculated for low temperatures (T = 0.1 to 1.1 K) and high field strengths (B = 4 to 14 T). The one-step term increases slowly with B, while the two-step term is rapidly decreasing. While the overall rate is quite small (∼5 x 10 -18 cm 2 /s) compared to recombination by two-body spin-relaxation, the results have important consequences in understanding the experimentally measured three-atom dipolar surface recombination rates. In three-atom recombination, where the role of spin-relaxation and the two-atom one-step processes are repressed, the role of the underlying two-atom, two-step process is enhanced. The field dependence of the process relevant to the three-atom system is calculated and found to be in fairly good agreement with the experimental three-atom data. The role of possible liquid excitations in enhancing the contribution of the two-step processes is also discussed. 33 refs.; 1 figure; 6 tabs

Looking for the optimal rate of recombination for evolutionary dynamics

Science.gov (United States)

Saakian, David B.

2018-01-01

We consider many-site mutation-recombination models of evolution with selection. We are looking for situations where the recombination increases the mean fitness of the population, and there is an optimal recombination rate. We found two fitness landscapes supporting such nonmonotonic behavior of the mean fitness versus the recombination rate. The first case is related to the evolution near the error threshold on a neutral-network-like fitness landscape, for moderate genome lengths and large population. The more realistic case is the second one, in which we consider the evolutionary dynamics of a finite population on a rugged fitness landscape (the smooth fitness landscape plus some random contributions to the fitness). We also give the solution to the horizontal gene transfer model in the case of asymmetric mutations. To obtain nonmonotonic behavior for both mutation and recombination, we need a specially designed (ideal) fitness landscape.

Rogue athletes and recombinant DNA technology: challenges for doping control.

Science.gov (United States)

Azzazy, Hassan M E; Mansour, Mai M H

2007-10-01

The quest for athletic excellence holds no limit for some athletes, and the advances in recombinant DNA technology have handed these athletes the ultimate doping weapons: recombinant proteins and gene doping. Some detection methods are now available for several recombinant proteins that are commercially available as pharmaceuticals and being abused by dopers. However, researchers are struggling to come up with efficient detection methods in preparation for the imminent threat of gene doping, expected in the 2008 Olympics. This Forum article presents the main detection strategies for recombinant proteins and the forthcoming detection strategies for gene doping as well as the prime analytical challenges facing them.

Recombination among multiple mitochondrial pseudogenes from a passerine genus

DEFF Research Database (Denmark)

Nielsen, Kirstine Klitgaard; Arctander, P.

2001-01-01

to the observed differences in substitution patterns 58% of the cloned sequences were identified as pseudogenes. Recombination could be traced in 19% of the inferred nuclear pseudogenes, but this figure probably represents a Significant underestimation of the factual recombination events. The nonrecombined...... pseudogenes consisted of multiple haplotypes found to diverge from 1 to 16% from the mitochondrial gene. The number of mitochondrial nuclear copies and their apparent frequent recombination suggest that pseudogenes constitute a serious potential risk in confounding phylogenetic studies and population genetic...

Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan.

Directory of Open Access Journals (Sweden)

Yue Chen

Full Text Available A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%, together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15% but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a while 12 (38% were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan.

Dissection of Recombination Attributes for Multiple Maize Populations Using a Common SNP Assay

Directory of Open Access Journals (Sweden)

Haiying Guan

2017-11-01

Full Text Available Recombination is a vital characteristic for quantitative trait loci mapping and breeding to enhance the yield potential of maize. However, recombination characteristics in globally used segregating populations have never been evaluated at similar genetic marker densities. This study aimed to divulge the characteristics of recombination events, recombinant chromosomal segments, and recombination frequency for four dissimilar populations. These populations were doubled haploid (DH, recombination inbred line (RIL, intermated B73xMo17 (IBM, and multi-parent advanced generation inter-cross (MAGIC, using the Illumina MaizeSNP50 BeadChip to provide markers. Our results revealed that the average number of recombination events was 16, 41, 72, and 86 per line in DH, RIL, IBM, and MAGIC populations, respectively. Accordingly, the average length of recombinant chromosomal segments was 84.8, 47.3, 29.2, and 20.4 Mb in DH, RIL, IBM, and MAGIC populations, respectively. Furtherly, the recombination frequency varied in different genomic regions and population types [DH (0–12.7 cM/Mb, RIL (0–15.5 cM/Mb, IBM (0–24.1 cM/Mb, MAGIC (0–42.3 cM/Mb]. Utilizing different sub-sets of lines, the recombination bin number and size were analyzed in each population. Additionally, different sub-sets of markers and lines were employed to estimate the recombination bin number and size via formulas for relationship in these populations. The relationship between recombination events and recombination bin length was also examined. Our results contribute to determining the most suitable number of genetic markers, lines in each population, and population type for successful mapping and breeding.

Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan

Science.gov (United States)

Chen, Yue; Hora, Bhavna; DeMarco, Todd; Shah, Sharaf Ali; Ahmed, Manzoor; Sanchez, Ana M.; Su, Chang; Carter, Meredith; Stone, Mars; Hasan, Rumina; Hasan, Zahra; Busch, Michael P.; Denny, Thomas N.; Gao, Feng

2016-01-01

A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG) sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%), together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a) within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15%) but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a) while 12 (38%) were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan. PMID:27973597

The use of detectors based on ionisation recombination in radiation protection

International Nuclear Information System (INIS)

Sullivan, A.H.

1984-01-01

Intitial recombination of ionisation in a gas depends on the ionisation density and hence on the linear energy transfer along the tracks of charged particles. This effect can be used as a basis for instruments that respond to different types of ionising radiation approximately in the way required by the quality factor-linear energy transfer relation recommended by the ICRP for use in radiation protection. Empirical instruments based on ionisation recombination that have been used for radiation protection measurements are reviewed, and relations are derived from recombination theory that show that the response of such detectors can be readily predicted. The usefulness of recombination instruments in radiation protection is discussed and their advantages and limitations assessed. It is shown that their main application will be as reference instruments against which other detectors can be calibrated. As an extension to using recombination detectors as reference instruments, the feasibility of specifying radiation quality in terms of ionisation recombination is investigated. (author)

High recombination rate in natural populations of Plasmodium falciparum

NARCIS (Netherlands)

Conway, D. J.; Roper, C.; Oduola, A. M.; Arnot, D. E.; Kremsner, P. G.; Grobusch, M. P.; Curtis, C. F.; Greenwood, B. M.

1999-01-01

Malaria parasites are sexually reproducing protozoa, although the extent of effective meiotic recombination in natural populations has been debated. If meiotic recombination occurs frequently, compared with point mutation and mitotic rearrangement, linkage disequilibrium between polymorphic sites is

Transcatheter arterial Chemoembolization for infiltrative hepatocellular carcinoma: Clinical safety and efficacy and factors influencing patient survival

International Nuclear Information System (INIS)

Han, Kichang; Kim, Jin Hyoung; Yoon, Hee Mang; Kim, Eun Joung; Gwon, Dong Il; Ko, Gi Young; Yoon, Hyun Ki; Ko, Heung Kyu

2014-01-01

To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) in patients with infiltrative hepatocellular carcinoma (HCC) and to identify the prognostic factors associated with patient survival. Fifty two patients who underwent TACE for infiltrative HCC were evaluated between 2007 and 2010. The maximum diameter of the tumors ranged from 7 cm to 22 cm (median 15 cm). Of 46 infiltrative HCC patients with portal vein tumor thrombosis, 32 patients received adjuvant radiation therapy for portal vein tumor thrombosis after TACE. The tumor response by European Association for the Study of the Liver criteria was partial in 18%, stable in 47%, and progressive in 35% of the patients. The median survival time was 5.7 months (Kaplan-Meier analysis). The survival rates were 48% at six months, 25% at one year, and 12% at two years. In the multivariable Cox regression analysis, Child-Pugh class (p = 0.02), adjuvant radiotherapy (p 0.003) and tumor response after TACE (p = 0.004) were significant factors associated with patient survival. Major complications occurred in nine patients. The major complication rate was significantly higher in patients with Child-Pugh B than in patients with Child-Pugh A (p = 0.049, x 2 test). Transcatheter arterial chemoembolization can be a safe treatment option in infiltrative HCC patients with Child Pugh class A. Child Pugh class A, radiotherapy for portal vein tumor thrombosis after TACE and tumor response are good prognostic factors for an increased survival after TACE in patients with infiltrative HCCs.

Traditional herbal medicine prevents postoperative recurrence of small hepatocellular carcinoma: A randomized controlled study.

Science.gov (United States)

Zhai, Xiao-Feng; Liu, Xiao-Lin; Shen, Feng; Fan, Jia; Ling, Chang-Quan

2018-05-15

To explore the clinical efficacy of traditional herbal medicine (THM) in the prevention of disease recurrence of small hepatocellular carcinoma after surgery, a prospective randomized controlled study was conducted between October 2006 and May 2010. The results indicated that THM prevented the recurrence of SHCC with an efficacy that was superior to that of transarterial chemoembolization (TACE) during a median follow-up of 26.61 months. The patients were followed up every 6 months, and the clinical data before October 20, 2015 were analyzed. The primary outcome measure was recurrence-free survival (RFS), and the secondary outcome measure was overall survival (OS). The 364 patients included 180 in the THM group and 184 in the TACE group. At the time of the data cutoff of October 20, 2015, a total of 205 patients demonstrated disease recurrence, including 85 patients in the THM group and 120 patients in the TACE group. The median RFS of the THM and TACE groups demonstrated a statistically significant difference (P<.001). Until October 20, 2105, there were 91 deaths, including 34 in the THM group and 57 in the TACE group. The median OS demonstrated a significant difference between the 2 groups (P = .008). Multivariate analysis indicated that THM was an independent factor influencing RFS and OS. The efficacy of THM was found to be superior to that of TACE in preventing disease recurrence in patients with small hepatocellular carcinoma and prolonging OS. Cancer 2018;124:2161-8. © 2018 American Cancer Society. © 2018 American Cancer Society.

Transarterial lidocaine-lipiodol emulsion administration for relief of pain during transarterial chemoembolization of malignant tumor

International Nuclear Information System (INIS)

Wu Anle; Yan Zhiping; Zhou Kangrong; Wang Jianhua; Cheng Jiemin; Qian Sheng; Luo Jianjun; Chen Yi

2004-01-01

Objective: To assess the feasibility and efficacy of transarterial lidocaine-lipiodol emulsion administration for controlling abdominal pain and preventing the arterial spasm resulting from TACE, and to evaluate the optimal amount of lidocaine administration. Methods: In a prospective trial of 120 consecutive patients with malignant tumor who underwent TACE were divided into three groups, those who received lidocaine-lipiodol emulsion administration (group A, n=40), those who received lidocaine bolus intraarterial infusion immediately before TACE (group B, n=40) and those who received no lidocaine injection before TACE, (group C, n=40). The degree of post-procedure pain was evaluated by a subjective method (using visual analogue scales from 0 to 10), and an objective method (amount of post-procedure analgesics). Incidence and degree of arterial spasm were assessed by DSA. Results: The correlative pain incidences between the three groups showed significant difference (P 0.05). Mean dose of intramuscular analgesics for controlling intolerable pain in group A and B was significantly lower than that of group C (P<0.05). There was no difference in the incidence of arterial spasm between group A and B but it was much lower in group C. Lipiodol deposit in malignant mass was densest in group A, especially in the metastatic nodules of the liver. Conclusions: Transarterial administration of lidocaine-lipiodol emulsion can not only reduce the incidence of pain during TACE, but also prevent the arterial spasm. It is much more effective than pre-TACE administration of pethidine and intraarterial infusion of lidocaine. The authors recommond routinely for the administration of lidocaine-lipiodol emulsion. (authors)

Asthma and Therapeutics: Recombinant Therapies in Asthma

Directory of Open Access Journals (Sweden)

Cockcroft Donald W

2005-03-01

Full Text Available Abstract Numerous recombinant therapies are being investigated for the treatment of asthma. This report reviews the current status of several of these novel agents. Anti-immunoglobulin (IgE (omalizumab, Xolair markedly inhibits all aspects of the allergen challenge in subjects who have reduction of free serum IgE to undetectable levels. Several clinical studies in atopic asthma have demonstrated benefit by improved symptoms and lung function and a reduction in corticosteroid requirements. Early use in atopic asthmatics may be even more effective. Several approaches target interleukin (IL-4. Soluble IL-4 receptor has been shown to effectively replace inhaled corticosteroid; further studies are under way. Recombinant anti-IL-5 and recombinant IL-12 inhibit blood and sputum eosinophils and allergen-induced eosinophilia without any effect on airway responsiveness, allergen-induced airway responses, or allergen-induced airway hyperresponsiveness. Efalizumab, a recombinant antibody that inhibits lymphocyte trafficking, is effective in psoriasis. A bronchoprovocation study showed a reduction in allergen-induced late asthmatic response and allergen-induced eosinophilia, which suggests that it should be effective in clinical asthma. These exciting novel therapies provide not only promise of new therapies for asthma but also valuable tools for investigation of asthma mechanisms.

Selective Advantage of Recombination in Evolving Protein Populations:. a Lattice Model Study

Science.gov (United States)

Williams, Paul D.; Pollock, David D.; Goldstein, Richard A.

Recent research has attempted to clarify the contributions of several mutational processes, such as substitutions or homologous recombination. Simplistic, tractable protein models, which determine the compact native structure phenotype from the sequence genotype, are well-suited to such studies. In this paper, we use a lattice-protein model to examine the effects of point mutation and homologous recombination on evolving populations of proteins. We find that while the majority of mutation and recombination events are neutral or deleterious, recombination is far more likely to be beneficial. This results in a faster increase in fitness during evolution, although the final fitness level is not significantly changed. This transient advantage provides an evolutionary advantage to subpopulations that undergo recombination, allowing fixation of recombination to occur in the population.

Recombinant human erythropoietin in sports: a review

Directory of Open Access Journals (Sweden)

Rafael Maia de Almeida Bento

2003-06-01

Full Text Available Erythropoietin is an endogenous hormone of glicoproteic nature secreted by the kidneys and is the main regulator of the erythropoiesis. An alteration in its production generates a disturbance in the plasmatic concentration giving rise to several types of pathologies related to the hematopoietic system. The recombinant forms of erythropoietin have indiscriminately been used by athletes, mainly in endurance sports, by increasing the erythrocytes concentration, generating a better delivery of oxygen to the muscle tissue. The administration of recombinant erythropoietin was prohibited by the International Olympic Committee and its use considered as doping. This review has the intention to describe the physical, biological and pharmacokinetic properties of the endogenous erythropoietin, as well as its recombinant form, describing also its use in sports and the process of searching methodologies for its detection in doping control.

Detection and frequency of recombination in tomato-infecting begomoviruses of South and Southeast Asia

Directory of Open Access Journals (Sweden)

Rai Mathura

2007-10-01

Full Text Available Abstract Background Tomato-infecting begomoviruses are widely distributed across the world and cause diseases of high economic impact on wide range of agriculturally important crops. Though recombination plays a pivotal role in diversification and evolution of these viruses, it is currently unknown whether there are differences in the number and quality of recombination events amongst different tomato-infecting begomovirus species. To examine this we sought to characterize the recombination events, estimate the frequency of recombination, and map recombination hotspots in tomato-infecting begomoviruses of South and Southeast Asia. Results Different methods used for recombination breakpoint analysis provided strong evidence for presence of recombination events in majority of the sequences analyzed. However, there was a clear evidence for absence or low Recombination events in viruses reported from North India. In addition, we provide evidence for non-random distribution of recombination events with the highest frequency of recombination being mapped in the portion of the N-terminal portion of Rep. Conclusion The variable recombination observed in these viruses signified that all begomoviruses are not equally prone to recombination. Distribution of recombination hotspots was found to be reliant on the relatedness of the genomic region involved in the exchange. Overall the frequency of phylogenetic violations and number of recombination events decreased with increasing parental sequence diversity. These findings provide valuable new information for understanding the diversity and evolution of tomato-infecting begomoviruses in Asia.

Recombination via point defects and their complexes in solar silicon

Energy Technology Data Exchange (ETDEWEB)

Peaker, A.R.; Markevich, V.P.; Hamilton, B. [Photon Science Institute, University of Manchester, Manchester M13 9PL (United Kingdom); Parada, G.; Dudas, A.; Pap, A. [Semilab, 2 Prielle Kornelia Str, 1117 Budapest (Hungary); Don, E. [Semimetrics, PO Box 36, Kings Langley, Herts WD4 9WB (United Kingdom); Lim, B.; Schmidt, J. [Institute for Solar Energy Research (ISFH) Hamlen, 31860 Emmerthal (Germany); Yu, L.; Yoon, Y.; Rozgonyi, G. [Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC 27695-7907 (United States)

2012-10-15

Electronic grade Czochralski and float zone silicon in the as grown state have a very low concentration of recombination generation centers (typically <10{sup 10} cm{sup -3}). Consequently, in integrated circuit technologies using such material, electrically active inadvertent impurities and structural defects are rarely detectable. The quest for cheap photovoltaic cells has led to the use of less pure silicon, multi-crystalline material, and low cost processing for solar applications. Cells made in this way have significant extrinsic recombination mechanisms. In this paper we review recombination involving defects and impurities in single crystal and in multi-crystalline solar silicon. Our main techniques for this work are recombination lifetime mapping measurements using microwave detected photoconductivity decay and variants of deep level transient spectroscopy (DLTS). In particular, we use Laplace DLTS to distinguish between isolated point defects, small precipitate complexes and decorated extended defects. We compare the behavior of some common metallic contaminants in solar silicon in relation to their effect on carrier lifetime and cell efficiency. Finally, we consider the role of hydrogen passivation in relation to transition metal contaminants, grain boundaries and dislocations. We conclude that recombination via point defects can be significant but in most multi-crystalline material the dominant recombination path is via decorated dislocation clusters within grains with little contribution to the overall recombination from grain boundaries. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Evolutionary advantage via common action of recombination and neutrality

Science.gov (United States)

Saakian, David B.; Hu, Chin-Kun

2013-11-01

We investigate evolution models with recombination and neutrality. We consider the Crow-Kimura (parallel) mutation-selection model with the neutral fitness landscape, in which there is a central peak with high fitness A, and some of 1-point mutants have the same high fitness A, while the fitness of other sequences is 0. We find that the effect of recombination and neutrality depends on the concrete version of both neutrality and recombination. We consider three versions of neutrality: (a) all the nearest neighbor sequences of the peak sequence have the same high fitness A; (b) all the l-point mutations in a piece of genome of length l≥1 are neutral; (c) the neutral sequences are randomly distributed among the nearest neighbors of the peak sequences. We also consider three versions of recombination: (I) the simple horizontal gene transfer (HGT) of one nucleotide; (II) the exchange of a piece of genome of length l, HGT-l; (III) two-point crossover recombination (2CR). For the case of (a), the 2CR gives a rather strong contribution to the mean fitness, much stronger than that of HGT for a large genome length L. For the random distribution of neutral sequences there is a critical degree of neutrality νc, and for μmutations affect the mean-field-like and fluctuation-like factors similarly. Consequently, recombination can accelerate the non-mean-field (fluctuation) type dynamics without considerably affecting the mean-field-like factors.

Dissociative recombination of small molecular ions

International Nuclear Information System (INIS)

Mul, P.M.

1981-01-01

In this thesis an analysis is given of merged electron-ion beam experiment and work on dissociative recombination of molecular ions and electrons is described. Chapter II covers a brief introduction of the theory of dissociative recombination. In chapter III, a description is given of the merged electron-ion beam experiment and a method is described which allows the determination of the mean angle between the electron and ion trajectories in a merged electron-ion beam experiment. In chapter IV a paper on the three dominant atmospheric diatomic ions NO + , O 2 + and N 2 + is presented and in chapter V the dissociative recombination for N 2 H + and N 2 D + is discussed. In chapter VI two papers on the polyatomic ions of the carbon-containing molecular ions are presented, and in chapter VII a letter with some results of the work presented in more detail in the chapters IV, V and VI is presented. The magnitude and the energy dependence of the cross-section measured by the merged beam technique and by other techniques is compared and discussed. (Auth.)

Hepatocellular Carcinoma Supplied From the Short Gastric Artery: Treatment With Chemoembolization

Energy Technology Data Exchange (ETDEWEB)

Jeon, Ung Bae, E-mail: junwb73@pnuyh.co.kr; Lee, Jun Woo, E-mail: jwlee@pusan.ac.kr; Baik, Seung Kug, E-mail: skbaik9@gmail.com; Kim, Tae Un, E-mail: kimtaeun78@hanmail.net; Choo, Ki Seok, E-mail: kschoo0618@naver.com; Kim, Kun Il, E-mail: kikim@pusan.ac.kr; Kim, Yong-Woo, E-mail: kyw47914@yahoo.co.kr; Moon, Tae-Yong, E-mail: tymn@pusan.ac.kr [Pusan National University Yangsan Hospital, Department of Radiology (Korea, Republic of)

2012-12-15

We report a case of transcatheter arterial chemoembolization (TACE) to treat hepatocellular carcinoma (HCC) that was supplied by the short gastric artery. A 67-year-old woman with two nodular HCCs underwent repeated TACE. One of the nodules was supplied by the short gastric artery.