To see the other types of publications on this topic, follow the link: ITRT.
Journal articles on the topic 'ITRT'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'ITRT.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Piatkowska, Magdalena, Jan Styczynski, Beata Kolodziej, Beata Kurylo-Rafinska, Malgorzata Kubicka, Monika Pogorzala, Krzysztof Czyzewski, et al. "Individualized Tumor Response Testing (ITRT) Profile Has a Prognostic Value in Childhood Acute Lymphoblastic Leukemia (ALL) and Acute Non-Lymphoblastic Leukemia (ANLL): The Multicenter Non-Interventional Long-Term Follow-up Study of Polish Pediatric Leukemia Study Group." Blood 118, no. 21 (November 18, 2011): 1456. http://dx.doi.org/10.1182/blood.v118.21.1456.1456.
Full textAbstract:
Abstract Abstract 1456 BACKGROUND: Individualized tumor response testing (ITRT) is a recently accepted term for ex vivo drug resistance profile testing in cancer patients. Previous studies have shown that ITRT results in children correspond with clinical response in initial acute lymphoblastic leukemia (iALL), but not in initial acute myeloid leukemia (iAML). ITRT combined profile to prednisolone, vincristine, and L-asparaginase (PVA score) showed a strong association with clinical outcome in iALL (Den Boer et al JCO; Hollemann et al, NEJM). OBJECTIVE: Polish Pediatric Leukemia Study Group carried out between 1999–2010 a multi-institutional, non-interventional study on correlation between ITRT profile and clinical response in long-term follow-up. The objective of the study was to assess the role of ITRT profile as prognostic factor in childhood iALL and iAML. MATERIALS AND METHODS: A total number of 998 children (median age 6.5 yrs, range 3 days - 21 yrs) were enrolled into the study, including 817 with initial ALL (iALL) and 181 children with initial AML (iAML). The median follow-up was 4.6 yrs (range 0–10,4). ITRT (ex vivo drug resistance profile) was determined by the MTT assay. Following drugs were tested: prednisolone (P), vincristine (V), L-asparaginase (A), daunorubicin (D), doxorubicin (Dox), idarubicin (I), mitoxantrone (M), cytarabine (C), busulfan (B) and etoposide (E). Apart from ITRT to single drugs, combined ex vivo drug resistance profiles PVA, PVADC, PVADoxC in iALL and CVIDM in iAML were also determined. Probability of DFS was estimated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed in Cox regression model. RESULTS: (1) For iALL patients, neither single drug nor 3-drugs PVA combined ITRT profile had prognostic value for pDFS. 5-drug PVADC and PVADoxC profiles had predictive values, with p-values 0.049 and 0.017, respectively. For 295 iALL patients with ITRT-sensitive PVADC profile, 5-year pDFS=0.892. No ITRT factor was discriminative between very early, early and late ALL relapses. In univariate analysis in Cox model, following factors had prognostic value for pDFS in iALL: steroid resistance by day 8 (p=0.002), bone marrow (BM) response by day 15 (p=0.005), BM response by day 33 (p=0.001) and PVADC ITRT profile (p=0.052). In multivariate analysis in Cox model, only BM response by day 33 (p=0.001) had prognostic value for pDFS in iALL, while bone marrow BM by day 15 had borderline significance (p=0.055). (2) For iAML patients, ITRT to cytarabine had an impact on pDFS (0.81 vs 0.63, p=0.047). For 55 iAML patients with ITRT-sensitive to cytarabine, 5-year pDFS=0.816. 5-drug CVIDM profile had also predictive values, with p-value 0.020. No ITRT factor was discriminative between very early, and late AML relapses. In univariate analysis in Cox model, no factor had prognostic value for pDFS in iAML, while ITRT to cytarabine almost reached significance (p=0.054). Multivariate analysis for iAML was not performed. CONCLUSION: Ex vivo drug resistance profile (ITRT) can be regarded as a risk factor in childhood acute leukemias. Combined ITRT profile to prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine (PVADC) has predictive value in pediatric iALL, while ITRT profile to cytarabine has prognostic value in pediatric iAML. ACKNOWLEDGEMENTS: Supported by grants: EFS-POKL.04.01.01-00-191/08-00 nr 1/2010; MNiSW Nr N N407 541339; MNiSW Nr N407 078 32/2964; UMK 09/2009; UMK 10/2009. Disclosures: No relevant conflicts of interest to declare.
2
Styczynski, Jan, Anna Jaworska-Posadzy, Malgorzata Kubicka, Robert Debski, Beata Kurylo-Rafinska, Beata Kolodziej, Monika Pogorzala, Magdalena Piatkowska, Krzysztof Czyzewski, and Mariusz Wysocki. "Patterns of Individual Tumor Response Testing (ITRT) and Bone Marrow Minimal Residual Disease (MRD) On Day 15 of Therapy in Childhood Precursor-B-Lineage Acute Lymphoblastic Leukemia (ALL): MRD and Ex Vivo Drug Resistance Have Similar Predictive Value of Relapse." Blood 120, no. 21 (November 16, 2012): 2448. http://dx.doi.org/10.1182/blood.v120.21.2448.2448.
Full textAbstract:
Abstract Abstract 2448 Introduction: The speed of blast clearance during therapy is a major prognostic factor of outcome in childhood acute lymphoblastic leukemia (ALL). Blast count in the peripheral blood on day 8, or in the bone marrow on day 15 and day 33, have been widely used to deliver risk-directed therapy. Another approach to measure the speed of leukemia clearance is the detection of minimal residual disease during induction therapy, as well as at days 33 and 78 of therapy. In vitro measurements of drug resistance (called recently as ITRT, individual tumor resistance testing) in leukemic cells obtained at diagnosis have been of prognostic significance in the prediction of clinical outcome in selected groups of patients. Objective: The analysis of the prognostic impact of (A) residual disease (MRD) at day 15 of induction therapy; (B) in vitro drug resistance at diagnosis (ITRT), (C) correlation of MRD and ITRT, and (D) multivariate analysis of prognostic role of MRD, ITRT, initial factors and initial therapy response to the risk of relapse. Patients and Methods: A total number of 87 children (aged 1–18 years) diagnosed for pre-B-ALL, treated either with ALL-BMF-90 or ALL-IC-2002 protocol were included into the study. ITRT was tested at diagnosis by the MTT assay. Residual disease at day 15 was measured by flow cytometry and determined for cut-off value BML15<0.5%. The median follow-up was 8.9 yrs (range, 0–11.5). Following drugs were tested: prednisolone, dexamethasone, vincristine, L-asparaginase, daunorubicin, doxorubicin, etoposide and cytarabine. PVA score was determined as combined ITRT profile to prednisolone, vincristine and L-asparaginase. Results: (A) The overall pDFS was 0.721±0.052 and the mean survival 9.1 yrs (95%CI=8.2–9.9). Patients with BML15<0.5% had pDFS=0.816±0.055, while those with BML15>0.5% had pDFS=0.542±0.098 (p=0.009, log-rank). The risk of relapse in BML15-positive patients was 3.0-fold higher (1.3–7.1, p=0.013). (B) pDFS was significantly better for patients with sensitive ITRT profile to: PVA (1.00±0.00 vs 0.61±0.06, p=0.002), prednisolone (0.89±0.05 vs 0.54±0.08, p=00002), vincristine (0.84±0.06 vs 0.61±0.08, p=0.035), daunorubicin (0.094±0.04 vs 0.51±0.08, p=0.00002), and L-asparaginase (0.84±0.06 vs 0.59±0.08, p=0.009). In multivariate analysis in Cox model, the prognostic value was retained only for ITRT for prednisolone (p=0.013, HR=0.08, 95%CI=0.01–0.6) and daunorubicin (p=0.004, HR=0.05, 95%CI=0.01–0.4), while ITRT for PVA score was below of significance (p=0.068, HR=0.03, 95%CI=0.01–1.3). (C) Patients with MRD-positive ALL at day 15 (BML15>0.5%) had higher ITRT for following drugs: doxorubicin (p=0.005, RR=1.8, Mann-Whitney U test), L-asparaginase (p=0.029, RR=3.2), and etoposide (p=0.055, RR=4.1), while no differences were found for other drugs. In multivariate logistic regression, the significance impact to development of BML15>0.5% was found for doxorubicin (p=0.035, OR=0.33) and etoposide (p=0.048, OR=0.14). (D) In multivariate analysis in Cox model for relapse risk, three factors had predictive value: BML15>0.5% (p=0.010, OR=3.3, 95%CI=1.3–8.2), ITRT for prednisolone (p=0.012, OR=4.4, 95%CI=1.4–13) and ITRT for daunorubicin (p=0.018, OR=5.9, 95%CI=1.4–26), while age, prednisolone-poor-response at day 8, BM response at day 15, BM response at day 33, and BCR-ABL rearrangement had no significant value. Conclusions: Patients with residual disease at day 15 had 3-fold higher risk of relapse. Patients with resistant ITRT profile to prednisolone and daunorubicin had respectively 12- and 20-fold higher risk of relapse. Presence of residual blasts at day 15 correlates with ITRT to etoposide and doxorubicin. Finally, persistence of blast in marrow at day 15 (BML15>0.5%) and ex vivo drug resistance (ITRT) to prednisolone and to daunorubicin were the strongest prognostic factors predicting relapse in childhood ALL. Disclosures: No relevant conflicts of interest to declare.
3
Li, Peng, Peng Guan, Jun Zheng, Bin Dou, Hong Tian, Xinsheng Duan, and Hejuan Liu. "Field Test and Numerical Simulation on Heat Transfer Performance of Coaxial Borehole Heat Exchanger." Energies 13, no. 20 (October 19, 2020): 5471. http://dx.doi.org/10.3390/en13205471.
Full textAbstract:
Ground thermal properties are the design basis of ground source heat pumps (GSHP). However, effective ground thermal properties cannot be obtained through the traditional thermal response test (TRT) method when it is used in the coaxial borehole heat exchanger (CBHE). In this paper, an improved TRT (ITRT) method for CBHE is proposed, and the field ITRT, based on the actual project, is carried out. The high accuracy of the new method is verified by laboratory experiments. Based on the results of the ITRT and laboratory experiment, the 3D numerical model for CBHE is established, in which the flow directions, sensitivity analysis of heat transfer characteristics, and optimization of circulation flow rate are studied, respectively. The results show that CBHE should adopt the anulus-in direction under the cooling condition, and the center-in direction under the heating condition. The influence of inlet temperature and flow rate on heat transfer rate is more significant than that of the backfill grout material, thermal conductivity of the inner pipe, and borehole depth. The circulating flow rate of CBHE between 0.3 m/s and 0.4 m/s can lead to better performance for the system.
4
Lin, Lanjin, Guohao Sun, Ziyang Cheng, and Zishu He. "Long-Time Coherent Integration for Maneuvering Target Detection Based on ITRT-MRFT." IEEE Sensors Journal 20, no. 7 (April 1, 2020): 3718–31. http://dx.doi.org/10.1109/jsen.2019.2960323.
Full text
5
Takayama, Toshio, Masahiko Tsurumaru, Yoshiaki Kajiyama, Yoshimi Iwanuma, Natsumi Tomita, Takayuki Amano, Fuyumi Isayama, and Tomoaki Ito. "Setting of the candidate exposure conditions in an individualized tumor response testing (ITRT) toward an individual chemotherapy for esophageal cancer." Esophagus 5, no. 2 (June 2008): 87–91. http://dx.doi.org/10.1007/s10388-008-0154-z.
Full text
6
Wunderlich, Kerstin, Esmeralda van der Helm, Dirk Spek, Mark Vermeulen, Adile Gecgel, Maria Grazia Pau, Jort Vellinga, and Jerome Custers. "An alternative to the adenovirus inverted terminal repeat sequence increases the viral genome replication rate and provides a selective advantage in vitro." Journal of General Virology 95, no. 7 (July 1, 2014): 1574–84. http://dx.doi.org/10.1099/vir.0.064840-0.
Full textAbstract:
During the development of human adenovirus 35-derived replication-incompetent (rAd35) vaccine vectors for prevention of infectious diseases, we detected mutations in the terminal 8 nt of the inverted terminal repeats (ITRs) of rAd35. The switch from the plasmid-encoded sequence 5′-CATCATCA-3′ to the alternative sequence 5′-CTATCTAT-3′ in the ITRs was found to be a general in vitro propagation phenomenon, as shown for several vectors carrying different transgenes or being derived from different adenovirus serotypes. In each tested case, the plasmid-encoded ITR sequence changed to exactly the same alternative ITR sequence, 5′-CTATCTAT-3′. The outgrowth of this alternative ITR version should result from a growth advantage conferred by the alternative ITR sequence. Indeed, replication kinetics studies of rAd35 harbouring either the original or alternative ITR sequence confirmed an increase in replication speed for rAd35 vectors with the alternative ITR sequence. These findings can be applied to generate recombinant adenoviral vectors harbouring the alternative ITR sequence, which will facilitate the generation of genetically homogeneous seed virus batches. Moreover, vector production may be accelerated by taking advantage of the observed improved replication kinetics associated with the alternative ITR sequence.
7
Styczynski, Jan, Beata Kurylo-Rafinska, Malgorzata Kubicka, Beata Kolodziej, Monika Pogorzala, Krzysztof Czyzewski, Robert Debski, et al. "Differential in Vitro Drug Resistance Profile Between First and Second Relapsed Acute Lymphoblastic Leukemia and Acute Myeloblastic Leukemia in Children." Blood 126, no. 23 (December 3, 2015): 3696. http://dx.doi.org/10.1182/blood.v126.23.3696.3696.
Full textAbstract:
Abstract Introduction: In vitro drug resistance profile has so far provided information on chemosensitivity of leukemic cells in acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). Previous studies have shown that for most tested drugs, patients with relapse had higher IRTR than those with de novo ALL or AML. The objective of this study was the analysis and comparison of the individualized tumor response testing (ITRT) between first and second relapse in children with ALL or AML. Patients: A total of 186 pediatric leukemic samples (154 ALL and 32 AML) were tested for ex vivo chemosensitivity for up to 22 drugs. ALL samples included 113 samples obtained at first relapse, and 41 obtained at second relapse. AML samples included 22 samples obtained at first relapse, and 10 obtained at second leukemic relapse. The distribution of patients between first and second relapse groups was comparable. Methods: In vitro drug resistance was tested by the MTT assay. The drug concentration that was inhibitory to 50% of the cells (IC50) was calculated from the dose-response curve and was used as a measure of ex vivo drug resistance for each sample. The relative resistance (RR) between groups analyzed for each drug was calculated as the ratio of the mean values of the IC50 of the respective groups for this drug. Only patients who had a successful MTT assay at diagnosis were included in the study. The following drugs were used: prednisolone, dexamethasone, vincristine, idarubicin, daunorubicin, doxorubicin, mitoxantrone, L-asparaginase, cytarabine, fludarabine, cladribine, clofarabine, treosulfan, thiotepa, melphalan, 4-HOO-cyclophosphamide, 4-HOO-ifosfamide, bortezomib, busulfan, 6-mercaptopurine, and 6-thioguanine. For patients with ALL, combined drug resistance profile to prednisolone, vincristine and L-asparaginase (PVA score) was also analyzed. Results: ALL: In comparison to first relapse, second relapsed childhood ALL were more resistant to most of tested drugs. Median PVA score in multiple relapsed patients was 8 vs 6 for patients at first relapse (p=0.004). The median relative resistance value between patients with multiple relapse and those with first relapse for all tested drugs was 2.0, indicating higher drug resistance on second relapse. Multiple relapsed ALL samples were more drug resistant to: prednisolone (>1.9-fold), dexamethasone (>1.5-fold), vincristine (3.1-fold), L-asparaginase (5-fold), mitoxantrone (2.4-fold), cytarabine (4.3-fold), mercaptopurine (2.2-fold), thioguanine (4.8-fold), etoposide (2.6-fold) and melphalan (2.7-fold). On the other hand, lymphoblasts at second relapse were comparably resistant to: daunorubicin, doxorubicin, 4-HOO-cyclophosphamide, 4-HOO-ifosfamide, busulfan, treosulfan, fludarabine, clofarabine and bortezomib. No drug showed a trend towards better cellular sensitivity at first versus second relapse. AML: No significant differences between ITRT at first and second relapse of childhood AML were found. Of the all drugs analyzed, no drug was found for which significantly higher resistance of myeloblasts was observed at second relapse when compared to first relapse of AML. The median RR value between second and first relapse of all tested drugs was 1.0; for 10 drugs the RR was less than 1 (i.e. assumed better sensitivity on subsequent relapse) and for another 11 drugs, the RR value was greater than 1 (i.e. higher drug resistance on subsequent relapse). No drug showed a trend towards better cellular sensitivity at first versus subsequent relapse, as the differences were not significant for each tested drug. Conclusion: In comparison to first relapse, leukemic blasts of children at second relapse of ALL are more in vitro resistant to most of tested drugs. Contrary, myeloblasts of children at second relapse of AML show drug resistance comparable to first relapse. (This study was supported by NCN Grant DEC-2011/03/D/NZ5/05749.) Disclosures No relevant conflicts of interest to declare.
8
Chiorini, John A., Sandra Afione, and Robert M. Kotin. "Adeno-Associated Virus (AAV) Type 5 Rep Protein Cleaves a Unique Terminal Resolution Site Compared with Other AAV Serotypes." Journal of Virology 73, no. 5 (May 1, 1999): 4293–98. http://dx.doi.org/10.1128/jvi.73.5.4293-4298.1999.
Full textAbstract:
ABSTRACT Adeno-associated virus (AAV) replication depends on two viral components for replication: the AAV nonstructural proteins (Rep) intrans, and inverted terminal repeat (ITR) sequences incis. AAV type 5 (AAV5) is a distinct virus compared to the other cloned AAV serotypes. Whereas the Rep proteins and ITRs of other serotypes are interchangeable and can be used to produce recombinant viral particles of a different serotype, AAV5 Rep proteins cannot cross-complement in the packaging of a genome with an AAV2 ITR. In vitro replication assays indicated that the block occurs at the level of replication instead of at viral assembly. AAV2 and AAV5 Rep binding activities demonstrate similar affinities for either an AAV2 or AAV5 ITR; however, comparison of terminal resolution site (TRS) endonuclease activities showed a difference in specificity for the two DNA sequences. AAV2 Rep78 cleaved only a type 2 ITR DNA sequence, and AAV5 Rep78 cleaved only a type 5 probe efficiently. Mapping of the AAV5 ITR TRS identified a distinct cleavage site (AGTG TGGC) which is absent from the ITRs of other AAV serotypes. Comparison of the TRSs in the AAV2 ITR, the AAV5 ITR, and the AAV chromosome 19 integration locus identified some conserved nucleotides downstream of the cleavage site but little homology upstream.
9
Wang, F., P. Zhang, Z. Y. Sun, and Q. L. Zhang. "A NONLINEAR CONVERSION MODEL FORM ITRFYY TO CGCS2000." ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XLII-3/W10 (February 7, 2020): 535–38. http://dx.doi.org/10.5194/isprs-archives-xlii-3-w10-535-2020.
Full textAbstract:
Abstract. At present, ITRS series reference frameworks are widely used in the world. The results of GNSS are mostly based on the ITRF framework. Transform from ITRF to CGCS2000 is not easy, which restricts the promotion and use of CGCS2000. The conversion relationship between CGCS2000 and ITRF framework has imminent practical significance. This paper constructs the epoch reduction and frame conversion two-steps model which estimated the nonlinear model to solve the appeal problem. Effective test show that the nonlinear model accesses an improvement in not only precession but also accuracy relative to the tradition model.
10
Bennett, Teresa A., Sandra Sapia, Daniel Primo, Lilia Suarez, Santiago Lago, Maria Matoses, Ana Espinosa, et al. "Personalized Medicine Test of Multi-Drug Protocols Ex Vivo for Hematological Malignancies." Blood 114, no. 22 (November 20, 2009): 2655. http://dx.doi.org/10.1182/blood.v114.22.2655.2655.
Full textAbstract:
Abstract Abstract 2655 Poster Board II-631 Introduction: The predictive power of measuring the effect of anticancer treatments on whole living tumor cells freshly removed from cancer patients, called Individualized Tumor Response Testing (ITRT), has been recently further validated in a clinical trial, the UK's LRF CLL4 trial (Bosanquet ASH 2007). It predicts resistance better than sensitivity. We present a novel approach to ITRT based on measuring drug induced apoptosis of tumor cells in whole blood ex vivo (in vitro using freshly extracted samples). It uses a novel automated flow cytometry platform (ExviTech) capable of evaluating hundreds of drugs and drug combinations used in current treatment protocols, and can address the significant scaling of potential future protocols induced by a number of new drug approvals in each indication. Patients and Methods: We evaluated 47 samples of peripheral blood or bone marrow from patients diagnosed with hematological malignancies: 20 chronic Lymphocytic Leukemia (CLL), 14 Acute Lymphoblastic Leukemia (ALL), 7 Multiple Myeloma (MM), and 6 Acute Myeloblastic Leukemia (AML). After informed consent, samples, collected into heparin, were processed the same or the next day. Whole blood was diluted and incubated with drugs for 24 and 48 hours. Whole blood was used to retain erythrocytes and serum proteins enabling more clinically relevant physiological conditions. Three types of drugs were tested: 1) Approved drugs for each indication, including all possible pair wise combinations, and combinations administered within current and experimental protocols as advised by the PETHEMA groups in Spain. 2) Concomitant medicines (Con-Meds), including alternative drugs within the same class of antacids, antiemetics, etc… to test whether they may also induce apoptosis 3) Drugs in clinical trials, preferentially Phase III drugs, alone and in combination with approved drugs, which may form the basis of future treatment protocols. Drugs were plated at a final concentration equivalent to their reported plasma Cmax concentration. Synergistic drug combinations were identified as one drug potentiating the effect of the other. Results: The efficacy of each drug and combination tested was categorized as highly resistant, intermediate or highly sensitive. Highly resistant drug results were contraindicated. Among the highly sensitive treatments ex vivo, often those that effectively killed all malignant cells, we selected those whose drugs were significantly less toxic as treatment guidelines, highlighting those treatment protocols that act faster ex vivo (24 vs 48 hours) and/or show synergistic combinations. The final result was a set of multiple reasonable ex vivo options for hematologists. The efficacy of individual drugs varied notably from patient to patient, , as reported earlier by other methods. Drug-drug combinations show surprising results. Some combinations, effective at high doses, kill 80% of malignant cells when combined in low concentrations at which the individual drugs kill only 10%20% of these cells. On the contrary, many drug combinations were antagonistic, effectively turning them into cytoprotectors and the patient into potential resistance. Specific combinations that show consistent efficacy across samples are indicative of potential new protocols. Surprisingly, for a proportion of patients, some of the Con-Meds were highly efficient in killing malignant cells selectively. For example, in a particular CLL patient an antacid and an antiviral drug had similar efficacies as the best approved cytotoxic drugs. In other patients, drugs still in clinical trials showed high sensitivity and highly selective apoptosis – suggesting that those patients could be referred for inclusion into these trials, which could represent new alternatives especially for refractory patients with few therapeutic options available. Conclusions: We have developed a Personalized Medicine Multi-Drug ex vivo test, evaluating the efficacy of hundreds of drugs and drug combinations in whole blood. This scale could address the predictable expansion of multi-drug potential treatments as the existing extensive drug pipeline delivers new drug approvals, exploring hundreds of new protocols ex vivo. Promising results obtained ex vivo (in vitro using freshly extracted samples) need to be verified in clinical trials. Disclosures: Bennett: Vivia Biotech: Employment. Sapia:Vivia Biotech SL: Employment. Primo:Vivia Biotech SL: Employment. Suarez:Vivia Biotech SL: Employment. Lago:Vivia Biotech SL: Employment. Matoses:Vivia Biotech SL: Employment. Espinosa:Vivia Biotech SL: Employment. Tudela:Vivia Biotech SL: Employment. Arroyo:Vivia Biotech SL: Employment. Gorrochategui:Vivia Biotech SL: Employment. Jackson:Vivia Biotech SL: Employment. Okun:Vivia Biotech SL: Research Funding. Lopez:Vivia Biotech SL: Employment. Gornemann:Vivia Biotech SL: Employment. Diez:Vivia Biotech SL: Employment. Gonzáalez:Vivia Biotech SL: Consultancy. Bosanquet:Vivia Biotech SL: Consultancy. Orfao:Vivia Biotech SL: Research Funding. Ballesteros:Vivia Biotech SL: Equity Ownership.
11
Mueller, Ivan I. "The First Decade of the IERS." International Astronomical Union Colloquium 178 (2000): 201–13. http://dx.doi.org/10.1017/s0252921100061340.
Full textAbstract:
AbstractThe International Earth Rotation Service (IERS) was established in 1987 by the International Astronomical Union (IAU) and the International Union of Geodesy and Geophysics (IUGG), and it began operation on 1 January 1988. The primary objectives of the IERS are to serve the astronomical, geodetic and geophysical communities by providing the following: •The International Celestial Reference System (ICRS) and its realization, the International Celestial Reference Frame (ICRF).•The International Terrestrial Reference System (ITRS) and its realization, the International Terrestrial Reference Frame (ITRF).•Earth orientation parameters required to study Earth orientation variations and to transform between the ICRF and the ITRF.•Geophysical data to interpret time/space variations of the ITRF with respect to the ICRF, i.e., of the Earth orientation parameters, and to model such variations.•Standards, constants and models (i.e., conventions) encouraging international adherence.This presentation primarily covers the first three IERS functions from the operational point of view.
12
Luedtke, Alexander R., and Mark J. van der Laan. "Optimal Individualized Treatments in Resource-Limited Settings." International Journal of Biostatistics 12, no. 1 (May 1, 2016): 283–303. http://dx.doi.org/10.1515/ijb-2015-0007.
Full textAbstract:
Abstract An individualized treatment rule (ITR) is a treatment rule which assigns treatments to individuals based on (a subset of) their measured covariates. An optimal ITR is the ITR which maximizes the population mean outcome. Previous works in this area have assumed that treatment is an unlimited resource so that the entire population can be treated if this strategy maximizes the population mean outcome. We consider optimal ITRs in settings where the treatment resource is limited so that there is a maximum proportion of the population which can be treated. We give a general closed-form expression for an optimal stochastic ITR in this resource-limited setting, and a closed-form expression for the optimal deterministic ITR under an additional assumption. We also present an estimator of the mean outcome under the optimal stochastic ITR in a large semiparametric model that at most places restrictions on the probability of treatment assignment given covariates. We give conditions under which our estimator is efficient among all regular and asymptotically linear estimators. All of our results are supported by simulations.
13
Pregowska, Agnieszka. "Signal Fluctuations and the Information Transmission Rates in Binary Communication Channels." Entropy 23, no. 1 (January 10, 2021): 92. http://dx.doi.org/10.3390/e23010092.
Full textAbstract:
In the nervous system, information is conveyed by sequence of action potentials, called spikes-trains. As MacKay and McCulloch suggested, spike-trains can be represented as bits sequences coming from Information Sources (IS). Previously, we studied relations between spikes’ Information Transmission Rates (ITR) and their correlations, and frequencies. Now, I concentrate on the problem of how spikes fluctuations affect ITR. The IS are typically modeled as stationary stochastic processes, which I consider here as two-state Markov processes. As a spike-trains’ fluctuation measure, I assume the standard deviation σ, which measures the average fluctuation of spikes around the average spike frequency. I found that the character of ITR and signal fluctuations relation strongly depends on the parameter s being a sum of transitions probabilities from a no spike state to spike state. The estimate of the Information Transmission Rate was found by expressions depending on the values of signal fluctuations and parameter s. It turned out that for smaller s<1, the quotient ITRσ has a maximum and can tend to zero depending on transition probabilities, while for 1<s, the ITRσ is separated from 0. Additionally, it was also shown that ITR quotient by variance behaves in a completely different way. Similar behavior was observed when classical Shannon entropy terms in the Markov entropy formula are replaced by their approximation with polynomials. My results suggest that in a noisier environment (1<s), to get appropriate reliability and efficiency of transmission, IS with higher tendency of transition from the no spike to spike state should be applied. Such selection of appropriate parameters plays an important role in designing learning mechanisms to obtain networks with higher performance.
14
Pregowska, Agnieszka. "Signal Fluctuations and the Information Transmission Rates in Binary Communication Channels." Entropy 23, no. 1 (January 10, 2021): 92. http://dx.doi.org/10.3390/e23010092.
Full textAbstract:
In the nervous system, information is conveyed by sequence of action potentials, called spikes-trains. As MacKay and McCulloch suggested, spike-trains can be represented as bits sequences coming from Information Sources (IS). Previously, we studied relations between spikes’ Information Transmission Rates (ITR) and their correlations, and frequencies. Now, I concentrate on the problem of how spikes fluctuations affect ITR. The IS are typically modeled as stationary stochastic processes, which I consider here as two-state Markov processes. As a spike-trains’ fluctuation measure, I assume the standard deviation σ, which measures the average fluctuation of spikes around the average spike frequency. I found that the character of ITR and signal fluctuations relation strongly depends on the parameter s being a sum of transitions probabilities from a no spike state to spike state. The estimate of the Information Transmission Rate was found by expressions depending on the values of signal fluctuations and parameter s. It turned out that for smaller s<1, the quotient ITRσ has a maximum and can tend to zero depending on transition probabilities, while for 1<s, the ITRσ is separated from 0. Additionally, it was also shown that ITR quotient by variance behaves in a completely different way. Similar behavior was observed when classical Shannon entropy terms in the Markov entropy formula are replaced by their approximation with polynomials. My results suggest that in a noisier environment (1<s), to get appropriate reliability and efficiency of transmission, IS with higher tendency of transition from the no spike to spike state should be applied. Such selection of appropriate parameters plays an important role in designing learning mechanisms to obtain networks with higher performance.
15
Edirisinghe Vincent, Nishani, and Robert Pinsker. "IT risk management: interrelationships based on strategy implementation." International Journal of Accounting & Information Management 28, no. 3 (March 18, 2020): 553–75. http://dx.doi.org/10.1108/ijaim-08-2019-0093.
Full textAbstract:
Purpose Risk management is an under-explored topic in information systems (IS) research that involves complex and interrelated activities. Consequently, the authors explore the importance of interrelated activities by examining how the maturity of one type of information technology risk management (ITRM) practice is influenced by the maturity of other types of ITRM practices. The purpose of this paper is to explore these relationships, the authors develop a model based on organizational strategy implementation theory and the COBIT framework. The model identifies four types of ITRM practices, namely, IT governance (ITG); communications; operations; and monitoring. Design/methodology/approach The authors use a survey methodology to collect data on senior information technology (IT) executives' perceptions on ITRM practices. The authors use an exploratory factor analysis (EFA) to identify four dimensions of ITR M practices and conduct a structural equation model to observe the associations. Findings The survey of senior IT executives' perceptions suggests that the maturity of ITRM practices related to ITG, communications and monitoring positively influence the maturity of operations-related ITRM practices. Further, the maturity of communications-related ITRM practices mediates the relationship between ITG and operations-related ITRM practices. The aggregate results demonstrate the inter-relatedness of ITRM practices and highlight the importance of taking a holistic view of ITRM. Research limitations/implications Given the content and complexity of the study, it is difficult to obtain senior executives’ responses in large firms. Therefore, this study did not use a separate sample to conduct the EFA to obtain the underlying four constructs. Also, the ITRM practices identified are perceptions. Even though the authors consider this to be a limitation, it also communicates the pressing areas that senior IT professionals are expected to focus given various external and internal pressures. This study focuses on large firms, hence, small to midsize firms are not well represented. Practical implications Given the demanding regulatory and financial reporting requirements and the complexity of IT, there is an increasing possibility that the accounting profession will require IT professionals to focus on operations-related ITRM practices, such as security, availability and confidentially of data and IS are closely related to internal controls. However, as this study demonstrates, the maturity of operations-related ITRM practices cannot be achieved by focusing solely on operations-related IT risks. Therefore, IT practitioners can use this study to raise awareness of the complex interrelationships among ITRM practices among managers to improve the overall ITRM practices in a firm. Social implications The study also shows the importance of establishing proper communication channels among various business functions with regard to ITRM. Extant IT research identifies the importance of the firm’s communication structure on various firm performance measures. For example, Krotov (2015) mentions the importance of communication in improving trust between the Chief Executive Officer and Chief Financial Officer. Firms with established communication channels have the necessary medium to educate and involve other departments with regard to the security of data. Thus, such firms are more likely to have mature risk management practices because of increased awareness of risks and preventive techniques. Originality/value The study contributes to ITG and risk management literature by identifying the role of monitoring-related ITRM practices on improving other areas of risk management. The study also extends the existing ITRM literature by providing an organizational strategy perspective to ITRM practices and showing how ITRM practices follow organizational strategy implementation. Further, the authors identify four underlying ITRM categories. Consequently, researchers could choose between two factors (Vincent et al., 2017) or four factors based on the level of detail required for the particular study.
16
Mannan, Malik M. Naeem, M. Ahmad Kamran, Shinil Kang, Hak Soo Choi, and Myung Yung Jeong. "A Hybrid Speller Design Using Eye Tracking and SSVEP Brain–Computer Interface." Sensors 20, no. 3 (February 7, 2020): 891. http://dx.doi.org/10.3390/s20030891.
Full textAbstract:
Steady-state visual evoked potentials (SSVEPs) have been extensively utilized to develop brain–computer interfaces (BCIs) due to the advantages of robustness, large number of commands, high classification accuracies, and information transfer rates (ITRs). However, the use of several simultaneous flickering stimuli often causes high levels of user discomfort, tiredness, annoyingness, and fatigue. Here we propose to design a stimuli-responsive hybrid speller by using electroencephalography (EEG) and video-based eye-tracking to increase user comfortability levels when presented with large numbers of simultaneously flickering stimuli. Interestingly, a canonical correlation analysis (CCA)-based framework was useful to identify target frequency with a 1 s duration of flickering signal. Our proposed BCI-speller uses only six frequencies to classify forty-eight targets, thus achieve greatly increased ITR, whereas basic SSVEP BCI-spellers use an equal number of frequencies to the number of targets. Using this speller, we obtained an average classification accuracy of 90.35 ± 3.597% with an average ITR of 184.06 ± 12.761 bits per minute in a cued-spelling task and an ITR of 190.73 ± 17.849 bits per minute in a free-spelling task. Consequently, our proposed speller is superior to the other spellers in terms of targets classified, classification accuracy, and ITR, while producing less fatigue, annoyingness, tiredness and discomfort. Together, our proposed hybrid eye tracking and SSVEP BCI-based system will ultimately enable a truly high-speed communication channel.
17
Gleißner, Jochen. "Lebensqual(ität)." Uro-News 16, no. 2 (February 2012): 3. http://dx.doi.org/10.1007/s00092-012-0042-7.
Full text
18
Csaba, László. "Has the great depression returned?" Gazdaság és Társadalom 1, no. 1 (2009): 5–17. http://dx.doi.org/10.21637/gt.2009.1.01.
Full text
19
Hashim, Hayder R., Alexandra Molnár, and Szabolcs Tengely. "Cryptanalysis of ITRU." Sv. 25(2021)=knj. 60 25(60) (2021): 181–93. http://dx.doi.org/10.21857/yrvgqtexl9.
Full text
20
Wang, Y., S. M. Camp, M. Niwano, X. Shen, J. C. Bakowska, X. O. Breakefield, and P. D. Allen. "Herpes Simplex Virus Type 1/Adeno-Associated Virus rep+ Hybrid Amplicon Vector Improves the Stability of Transgene Expression in Human Cells by Site-Specific Integration." Journal of Virology 76, no. 14 (July 15, 2002): 7150–62. http://dx.doi.org/10.1128/jvi.76.14.7150-7162.2002.
Full textAbstract:
ABSTRACT Herpes simplex virus type 1 (HSV-1) amplicon vectors are promising gene delivery tools, but their utility in gene therapy has been impeded to some extent by their inability to achieve stable transgene expression. In this study, we examined the possibility of improving transduction stability in cultured human cells via site-specific genomic integration mediated by adeno-associated virus (AAV) Rep and inverted terminal repeats (ITRs). A rep − HSV/AAV hybrid amplicon vector was made by inserting a transgene cassette flanked with AAV ITRs into an HSV-1 amplicon backbone, and a rep + HSV/AAV hybrid amplicon was made by inserting rep68/78 outside the rep − vector 3′ AAV ITR sequence. Both vectors also had a pair of loxP sites flanking the ITRs. The resulting hybrid amplicon vectors were successfully packaged and compared to a standard amplicon vector for stable transduction frequency (STF) in human 293 and Gli36 cell lines and primary myoblasts. The rep +, but not the rep −, hybrid vector improved STF in all three types of cells; 84% of Gli36 and 40% of 293 stable clones transduced by the rep + hybrid vector integrated the transgene into the AAVS1 site. Due to the difficulty in expanding primary myoblasts, we did not assess site-specific integration in these cells. A strategy to attempt further improvement of STF by “deconcatenating” the hybrid amplicon DNA via Cre-loxP recombination was tested, but it did not increase STF. These data demonstrate that introducing the integrating elements of AAV into HSV-1 amplicon vectors can significantly improve their ability to achieve stable gene transduction by conferring the AAV-like capability of site-specific genomic integration in dividing cells.
21
Palombo, Fabio, Andrea Monciotti, Alessandra Recchia, Riccardo Cortese, Gennaro Ciliberto, and Nicola La Monica. "Site-Specific Integration in Mammalian Cells Mediated by a New Hybrid Baculovirus–Adeno-Associated Virus Vector." Journal of Virology 72, no. 6 (June 1, 1998): 5025–34. http://dx.doi.org/10.1128/jvi.72.6.5025-5034.1998.
Full textAbstract:
ABSTRACT Baculovirus can transiently transduce primary human and rat hepatocytes, as well as a subset of stable cell lines. To prolong transgene expression, we have developed new hybrid vectors which associate key elements from adeno-associated virus (AAV) with the elevated transducing capacity of baculovirus. The hybrid vectors contain a transgene cassette composed of the β-galactosidase (β-Gal) reporter gene and the hygromycin resistance (Hygr) gene flanked by the AAV inverted terminal repeats (ITRs), which are necessary for AAV replication and integration in the host genome. Constructs were derived both with and without the AAVrep gene under the p5 and p19 promoters cloned in different positions with respect to the baculovirus polyheidrin promoter. A high-titer preparation of baculovirus-AAV (Bac-AAV) chimeric virus containing the ITR–Hygr–β-Gal sequence was obtained with insect cells only when the rep gene was placed in an antisense orientation to the polyheidrin promoter. Infection of 293 cells with Bac-AAV virus expressing the rep gene results in a 10- to 50-fold increase in the number of Hygr stable cell clones. Additionally, rep expression determined the localization of the transgene cassette in the aavs1 site in approximately 41% of cases as detected by both Southern blotting and fluorescent in situ hybridization analysis. Moreover, site-specific integration of the ITR-flanked DNA was also detected by PCR amplification of the ITR-aavs1 junction in transduced human fibroblasts. These data indicate that Bac-AAV hybrid vectors can allow permanent, nontoxic gene delivery of DNA constructs for ex vivo treatment of primary human cells.
22
McAlister, Victor J., and Roland A. Owens. "Preferential Integration of Adeno-Associated Virus Type 2 into a Polypyrimidine/Polypurine-Rich Region within AAVS1." Journal of Virology 81, no. 18 (July 11, 2007): 9718–26. http://dx.doi.org/10.1128/jvi.00746-07.
Full textAbstract:
ABSTRACT Adeno-associated virus type 2 (AAV2) preferentially integrates its genome into the AAVS1 locus on human chromosome 19. Preferential integration requires the AAV2 Rep68 or Rep78 protein (Rep68/78), a Rep68/78 binding site (RBS), and a nicking site within AAVS1 and may also require an RBS within the virus genome. To obtain further information that might help to elucidate the mechanism and preferred substrate configurations of preferential integration, we amplified junctions between AAV2 DNA and AAVS1 from AAV2-infected HeLaJW cells and cells with defective Artemis or xeroderma pigmentosum group A genes. We sequenced 61 distinct junctions. The integration junction sequences show the three classical types of nonhomologous-end-joining joints: microhomology at junctions (57%), insertion of sequences that are not normally contiguous with either the AAV2 or the AAVS1 sequences at the junction (31%), and direct joining (11%). These junctions were spread over 750 bases and were all downstream of the Rep68/78 nicking site within AAVS1. Two-thirds of the junctions map to 350 bases of AAVS1 that are rich in polypyrimidine tracts on the nicked strand. The majority of AAV2 breakpoints were within the inverted terminal repeat (ITR) sequences, which contain RBSs. We never detected a complete ITR at a junction. Residual ITRs at junctions never contained more than one RBS, suggesting that the hairpin form, rather than the linear ITR, is the more frequent integration substrate. Our data are consistent with a model in which a cellular protein other than Artemis cleaves AAV2 hairpins to produce free ends for integration.
23
Wang, Hongjie, and André Lieber. "A Helper-Dependent Capsid-Modified Adenovirus Vector Expressing Adeno-Associated Virus Rep78 Mediates Site-Specific Integration of a 27-Kilobase Transgene Cassette." Journal of Virology 80, no. 23 (September 20, 2006): 11699–709. http://dx.doi.org/10.1128/jvi.00779-06.
Full textAbstract:
ABSTRACT Random integration of viral gene therapy vectors and subsequent activation or disruption of cellular genes poses safety risks. Major efforts in the field are aimed toward targeting vector integration to specific sites in the host genome. The adeno-associated virus (AAV) Rep78 protein is able to target AAV integration to a specific site on human chromosome 19, called AAVS1. We studied whether this ability could be harnessed to achieve site-specific integration of a 27-kb transgene cassette into a model cell line for human hematopoietic cells (Mo7e). To deliver rep78 and the transgene to Mo7e cells, we used helper-dependent adenovirus (Ad) vectors containing Ad serotype 35 fiber knob domains (HD-Ad). An HD-Ad vector containing the rep78 gene under the control of the globin locus control region (LCR) (Ad.LCR-rep78) conferred Rep78 expression on Mo7e cells. Upon coinfection of Ad.LCR-rep78 with an HD-Ad vector containing a 27-kb globin-LCR-green fluorescent protein (GFP) transgene cassette flanked by AAV inverted terminal repeats (ITRs) (Ad.AAV-LCR-GFP), transduced cells were cloned and expanded (without selection pressure), and vector integration was analyzed in clones with more than 30% GFP-positive cells. Vector integration into the AAVS1 region was seen in 30% of analyzed integration sites, and GFP expression from these integrants was stable over time. Of the remaining integration sites, 25% were within the genomic globin LCR. In almost 90% of sites, transgene integration occurred via the Ad ITR. This indicates that rescue of the AAV ITR-flanked transgene cassette from Ad.AAV-LCR-GFP is not required for Rep78-mediated integration into AAVS1 and that free ends within the vector genome can be created by breaks within the Ad ITRs, whose structure is apparently recognized by cellular “nicking” enzymes. The finding that 55% of all analyzed integration sites were either within the AAVS1 or globin LCR region demonstrates that a high frequency of targeted integration of a large transgene cassette can be achieved in human hematopoietic stem cell lines.
24
SELÇUK, Murat, Eser AKAL, and Muzaffer ÇELEBİ. "In V itro Evaluatıon o f Frozen Bull Sperm Thawed i n The D i fferent Systems." Kocatepe Veterinary Journal 7, no. 1 (May 22, 2014): 33–37. http://dx.doi.org/10.5578/kvj.7451.
Full text
25
Tang, Jiabei, Minpeng Xu, Jin Han, Miao Liu, Tingfei Dai, Shanguang Chen, and Dong Ming. "Optimizing SSVEP-Based BCI System towards Practical High-Speed Spelling." Sensors 20, no. 15 (July 28, 2020): 4186. http://dx.doi.org/10.3390/s20154186.
Full textAbstract:
The brain–computer interface (BCI) spellers based on steady-state visual evoked potentials (SSVEPs) have recently been widely investigated for their high information transfer rates (ITRs). This paper aims to improve the practicability of the SSVEP-BCIs for high-speed spelling. The system acquired the electroencephalogram (EEG) data from a self-developed dedicated EEG device and the stimulation was arranged as a keyboard. The task-related component analysis (TRCA) spatial filter was modified (mTRCA) for target classification and showed significantly higher performance compared with the original TRCA in the offline analysis. In the online system, the dynamic stopping (DS) strategy based on Bayesian posterior probability was utilized to realize alterable stimulating time. In addition, the temporal filtering process and the programs were optimized to facilitate the online DS operation. Notably, the online ITR reached 330.4 ± 45.4 bits/min on average, which is significantly higher than that of fixed stopping (FS) strategy, and the peak value of 420.2 bits/min is the highest online spelling ITR with a SSVEP-BCI up to now. The proposed system with portable EEG acquisition, friendly interaction, and alterable time of command output provides more flexibility for SSVEP-based BCIs and is promising for practical high-speed spelling.
26
Glauser, Daniel L., Okay Saydam, N. Alexander Balsiger, Irma Heid, R. Michael Linden, Mathias Ackermann, and Cornel Fraefel. "Four-Dimensional Visualization of the Simultaneous Activity of Alternative Adeno-Associated Virus Replication Origins." Journal of Virology 79, no. 19 (October 1, 2005): 12218–30. http://dx.doi.org/10.1128/jvi.79.19.12218-12230.2005.
Full textAbstract:
ABSTRACT The adeno-associated virus (AAV) inverted terminal repeats (ITRs) contain the AAV Rep protein-binding site (RBS) and the terminal resolution site (TRS), which together act as a minimal origin of DNA replication. The AAV p5 promoter also contains an RBS, which is involved in Rep-mediated regulation of promoter activity, as well as a functional TRS, and origin activity of these signals has in fact been demonstrated previously in the presence of adenovirus helper functions. Here, we show that in the presence of herpes simplex virus type 1 (HSV-1) and AAV Rep protein, p5 promoter-bearing plasmids are efficiently amplified to form large head-to-tail concatemers, which are readily packaged in HSV-1 virions if an HSV-1 DNA-packaging/cleavage signal is provided in cis. We also demonstrate simultaneous and independent replication from the two alternative AAV replication origins, p5 and ITR, on the single-cell level using multicolor-fluorescence live imaging, a finding which raises the possibility that both origins may contribute to the AAV life cycle. Furthermore, we assess the differential affinities of Rep for the two different replication origins, p5 and ITR, both in vitro and in live cells and identify this as a potential mechanism to control the replicative and promoter activities of p5.
27
Lamartina, Stefania, Giuseppe Roscilli, Daniela Rinaudo, Paola Delmastro, and Carlo Toniatti. "Lipofection of Purified Adeno-Associated Virus Rep68 Protein: toward a Chromosome-Targeting Nonviral Particle." Journal of Virology 72, no. 9 (September 1, 1998): 7653–58. http://dx.doi.org/10.1128/jvi.72.9.7653-7658.1998.
Full textAbstract:
ABSTRACT Adeno-associated virus (AAV) integrates very efficiently into a specific site (AAVS1) of human chromosome 19. Two elements of the AAV genome are sufficient: the inverted terminal repeats (ITRs) and the Rep78 or Rep68 protein. The incorporation of the AAV integration machinery in nonviral delivery systems is of great interest for gene therapy. We demonstrate that purified recombinant Rep68 protein is functionally active when directly delivered into human cells by using the polycationic liposome Lipofectamine, promoting the rescue-replication of a codelivered ITR-flanked cassette in adenovirus-infected cells and its site-specific integration in noninfected cells. The sequencing of cloned virus-host DNA junctions confirmed that lipofected Rep68 protein triggers site-specific integration at the same sites in chromosome 19 already characterized in cells latently infected with AAV.
28
Nakai, Hiroyuki, Yuichi Iwaki, Mark A. Kay, and Linda B. Couto. "Isolation of Recombinant Adeno-Associated Virus Vector-Cellular DNA Junctions from Mouse Liver." Journal of Virology 73, no. 7 (July 1, 1999): 5438–47. http://dx.doi.org/10.1128/jvi.73.7.5438-5447.1999.
Full textAbstract:
ABSTRACT Recombinant adeno-associated virus (rAAV) vectors allow for sustained expression of transgene products from mouse liver following a single portal vein administration. Here a rAAV vector expressing human coagulation factor F.IX (hF.IX), AAV-EF1α-F.IX (hF.IX expression was controlled by the human elongation factor 1α [EF1α] enhancer-promoter) was injected into mice via the portal vein or tail vein, or directly into the liver parenchyma, and the forms of rAAV vector DNA extracted from the liver were analyzed. Southern blot analyses suggested that rAAV vector integrated into the host genome, forming mainly head-to-tail concatemers with occasional deletions of the inverted terminal repeats (ITRs) and their flanking sequences. To further confirm vector integration, we developed a shuttle vector system and isolated and sequenced rAAV vector-cellular DNA junctions from transduced mouse livers. Analysis of 18 junctions revealed various rearrangements, including ITR deletions and amplifications of the vector and cellular DNA sequences. The breakpoints of the vector were mostly located within the ITRs, and cellular DNA sequences were recombined with the vector genome in a nonhomologous manner. Two rAAV-targeted DNA sequences were identified as the mouse rRNA gene and the α1 collagen gene. These observations serve as direct evidence of rAAV integration into the host genome of mouse liver and allow us to begin to elucidate the mechanisms involved in rAAV integration into tissues in vivo.
29
Tai, Phillip W. L. "ITRs: The Terminal Frontier." Human Gene Therapy 31, no. 3-4 (February 1, 2020): 143–44. http://dx.doi.org/10.1089/hum.2020.29108.pwt.
Full text
30
Kim, Hyun Jung, Taewon Han, Yun Tai Kim, Insuk So, and Byung Joo Kim. "Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M2 and M3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal." Cellular Physiology and Biochemistry 43, no. 5 (2017): 1790–802. http://dx.doi.org/10.1159/000484065.
Full textAbstract:
Background: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are traditional Chinese medicines widely used for gastrointestinal (GI) tract motility disorder in Asian countries. We investigated the effects of an ethanol extract of M. officinalis (MOE) on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs) were investigated in normal and GI motility dysfunction (GMD) mice models in vivo. Results: MOE depolarized ICC pacemaker potentials dose-dependently. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the pacemaker potential relative to treatment with MOE alone. In addition, MOE depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values were significantly and dose-dependently increased by MOE. In loperamide-and cisplatin-induced GE delay models, MOE administration reversed the GE deficits. The ITRs of the GMD mice were significantly reduced relative to those of normal mice, which were significantly and dose-dependently reversed by MOE. Conclusion: These results suggest that MOE dose-dependently depolarizes ICCs pacemaker potentials through M2 and M3 receptors via internal and external Ca2+ regulation through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo in normal and GMD mouse models. Taken together, the results of this study show that MOE have the potential for development as a gastroprokinetic agent in GI motility function.
31
Heister, Thomas, Irma Heid, Mathias Ackermann, and Cornel Fraefel. "Herpes Simplex Virus Type 1/Adeno-Associated Virus Hybrid Vectors Mediate Site-Specific Integration at the Adeno-Associated Virus Preintegration Site, AAVS1, on Human Chromosome 19." Journal of Virology 76, no. 14 (July 15, 2002): 7163–73. http://dx.doi.org/10.1128/jvi.76.14.7163-7173.2002.
Full textAbstract:
ABSTRACT Herpes simplex virus type 1 (HSV-1)-based amplicon vectors have a large transgene capacity and can efficiently infect many different cell types. One disadvantage of HSV-1 vectors is their instability of transgene expression. By contrast, vectors based on adeno-associated virus (AAV) can either persist in an episomal form or integrate into the host cell genome, thereby supporting long-term gene expression. AAV expresses four rep genes, rep68, -78, -40, and -52. Of those, rep68 or rep78 are sufficient to mediate site-specific integration of the AAV DNA into the host cell genome. The major disadvantage of AAV vectors is the small transgene capacity (∼4.6 kb). In this study, we constructed HSV/AAV hybrid vectors that contained, in addition to the standard HSV-1 amplicon elements, AAV rep68, rep78, both rep68 and -78, or all four rep genes and a reporter gene that was flanked by the AAV inverted terminal repeats (ITRs). Southern blots of Hirt DNA from cells transfected with the hybrid vectors and HSV-1 helper DNA demonstrated that both the AAV elements and the HSV-1 elements were functional in the context of the hybrid vector. All hybrid vectors could be packaged into HSV-1 virions, although those containing rep sequences had lower titers than vectors that did not. Site-specific integration at AAVS1 on human chromosome 19 was directly demonstrated by PCR and sequence analysis of ITR-AAVS1 junctions in hybrid vector-transduced 293 cells. Cell clones that stably expressed the transgene for at least 12 months could easily be isolated without chemical selection. In the majority of these clones, the transgene cassette was integrated at AAVS1, and no sequences outside the ITR cassette, rep in particular, were present as determined by PCR, ITR rescue/replication assays, and Southern analysis. Some of the clones contained random integrations of the transgene cassette alone or together with sequences outside the ITR cassette. These data indicate that the long-term transgene expression observed following transduction with HSV/AAV hybrid vectors is, at least in part, supported by chromosomal integration of the transgene cassette, both randomly and site specifically.
32
Kaya, Ibrahim, Jorge Bohórquez, and Özcan Özdamar. "A BCI Gaze Sensing Method Using Low Jitter Code Modulated VEP." Sensors 19, no. 17 (September 2, 2019): 3797. http://dx.doi.org/10.3390/s19173797.
Full textAbstract:
Visual evoked potentials (VEPs) are used in clinical applications in ophthalmology, neurology, and extensively in brain–computer interface (BCI) research. Many BCI implementations utilize steady-state VEP (SSVEP) and/or code modulated VEP (c-VEP) as inputs, in tandem with sophisticated methods to improve information transfer rates (ITR). There is a gap in knowledge regarding the adaptation dynamics and physiological generation mechanisms of the VEP response, and the relation of these factors with BCI performance. A simple, dual pattern display setup was used to evoke VEPs and to test signatures elicited by non-isochronic, non-singular, low jitter stimuli at the rates of 10, 32, 50, and 70 reversals per second (rps). Non-isochronic, low-jitter stimulation elicits quasi-steady-state VEPs (QSS-VEPs) that are utilized for the simultaneous generation of transient VEP and QSS-VEP. QSS-VEP is a special case of c-VEPs, and it is assumed that it shares similar generators of the SSVEPs. Eight subjects were recorded, and the performance of the overall system was analyzed using receiver operating characteristic (ROC) curves, accuracy plots, and ITRs. In summary, QSS-VEPs performed better than transient VEPs (TR-VEP). It was found that in general, 32 rps stimulation had the highest ROC area, accuracy, and ITRs. Moreover, QSS-VEPs were found to lead to higher accuracy by template matching compared to SSVEPs at 32 rps. To investigate the reasons behind this, adaptation dynamics of transient VEPs and QSS-VEPs at all four rates were analyzed and speculated.
33
Roberts, Gareth. "Bilingual Teaching in ITET Courses." Welsh Journal of Education / Cylchgrawn Addysg Cymru 11, no. 2 (December 2002): 109–15. http://dx.doi.org/10.16922/wje.11.2.8.
Full text
34
&NA;. "Gastro 2015 and ITCT Wolverhampton." Journal of Clinical Gastroenterology 49, no. 1 (January 2015): i—ii. http://dx.doi.org/10.1097/mcg.0000000000000263.
Full text
35
Abedi, Jamal. "Interrater/Test Reliability System (ITRS)." Multivariate Behavioral Research 31, no. 4 (October 1996): 409–17. http://dx.doi.org/10.1207/s15327906mbr3104_1.
Full text
36
Altamimi, Z., and X. Collilieux. "IGS contribution to the ITRF." Journal of Geodesy 83, no. 3-4 (December 30, 2008): 375–83. http://dx.doi.org/10.1007/s00190-008-0294-x.
Full text
37
Kouba, Jan. "The GPS Toolbox ITRF Transformations." GPS Solutions 5, no. 3 (January 2002): 88–90. http://dx.doi.org/10.1007/pl00012903.
Full text
38
Cheah, Wee Kooi, Huey Charn Han, Mei Sian Chong, Philomena Vasantha Anthony, and Wee Shiong Lim. "Multidimensionality of the Zarit Burden Interview across the severity spectrum of cognitive impairment: an Asian perspective." International Psychogeriatrics 24, no. 11 (July 3, 2012): 1846–54. http://dx.doi.org/10.1017/s104161021200110x.
Full textAbstract:
ABSTRACTBackground: We aimed to examine the multidimensionality of the Zarit Burden Interview (ZBI) beyond the conventional dual-factor structure among caregivers of persons with cognitive impairment in a predominantly Chinese multiethnic Asian population, and ascertain how these dimensions vary across the spectrum of disease severity.Methods: We studied 130 consecutive dyads of primary caregivers and patients attending a memory clinic over a six-month period. Caregiver burden was measured by the 22-item ZBI, and disease severity was staged via the Clinical Dementia Rating (CDR) scale. We performed principal component analysis (PCA) with varimax rotation to determine the factor structure of the ZBI. The magnitude of burden in each factor was expressed as the item to total ratio (ITR) and plotted against the stages of cognitive impairment. Descriptive and inferential statistics were applied to study the relationships between dimensions with disease and caregiver characteristics.Results: We identified four factors: demands of care and social impact, control over the situation, psychological impact, and worry about caregiving performance. ITRs of the first three factors increased with severity of disease and were related to recipients’ functional status and disease characteristics. ITR in the dimension of worry about performance was endorsed highest across the spectrum of disease severity, starting as early as the stage of mild cognitive impairment and peaking at CDR 1.Conclusion: Multidimensionality of ZBI was confirmed in our local setting. Each dimension of burden was unique and expressed differentially across disease severity. The dimension of worry about performance merits further study.
39
Clay, Bridget. "CPD and ITT." SecEd 2015, no. 5 (February 5, 2015): 11. http://dx.doi.org/10.12968/sece.2015.5.11.
Full text
40
Patra, Arijit, and Chanchal Kundu. "Stochastic comparisons and ageing properties of RLRT (ITRT) based on variance residual life." Communications in Statistics - Theory and Methods, August 31, 2020, 1–20. http://dx.doi.org/10.1080/03610926.2020.1812655.
Full text
41
Lyu, Li Kang, Jian Shuang Li, Xiao Jie Wang, Yi Jia Yao, Ji Fang Li, Yun Li, Hai Shen Wen, and Xin Qi. "Arg-Vasotocin Directly Activates Isotocin Receptors and Induces COX2 Expression in Ovoviviparous Guppies." Frontiers in Endocrinology 12 (April 23, 2021). http://dx.doi.org/10.3389/fendo.2021.617580.
Full textAbstract:
Oxytocin (OT) is a crucial regulator of reproductive behaviors, including parturition in mammals. Arg-vasopressin (AVP) is a nonapeptide homologous to Arg-vasotocin (AVT) in teleosts that has comparable affinity for the OT receptor. In the present study, ovoviviparous guppies (Poecilia reticulata) were used to study the effect of AVT on delivery mediated by the activation of prostaglandin (PG) biosynthesis via isotocin (IT) receptors (ITRs). One copy each of it and avt and two copies of itrs were identified in guppies. The results of the affinity assay showed that various concentrations of AVT and IT (10−6, 10−7, and 10−8 mol/L) significantly activated itr1 (P < 0.05). In vitro experiments revealed significant upregulation (P < 0.05) of cyclooxygenase 2 (cox2), which is the rate-limiting enzyme involved in PG biosynthesis, and itr1 by AVT and IT. Furthermore, dual in situ hybridization detected positive signals for itr1 and cox2 at the same site, implying that ITR1 may regulate cox2 gene expression. Measurement of prostaglandin F2a (PGF2a) concentrations showed that AVT induced PGF2a synthesis (P < 0.05) and that the effect of IT was not significant. Finally, intraperitoneal administration of PGF2a significantly induced premature parturition of guppies. This study is the first to identify and characterize AVT and ITRs in guppies. The findings suggest that AVT promotes PG biosynthesis via ITR and that PGF2a induces delivery behavior in ovoviviparous guppies.
42
Yetkin, Mevlut, and Kutubuddin Ansari. "On the determination of transformation parameters between different ITRS realizations using Procrustes approach in Turkey." Journal of Applied Geodesy 11, no. 3 (January 26, 2017). http://dx.doi.org/10.1515/jag-2016-0048.
Full textAbstract:
AbstractThe International Terrestrial Reference Frame (ITRF) solutions that are published by the International Earth Rotation and Reference Systems Service (IERS) are annual realizations of the ITRS (International Terrestrial Reference System). The results expressed in two different ITRS realizations can be compared using the transformation parameters that provide a link between different ITRF solutions. Generally, the 7-parameter (the three translation parameters, three rotation parameters and one scale factor) Helmert transformation is employed to compute the transformation parameters. However, the number of transformation parameters can be increased for better understanding. For example, 3 different scale factors may be computed instead of one scale factor. In this paper, the 9-parameter (the three translation parameters, three rotation parameters and three scale factors) transformation model and its solution by Procrustes approach is considered. Transformation parameters between ITRF 05 and ITRF 08 for Turkey have been computed in both 7-parameter model and 9-parameter model and a numerical example has been given to understand the difference between two models in a better way. An explanation about the proposed methodology as a flow chart also has been shown in appendix.
43
Breton, Camilo, Peter M. Clark, Lili Wang, Jenny A. Greig, and James M. Wilson. "ITR-Seq, a next-generation sequencing assay, identifies genome-wide DNA editing sites in vivo following adeno-associated viral vector-mediated genome editing." BMC Genomics 21, no. 1 (March 17, 2020). http://dx.doi.org/10.1186/s12864-020-6655-4.
Full textAbstract:
Abstract Background Identifying nuclease-induced double-stranded breaks in DNA on a genome-wide scale is critical for assessing the safety and efficacy of genome editing therapies. We previously demonstrated that after administering adeno-associated viral (AAV) vector-mediated genome-editing strategies in vivo, vector sequences integrated into the host organism’s genomic DNA at double-stranded breaks. Thus, identifying the genomic location of inserted AAV sequences would enable us to identify DSB events, mainly derived from the nuclease on- and off-target activity. Results Here, we developed a next-generation sequencing assay that detects insertions of specific AAV vector sequences called inverted terminal repeats (ITRs). This assay, ITR-Seq, enables us to identify off-target nuclease activity in vivo. Using ITR-Seq, we analyzed liver DNA samples of rhesus macaques treated with AAV vectors expressing a meganuclease. We found dose-dependent off-target activity and reductions in off-target events induced by further meganuclease development. In mice, we identified the genomic locations of ITR integration after treatment with Cas9 nucleases and their corresponding single-guide RNAs. Conclusions In sum, ITR-Seq is a powerful method for identifying off-target sequences induced by AAV vector-delivered genome-editing nucleases. ITR-Seq will help us understand the specificity and efficacy of different genome-editing nucleases in animal models and clinical studies. This information can help enhance the safety profile of gene-editing therapies.
44
Porollo, Aleksey, Thomas M. Sesterhenn, Margaret S. Collins, Jeffrey A. Welge, and Melanie T. Cushion. "Comparative Genomics of Pneumocystis Species Suggests the Absence of Genes for myo-Inositol Synthesis and Reliance on Inositol Transport and Metabolism." mBio 5, no. 6 (November 4, 2014). http://dx.doi.org/10.1128/mbio.01834-14.
Full textAbstract:
ABSTRACTIn the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genusPneumocystis, the genomes of three species (P. carinii,P. murina, andP. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe). The underrepresentation of amino acid metabolism pathways compared to those inS. pombe, as well as the incomplete steroid biosynthesis pathway, were confirmed forP. cariniiandP. jiroveciiand extended toP. murina. All threePneumocystisspecies showed overrepresentation of the inositol phosphate metabolism pathway compared to that in the fission yeast. In addition to those known inS. pombe, four genes, encoding inositol-polyphosphate multikinase (EC 2.7.1.151), inositol-pentakisphosphate 2-kinase (EC 2.7.1.158), phosphoinositide 5-phosphatase (EC 3.1.3.36), and inositol-1,4-bisphosphate 1-phosphatase (EC 3.1.3.57), were identified in the two rodentPneumocystisgenomes,P. cariniiandP. murina. TheP. jiroveciigenome appeared to contain three of these genes but lacked phosphoinositide 5-phosphatase. Notably, two genes encoding enzymes essential formyo-inositol synthesis, inositol-1-phosphate synthase (INO1) and inositol monophosphatase (INM1), were absent from all three genomes, suggesting thatPneumocystisspecies are inositol auxotrophs. In keeping with the need to acquire exogenous inositol, two genes with products homologous to fungal inositol transporters, ITR1 and ITR2, were identified inP. cariniiandP. murina, whileP. jiroveciicontained only the ITR1 homolog. The ITR and inositol metabolism genes inP. murinaandP. cariniiwere expressed during fulminant infection as determined by reverse transcriptase real-time PCR of cDNA from infected lung tissue. Supplementation ofin vitroculture with inositol yielded significant improvement of the viability ofP. cariniifor days 7 through 14.IMPORTANCEMicrobes in the genusPneumocystisare obligate pathogenic fungi that reside in mammalian lungs and causePneumocystispneumonia in hosts with weakened immune systems. These fungal infections are not responsive to standard antifungal therapy. A long-termin vitroculture system is not available for these fungi, impeding the study of their biology and genetics and new drug development. Given that all genomes of thePneumocystisspecies analyzed lack the genes for inositol synthesis and contain inositol transporters,Pneumocystisfungi, likeS. pombe, appear to be inositol auxotrophs. Inositol is important for the pathogenesis, virulence, and mating processes inCandida albicansandCryptococcus neoformans, suggesting similar importance within thePneumocystisspecies as well. This is the first report to (i) characterize genes in the inositol phosphate metabolism and transport pathways inPneumocystisspecies and (ii) identify inositol as a supplement that improved the viability ofP. cariniiinin vitroculture.
45
"2019 ITRW." IEEE Power Electronics Magazine 7, no. 1 (March 2020): 82. http://dx.doi.org/10.1109/mpel.2019.2959894.
Full text
46
"ITRI-227." Drug Data Report 31, no. 5 (2009): 507. http://dx.doi.org/10.1358/ddr.2009.031.05.1354045.
Full text
47
"ITT Industries becomes ITT Corporation." Pump Industry Analyst 2006, no. 7 (July 2006): 12. http://dx.doi.org/10.1016/s1359-6128(06)71445-8.
Full text
48
"ITT Industries becomes ITT Corporation." Filtration Industry Analyst 2006, no. 7 (July 2006): 2. http://dx.doi.org/10.1016/s1365-6937(06)71187-x.
Full text
49
"ITNT Proceedings Preface." Journal of Physics: Conference Series 1368 (November 2019): 011001. http://dx.doi.org/10.1088/1742-6596/1368/1/011001.
Full text
50
"ITT Flygt." World Pumps 1999, no. 399 (December 1999): 46. http://dx.doi.org/10.1016/s0262-1762(00)87407-6.
Full text