449 research outputs found
Haloplex target DNA enrichment allows investigation of copy number and mutational status of key genes in acute myeloid leukaemia with normal karyotype
No full textBackground: Acute myeloid leukaemia (AML) is a deadly haematological malignancy for which individualized treatment based on prognostic stratifica- tion is essential to maximize chances of survival. Karyotypic abnormalities car- ry prognostic significance, but are absent in about 50% of patients (NK-AML), and in this subgroup analysis of gene mutations can be used to stratify patients. Recent advances in AML genomics have defined the set of genes which are recurrently mutated in NK-AML, whilst the prognostic impact of many of these has been determined. Therefore, clinical-grade sequencing platforms will be increasingly useful in clinical practice in the next few years, and this highlights the need for reliable methods targeted gene re-sequencing.
Aims: HaloPlex is a novel, rapid approach for targeted DNA enrichment that requires low amounts of input DNA. We evaluated its performance in detect- ing abnormalities in coding sequence and copy number of genes recurrently mutated in NK-AML, with special focus on reproducibility and on the quantita- tive value of data.
Methods: Genomic DNA from 43 NK-AML samples from 40 patients was sub- jected to Haloplex target enrichment for 24 genes. Target-enriched DNA was sequenced on HiSeq2000, and reads were aligned using BWA. Substitutions and indels were called using standard algorithms and mutations called as pre- viously described (Papaemmanuil et al., Blood 2013).
Results: We sequenced 32.26 gigabases (Gb). A mean of 66.13% mapped on- target (62.94%>74.15%). The mean coverage of the target region was 3674.69x and 91.16% of bases were covered at >30X. Read depth showed sig- nificant variability, and coverage across consecutive bases could vary by sev- eral folds. This variability was expected as HaloPlex target-enrichment employs digestion of genomic DNA and specific capture of variable-length fragments with subsequent PCR amplification. Nevertheless, we found that this variabil- ity in coverage was predictable and highly consistent across samples. Conse- quently, using normalized data we were able to identify an interstitial deletion of BCOR and three MLL partial tandem duplications. We also report an ampli- fication of KRAS, an event with driver potential in solid cancers but not previ- ously described in AML. The quantitative nature if the data was retained when looking at point mutations, as demonstrated by a narrow range of allelic fre- quency of heterozygous SNPs. We identified likely oncogenic mutations in 38/40 samples with a median of 3 (1-5) per sample. NPM1 mutations were the most frequent (69%), followed by FLT3 (58%), DNMT3A (35%) and TET2 (32%). As described, NPM1 mutations co-occurred with FLT3 and DNMT3A. Both mono- and bi-allelic FLT3-ITDs were reliably identified. The recurrence rates were consistent with previously published data. We estimated allelic fre- quency of each mutation and reconstructed the phylogeny of mutations in each. In 2 cases with serial samples we studied the dynamics of tumour evolution and described variants lost and gained at relapse, implying that subclonal evolu- tion can be inferred using Haloplex targeted data.
Summary and Conclusions: Haloplex target enrichment followed by mas- sively parallel sequencing is a simple, rapid and robust method for high through- put screening of gene alterations in NK-AML. It may help prognostic stratifica- tion, treatment decisions and minimal residual disease assessment in clinical practice. It can reliably call copy number alterations, substitutions and indels. However, the targeting design
THE INVESTIGATIONS OF SOME THERMO-ELASTIC PROPERTIES OF ALIMINIUM -IRIDIYUM AND ALIMINIUM-RHODIUM ALLOYS USING SUTTON CHAN-MOLECULAR DYNAMICAL SIMULATIONS METHOD
No full textBu çalışmada, Al-Ir ve Al-Rh alaşımlarının faz diyagramları (P-T eğrileri), bazı
elastik ve termodinamik özellikleri ile metalik glas (camsı yapı) oluşumu,
Gömülmüş-Atom Metod (EAM) Moleküler dinamik yöntem kullanılarak çeşitli
sıcaklık ve basınç altında incelenmiştir. Elde edilen sonuçların mevcut teorik ve
deneysel değerlerle uyum içinde olduğu gözlenmiştir.
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In this work, the phase diagrams(P-T curves ), some thermo-elastic properties
,and the formation of metallic glass ,for Al-50%Ir and Al-50%Rh alloys, are
investigated at various temperatures and pressures by using Embedded Atom
Method (EAM) molecular dynamic simulation. Our reasonable results are in
agreement with the available experimental and other theoretical findings
Toplam verimli bakım planlamasının hava araçlarına uygulanması: Cessna model R172H (T-41D) uçağı pervane çatlak çentik kontrolleri üzerinde uygulama
No full textBu çalışmada, çok pahalı olan ve hayati riskler taşıyan hava araçları için bakım ve havacılık organizasyonlarının yönetiminde Toplam Verimli Bakım (TVB)'ın kaza kırım riskinin azaltılması, verimliliğin arttırılması ve pilot istihdamı açısından taşıdığı önem vurgulanmıştır. Hava aracı bakım yönetimi, Türk sivil havacılığındaki gelişmeler, TVB ile ilgili genel bilgi verilmiş, Türkiye'de başarılı TVB uygulama örnekleri anlatılmıştır. hava araçlarına yönelik seviye 2 bakım kademesinde kullanılabilecek günlük faaliyet durum çizelgesi bu çalışmada geliştirilerek bakım onarım faaliyetleri 8 ay süre ile kayıt altına alınmıştır. Bu süre zarfında yapılan bakım onarım faaliyetleri değerlendirilmiş ve Cessna Model R172H (T-41D) uçağı pervane çatlak çentik kontrolleri bakım onarım faaliyetinin problem sahası teşkil ettiği belirlenmiştir. TVB yaklaşımının problem sahasına uygulanması ile bu sorunun giderileceği düşüncesi ile çalışma başlatılmıştır. 4 aylık süreçte TVB uygulaması ile T-41D uçağının pervane çatlak çentik kontrolleri bakım onarım işlemi için TVB uygulaması ile %36 verimlilik artışı sağlandığı görülmüştür. T-41D uçağının pervane çatlak çentik kontrollerinde TVB uygulaması sonucu ulaşılan değerler dikkate alındığında TVB uygulamasının hava araçları bakım yönetiminde ve tüm havacılık organizasyonlarının etkin yönetiminde başarılı bir şekilde uygulanıp verimli sonuçlara ulaşılabileceği değerlendirilmiştir. izmir gundem komik videolar cizgi film izle cizgi film 3d oyunlar oyunlar In this research, importance of Total Productive Maintenance (TPM) for the management of maintenance of the very expensive aircrafts and aviation organizations, the effect of TPM for reducing the risk of the aircrafts' accidents, increasing the productivity and pilots employment have been pointed out. Management of aircraft maintenance, information on TPM, successful TPM application examples in Turkey have been expressed. Daily work plan chart which can be used in aviation intermediate maintenance organization have been developed and all maintenance and repair works recorded for 8 mounts period. After recognition of this period works it identified that Cessna Model R172H (T-41D) airplane propellar scracth crack inspection maintenance works have a problem area. With the thought of solving the problem by application of TPM approach research has been initiated. By TPM application on T-41D propellar maintenance works for 4 months it has been seen that 36% productivity increase occured. When taking in to the consideration of values after TPM application on T-41D airplane propellar scracth crack controls it has been recognized that TPM can be succesfully used for management of aircraft maintenance and effective management of all aviation organizations
APPLICATION OF TOTOL PRODUCTIVE MAINTENANCE ON AIRCRAFTS: APPLICATION OVER CESSNA MODEL R172H (T-41D) AIRPLANE PROPELLAR SCRATCH AND CRACK CONTROLS
No full textBu çalışmada, çok pahalı olan ve hayati riskler taşıyan hava araçları için
bakım ve havacılık organizasyonlarının yönetiminde Toplam Verimli
Bakım (TVB)'ın kaza kırım riskinin azaltılması, verimliliğin arttırılması ve
pilot istihdamı açısından taşıdığı önem vurgulanmıştır. Hava aracı
bakım yönetimi, Türk sivil havacılığındaki gelişmeler, TVB ile ilgili genel
bilgi verilmiş, Türkiye'de başarılı TVB uygulama örnekleri anlatılmıştır.
hava araçlarına yönelik seviye 2 bakım kademesinde kullanılabilecek
günlük faaliyet durum çizelgesi bu çalışmada geliştirilerek bakım
onarım faaliyetleri 8 ay süre ile kayıt altına alınmıştır. Bu süre zarfında
yapılan bakım onarım faaliyetleri değerlendirilmiş ve Cessna Model
R172H (T-41D) uçağı pervane çatlak çentik kontrolleri bakım onarım
faaliyetinin problem sahası teşkil ettiği belirlenmiştir. TVB yaklaşımının
problem sahasına uygulanması ile bu sorunun giderileceği düşüncesi
ile çalışma başlatılmıştır. 4 aylık süreçte TVB uygulaması ile T-41D
uçağının pervane çatlak çentik kontrolleri bakım onarım işlemi için TVB
uygulaması ile %36 verimlilik artışı sağlandığı görülmüştür. T-41D
uçağının pervane çatlak çentik kontrollerinde TVB uygulaması sonucu
ulaşılan değerler dikkate alındığında TVB uygulamasının hava araçları
bakım yönetiminde ve tüm havacılık organizasyonlarının etkin yönetiminde başarılı bir şekilde uygulanıp verimli sonuçlara ulaşılabileceği değerlendirilmiştir.
izmir gundem
komik videolar
cizgi film izle
cizgi film
3d oyunlar
oyunlar
In this research, importance of Total Productive Maintenance (TPM) for
the management of maintenance of the very expensive aircrafts and
aviation organizations, the effect of TPM for reducing the risk of the
aircrafts' accidents, increasing the productivity and pilots employment
have been pointed out. Management of aircraft maintenance,
information on TPM, successful TPM application examples in Turkey
have been expressed. Daily work plan chart which can be used in
aviation intermediate maintenance organization have been developed
and all maintenance and repair works recorded for 8 mounts period.
After recognition of this period works it identified that Cessna Model
R172H (T-41D) airplane propellar scracth crack inspection maintenance
works have a problem area. With the thought of solving the problem by
application of TPM approach research has been initiated. By TPM
application on T-41D propellar maintenance works for 4 months it has
been seen that 36% productivity increase occured. When taking in to the consideration of values after TPM application on
T-41D airplane propellar scracth crack controls it has been recognized
that TPM can be succesfully used for management of aircraft
maintenance and effective management of all aviation organizations
Characterization of gene mutations and copy number changes in acute myeloid leukemia using a rapid target enrichment protocol
No full textPrognostic stratification is critical for making therapeutic decisions and maximizing survival of patients with acute myeloid leukemia. Advances in the genomics of acute myeloid leukemia have identified several recurrent gene mutations whose prognostic impact is being deciphered. We used HaloPlex target enrichment and Illumina-based next generation sequencing to study 24 recurrently mutated genes in 42 samples of acute myeloid leukemia with a normal karyotype. Read depth varied between and within genes for the same sample, but was predictable and highly consistent across samples. Consequently, we were able to detect copy number changes, such as an interstitial deletion of BCOR, three MLL partial tandem duplications, and a novel KRAS amplification. With regards to coding mutations, we identified likely oncogenic variants in 41 of 42 samples. NPM1 mutations were the most frequent, followed by FLT3, DNMT3A and TET2. NPM1 and FLT3 indels were reported with good efficiency. We also showed that DNMT3A mutations can persist post-chemotherapy and in 2 cases studied at diagnosis and relapse, we were able to delineate the dynamics of tumor evolution and give insights into order of acquisition of variants. HaloPlex is a quick and reliable target enrichment method that can aid diagnosis and prognostic stratification of acute myeloid leukemia patients.This project was funded by the Wellcome Trust. NB is a fellow of the European
Hematology Association and was supported by the Academy of Medical Sciences.
EP is a European Hematology Association Advanced Research Fellow. GV is a
Wellcome Trust Senior Fellow in Clinical Science. IV is funded by Spanish
Ministerio de Economía y Competitividad subprograma Ramón y Cajal
THE STUDY OF VIBRATION OF DECAHYDROQUINOLINE MOLECULE THROUGH THEORETICAL METHODS
No full textBu çalışmada, Dekahidrokinolin molekülü için Gaussian 03 W programı
kullanılarak molekülün en kararlı olduğu durumdaki geometrik parametreleri
ve titreşim frekansları teorik olarak hesaplandı. Bu titreşim frekanslarının
işaretlemeleri yapılarak frekanslara ait Infrared ve Raman şiddetleri belirlendi.
Bunun için teorik olarak hesaplanan frekanslarla deneysel olarak gözlenen
frekanslar birbirleriyle karşılaştırılarak korelasyon grafikleri çizildi. Bu
grafikler yardımıyla hesaplama metotları arasında karşılaştırma yapıldı. BLYP
ve B3LYP metotları ile yapılan frekans hesaplamaların, HF metodu ile yapılan
hesaplamalardan daha iyi sonuçlar verdiği gözlendi.
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In thıs study, the geometrical and vibratioral frequencies of decahydroquinoline
molecule are theotretically calculated in the most stable condition with the
Gaussian 03 W programme. The geometrical parameters and vibrational
frequencies of the most stable condition was theoretically calculated. Through
the assigment of these frequencies, the Infrared and Raman intensity was
determined. The correlation graphs were drawn by comparing the theoretically
calculated frequencies with the experimental ones. Comparisions among the
calculation methods were made by means of these graphs. It was observed that
the frequency calculations made by the BLYP and B3LYP methods gave beter
results with compared to those made by the HF method
First Measurement of the |t | Dependence of Incoherent J/ψ Photonuclear Production
No full textThe first measurement of the cross section for incoherent photonuclear production of J/ψ vector mesons as a function of the Mandelstam |t| variable is presented. The measurement was carried out with the ALICE detector at midrapidity, |y|<0.8, using ultraperipheral collisions of Pb nuclei at a center-of-mass energy per nucleon pair of sNN=5.02 TeV. This rapidity interval corresponds to a Bjorken-x range (0.3-1.4)×10-3. Cross sections are given in five |t| intervals in the range 0.04<|t|<1 GeV2 and compared to the predictions by different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a |t| dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data
Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
No full textauthor correctio
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