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We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4â meV at 530â eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5â eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.
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Objective: To explore the coexisting mutations in NPM1 mutated elderly patients with acute myeloid leukemia(AML). Methods: The clinical data of 152 elderly adults(aged≥60 years) and 49 young adults(aged 18-45 years) with AML between June 2013 and December 2018 in outpatient and hospitalized patients of Changzhou Second People's Hospital and Wuxi Second People's Hospital were retrospectively analyzed. A total of 51 gene mutations were detected using targeted next-generation sequencing (NGS) and sanger sequencing. The general clinical characteristics, the occurrence of coexistence gene mutations, the correlation between coexistence gene mutations and some clinical parameters, and the initial induction remission rate between elderly and young adult AML patients with NPM1 mutations were analyzed and compared. Results: NPM1 mutations were detected in 46 of 152 elderly AML patients. Thirty eight patients (82.6%) with NPM1 mutations carried other gene mutations at the same time, among whom 8 patients (17.4%) carried NPM1 mutations alone, while 14(30.4%) carried 2, 16 (34.8%) carried 3, and 8 (17.4%) carried ≥ 4 mutations. NPM1 mutations frequently co-occurred with FLT3-ITD15 cases (32.6%) , DNMT3A10 (21.7%) , TET26 (13.4%) and FLT3-TKD5 (10.9%) . Compared with young adults with NPM1 mutations, elderly patients had higher TP53, FLT3-TKD rates, lower incidence of DNMT3A, RAS mutation (all P<0.05) and lower coexistence rate of 4 gene mutations (P=0.002).The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than those in patients with single, double and 3 mutations coexisted in elderly adults AML patients(all P<0.05). With the increase of the amount of mutations, the complete remission(CR) rate decreased gradually after the initial induction. Patients who carried 3 or more mutations showed a lower CR rate than those with single gene mutations (all P<0.05) . Patients who carried>4 genes also showed a significantly lower CR rate than those with double gene mutations (P=0.031). Patients with FLT3-ITD mutations exhibited higher white blood level and lower CR rate than that in nonmutant type group (all P<0.05). The CR rate of patients with DNMT3A mutation was also significantly lower than that with nonmutant type (P=0.033). However, patients with FLT3-TKD mutations showed a higher platelet level than that with nonmutant type (P=0.019). There was no significant difference in CR rate and peripheral blood cell level between TET2 mutated and nonmutant type. Conclusion: NPM1 mutated elderly patients with AML commonly show additional mutations, and the amount and type of coexisting mutations have an influence on the clinical features and CR rate of elderly patients with AML.
Subject(s)
Leukemia, Myeloid, Acute , Nuclear Proteins/genetics , Adolescent , Adult , Humans , Middle Aged , Mutation , Nucleophosmin , Prognosis , Retrospective Studies , Young Adult , fms-Like Tyrosine Kinase 3ABSTRACT
Vertically aligned ZnO/ZnTe core-shell nanowires were grown on a-plane sapphire substrate by using chemical vapor deposition with gold as catalyst for the growth of ZnO core and then followed by growing ZnTe shell using metal-organic chemical vapor deposition (MOCVD). Transmission electron microscope (TEM) and Raman scattering indicate that the core-shell nanostructures have good crystalline quality. Three-dimensional fluorescence images obtained by using laser scanning confocal microscope demonstrate that the nanowires have good optical properties. The core-shell nanowire was then fabricated into single nanowire field effect transistor by standard e-beam photolithography. Electrical measurements reveals that the p-type ZnO/ZnTe FET device has a turn on voltage of -1.65 V and the hole mobility is 13.3 cm2/V s.
Subject(s)
Nanostructures/chemistry , Nanostructures/ultrastructure , Tellurium/chemistry , Transistors, Electronic , Zinc Oxide/chemistry , Crystallization/methods , Electric Conductivity , Equipment Design , Equipment Failure Analysis , Materials Testing , Nanotechnology/instrumentation , Particle Size , Surface PropertiesABSTRACT
The Janus kinase 2 (JAK2) V617F mutation has considerably helped understanding of the molecular pathogenesis of chronic myeloproliferative disorders (MPD), hence this study investigated for the first time the mutational status and relative quantitation of JAK2 V617F mRNA in Chinese patients with chronic MPD. The study cohort comprised 123 chronic MPD patients (35 with polycythaemia vera [PV], 85 with essential thrombocythaemia [ET], three with idiopathic myelofibrosis [IMF]). Blood samples examined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and capillary electrophoresis showed that the prevalence of the JAK2 V617F mutation was 100%, 62.4% and 66.7% in PV, ET and IMF patients, respectively. The proportion of JAK2 V617F mutated mRNA was 89.5% in homozygotes and 57.9% in heterozygotes; 18 PV heterozygous patients showed significantly higher mutated JAK2 mRNA levels than 36 heterozygous ET patients. Six of 93 patients exhibited abnormal karyotypes, but specific chromosomal abnormality was not found. The combination of ARMS-PCR and capillary electrophoresis enables quantitative assay of JAK2 V617F mutation, which helps in chronic MPD diagnosis and estimation of minimal residual disease.
Subject(s)
Asian People/genetics , Janus Kinase 2/analysis , Janus Kinase 2/genetics , Myeloproliferative Disorders/enzymology , Myeloproliferative Disorders/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , Chronic Disease , Cytogenetics , Humans , Janus Kinase 2/metabolism , Middle Aged , Mutation/genetics , Myeloproliferative Disorders/bloodABSTRACT
Objective: To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro. Methods: Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1. Results: BGJ398 effectively inhibited cell proliferation by dose-dependent manners. BGJ398(1.4 µmol/L) induced apoptosis of KG-1 cells by 36.4%, compared with 4.5% in the control group(P<0.001). Treatment with BGJ398 at 1.4 µmol/L led to significant increases in the expression levels of caspase-3, and decreases in the expression of Bcl-2 (P<0.005). In accordance with these results, Western blot analysis further confirmed the increased expression of Bcl-2 protein along with elevated caspase-3 activity. In addition, BGJ398 markedly down-regulated FGFR1OP2-FGFR1 fusion protein, p-AKT and p-S6K expression, but not p-ERK expression. Conclusion: Novel pan-FGFR inhibitor BGJ398 substantially suppressed KG-1 cell growth and induced apoptosis by inhibiting the expression of FGFR1, p-AKT, p-S6K and regulating apoptosis-related proteins.
Subject(s)
Phenylurea Compounds/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Apoptosis , Caspase 3 , Cell Line, Tumor , Cell Proliferation , HumansABSTRACT
Objective: To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group. Methods: The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing. Results: â The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. â¡The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] (P<0.001) , but not for patients with CALR[57 (17-89) y] or MPL mutation[59 (22-71) y] (P>0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level (P<0.05) when compared with patients with CALR mutation or without mutations, or only significantly higher white blood cell count when compared with patients with MPL mutation (P=0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×10(9)/L vs 800 (198-3 730) ×10(9)/L, P<0.001]. â¢Karyotype analysis was conducted in 1 160 patients with MPNs, the rates of karyotype abnormality of patients with and without CALR mutation were 9.8% (8/82) and 7.4% (80/1 078) (P=0.441) respectively; The rates of karyotype abnormality of patients with and without JAK2V617F mutation were 7.7% (75/971) and 6.9% (13/189) (P=0.688) respectively. The incidence of karyotype abnormality of patients with CALR mutation was higher than of with JAK2V617F[9.8% (8/82) vs 7.7% (75/971) ] without statistically significant difference (P=0.512) . The karyotype analysis of 7 cases of JAK2 exon12 mutation and 6 ones with MPL gene mutation revealed normal karyotype. Conclusions: Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter lead to unique clinical phenotype.
Subject(s)
Mutation , Myeloproliferative Disorders , Philadelphia Chromosome , Calreticulin , Exons , Humans , Janus Kinase 2 , Karyotype , Karyotyping , Phenotype , Prevalence , Prognosis , Receptors, ThrombopoietinABSTRACT
An open label study was conducted in the department of neurosurgery, Beijing Tiantan Hospital in China to determine the incidence of postoperative infections following the use of one or two doses of ceftriaxone administered perioperatively. A total of 343 patients, who required neurosurgery and had satisfied the inclusion criteria, was recruited during a 12 month study period. Of these 343 patients, there were 97 and 107 cases of malignant and benign tumours, respectively, 52 cases of aneurysm, 34 cases of arteriovenous malformation, and 53 other cases who underwent neurosurgery for drainage of sub-dural haematoma, relief of cerebral oedema and other indications. A total of 6 (1.75%) cases of postoperative infection was observed, of which 4 were found in the malignant tumour group, and 2 in the arteriovenous malformation group. All six patients were suffering from meningitis. During the 12 month period immediately prior to the present study, when postoperative penicillin and gentamicin was administered twice daily for 5-7 days as regular prophylaxis against infection, the incidence of postoperative infection was 7.2% in the same department managed by the same staff. Results of our present study suggest that one to two doses of ceftriaxone administered perioperatively are effective in reducing the rate of postoperative infections.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Brain/surgery , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic use , Neurosurgery , Postoperative Care , Adult , Blood-Brain Barrier/drug effects , Ceftriaxone/administration & dosage , Female , Humans , Injections, Intravenous , Male , Middle Aged , Staphylococcus/drug effectsABSTRACT
INTRODUCTION: Gene mutations play an important role in acute myeloid leukemia (AML) pathogenesis. Several genes have been identified in AML, such as FLT3, KIT, NPM1, and JAK2. This study investigated the frequency of novel mutations in IDH1 (amino acid R132) and IDH2 (R140 and R172) and analyzed their impact on disease biology and interaction with other mutations in Chinese patients with de novo AML. METHODS: A total of 195 patients were screened for mutations in the IDH1, IDH2, JAK2 V617F, NPM1, FLT3, and KIT genes, using polymerase chain reaction (PCR)-based and direct sequencing assays. RESULTS: IDH mutations occurred at a considerable frequency of 15.89% in Chinese AML cases; IDH2 R140Q was the most frequent genetic alteration and was associated with older age, normal karyotype, and French-American-British classification M2 at diagnosis. There was a strong association of IDH2 mutation with NPM1 mutations and a trend with FLT3-internal-tandem duplication. CONCLUSION: IDH mutations may be a novel genetic marker in cytogenetically normal AML and may cooperate in leukemogenesis.
Subject(s)
Genetic Predisposition to Disease/genetics , Isocitrate Dehydrogenase/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , Nuclear Proteins/genetics , Adolescent , Adult , Aged , Amino Acid Substitution , Asian People/genetics , Base Sequence , China , Chromosome Aberrations , DNA Mutational Analysis , Gene Frequency , Genotype , Humans , Janus Kinase 2/genetics , Leukemia, Myeloid, Acute/ethnology , Middle Aged , Nucleophosmin , Proto-Oncogene Proteins c-kit/genetics , fms-Like Tyrosine Kinase 3/geneticsABSTRACT
Homogenates of growing regions of the pea (Pisum sativum L.) epicotyl contain soluble factors (130,000g supernatant) which alter pea beta-glucan synthetase activity, as assayed using the substrate UDP-glucose and either particulate fractions or tissue slices as source of enzyme. A heat-stable dialyzable component is present which enhances as much as 3-fold the synthesis of alkali-soluble and -insoluble products from millimolar levels of substrate. A heat-labile nondialyzable component is also present which suppresses synthesis. This component dominates (the net effect of total crude extract) when low (mum) levels of substrate are employed. Methylation analysis shows that both components primarily affect the proportion of beta-1,4 rather than beta-1,3 linkages which are synthesized. The enhancing factor increases V(max) of the synthetase system and only activates in the presence of high levels of substrate. The suppressing factor appears to inactivate the synthetase, since losses of product or substrate are not significant during brief incubation with extract, the factor acts progressively with time with a pH optimum, and it destroys activity during preincubation with particles or slices. It co-precipitates with a protease (gelatinase) at between 20% and 40%-saturated (NH(4))(2)SO(4), and it co-fractionates with a major component of total protease on Sephadex gel columns (G-200) with an elution volume corresponding to molecular weight 65,000. The concentrations of these factors are such that they could be natural moderators of synthetase activity in vivo if the two were ever brought in contact, and the inactivator could account for the lability of beta1,4-glucan synthetase which occurs upon tissue homogenization.
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The synthesis and X-ray structural and spectroscopic characterization for LAuC triple bond CAuL x 4CHCl(3) and LAuC triple bond C--C triple bond CAuL x 2CH(2)Cl(2) (1 x 4CHCl(3) and 2 x 2CH(2)Cl(2), respectively; L = PCy(3), tricyclohexylphosphine) are reported. The bridging C(n)(2-) units are structurally characterized as acetylene or diacetylene units, with C triple bond C distances of 1.19(1) and 1.199(8) A for 1 x 4CHCl(3) and 2 x 2CH(2)Cl(2), respectively. An important consequence of bonding to Au(I) for the C(n)(2-) moieties is that the lowest-energy electronic excited states, which are essentially acetylenic (3)(pi pi*) in nature, acquire sufficient allowedness via Au spin-orbit coupling to appear prominently in both electronic absorption and emission spectra. The origin lines for both complexes are well-defined and are observed at 331 and 413 nm for 1 and 2, respectively. Sharp vibronic progressions corresponding to v(C triple bond C) are observed in both emission and absorption spectra. The acetylenic (3)(pi pi) excited state of 2 has a long lifetime (tau(0) = 10.8 mus) in dichloromethane at room temperature and is a powerful reductant (E degrees [Au(2)(+)/Au(2)] < or = -1.85 V vs SSCE).
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The penicillin G acylase gene (pac gene) from Escherichia coli ATCC 9637 has been isolated. It conferred the production of penicillin G acylase upon E. coli HB101 and other enteric bacilli. Restriction enzyme analysis and subcloning studies reveal that the gene is contained within a 2.3 kb HindIII-SmaI DNA fragment. In vitro protein synthesis study suggests a gene product of approximately 90 kDa. By using the genetically engineered bacteria which harbor a novel recombinant plasmid (pGL5) bearing a constitutively expressible pac gene, a 20-fold increased production yield of penicillin G acylase activity was obtained as compared with that produced by the original strain, E. coli ATCC 9637.
Subject(s)
Bacterial Proteins/biosynthesis , Escherichia coli/genetics , Genes, Bacterial , Penicillin Amidase/biosynthesis , Recombinant Fusion Proteins/biosynthesis , Bacterial Proteins/genetics , Cloning, Molecular , DNA, Bacterial/genetics , Enterobacteriaceae/enzymology , Escherichia coli/enzymology , Genetic Vectors , Penicillin Amidase/genetics , Recombinant Fusion Proteins/genetics , Species SpecificityABSTRACT
The airborne fungal spore count was determined daily from 1975 to 1979 at six different stations in the Taipei Area. The count per year was 5656/cm2 in average. More than 75% of the spores could be identified microscopically and classified into 14 genera. The spore season was found from May to October in the Taipei Area. The count per month during this period reached 632/cm2. Only 311/cm2/month was found from November to April. Data collected from the six stations differed slghtly, the count was low in the city (4853/cm2/year) and high in the suburbs (8801/cm2/year). The counts were very close in the first four years (4325-4677/cm2/year), but dropped dramatically in the fifth year (2017/cm2/year). The spore count was influenced by temperature, humidity, rainfall as well as wind velocity. Among the 14 genera found by the slide method, six could not be isolated by the plate culture method. Other 24 genera isolated with plates did not appear on the slides.