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BACKGROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1 inhibitors at five institutes. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mb of sequenced DNA and reported as mutations/Mb. Potential biomarkers of response and time to progression were analyzed by univariate and multivariate analyses. Once TMB was confirmed as a predictive biomarker, a larger dataset of 18 140 unique CRC patients was analyzed to define the relevance of the identified TMB cut-point. RESULTS: A total of 22 patients were treated with PD-1/L1 inhibitors including 19 with pembrolizumab monotherapy. Among tested variables, TMB showed the strongest association with objective response (OR; P < 0.001) and PFS, by univariate (P < 0.001) and multivariate analysis (P < 0.01). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37 and 41 mutations/Mb. All 13 TMBhigh cases responded, while 6/9 TMBlow cases had progressive disease. The median PFS for TMBhigh has not been reached (median follow-up >18 months) while the median PFS for TMBlow was 2 months. A TMB of 37.4 mutations/Mb in a large MSI-H mCRC population (821/18, 140 cases; 4.5%) evaluated by NGS corresponded to the 35th percentile cut-point. CONCLUSIONS: TMB appears to be an important independent biomarker within MSI-H mCRC to stratify patients for likelihood of response to ICPIs. If validated in prospective studies, TMB may play an important role in guiding the sequencing and/or combinations of ICPIs in MSI-H mCRC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Mutação , Neoplasias Peritoneais/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/genética , Metástase Linfática , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/genética , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Fully-hydrogenated germanene, named germanane, represents a new nanostructured material for a variety of potential applications, such as electronics and optoelectronics. However, a critical requirement for developing practical and reliable electronic devices based on germanane consists of achieving a flexibly controllable charge carrier and doping level. Different to the conventional doping methods such as ion implantation and diffusion, by first-principles calculations we demonstrate that tetracyanobenzene (TCNB) molecular adsorption could introduce effective p-type doping in germanane due to the combination of germanane with electroactive acceptor molecule TCNB. The corresponding energy difference between the empty band minimum of the dopant and the valence band maximum for electron excitation is 0.173 eV. More importantly, this nondestructive p-type doping could be linearly tuned under an external E-field. Analysis of charge transfer by means of the equivalent capacitor model and the shift of energy levels in the superstructure of germanane/TCNB further reveals that the superposition of the external E-field and molecular adsorption-induced internal E-field plays a key role in the charge transfer between TCNB and germanane, especially in achieving a controllable p-type molecular doping level in germanane. Such convenient and flexible E-field-engineering of p-type molecular doping in germanane would be very helpful for potential applications of germanane-based electronic and optoelectronic devices in the future.
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Germanane, fully hydrogenated germanene, has recently attracted great interest, both theoretical and experimental. In this paper we thoroughly study strain-tunable n/p-type doping in germanane by adsorption of tetrathiafulvalene (TTF)/tetracyanoquinodimethane (TCNQ) molecules through first-principles calculations. The results show that both TTF and TCNQ molecules can non-covalently functionalize the electronic properties of germanane. Not surprisingly, TTF molecular adsorption induces n-type doping in germanane because the TTF molecule is a typical electron donor. Moreover, a linearly tunable band gap of germanane and differing n-type doping strengths can be realized by a biaxial strain ranging from -3% to 3%. Analysis indicates that tensile strain would promote the doping effect whereas compressive strain would inhibit it. Comparatively, TCNQ molecular adsorption induces a germanane/TCNQ system which exhibits metallic characteristics. Surprisingly, however, under a tensile strain of 2.5%, a strong p-type doping effect is achieved in germanene/TCNQ. In particular, with increasing tensile strain over the range 2.5%-3%, the strain-tunable p-type doping effect decreases gradually. Such a multiple effect of molecular adsorption and strain on the electronic properties of germanane could be helpful for potential future applications of germanane-based electron devices.
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Objective: To investigate the clinical outcomes of Pre-descement membrane endothelial keratoplasty (PDEK) for treatment of patients with corneal endothelial decompensation. Methods: Retrospective study of case series. The cases of 20 patients (20 eyes) who were diagnosed with corneal endothelial decompensation induced by various original diseases and received PDEK during July 2016 and December 2016 at Zhongshan Ophthalmic Center have been analyzed. The participants included 8 males and 12 females with an average age of (59.3±11.8) years. All 20 patients received PDEK operation, the Dua's layer, descement membrane and endothelium of donor tissue were separated from the underlying stroma with the application of big-bubble technique, and donor discs with diameters of 7.75 or 8.00 mm were harvested with scissors. The donor discs were stained with 0.06% trypan blue and loaded on inserters which were then gently inserted into the anterior chamber of the recipient. When the rolled inserted graft was unfolded, air was carefully injected into the anterior chamber underneath the graft so that the graft can attach to the stroma of the recipient. Post-operation follow-ups of over 6 months have been conducted for all patients, the best spectacle corrected visual acuity (BSCVA), the position of donor disc, corneal thickness and corneal endothelial cell density (ECD) were documented. The pre-operation and post-operation (6 months postoperatively) corneal thickness data of the patients were analyzed with paired sample t test. Results: The success rate of preparing PDMEK donor disc with big-bubble technique is 90% (18/20). Eighteen patients (90%) received PDMEK surgery successfully. Anterior segment optical coherence tomography (AS-OCT) results indicated that sixteen donor discs (16/18) were well attached to the back surface of the recipient stroma, and that two discs (2/18) dislocated at 6 days after surgery. At 6 months post-operatively, the corneas of 14 patients (14/18) turned clear with their BSCVA ranging 0.4 to 1.0, and the ECD was (1 389.3±373.2) cells/mm(2) for the patients with clear corneas. At 6 months post-operatively, the average corneal thickness of the patients reduced to (605±45) µm from the preoperative level of (655±56) µm, and the differences are of statistical significance (t=2.137, P=0.032). Conclusions: Application of big-bubble technique could effectively secure the success rate of PDEK disc preparation and control the loss of donated corneas. PDEK disc can be easily handled and unrolled in the anterior chamber, which could improve the postoperative clinical outcomes. (Chin J Ophthalmol, 2018, 54: 105-110).
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Doenças da Córnea , Transplante de Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Endotélio Corneano , Idoso , Doenças da Córnea/cirurgia , Lâmina Limitante Posterior , Endotélio Corneano/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de TecidosRESUMO
Objective: To evaluate the clinical outcomes of Descemet's membrane endothelial keratoplasty (DMEK) for treatment of patients with corneal endothelial decompensation in China. Methods: Interventional case series. Ten patients (10 eyes) with the diagnosis of corneal endothelial decompensation received DMEK during July 2016 and September 2016 in Zhongshan Ophthalmic Center. Descemet's membrane of the donor tissue was carefully stripped from the underlying stroma manually and cut with a 7.75- or 8.0-mm-diameter donor punch. After stained with 0.06% typan blue, the donor disc loaded on an inserter was gently inserted into the anterior chamber of the recipient. When the rolled graft was unfolded, air was carefully injected into the anterior chamber underneath the graft, so that the graft attached to the stroma of the recipient. All patients were followed up for 3-6 months. The best spectacle corrected visual acuity, the status of donor disc, corneal thickness and corneal endothelial cell density were documented and analyzed. Results: At 1 day after surgery, 1 donor disc presented a rolled edge, and repeated DMEK surgery was performed for this patient. The remaining 9 donor discs presented in place well. At 1 month after surgery, 7 donor discs were found to well attach to the back surface of the recipient stroma with normal corneal posterior surface using anterior segment optical coherence tomography. The average corneal thickness reduced to (620±67) µm from preoperative (680±78.3) µm (t=2.677, P=0.025). At 3 months after surgery, 6 patients achieved clear corneas with best spectacle corrected visual acuity ranging from 0.4 to 0.8. The endothelial cell density was 1 342.3±436.5 (872 to 1 933) cells/mm(2) in the patients with clear corneas. The average corneal thickness reduced to (612±70) µm (t=2.971, P=0.016). Conclusions: DMEK could improve visual acuity for corneal endothelial decompensation, but there were more technical difficulties in Chinese eyes. (Chin J Ophthalmol, 2017, 53: 534-539).
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Doenças da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , China , Doenças da Córnea/cirurgia , Lâmina Limitante Posterior , Endotélio Corneano , HumanosRESUMO
OBJECTIVE: To evaluate the effect of thiazovivin, a novel ROCK inhibitor, on the morphology and function of human corneal endothelial cells(HCECs). METHODS: The primary HCECs were identified by light microscopy and immunofluorescence staining of neuron-specific enolase. To screen the optimal concentration and action time of thiazovivin for maintaining the morphology and function of primary HCECs, Na (+)/K (+)-ATPase and N-cadherin were chosen as indicators, and the morphology and function of HCECs in various concentrations(0 µmol/L, 2 µmol/L, 4 µmol/L, and 6 µmol/L)for different durations(24 h and 48 h)were examined by immunofluorescence experiments. The effect of thiazovivin on the expression of ROCK was investigated by immunofluorescence and Western blot. RESULTS: The primary HCECs cultured were hexagonal, closely packed, homogeneously and obviously stained by neuron-specific enolase. The immunofluorescence staining of Na(+)/K(+)-ATPase showed that when the primary HCECs cultured with various concentrations of thiazovivin(0, 2, 4, 6 µmol/L)for 24 h, the fluorescence were obvious, and the average absorbance values(A)were 1.27±0.08, 3.72±0.17, 21.07±4.67, 3.69±0.34, respectively. And the immunofluorescence staining of N-cadherin revealed that when the primary HCECs treated with 4 µmol/L thiazovivin for 24 h, the cell boundary was clear and the structure of the cells was intact. While the treating time of thiazovivin(4 µmol/L)on HCECs extended to 48 h, the immunofluorescence staining of Na(+)/K(+)-ATPase and N-cadherin showed that compared to HCECs treated with thiazovivin(4 µmol/L)for 24 h, the fluorescence intensity did not change significantly, but the cells arranged slightly untidy. In addition, the immunofluorescence staining of ROCK was weakened and the expression of ROCK was reduced by thiazovivin. Thiazovivin was effective for protecting the morphology and function of HCECs. An optimal improvement in the morphology, connection and function of HCECs was found when the primary HCECs were cultured with 4 µmol/L thiazovivin for 24 h. Moreover, the expression of ROCK protein could be significantly inhibited by thiazovivin. (Chin J Ophthalmol, 2016, 52: 686-692).
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Endotélio Corneano/citologia , Células Epiteliais/efeitos dos fármacos , Pirimidinas/farmacologia , Tiazóis/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Caderinas/análise , Células Cultivadas , Endotélio Corneano/metabolismo , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Fluorescência , Humanos , Fosfopiruvato Hidratase , Pirimidinas/administração & dosagem , ATPase Trocadora de Sódio-Potássio/análise , Tiazóis/administração & dosagem , Quinases Associadas a rho/metabolismoRESUMO
UNLABELLED: Fibroblast growth factor 23(FGF23) is a bone-derived hormone which regulates mineral homeostasis but may also have a role in cardiovascular disease. Here, we found that higher plasma FGF23 was independently associated with decreased heart rate variability in stage 5 CKD patients and parathyroidectomy may reverse these abnormal indicators. INTRODUCTION: Lower heart rate variability (HRV) in patients with chronic kidney disease (CKD) compared with healthy controls is associated with increased risk of cardiovascular disease (CVD). Higher levels of plasma FGF23 also predict higher risk of CVD. Here, we aimed to evaluate the relationship between plasma FGF23 levels and HRV in patients with stage 5 CKD and to investigate longitudinal changes of them together with the correlation between their changes in two severe secondary hyperparathyroidism (SHPT) subgroups with successful parathyroidectomy (PTX) and persistent SHPT. METHODS: This cross-sectional study included 100 stage 5 CKD patients, 78 controls, and a prospective study in two PTX subgroups classified as successful PTX (n = 24) and persistent SHPT (n = 4) follow-up. Blood examination and 24-h Holter monitoring for HRV were measured. RESULTS: Most HRV indices were lower in stage 5 CKD patients than in healthy controls, and plasma FGF23 levels were higher. In multivariate stepwise regression models, levels of plasma FGF23 and serum parathyroid hormone (PTH) were correlated with HRV. The successful PTX subgroup had significant improvements over baseline in HRV indices. Persistent SHPT subgroup had numerically similar changes in HRV indices. However, plasma FGF23 levels decreased in both subgroups. CONCLUSIONS: Plasma FGF23 levels were higher in CKD patients than in controls, much higher in patients with severe SHPT. FGF23 was independently associated with decreased HRV in stage 5 CKD. Successful PTX may reverse these abnormal indicators and contribute to decreases in the risk of cardiovascular disease.
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Fatores de Crescimento de Fibroblastos/sangue , Frequência Cardíaca/fisiologia , Insuficiência Renal Crônica/sangue , Adulto , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Estudos Transversais , Eletrocardiografia Ambulatorial/métodos , Feminino , Fator de Crescimento de Fibroblastos 23 , Seguimentos , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Masculino , Pessoa de Meia-Idade , Paratireoidectomia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologiaRESUMO
Marigold (Tagetes erecta) is an important commercial crop and 200 ha are planted every year in the Beijing district of China. A leaf spot disease of T. erecta was observed during 2012 and 2013 in the Beijing district. The disease was widespread, with 60 to 75% of the fields affected. Leaves of the affected plants had small, brown, necrotic spots on most of the foliage. Yield losses of flowers of up to 20 to 30% were reported. The spots gradually enlarged, becoming irregular in shape, or remained circular, and with concentric rings or zones. In the later stages of infection, the spots coalesced, and the leaves withered, dried, and fell from the plants (4). A fungus was consistently isolated on potato dextrose agar (PDA) from the infected leaves of T. erecta. After 6 days of incubation at 26°C and a 12-h photoperiod, the fungus produced colonies that were flat, with a rough upper surface (2). The conidiophores were short. Conidia varied from 18 × 6 to 47 × 15 µm and were medium to dark brown or olive-brown in color, short beaked, borne in long chains, oval and bean shaped, with 1 to 5 transverse septa and 0 to 2 longitudinal septa. The rDNA of the internal transcribed spacer regions 1 and 2 and the 5.8S gene in seven isolates were amplified using primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3'). The nucleotide sequence was the same as isolate No. 7, which was deposited in GenBank (Accession No. KF307207). A BLAST search showed 97% identity with the strain Alternaria alternata GNU-F10 (KC752593). Seven isolates were also confirmed as A. alternata by PCR identification performed by specific primers (C_for/C_rev) of A. alternata (1). Seven isolates were grown on PDA for 2 weeks and the conidia harvested. A 5-µl drop of spore suspension (1 × 105 spores/ml) was placed on each leaflet of 140 detached, surface-sterilized T. erecta leaves. Twenty leaves were inoculated with sterile distilled water as a control. The leaves were incubated in a growth chamber at 80 to 90% relative humidity, 50 to 60 klx/m2 light intensity, and a 12-h photoperiod. After 6 days, leaf spots similar to the original developed at inoculation sites for all isolates and A. alternata was consistently re-isolated. The control leaves remained symptomless. The pathogenicity test was performed three times. Leaf spot of T. erecta caused by Alternaria spp. is well known in Asian countries such as Japan (3). To our knowledge, this is the first report of A. alternata on T. erecta in the Beijing district of China. References: (1) T. Gat. Plant Dis. 96:1513, 2012. (2) E. Mirkova. J. Phytopathol. 151:323, 2003. (3) K. Tomioka. J. Gen. Plant Pathol. 66:294, 2000. (4) T. Y. Zhang. Page 284 in: Flora Fungorum Sinicorum, Volume 16: Alternaria. Science Press, Beijing, 2003.
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Ginger (Zingiber officinale Roscoe) is an important commercial crop that is planted in 60,000 to 70,000 ha every year in Shandong Province, China. In 2010, rotted rhizomes of cultivar Laiwu Big Ginger were reported on 20 ha in Anqiu, Shandong Province, and yield losses of up to 70% were reported. The aboveground symptoms were the water-conducting portion of symptomatic rhizomes was discolored brown and had a black dry rot of the cortex tissues (3). Thirty symptomatic rhizomes were sampled from six fields in six farms. Komada's method (1) was used to isolate the pathogen. Ten pieces from each rhizome were washed with sterile distilled water and plated on Komada selective medium at 25°C. White fungal colonies turned orchid after 7 days of incubation. Two types of asexual spores were associated with the colonies: microconidia and macroconidia. The microconidia were the most abundantly produced spores and were oval, elliptical or kidney shaped, and produced on aerial mycelia. Macroconidia had three to five cells and gradually pointed or curved edges, varied in size from 3 to 5 × 19 to 36 µm. The rDNA of the internal transcribed spacer regions 1 and 2 and the 5.8S gene in five isolates were amplified using primers ITS1 and ITS4, and the nucleotide sequence was the same as isolate no. 3, which was deposited in GenBank (Accession No. KC594035). A BLAST search showed 99% identity with the strain Z9 of Fusarium oxysporum (EF611088). Pathogenicity tests of five isolates were carried out in a greenhouse and the pathogenicity test of isolate no. 3 was selected for the method description. Ten 1-month-old ginger plants (cv. Laiwu Big Ginger) were grown in plastic pots (diameter 20 cm) with sandy soil and inoculated. Ten plants were used as untreated controls. Isolate no. 3 was grown on casein hydrolysate medium (4) for 72 h and the spores were harvested in sterile distilled water. Aqueous spore suspensions of isolate no. 3 were adjusted with deionized water to 1 × 108 CFU/ml as the inoculum. The prepared inoculum was injected with a syringe into the soil around the rhizome of ginger plants. Inoculated plants were placed in the greenhouse at 24 to 26°C and assessed for rhizome rot on the 14th day after inoculation. Disease severity was recorded based on a scale in which - = no symptoms; 1 = small lesions on seedlings, no rot; 2 = seedling rot; and 3 = plant dead. Similar rhizome rot symptoms were observed after inoculation. The inoculated isolate was re-isolated from diseased rhizomes, confirming its pathogenicity. To our knowledge, this is the first report of rhizome rot of ginger caused by F. oxysporum in China. Rhizome rot of ginger caused by Fusarium spp. is well known in Asian countries such as India (2). References: (1) H. Komada. Rev. Plant Prot. Res. 8:114, 1975. (2) V. Shanmugam et al. Biol Control. 66:1, 2013. (3) E. E. Trujillo. Diseases of Ginger (Zingiber officinale) in Hawaii, Circular 62, Hawaii Agricultural Experiment Station, University of Hawaii, December, 1964. (4) G. E. Wessman. Appl. Microbiol. 13:426, 1965.
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Ginger (Zingiber officinale Roscoe) is an important commercial crop planted on more than 13,000 ha annually in Anqiu city, Shandong Province, China. From 2010 to 2011, the incidence of Pythium soft rot disease on cv. Laiwu Big Ginger reached 40 to 75% in Anqiu and yield losses of up to 60% were observed. The disease symptoms included brown spots on ginger rhizomes followed by soft rot, stems and leaves above ground becoming withered and yellow, and water soaking on the collar region. The soft rot did not produce offensive odors, which is different from bacterial rots (2). Forty symptomatic rhizomes were sampled from eight farms. Martin's method (1) was used to isolate the pathogen. Ten pieces from each rhizome were washed with sterile distilled water for 30 s and plated on Martin's selective medium at 26°C in a chamber without light. Colonies grew with cottony aerial mycelium. Main hyphae were 5.7 to 9.6 µm wide. Globose sporangia consisting of terminal complexes of swollen hyphal branches were 11.4 to 18.3 µm wide. The average diameter of zoospores was 9.2 µm. The oogonia were globose and smooth, with a diameter of 21 to 33 µm. The sequences of the rRNA gene internal transcribed spacer (ITS) regions 1 and 2 and the 5.8S gene of five isolates were amplified using primers ITS1 and ITS4 (4), and the nucleotide sequence was the same as isolate No. 2, which was deposited in GenBank (Accession No. KC594034). A BLAST search showed 99% identity with Pythium aphanidermatum strain 11-R-8 (Accession No. JQ898455.1). Pathogenicity tests of five isolates were carried out in a greenhouse. Sixty plants (cv. Laiwu Big Ginger) were grown for 30 days in plastic pots (diameter 20 cm) in sandy soil (pH 5.48) and inoculated. Ten plants were used as untreated controls. Five isolates were grown on Martin's liquid medium for 72 h and the spores were harvested in sterile distilled water. Aqueous spore suspensions of the five isolates were adjusted with deionized water to 1 × 108 CFU/ml and injected with a syringe into the soil around the rhizome of the plants. Plants were then placed in the greenhouse at 24 to 26°C and assessed for rhizome rot on the 14th day after inoculation. The inoculated isolates were recovered from the diseased rhizomes, confirming their pathogenicity. To our knowledge, this is the first report of ginger Pythium soft rot caused by P. aphanidermatum in China. Ginger Pythium soft rot caused by P. myriotylum is reported in Taiwan (3). References: (1) F. N. Martin. Page 39 in: The Genus Pythium. American Phytopathological Society, St. Paul, MN, 1992. (2) E. E. Trujillo. Diseases of Ginger (Zingiber officinale) in Hawaii, Circular 62, Hawaii Agricultural Experiment Station, University of Hawaii, December 1964. (3) P. H. Wang. Lett. Appl. Microbiol. 36:116, 2003. (4) T. J. White. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.
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The platinum copper alloy nanocrystals (NCs) have generated much interest because of their wide applications in fuel cells due primarily to their good catalytic performance and to decreasing sensitivity toward CO poisoning. The exact atomic-level morphology of platinum copper alloy NCs is still not clear in the literature, and research to understanding the poisoning mechanism is still insufficient to date. In this article, we report on density functional calculations of small PtnCu clusters and their adsorption of a CO molecule that provide evidence for degrading adsorption of the CO molecule compared to pure platinum clusters. The lowest-energy geometries of PtnCu and PtnCuCO clusters have been identified. The CO molecule prefers to be adsorbed on the nearest platinum atom by the C-end-on mode, forming linear or quasi-linear O-C-Pt structures. The adsorption energies indicate that the introduction of a copper atom decreases the adsorption ability of the CO molecule. The local density of states of the representative clusters is used to characterize the adsorption properties of the CO molecule on the PtnCu clusters. Results from our theoretical calculations can be helpful for understanding the poisoning mechanism of the CO molecule on the platinum copper alloy NCs.
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Laser diodes (LDs) are used in a wide range of applications, such as optical wireless communications and LIDAR. To meet the demanding requirements of LDs for high accuracy and stability of the injection current, a high-precision, high stability LD driver with overvoltage protection is proposed. A novel structure based on enhanced Howland current source is described: composite topology enhanced Howland current source (CTEHCS), which has the advantages of high precision, high stability, and extensive regulation range. A 20-bit DAC and high-precision reference source are used to form a front-stage DAC circuit for precise and stable voltage reference. A closed-loop feedback calibration loop is applied to eliminate significantly the absolute errors and auxiliary calibrating of the effect of power operational amplifier on the temperature rise of critical devices. An innovative overvoltage protection circuit is designed for the load side of the CTEHCS, and the protection range can be flexibly set to 4/5/6 V to avoid damage to loads such as LDs. The noise performance, accuracy and stability, modulation bandwidth, nonlinear error, overvoltage protection performance, and turn-on and turn-off time of the experimental prototype are described in detail.
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Structural and electronic properties of the λ-MnO(2)(001) surface are investigated applying density functional theory approach. The calculations show that all Mn ions at unreconstructed smooth surface preserve the +4 oxidation state observed in the bulk. Upon the λ-MnO(2)(001) reconstruction, one fourth of Mn ions at the surface undergo a change of the oxidation state from +4 to +3, although the reconstruction does not change the Mn coordination number with oxygen. This is accompanied with the filling of initially empty 3d(z(2) ) states localized on cations with one electron denoted by two neighboring O atoms. Although the reconstruction leads to an energy gain of 0.04 eV per surface unit cell, it is not a spontaneous process since it proceeds with an activation energy of 0.12 eV.
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We have investigated the contribution of specific TATA-binding protein (TBP)-TATA interactions to the promoter activity of a constitutively expressed silkworm tRNA(C)(Ala) gene and have also asked whether the lack of similar interactions accounts for the low promoter activity of a silk gland-specific tRNA(SG)(Ala) gene. We compared TBP binding, TFIIIB-promoter complex stability (measured by heparin resistance), and in vitro transcriptional activity in a series of mutant tRNA(C)(Ala) promoters and found that specific TBP-TATA contacts are important for TFIIIB-promoter interaction and for transcriptional activity. Although the wild-type tRNA(C)(Ala) promoter contains two functional TBP binding sequences that overlap, the tRNA(SG)(Ala) promoter lacks any TBP binding site in the corresponding region. This feature appears to account for the inefficiency of the tRNA(SG)(Ala) promoter since provision of either of the wild-type TATA sequences derived from the tRNA(C)(Ala) promoter confers robust transcriptional activity. Transcriptional impairment of the wild-type tRNA(SG)(Ala) gene is not due to reduced incorporation of TBP into transcription complexes since both the tRNA(C)(Ala) and tRNA(SG)(Ala) promoters form transcription complexes that contain the same amount of TBP. Thus, the deleterious consequences of the lack of appropriate TBP-TATA contacts in the tRNA(SG)(Ala) promoter must come from failure to incorporate some other essential transcription factor(s) or to stabilize the complete complex in an active conformation.
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Bombyx/genética , Bombyx/metabolismo , Proteínas de Ligação a DNA/metabolismo , RNA de Transferência de Alanina/genética , TATA Box , Fatores de Transcrição/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , DNA/genética , DNA/metabolismo , Genes de Insetos , Modelos Biológicos , Regiões Promotoras Genéticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteína de Ligação a TATA-Box , Fator de Transcrição TFIIIB , Transcrição GênicaRESUMO
The major pathobiological mechanisms of IR injury include excitotoxicity, oxidative stress, and inflammation. TF3, a major constituent of black tea, possesses biological functions such as anti-oxidative and anti-inflammatory activities. The purpose of this study was to verify the neuronal protective potential of TF3 and its mechanisms against cerebral IR injury in rats. TF3 administration (10 and 20 mg.kg-1) ameliorated the infarct volume. TF3 also decreased the content of MDA and NO. TF3 significantly increased the activity of SOD and GSH-Px, which were reduced by IR injury. Administration of TF3 decreased mRNA and protein expression of COX-2 and iNOS. DNA binding and Western blotting revealed an increase in NF-kappaB activation and IkappaB depletion in IR brain tissue. Pretreatment with TF3 markedly inhibited IRinduced increase in nuclear localization of NF-kappaB, and preserved IkappaB in the cytoplasm. The results show that TF3 exerts protective effects against cerebral IR injury by reducing oxidative stress and modulating the NF-kappaB activation.
Assuntos
Biflavonoides/farmacologia , Isquemia Encefálica/metabolismo , Catequina/farmacologia , Ácido Gálico/análogos & derivados , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Animais , Encéfalo/enzimologia , Encéfalo/patologia , Isquemia Encefálica/enzimologia , Extratos Celulares , Infarto Cerebral/enzimologia , Infarto Cerebral/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Ácido Gálico/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Proteínas I-kappa B/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Inibidor de NF-kappaB alfa , Doenças do Sistema Nervoso/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Traumatismo por Reperfusão/enzimologia , Superóxido Dismutase/metabolismoRESUMO
The Water Resources Agency (WRA), Ministry of Economic Affairs (MOEA) has predicted that the annual water demand in Taiwan will reach approximately 20 billion m3 by 2021. However, the present water supply is only 18 billion m3 per year. This means that an additional 2 billion m3 have to be developed in the next 17 years. The reuse of treated wastewater effluent from municipal wastewater treatment plants could be one target for the development of new water resources. The responsible government departments already have plans to construct public sewerage systems in order to improve the quality of life of the populace and protect the environment. The treated wastewater effluent from such municipal wastewater treatment plants could be a very stable and readily available secondary type of water resource, different from the traditional types of water resources. The major areas where reclaimed municipal wastewater can be used to replace traditional fresh water resources include agricultural and landscape irrigation, street cleaning, toilet flushing, secondary industrial reuse and environmental uses. However, necessary wastewater reclamation and reuse systems have not yet been established. The requirements for their establishment include water reuse guidelines and criteria, the elimination of health risks ensuring safe use, the determination of the wastewater treatment level appropriate for the reuse category, as well as the development and application of management systems reuse. An integrated system for water reuse would be of great benefit to us all by providing more efficient ways to utilise the water resources.
Assuntos
Conservação dos Recursos Naturais/métodos , Eliminação de Resíduos Líquidos , Purificação da Água/métodos , Abastecimento de Água , Conservação dos Recursos Naturais/economia , Conservação dos Recursos Naturais/estatística & dados numéricos , TaiwanRESUMO
Four experiments of coagulation and flocculation were conducted to investigate the characteristics of colloidal silica removal in a high-tech industrial wastewater treatment plant for reclamation and reuse of the effluent. Experimental results illustrated that poly-aluminium chloride (PACl) showed higher performances on colloidal silica removal than alum. Interestingly, the two coagulants demonstrated the same capacity on silica removal. The specific silica removal capacity was approximately 0.135 mg SiO2/mg Al2O3 when the dosage of coagulants was in the range 30-150 mg/L Al2O3. In addition, the silica was reduced significantly at the condition of pH above 8. Experimental data implied that precipitation of aluminium flocs was the major mechanism for colloid silica removal in PACl and alum coagulation, besides, charge adsorption was also important for improving removal efficiency. Moreover, the addition of polyacrylic acid (PAA) as a flocculant could slightly advance silica removal in the PACl coagulation. The combined PACl/PAA/flocs coagulation was effective for the removal of colloidal silica, soluble COD, and turbidity and also suitable as a pretreatment unit in wastewater reclamation and reuse processes.
Assuntos
Resíduos Industriais , Dióxido de Silício/isolamento & purificação , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/isolamento & purificação , Compostos de Alúmen/química , Cloreto de Alumínio , Compostos de Alumínio/química , Precipitação Química , Cloretos/química , Concentração de Íons de Hidrogênio , Purificação da Água/métodosRESUMO
By means of DEAE-Sephadex A-50 column chromatography, Trimeresurus gramineus venom was separated into 12 fractions. Fraction 8 had marked anticoagulant action in the tests of whole blood clotting time, calcium clotting time and plasma prothrombin time. Fraction 8 was rechromatographed on Sephadex G-100, then on DEAE-Sephadex A-50 again, and finally on Sephadex G-100, and a single peak was obtained. The patterns of microzone and disc electrophoresis also showed a single band. A single symmetrical boundary with 1.70 Svedberg units was obtained by ultracentrifugation. The estimated molecular weight was 19 500. The isoelectric point was pH 4.5. Chemical analysis showed that the anticoagulant principle was a glycoprotein and that it was thermolabile. The anticoagulant activity of this purified principle was 3.5 times higher than that of the crude venom. Fraction 5 potentiated its anticoagulant activity to 10 times higher than that of the crude venom. This principle did not possess caseinolytic, tosyl-L-arginine methyl ester esterase, phospholipase A, phosphodiesterase, alkaline phosphomonoesterase, fibrinolytic, hemorrhagic or local irritating activities. The purified anticoagulant principle did not destroy fibrinogen, induce fibrinolysis, inactivate thrombin nor interfere with the interaction between thrombin and fibrinogen. However, a marked inhibition of prothrombin activation was caused by the anticoagulant principle. The inhibition of prothrombin activation was not due to the destruction of prothrombin or its activation factors, but due to an interference in the interaction between prothrombin and its activation factors because of the reversible binding of these factors with the anticoagulant principle of the venom.
Assuntos
Anticoagulantes/farmacologia , Venenos de Serpentes/análise , Peçonhas/análise , Aminoácidos/análise , Animais , Anticoagulantes/isolamento & purificação , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Cromatografia em Gel , Fibrinogênio/metabolismo , Fibrinólise/efeitos dos fármacos , Dose Letal Mediana , Camundongos , Peso Molecular , Tempo de Protrombina , Temperatura , Trombina/metabolismo , Tromboplastina/metabolismoRESUMO
By means of DEAE-Sephadex A-50 Column chromatography, Trimeresurus gramineus venom was separated into twelve fractions. The fibrinogenolytic activities were distributed in Fractions 1 and 10. These enzymes were further purified by gel filtration and were homogeneous as judged by cellulose acetate membrane, sodium dodecyl sulfate polyacrylamide gel electrophoresis and ultracentrifugal analysis. Both of them were single peptide chains. The sedimentation constants of alpha- (Fraction 1) and beta-fibrinogenases (Fraction 10) were 2.20 and 3.60, respectively. The molecular weights of alpha- and beta-fibrinogenases were 23 500 and 25 000 respectively. The contents of proline and glycine were higher in beta-fibrinogenase than in alpha-fibrinogenase. The isoelectric points of alpha-fibrinogenase and beta-fibrinogenase were pH greater than 10 and 4.5, respectively. The optimal pH of alpha-fibrinogenase was approx. 7.4 and that of beta-fibrinogenase was approx. 9.0. The activity of alpha-fibrinogenase was completely destroyed after 30 min at 60 degrees C, pH 5.4, 7.4 and 9.0, while that of beta-fibrinogenase was much less affected by the same treatment. The specific fibrinogenolytic activity alpha-fibrinogenase was 31 mg fibrinogen/min per mg protein, while that of beta-fibrinogenase was 9 mg fibrinogen/min per mg protein. alpha-Fibrinogenase cleaved specifically the alpha(A) chain of monomeric fibrinogen without cleaving the beta(B) chain and gamma-chain. beta-fibrinogenase preferentially cleaved the beta(B) chain, and the alpha(A) chain was also partially cleaved by beta-fibrinogenase, if the incubation time was prolonged. Both enzymes showed proteolytic activities toward fibrinogen, fibrin and casein, but were devoid of phospholipase A, alkaline phosphomonoesterase and phosphodiesterase activities found in the crude venom. The tosyl-L-arginine methylester esterase activity of beta-fibrinogenase was about 14 times that of crude venom, while alpha-fibrinogenase was completely devoid of this activity. The fibrinogenolytic activity of alpha-fibrinogenase was markedly inhibited by EDTA and cysteine, while that of beta-fibrinogenase was inhibited markedly by phenylmethanesulfonylfluoride. alpha- and beta-fibrinogenases exert their fibrinogenolytic activity by a direct action on fibrinogen or fibrin without activation of plasminogen.
Assuntos
Endopeptidases/isolamento & purificação , Venenos de Serpentes/metabolismo , Serpentes/metabolismo , Animais , Venenos de Crotalídeos/metabolismo , Cisteína/farmacologia , Ácido Edético/farmacologia , Endopeptidases/metabolismo , Fibrinogênio , Temperatura Alta , Concentração de Íons de Hidrogênio , Peso MolecularRESUMO
By means of CM-Sephadex C-50 column chromatography, Trimeresurus mucrosquamatus venom was separated into twenty fractions. The fibrinogenolytic activity was concentrated in Fractions 8, 10, 12, 13 and 14. Fractions 8 adn 13 had the highest ratio of fibrinogenolytic and caseinolytic activities. Fraction 8 possessed tosyl-L-arginine methyl esterase activity, while the others did not. The caseinolytic activities of Fractions 10, 12, 13 and 14 were inhibited by EDTA, while that of Fraction 8 was not. Fractions 8 and 13 were further purified by CM-cellulose and gel filtration and were homogeneous as judged by electrophoresis on polyacrylamide gel and cellulose acetate membrane. The molecular weights of the purified Fractions 8 and 13 were 26 000 and 22 400, respectively. Both were single peptide chains. The specific fibrinogenolytic activity of Fraction 8 was 17 mg fibrinogen/min/mg protein, while that of Fraction 13was 100 mg fibrinogen/min/mg protein. Fraction 13 digested specifically the alpha(A) chain of monomeric fibrinogen to yield two cleavage products. Fraction 8 digested the beta(B) chain first to yield four cleavage products. When the incubation time was prolonged, the alpha(A) chain was also partially digested by Fraction 8 to yield two cleavage products.