Some important optoelectronic properties of naphtho[2,1-b:6,5-b′]difuran (DPNDF) and its two derivatives have been limelighted by applying the density functional theory (DFT). Due to their low cost, high stability and earth abundance, the DPNDF and its derivatives are considered as potential organic semiconductor materials for their optoelectronics applications. Highly proficient derivatives are obtained systematically by attaching –CN (cyanide) to DPNDF at various sites. Our calculations indicate that DPNDF has a wide and direct band gap with an energy gap of 3.157 eV. Whereas the band gaps of its derivatives are found to be decreased by 88 meV for derivative “a” and 300 meV for derivative “b” as a consequence of p orbitals present in C and N atoms in derivative structures. The narrowing of the energy gap and density of states for the derivatives of DPNDF in the present investigation suggest that energy gap can be engineered for desirable optoelectronic applications via derivatives designing. Furthermore, their obtained results for optical parameters such as the dielectric and conductivity functions, reflectivity, refractive index, and the extinction coefficients endorses their aptness for optoelectronic applications.
This study elucidates the involvement of auxin with Zn-efficiency (ZE) in Zn-efficient rice var. Pokkali. Pokkali showed no significant decrease in morpho-physiological features, electrolyte leakage and total soluble proteins due to Zn deficiency as compared with Zn-sufficient seedlings. However, auxin inhibitor under Zn deficiency severely affected these characteristics, suggesting that ZE is associated with auxin signaling in rice. Results further revealed significant decreases in the expression of Zn transporter genes (OsIRT1, OsZIP4 and OsZIP1), OsDMAS1 (deoxymugeneic acid synthase) and phytochelatin in roots due to auxin inhibitor. It implies that auxin signaling may trigger Zn uptake, transport and chelation in rice seedlings to withstand Zn-deficiency. Further, significant reduction of major S-metabolites (cysteine, methionine, glutathione) and antioxidant enzymes (superoxide dismutase and glutathione reductase) along with increased H2O2 content, due to auxin inhibitor under Zn deficiency compared with controls. Taken together, these findings reveal that mechanisms associated with ZE in Pokkali are dependent on auxin signaling. 相似文献
Estimation of any probability distribution parameters is vital because imprecise and biased estimates can be misleading. In this study, we investigate a flexible power function distribution and introduced new two methods such as, probability weighted moments, and generalized probability weighted methods for its parameters. We compare their results with L-moments, trimmed L-moments by a simulation study and a real data example based on performance measures such as, mean square error and total deviation. We concluded that all the methods perform well in the case of large sample size (n>30), however, the generalized probability weighted moment method performs better for small sample size. 相似文献
Intragenic 5‐methylcytosine and CTCF mediate opposing effects on pre‐mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5‐methylcytosine evicts CTCF, leading to exon exclusion. However, the mechanisms governing dynamic DNA methylation at CTCF‐binding sites were unclear. Here, we reveal the methylcytosine dioxygenases TET1 and TET2 as active regulators of CTCF‐mediated alternative splicing through conversion of 5‐methylcytosine to its oxidation derivatives. 5‐hydroxymethylcytosine and 5‐carboxylcytosine are enriched at an intragenic CTCF‐binding sites in the CD45 model gene and are associated with alternative exon inclusion. Reduced TET levels culminate in increased 5‐methylcytosine, resulting in CTCF eviction and exon exclusion. In vitro analyses establish the oxidation derivatives are not sufficient to stimulate splicing, but efficiently promote CTCF association. We further show genomewide that reciprocal exchange of 5‐hydroxymethylcytosine and 5‐methylcytosine at downstream CTCF‐binding sites is a general feature of alternative splicing in naïve and activated CD4+ T cells. These findings significantly expand our current concept of the pre‐mRNA “splicing code” to include dynamic intragenic DNA methylation catalyzed by the TET proteins. 相似文献
Improving human health is a long-lasting endeavour of mankind. In the field of social life cycle assessment (SLCA), the importance of human health is often highlighted, and further development of impact assessment methods has been recommended. The purpose of this article is to present a method for assessing human health impacts within SLCA.
Methods
By using a systematic combining approach, knowledge and experience about assessing human health impacts were obtained from three previously conducted case studies. The first case study was about an airbag system, the second about a catalytic converter and the third about gold jewellery. The disability-adjusted life years (DALY) indicator was used for impact assessment in all three case studies.
Results and discussion
Both positive and negative human health impacts associated with the products were identified and assessed in the three case studies. For the airbag system, avoided health impacts in the use phase outweighed health impacts during production. For the catalytic converter, whether health impacts avoided exceeded health impacts caused or not depended on which time perspective regarding impacts was employed. Gold jewellery does not help avoiding any health impacts but caused considerable health impacts when produced at a certain location. Based on experience from these case studies, a generic human health impact assessment method was developed, and a life cycle human health typology for products was developed based on the method. The method provides a basis for analysis and interpretation of health impacts along product life cycles, and it is therefore important to report both positive and negative health impacts separately for different actors.
Conclusions
The developed human health impact assessment method involves the assessment and comparison of both positive and negative human health impacts along product life cycles. In addition to the products assessed in the three case studies, we suggest additional products that could be particularly interesting to assess with the developed method, including medicines, seat belts, other conflict minerals, alcoholic beverages and products with a high chemical impact.
Inborn errors of metabolism (IEMs) are a group of inherited metabolic disorders which are caused by mutations in the specific genes that lead to impaired proteins or enzymes production. Different metabolic pathways are perturbed due to the deficiency or lack of enzymes. To date, more than 500 IEMs have been reported with most of them being untreatable. However, fortunately 91 such disorders are potentially treatable, if diagnosed at an earlier stage of life. IEMs have been classified into different categories and one class of IEMs, characterized by the physiological disturbances of amino acids is called as aminoacidopathies. Out of 91 treatable IEM, thirteen disorders are amino acid related. Aminoacidopathies can be detected by chromatography and mass spectrometry based analytical techniques (e.g., HPLC, GC–MS, LC–MS/MS) for amino acid level changes, and through genetic assays (e.g., PCR, TaqMan Genotyping, DNA sequencing) at the mutation level in the corresponding genes. Hence, this review is focused to describe thirteen common aminoacidopathies namely: Phenylketonuria (PKU), Maple Syrup Urine Disease (MSUD), Homocystinuria/Methylene Tetrahydrofolate Reductase (MTHFR) deficiency, Tyrosinemia type II, Citrullinemia type I and type II, Argininosuccinic aciduria, Carbamoyl Phosphate Synthetase I (CPS) deficiency, Argininemia (arginase deficiency), Hyperornithinemia–Hyperammonemia–Homocitrullinuria (HHH) syndrome, N-Acetylglutamate Synthase (NAGS) deficiency, Ornithine Transcarbamylase (OTC) deficiency, and Pyruvate Dehydrogenase (PDH) complex deficiency. Furthermore, the etiology, prevalence and commonly used analytical techniques for screening of aminoacidopathies are briefly described. This information would be helpful to researchers and clinicians especially from developing countries to initiate newborn screening programs for aminoacidopathies. 相似文献
Somatic embryogenesis offers many benefits for clonal propagation in large-scale plant production of conifers. A key rate-limiting step is the conversion from early-stage somatic embryos in pro-embryogenic masses (PEMs) to the maturation stage. Immature embryos in PEMs are present at different developmental stages, where some are unable to respond to the maturation treatment, thus limiting yields of mature embryos. Synchronization of early somatic embryo development in PEMs could greatly improve subsequent yields of mature embryos. A temporary immersion bioreactor designed for Norway spruce (Picea abies (L.) H.Karst.) was used in this study. Through a specific system for dispersion, connected tissue of PEMs, composed of immature embryos grown in liquid medium in the temporary immersion bioreactors or on solid medium as a control, was dispersed and redistributed in a more uniform spatial arrangement. It was demonstrated that development of mature embryos could be significantly stimulated by dispersion, compared to controls, in both medium types. Synchronization of maturation was evaluated by a statistical approach. The present study shows that the yield of mature embryos from dispersed PEMs was three to five times higher than that from non-dispersed controls in three of four cell lines of Norway spruce tested, both in bioreactors and on solid medium. 相似文献
Chemical industries are constantly in search of an expeditious and environmentally benign method for producing chiral synthons. Ketoreductases have been used as catalysts for enantioselective conversion of desired prochiral ketones to their corresponding alcohol. We chose reported promiscuous ketoreductases belonging to different protein families and expressed them in E.coli to evaluate their ability as whole-cell catalysts for obtaining chiral alcohol intermediates of pharmaceutical importance. Apart from establishing a method to produce high value (S)-specific alcohols that have not been evaluated before, we propose an in silico analysis procedure to predict product chirality.
Results
Six enzymes originating from Sulfolobussulfotaricus, Zygosaccharomycesrouxii, Hansenulapolymorpha, Corynebacterium sp. ST-10, Synechococcus sp. PCC 7942 and Bacillus sp. ECU0013 with reported efficient activity for dissimilar substrates are compared here to arrive at an optimal enzyme for the method. Whole–cell catalysis of ketone intermediates for drugs like Aprepitant, Sitagliptin and Dolastatin using E.coli over-expressing these enzymes yielded (S)-specific chiral alcohols. We explain this chiral specificity for the best-performing enzyme, i.e., Z.rouxii ketoreductase using in silico modelling and MD simulations. This rationale was applied to five additional ketones that are used in the synthesis of Crizotinib, MA-20565 (an antifungal agent), Sulopenem, Rivastigmine, Talampanel and Barnidipine and predicted the yield of (S) enantiomers. Experimental evaluation matched the in silico analysis wherein?~?95% (S)-specific alcohol with a chemical yield of 23–79% was obtained through biotransformation. Further, the cofactor re-cycling was optimized by switching the carbon source from glucose to sorbitol that improved the chemical yield to 85–99%.
Conclusions
Here, we present a strategy to synthesize pharmaceutically relevant chiral alcohols by ketoreductases using a cofactor balanced whole-cell catalysis scheme that is useful for the industry. Based on the results obtained in these trials, Zygosaccharomycesrouxii ketoreductase was identified as a proficient enzyme to obtain (S)-specific alcohols from their respective ketones. The whole–cell catalyst when combined with nutrient modulation of using sorbitol as a carbon source helped obtain high enantiomeric and chemical yield.
Background The cellular regulatory protein p53 is overexpressed by almost 50% of all malignancies making it an attractive target for
a vaccine approach to cancer. A number of immunotherapy approaches targeting p53 have been evaluated successfully in murine
models, but translation of these preclinical findings to the clinic has been unsuccessful. Prior studies in our laboratory
employing murine models demonstrated that a modified vaccinia virus Ankara (MVA) vaccine expressing murine p53 could stimulate
p53 specific immunity. Systemic administration of the MVA vaccine was able to effect the rejection of established tumors.
To better understand the immunologic mechanisms that underlie the vaccine function of human p53, we utilized a murine model
in which the murine germ line copy of p53 was replaced with a modified human one. These mice, referred to as Hupki, were evaluated
as a tolerant model to explore the capacity of MVA expressing human p53 to overcome tolerance and reject human p53-expressing
tumors.
Results MVAp53 immunization of Hupki mice resulted in the generation of p53-specific CD8+ T cells and the rejection of a highly aggressive murine mammary carcinoma cell line 4T1(H-2d) transfected with human p53
(4T1p53). An immunologic correlate of tumor protection was evaluated utilizing an overlapping peptide library spanning the
full length of human p53. This reagent was also used in combination with MVAp53 to stimulate p53-specific CD8+ T cell responses in cancer patients.
Conclusion These studies demonstrate the potential of MVAp53 to overcome tolerance to p53 for cancer immunotherapy. 相似文献