Tuning the responsible parameters for gain characteristics of the novel type-II D-QW (InGaAs) heterostructure

2022 ◽  
Vol 140 ◽  
pp. 106377
Author(s):  
Md Riyaj ◽  
A.M. Quraishi ◽  
P.M.Z. Hasan ◽  
Reem Darwesh ◽  
Sandhya Kattayat ◽  
...  
Keyword(s):  
2005 ◽  
Vol 71 (5) ◽  
pp. 2642-2652 ◽  
Author(s):  
Hans-Peter Horz ◽  
Virginia Rich ◽  
Sharon Avrahami ◽  
Brendan J. M. Bohannan

ABSTRACT We investigated the diversity of methane-oxidizing bacteria (i.e., methanotrophs) in an annual upland grassland in northern California, using comparative sequence analysis of the pmoA gene. In addition to identifying type II methanotrophs commonly found in soils, we discovered three novel pmoA lineages for which no cultivated members have been previously reported. These novel pmoA clades clustered together either with clone sequences related to “RA 14” or “WB5FH-A,” which both represent clusters of environmentally retrieved sequences of putative atmospheric methane oxidizers. Conservation of amino acid residues and rates of nonsynonymous versus synonymous nucleotide substitution in these novel lineages suggests that the pmoA genes in these clades code for functionally active methane monooxygenases. The novel clades responded to simulated global changes differently than the type II methanotrophs. We observed that the relative abundance of type II methanotrophs declined in response to increased precipitation and increased atmospheric temperature, with a significant antagonistic interaction between these factors such that the effect of both together was less than that expected from their individual effects. Two of the novel clades were not observed to respond significantly to these environmental changes, while one of the novel clades had an opposite response, increasing in relative abundance in response to increased precipitation and atmospheric temperature, with a significant antagonistic interaction between these factors.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3069-3069
Author(s):  
Toshio Yoshizawa ◽  
Tomoko Yasuhiro ◽  
Joseph TP Birkett ◽  
Christian Klein ◽  
Kazuhito Kawabata

Abstract Purpose The activated B-cell-like (ABC) sub-type of diffuse large B-cell lymphoma (DLBCL) correlates with poor prognosis. There is still a high medical need for new therapies, preferably chemo-sparing, to help treat patients with ABC-DLBCL and CLL as well as other B-cell malignancies. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given Btk is a downstream mediator of BCR signalling, Btk constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the novel Btk inhibitor ONO-4059, it was hypothesized that, the anti-tumour activity of ONO-4059 could be further enhanced by combining it with the anti-CD20 Abs, Obinutuzumab (GA101) or Rituximab (RTX), as a novel therapeutic strategy. Methods TMD-8 tumour cells, a human ABC-DLBCL cell line, were implanted sub-cutaneously into female SCID mice. Randomization of mice occurred when mean tumour volume was 400-450 mm3. ONO-4059 was administered orally at a dose of 10 mg/kg bid, and GA101 or RTX were administered intravenously both at a sub-optimal dose of 3 mg/kg once weekly. Tumour volumes were measured twice a week after initiation of treatment, and tumour volumes were determined using the formula volume (= width2 x length)/2. Animals were euthanized when the tumours reached a maximum volume of 3,000 mm3. Results Treatment with ONO-4059 combined with either GA101 or RTX resulted in a significant inhibition of tumour growth in the TMD-8 xenograft model. GA101 monotherapy showed superior anti-tumour activity compared with RTX monotherapy in terms of tumor growth inhibition (TGI 78% vs 54% at day 21). ONO-4059 combined with GA101 or RTX at sub-optimal doses was significantly better than the respective Abs or ONO-4059 given as monotherapy with TGI of 90% for the GA101 combination and 86% for the rituximab combination. ONO-4059 as single agent mediated a TGI of 63%. In addition combination treatment with GA101 resulted in tumour remission in 3/10 animals, whereas combination treatment with rituximab resulted in tumor remission in only1/10 animals. GA101 monotherapy resulted in 1/10 tumor-free animals, whereas no tumor free animals were observed in the rituximab and ONO-4059 monotherapy groups. Conclusion Recent studies indicate that targeting Btk is effective in the treatment of B-cell malignancies. Our results demonstrate that treatment with ONO-4059 in combination with GA101 or rituximab results in a combined effect in vivo and is superior to the respective monotherapies. Furthermore, ONO-4059 in combination with the novel glycoengineered Type II CD20 antibody GA101 is more effective than the combination of ONO-4059 with rituximab in this DLBCL xenograft model. When interpreting these data it should be noted that both, obinutuzumab and rituximab were dosed at sub-optimal doses as they can induce tumor remission when dosed at 10 mg/kg. Taken together these data indicate that the combination of ONO-4059 with rituximab, and particularily obinutuzumab may be an effective treatment for ABC-DLBCL. Disclosures: Yoshizawa: Ono Pharmaceutical CO., Ltd: Employment. Yasuhiro:Ono Pharmaceutical Co., Ltd.: Employment. Birkett:Ono Pharma UK: Employment. Klein:Roche Glycart AG: Employment. Kawabata:Ono Pharmaceutical Co., Ltd.: Employment.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nguyen PT Huynh ◽  
Catherine C Gloss ◽  
Jeremiah Lorentz ◽  
Ruhang Tang ◽  
Jonathan M Brunger ◽  
...  

The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA GRASLND (originally named RNF144A-AS1) as a regulator of mesenchymal stem cell (MSC) chondrogenesis. GRASLND, a primate-specific lncRNA, is upregulated during MSC chondrogenesis and appears to act directly downstream of SOX9, but not TGF-β3. We showed that the silencing of GRASLND resulted in lower accumulation of cartilage-like extracellular matrix in a pellet assay, while GRASLND overexpression – either via transgene ectopic expression or by endogenous activation via CRISPR-dCas9-VP64 – significantly enhanced cartilage matrix production. GRASLND acts to inhibit IFN-γ by binding to EIF2AK2, and we further demonstrated that GRASLND exhibits a protective effect in engineered cartilage against interferon type II. Our results indicate an important role of GRASLND in regulating stem cell chondrogenesis, as well as its therapeutic potential in the treatment of cartilage-related diseases, such as osteoarthritis.


2013 ◽  
Vol 9 (1) ◽  
pp. e1003117 ◽  
Author(s):  
Rhys A. Dunstan ◽  
Eva Heinz ◽  
Lakshmi C. Wijeyewickrema ◽  
Robert N. Pike ◽  
Anthony W. Purcell ◽  
...  

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3726-3726 ◽  
Author(s):  
Gerhard J Niederfellner ◽  
Alfred Lammens ◽  
Manfred Schwaiger ◽  
Guy Georges ◽  
Kornelius Wiechmann ◽  
...  

Abstract Abstract 3726 Poster Board III-662 CD20 is a specific cell surface marker found on normal as well as malignant B cells. Rituximab, a monoclonal antibody directed against CD20, has a major impact on treatment of malignant lymphomas. Although all therapeutic CD20 antibodies are directed against the two relatively small extracellular loops of CD20, such antibodies can be classified into Type I CD20 antibodies like Rituximab, Ofatumumab or Ocrelizumab or Type II CD20 antibodies like the novel glycoengineered humanized CD20 antibody GA101 or the murine antibody Tositumumab. Type I and Type II antibodies differ significantly in their mode of action and mechanisms of killing malignant B-cells. The molecular basis of this is not understood. We use data from epitope mapping, X-ray crystallography, isothermal titration calorimetry, and point mutagenesis i) to accurately map the epitopes of different anti-CD20 antibodies, in particular GA101, and ii) to compare the molecular interactions involved in their binding. Although the epitope regions of these antibodies largely overlap, the crystal structure shows that GA101 binds CD20 in a completely different orientation from Rituximab, Ocrelizumab and Ofatumumab and that its binding also involves a larger surface area. In agreement with predictions based on the crystallographic data, point mutagenesis of single amino acid residues confirmed that exchanges at certain positions in CD20 affect binding of Rituximab and GA101 differently. Our data suggest that engagement of CD20 by these antibodies favors different conformations of CD20, which could form the molecular basis for the observed differences in cellular signals triggered by the respective antibodies. Disclosures: Niederfellner: Roche: Employment. Schwaiger:Roche: Employment. Georges:Roche: Employment. Wiechmann:Roche: Research Funding. Franke:Roche: Research Funding. Schaefer:Roche: Employment. Jenewein:Roche: Employment. Slootstra:Pepscan: Employment, Patents & Royalties. Moessner:Glycart: Employment, Equity Ownership, Patents & Royalties. Umana:Glycart: Employment, Equity Ownership, Patents & Royalties. Hopfner:Roche: Research Funding. Klein:Roche: Employment, Equity Ownership, Patents & Royalties.


2007 ◽  
Vol 18 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Qiyu Qiu ◽  
Juozas Domarkas ◽  
Ranjita Banerjee ◽  
Athanasia Katsoulas ◽  
James P. McNamee ◽  
...  
Keyword(s):  

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Dimitrios Vlachakis ◽  
Dimitrios Georgios Kontopoulos ◽  
Sophia Kossida

Protein structure is more conserved than sequence in nature. In this direction we developed a novel methodology that significantly improves conventional homology modelling when sequence identity is low, by taking into consideration 3D structural features of the template, such as size and shape. Herein, our new homology modelling approach was applied to the homology modelling of the RNA-dependent RNA polymerase (RdRp) of dengue (type II) virus. The RdRp of dengue was chosen due to the low sequence similarity shared between the dengue virus polymerase and the available templates, while purposely avoiding to use the actual X-ray structure that is available for the dengue RdRp. The novel approach takes advantage of 3D space corresponding to protein shape and size by creating a 3D scaffold of the template structure. The dengue polymerase model built by the novel approach exhibited all features of RNA-dependent RNA polymerases and was almost identical to the X-ray structure of the dengue RdRp, as opposed to the model built by conventional homology modelling. Therefore, we propose that the space-aided homology modelling approach can be of a more general use to homology modelling of enzymes sharing low sequence similarity with the template structures.


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