211,789 research outputs found
A. Klokke-Coster, A.H. Klokke, M. Saha, De Slimme en de Domine. Ngaju-Dajaksche Volksverhalen
Usop KMA M. A. Klokke-Coster, A.H. Klokke, M. Saha, De Slimme en de Domine. Ngaju-Dajaksche Volksverhalen. In: Archipel, volume 19, 1980. pp. 309-311
Prof. M N Saha in UGC Meeting at Calcutta, 1949
Prof. M N Saha in UGC Meeting at Calcutta during 194
Prof. M N Saha with Indian Students of London
Prof. M N Saha with Indian Students in London during 194
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Characterization of UGTs Active against SAHA and Association between SAHA Glucuronidation Activity Phenotype with UGT Genotype
Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor used in the treatment of cutaneous T-cell lymphoma and in clinical trials for treatment of multiple other cancers. A major mode of SAHA metabolism is by glucuronidation via the UDP-glucuronosyltransferase (UGT) family of enzymes. To characterize the UGTs active against SAHA, homogenates from HEK293 cell lines overexpressing UGT wild-type or variant UGT were used. The hepatic UGTs 2B17 and 1A9 and the extrahepatic UGTs 1A8 and 1A10 exhibited the highest overall activity against SAHA as determined by
V
max
/K
M
(16 ± 6.5, 7.1 ± 2.2, 33 ± 6.3, and 24 ± 2.4 nL·min
−1.
μg UGT protein
−1
, respectively), with UGT2B17 exhibiting the lowest K
M
(300 μmol/L) against SAHA of any UGT
in vitro
. Whereas the UGT1A8p.Ala173Gly variant exhibited a 3-fold (
P
< 0.005) decrease in glucuronidation activity against SAHA compared with wild-type UGT1A8, the UGT1A8p.Cys277Tyr variant exhibited no detectable glucuronidation activity; a similar lack of detectable glucuronidation activity was observed for the UGT1A10p.Gly139Lys variant. To analyze the effects of the
UGT2B17
gene deletion variant (
UGT2B17
*
2
) on SAHA glucuronidation phenotype, human liver microsomes (HLM) were analyzed for glucuronidation activity against SAHA and compared with
UGT2B17
genotype. HLM from subjects homozygous for
UGT2B17
*
2
exhibited a 45% (
P
< 0.01) decrease in glucuronidation activity and a 75% (
P
< 0.002) increase in K
M
compared with HLMs from subjects homozygous for the wild-type
UGT2B17
*
1
allele. Overall, these results suggest that several UGTs play an important role in the metabolism of SAHA and that UGT2B17-null individuals could potentially exhibit altered SAHA clearance rates with differences in overall response
Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent
Introduction: \ud
Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence. The caspase 8 inhibitor FLIP is an anti-apoptotic protein over-expressed in several cancer types including MPM. The histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) is currently being evaluated in relapsed mesothelioma. We examined the roles of FLIP and caspase 8 in regulating SAHA-induced apoptosis in MPM. \ud
\ud
Methods: \ud
The mechanism of SAHA-induced apoptosis was assessed in 7 MPM cell lines and in a multicellular spheroid model. SiRNA and overexpression approaches were used, and cell death was assessed by flow cytometry, Western blotting and clonogenic assays. Results: RNAi-mediated FLIP silencing resulted in caspase 8-dependent apoptosis in MPM cell line models. SAHA potently down-regulated FLIP protein expression in all 7 MPM cell lines and in a multicellular spheroid model of MPM. In 6/7 MPM cell lines, SAHA treatment resulted in significant levels of apoptosis induction. Moreover, this apoptosis was caspase 8-dependent in all six sensitive cell lines. SAHA-induced apoptosis was also inhibited by stable FLIP overexpression. In contrast, down-regulation of HR23B, a candidate predictive biomarker for HDAC inhibitors, significantly inhibited SAHA-induced apoptosis in only 1/6 SAHA-sensitive MPM cell lines. Analysis of MPM patient samples demonstrated significant inter-patient variations in FLIP and caspase 8 expressions. In addition, SAHA enhanced cisplatin-induced apoptosis in a FLIP-dependent manner. \ud
\ud
Conclusions: \ud
These results indicate that FLIP is a major target for SAHA in MPM and identifies FLIP, caspase 8 and associated signalling molecules as candidate biomarkers for SAHA in this disease. © 2011 Elsevier Ltd. All rights reserved
Scolytoplatypus lopchuensis Maiti & Saha
11. Scolytoplatypus lopchuensis Maiti & Saha * Scolytoplatypus lopchuensis Maiti & Saha, 2009: 90. Thai distribution: N: Chiang Mai. New to Thailand. New record: Chiang Mai, Doi Inthanon NP, Checkpoint 2, 18° 31.55' N, 98° 29.94' E, 1700 m, MT, 8–15.v.2007 (Y. Areeluck) (1). Other distribution: India (W. Bengal). (2) Taxonomy: In their description of the male, Maiti and Saha (2009) fail to mention the prosternum, which is a valuable taxonomic character in Scolytoplatypus (Beaver & Gebhardt 2006). It is broadly flattened posteriorly, but tapers anteriorly to a sharp point which is more strongly sclerotised. The tapering part bears long, backwardly pointing hairs, and at the tip on each side, a small tuft of short, forwardly pointing hairs. Maiti and Saha (2009) do not mention also the extremely long tufts of hairs on the anterior coxae. These are longer than in any other species of Scolytoplatypus known to us, the longest hairs extending two-thirds of the body length. Biology: Maiti and Saha (2009) list three host species in three different families (Lauraceae, Rutaceae, Symplocaceae). Given the localities listed by Maiti & Saha (2009), and above, probably a montane species. Illustrations: D (Maiti & Saha 2009).Published as part of Beaver, R. A., Sittichaya, W. & Liu, L-Y., 2014, A Synopsis of the Scolytine Ambrosia Beetles of Thailand (Coleoptera: Curculionidae: Scolytinae), pp. 1-82 in Zootaxa 3875 (1) on pages 17-18, DOI: 10.11646/zootaxa.3875.1.1, http://zenodo.org/record/513058
Internet-of-Forensic (IoF): A blockchain based digital forensics framework for IoT applications
Digital forensic in Internet-of-Thing (IoT) paradigm is critical due to its heterogeneity and lack of transparency of evidence processing. Moreover, cross-border legalization makes a hindrance in such process pertaining to the cloud forensic issues. This urges a forensic framework for IoT which provides distributed computing, decentralization, and transparency of forensic investigation of digital evidences in cross-border perspectives. To this end, we propose a framework for IoT forensics that addresses the above mentioned issues. The proposed solution called Internet-of-Forensics (IoF) considers a blockchain tailored IoT framework for digital forensics. It provides a transparent view of the investigation process that involves all the stakeholders (e.g., heterogeneous devices, and cloud service providers) in a single framework. It uses blockchain-based case chain to deal with the investigation process including chain-of-custody and evidence chain. Consensus is used for consortium to solve the problems of cross-border legalization. This is also beneficial for a transparent and ease of forensic reference. The programmable lattice-based cryptographic primitives produce reduced complexities. It shows benefits for power-aware devices and puts an add-on to the novelty of the presented idea. IoF is generic; hence, it can be used by autonomous security operation centers, cyber-forensic investigators and manually initiated evidences under chain-of-custody for man-made crimes. Security services are assured as required by the framework. IoF is experimented and compared with the other state-of-the-art frameworks. The outcomes and analysis prove the efficiency of IoF concerning complexity, time consumption, memory and CPU utilization, gas consumption, and energy analysis
A distributed amplifier system for bilayer lipid membrane (BLM) arrays with noise and individual offset cancellation
Lipid bilayer membrane (BLM) arrays are required for high throughput analysis, for example drug screening or advanced DNA sequencing. Complex microfluidic devices are being developed but these are restricted in terms of array size and structure or have integrated electronic sensing with limited noise performance. We present a compact and scalable multichannel electrophysiology platform based on a hybrid approach that combines integrated state-of-the-art microelectronics with low-cost disposable fluidics providing a platform for high-quality parallel single ion channel recording. Specifically, we have developed a new integrated circuit amplifier based on a novel noise cancellation scheme that eliminates flicker noise derived from devices under test and amplifiers. The system is demonstrated through the simultaneous recording of ion channel activity from eight bilayer membranes. The platform is scalable and could be extended to much larger array sizes, limited only by electronic data decimation and communication capabilities
Continuous intracranial administration of suberoylanilide hydroxamic acid (SAHA) inhibits tumor growth in an orthotopic glioma model
Object Current treatments for malignant gliomas produce only a modest increase in survival time. New therapeutic approaches are desperately needed. Suberoylanilide hydroxamic acid (SAHA) is an effective inhibitor of the growth of many solid and hematological malignancies. Nevertheless, very few studies have investigated the effects of SAHA on glial tumors. The present study was designed to investigate the therapeutic effects of the intracranial local delivery of SAHA in an orthotopic glioma model.
Methods The antiproliferative effect of SAHA was examined in six glioblastoma and one endothelial cell lines in vitro. In addition, one glioblastoma cell line (U87MG) used in in vivo short term (14 days) and survival studies in an orthotopic human glioma athymic mice model. Tumor volume, apoptosis rate, microvessel density, and proliferation index were determined by immunohistochemistry.
Results SAHA treatment inhibited the growth of all cell lines in concentrations ranging from 1 mu M to 30 mu M. For short-term studies, histological analysis showed an 80% reduction of tumor volume in the treatment group (P < 0.001). This reduction in tumor volume was associated with a significant increase in the apoptosis rate (31.9%, P < 0.001), a significant decrease in the proliferation (36.8%, P < 0.001) and angiogenesis rates (30%, P < 0.05). For survival studies, the mean survival time was 22 days in the control group, whereas it was 42 days in the treatment group.
Conclusions These results suggest that local delivery with SAHA inhibits intracranial glioma growth in vitro and in vivo. SAHA is a promising candidate for further preclinical and clinical studies on glial tumors
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