Client side decompression technique provides faster DNA sequence data delivery

DNA sequences are generally very long chains of sequentially linked nucleotides. There are four different nucleotides and combinations of these build the nucleotide information of sequence files contained in data sources. When a user searches for any sequence for an organism, a compressed sequence file can be sent from the data source to the user. The compressed file then can be decompressed at the client end resulting in reduced transmission time over the Internet. A compression algorithm that provides a moderately high compression rate with minimal decompression time is proposed in this paper. We also compare a number of different compression techniques for achieving efficient delivery methods from an intelligent genomic search agent over the Interne

Cell-type-specific signaling networks in heterocellular organoids

Despite the widespread adoption of organoids as biomimetic tissue models, methods to comprehensively analyze cell-type-specific post-translational modification (PTM) signaling networks in organoids are absent. Here, we report multivariate single-cell analysis of such networks in organoids and organoid cocultures. Simultaneous analysis by mass cytometry of 28 PTMs in >1 million single cells derived from small intestinal organoids reveals cell-type- and cell-state-specific signaling networks in stem, Paneth, enteroendocrine, tuft and goblet cells, as well as enterocytes. Integrating single-cell PTM analysis with thiol-reactive organoid barcoding in situ (TOBis) enables high-throughput comparison of signaling networks between organoid cultures. Cell-type-specific PTM analysis of colorectal cancer organoid cocultures reveals that shApc, KrasG12D and Trp53R172H cell-autonomously mimic signaling states normally induced by stromal fibroblasts and macrophages. These results demonstrate how standard mass cytometry workflows can be modified to perform high-throughput multivariate cell-type-specific signaling analysis of healthy and cancerous organoids

Multiplexed single-cell analysis of organoid signaling networks

Organoids are biomimetic tissue models comprising multiple cell types and cell states. Post-translational modification (PTM) signaling networks control cellular phenotypes and are frequently dysregulated in diseases such as cancer. Although signaling networks vary across cell types, there are limited techniques to study cell type–specific PTMs in heterocellular organoids. Here, we present a multiplexed mass cytometry (MC) protocol for single-cell analysis of PTM signaling and cell states in organoids and organoids co-cultured with fibroblasts and leukocytes. We describe how thiol-reactive organoid barcoding in situ (TOBis) enables 35-plex and 126-plex single-cell comparison of organoid cultures and provide a cytometry by time of flight (CyTOF) signaling analysis pipeline (CyGNAL) for computing cell type–specific PTM signaling networks. The TOBis MC protocol takes ~3 d from organoid fixation to data acquisition and can generate single-cell data for >40 antibodies from millions of cells across 126 organoid cultures in a single MC run

SIGNAL-seq:Multimodal Single-cell Inter- and Intra-cellular Signalling Analysis

We present SIGNAL-seq (Split-pool Indexing siG-Nalling AnaLysis by sequencing): a multiplexed splitpool combinatorial barcoding method that simultaneously measures RNA and post-translational modifications (PTMs) in fixed single cells from 3D models. SIGNAL-seq PTM measurements are equivalent to mass cytometry and RNA gene detection is analogous to split-pool barcoding scRNA-seq. By measuring both mRNA ligand-receptor pairs and PTMs in single cells, SIGNAL-seq can simultaneously uncover inter- and intra-cellular regulation of tumour microenvironment plasticity

Разработка технических средств повышения эффективности солнечных установок

In this paper a method and means of increasing the power generated by solar installations during the day are considered. It is recommended to use acrylic concentrator and solar tracker with active type of tracking based on the control board without microcontrollers. This feature allows using DC commutator motor as an electric drive component, which simplifies the construction of the whole system significantly

Inhibition of mapk signalling promotes cell cycle arrest and sensitises intrahepatic cholangiocarcinoma cells to chemotherapy

Introduction: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, accounting for approximately 15% of cases of primary liver cancer. Although new treatments have increased survival for many other cancers, including the more common primary hepatocellular carcinoma, treatment strategies and survival for patients with ICC have seen little improvement. Our previous studies suggest that the mitogen-activated protein kinase (MAPK) signalling plays a central role in the regulation of cell proliferation in human ICC. However the molecular mechanisms are poorly understood. In this study, we aim to explore whether inhibition of the MAPK pathway and its downstream effectors enhances the sensitisation of ICC cells to the chemotherapeutic agent cisplatinum. Method: We used a combinatorial approach of immunohistochemical and gene expression analyses to investigate the expression of MAPK-related genes in ICC tumours. Furthermore, by using in-vitroand in-vivoanalyses we have characterised the function of a novel MAPK downstream effector in ICC cells. Results: The expression of MAPK signalling was determined by immunohistochemical staining in tumour samples from a cohort of 14 ICC patients. High expression of phospho-activated MAPK was observed in 71.4% (10/14) of ICC cases as compared with surrounding nontumour tissue. Likewise, expression of JDP, a downstream effector of the MAPK signalling, was scored as high intensity in 64.3% (9/14). Strikingly, elevated expression of JDP transcripts was also observed in two independent cohorts of human ICC (n = 149 and n = 109 per group, respectively) compared to surrounding normal liver tissue. Consistent with the in-vivo analyses of human samples, immunoblotting analyses showed constitutive activation of MAPK and expression of JDP in ICC-derived cells (i.e. SG231, CCLP-1 and HuCCT1). Using loss-of-function analyses, we demonstrates that knockdown of JDP in ICC-derived cells resulted in cell cycle arrest and reduced expression of cell cycle regulators (i.e. cyclins), and had minimal effect on apoptosis. Chemical inhibition of JDP significantly sensitises ICC-derived cells to cisplatinum (P < 0.001). Conclusion: These results demonstrate that enhanced activation of MAPK signalling is important for ICC cell proliferation and suggest that targeting its downstream effectors is a potential therapeutic strategy for ICC

Oncogenic PIK3CA corrupts growth factor signaling specificity

Pathological activation of the PI3K/AKT pathway is among the most frequent defects in human cancer and is also the cause of rare overgrowth disorders. Yet, there is currently no systematic understanding of the quantitative flow of information within PI3K/AKT signaling and how it is perturbed by disease-causing mutations. Here, we develop scalable, single-cell approaches for systematic analyses of signal processing within the PI3K pathway, enabling precise calculations of its information transfer for different growth factors. Using genetically-engineered human cell models with allele dose-dependent expression of PIK3CAH1047R, we show that this oncogene is not a simple, constitutive pathway activator but a context-dependent modulator of extracellular signal transfer. PIK3CAH1047Rreduces information transmission downstream of IGF1 while selectively enhancing EGF-induced signaling and transcriptional responses. This leads to a gross reduction in signaling specificity, akin to “blurred” signal perception. The associated increase in signaling heterogeneity promotes phenotypic diversity in a human cervical cancer cell line model and in human induced pluripotent stem cells. Collectively, these findings and the accompanying methodological advances lay the foundations for a systematic mapping of the quantitative mechanisms of PI3K/AKT-dependent signal processing and phenotypic control in health and disease

Multi-walled carbon nanotubes grow under low pressure hydrogen, air, and argon ambient by arc discharge plasma

Multi-walled carbon nanotubes (MWCNTs) were grown on cathode deposit by arc discharge plasma under H2, Ar, and air ambient environment. The influence of ambient gas pressure on the structure and physical properties of carbon nanotube were compared. Herein, we highlight the influence of ambient environment and pressure to grow high quality carbon nanotubes. Field emission scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray diffraction were used for structural characterization and yield determination. The result revealed that background gas and pressure were crucial factor for growing highly crystalline and highly graphitic with ID/IG ratio 0.237 obtained for MWCNTs’ synthesized in H2 environment with extreme low defects

ADHD presenting as recurrent epistaxis: a case report

Epistaxis is an important otorhinolaryngological emergency, which usually has an apparent etiology, frequently local trauma in children. Here we present a case report wherein the epistaxis was recalcitrant, and proved to have a psychiatric disorder as an underlying basis. The child was diagnosed with Attention Deficit/Hyperactivity Disorder, hyperactive type, which led to trauma to nasal mucosa due to frequent and uncontrolled nose picking. Treatment with atomoxetine controlled the patient's symptoms and led to a remission of epistaxis

Dealer Financial Conditions and Lender-of-Last Resort Facilities

We examine the financial conditions of dealers that participated in two of the Federal Reserve's lender-of-last-resort (LOLR) facilities - the Term Securities Lending Facility (TSLF) and the Primary Dealer Credit Facility (PDCF) - that provided liquidity against a range of assets during 2008-09. Dealers with lower equity returns and greater leverage prior to borrowing from the facilities were more likely to participate in the programs, borrow more, and - in the case of the TSLF - at higher bidding rates. Dealers with less liquid collateral on their balance sheets before the facilities were introduced also tended to borrow more. There also appear to be some interaction effects between financial performance and balance sheet liquidity in explaining dealer behavior. The results suggest that both financial performance and balance sheet liquidity play a role in LOLR utilization