Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, has been reported to successfully treat advanced non-small cell lung cancer patients with genetic mutations in EGFR. The aim of this study was to investigate the existence of EGFR mutations in carcinoma of esophagogastric junction, and also to explore the possibility of treating carcinoma of esophagogastric junction using gefitinib.</p> <p>Methods</p> <p>From Aug. 2009 to Jun. 2010, 65 patients with carcinoma of esophagogastric junction underwent surgical resection. The tumor tissue and corresponding blood specimens were collected from all cases. The DNA was extracted and PCR amplification was accomplished based on designed primers for exons 18, 19, 20, and 21. EGFR exons 18, 19, 20 and 21 of both cancer cell and white blood cell were finally successfully sequenced.</p> <p>Results</p> <p>In exon 20, a variant from CAG to CAA at codon 787 (2361G-> A) was identified in 19 patients, which was a genomic variation of EGFR since it was found in both cancer tissue and white blood cells. This EGFR alteration was a synonymous single nucleotide polymorphism (SNP) since CAA and CAG were encoding the same amino-acid of Glutamine (Q787Q, NCBI database 162093G > A, SNP ID: rs10251977). No genetic alteration was found in exons 18, 19 or 21.</p> <p>Conclusions</p> <p>Adenocarcinoma of esophagogastric junction rarely presents EGFR mutation, especially gefitinib-associated mutations such as L858R, or delE746-A750. This means that the gefitinib-based gene target therapy should not be recommended for treating carcinoma of esophagogastric junction.</p

On Dynamic Resource Allocation for Blockchain Assisted Federated Learning over Wireless Channels

Blockchain assisted federated learning (BFL) has been intensively studied as a promising technology to process data at the network edge in a distributed manner. In this paper, we focus on BFL over wireless environments with varying channels and energy harvesting at clients. We are interested in proposing dynamic resource allocation (i.e., transmit power, computation frequency for model training and block mining for each client) and client scheduling (DRACS) to maximize the long-term time average (LTA) training data size with an LTA energy consumption constraint. Specifically, we first define the Lyapunov drift by converting the LTA energy consumption to a queue stability constraint. Then, we construct a Lyapunov drift-plus-penalty ratio function to decouple the original stochastic problem into multiple deterministic optimizations along the time line. Our construction is capable of dealing with uneven durations of communication rounds. To make the one-shot deterministic optimization problem of combinatorial fractional form tractable, we next convert the fractional problem into a subtractive-form one by Dinkelbach method, which leads to the asymptotically optimal solution in an iterative way. In addition, the closed-form of the optimal resource allocation and client scheduling is obtained in each iteration with a low complexity. Furthermore, we conduct the performance analysis for the proposed algorithm, and discover that the LTA training data size and energy consumption obey an [$\mathcal{O}(1/V)$, $\mathcal{O}(\sqrt{V})$] trade-off. Our experimental results show that the proposed algorithm can provide both higher learning accuracy and faster convergence with limited time and energy consumption based on the MNIST and Fashion-MNIST datasets

Self-Adaptive Artificial Bee Colony for Function Optimization

Artificial bee colony (ABC) is a novel population-based optimization method, having the advantage of less control parameters, being easy to implement, and having strong global optimization ability. However, ABC algorithm has some shortcomings concerning its position-updated equation, which is skilled in global search and bad at local search. In order to coordinate the ability of global and local search, we first propose a self-adaptive ABC algorithm (denoted as SABC) in which an improved position-updated equation is used to guide the search of new candidate individuals. In addition, good-point-set approach is introduced to produce the initial population and scout bees. The proposed SABC is tested on 12 well-known problems. The simulation results demonstrate that the proposed SABC algorithm has better search ability with other several ABC variants

Ecological vulnerability assessment of coral islands and reefs in the South China Sea based on remote sensing and reanalysis data

Coral reefs are ecosystems that are highly vulnerable to external environmental impacts, including changes associated with ocean acidification and global warming. Assessing the vulnerability of coral reef growth environments over large areas of the sea is a difficult and complex process, as it is influenced by many variables. There are few studies on environmental vulnerability assessment of coral islands and reefs in the South China Sea. It is therefore particularly important to understand the environmental sensitivity of corals and how coral communities respond to changes in climate-related environmental variables. In this study, indicators were selected mainly from natural environmental factors that hinder the development of coral reefs. The sea surface temperature (SST), sea surface salinity (SSS), wind velocity (WV) and direction, sea level height (SL), ocean currents (OC), and chlorophyll concentration (Chl) of coral reefs in South China Sea Island were integrated to calculate the coral reef environmental vulnerability region. In a GIS environment, Spatial Principal Component Analysis (SPCA) was used to develop sensitivity models and evaluate the ecological vulnerability of coral reefs. Based on the Environmental vulnerability indicator (EVI) values, the study area was classified as 5 grades of ecological vulnerability: Potential (0.000–0.577), Light (0.577–0.780), Medium (0.780–0.886), Heavy (0.886–0.993) and Very Heavy (0.993–1.131). Sensitivity models identified regional gradients of environmental stress and found that some coral reefs in western Malaysia and southwestern Philippines have higher vulnerability. Meanwhile, the study found that the reefs of Paracel Islands and Macclesfield Bank areas of medium vulnerability. Future use of high-precision data from long time series will allow better estimates of site-specific vulnerability and allow for the precise establishment of marine protected areas so that the ecological diversity of coral reefs can be sustained

Tumor-released autophagosomes induces CD4

BACKGROUND: CD4 METHODS: TRAPs isolated from tumor cell lines and pleural effusions or ascites of cancer patients were incubated with CD4 RESULTS: Heat shock protein 90α (HSP90α) on the surface of TRAPs from malignant effusions of cancer patients and tumor cell lines stimulated CD4 CONCLUSIONS: HSP90α on the surface of TRAPs programs the immunosuppressive functions of CD

Identification and characterization of a novel fumarase gene by metagenome expression cloning from marine microorganisms

<p>Abstract</p> <p>Background</p> <p>Fumarase catalyzes the reversible hydration of fumarate to <smcaps>L</smcaps>-malate and is a key enzyme in the tricarboxylic acid (TCA) cycle and in amino acid metabolism. Fumarase is also used for the industrial production of <smcaps>L</smcaps>-malate from the substrate fumarate. Thermostable and high-activity fumarases from organisms that inhabit extreme environments may have great potential in industry, biotechnology, and basic research. The marine environment is highly complex and considered one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms are inaccessible in nature and are not easily cultivated in the laboratory. Metagenomic approaches provide a powerful tool to isolate and identify enzymes with novel biocatalytic activities for various biotechnological applications.</p> <p>Results</p> <p>A plasmid metagenomic library was constructed from uncultivated marine microorganisms within marine water samples. Through sequence-based screening of the DNA library, a gene encoding a novel fumarase (named FumF) was isolated. Amino acid sequence analysis revealed that the FumF protein shared the greatest homology with Class II fumarate hydratases from <it>Bacteroides </it>sp. 2_1_33B and <it>Parabacteroides distasonis </it>ATCC 8503 (26% identical and 43% similar). The putative fumarase gene was subcloned into pETBlue-2 vector and expressed in <it>E. coli </it>BL21(DE3)pLysS. The recombinant protein was purified to homogeneity. Functional characterization by high performance liquid chromatography confirmed that the recombinant FumF protein catalyzed the hydration of fumarate to form <smcaps>L</smcaps>-malate. The maximum activity for FumF protein occurred at pH 8.5 and 55°C in 5 mM Mg²⁺. The enzyme showed higher affinity and catalytic efficiency under optimal reaction conditions: <it>K</it>_m= 0.48 mM, <it>V</it>_max= 827 μM/min/mg, and <it>k</it>_cat/<it>K</it>_m= 1900 mM/s.</p> <p>Conclusions</p> <p>We isolated a novel fumarase gene, <it>fumF</it>, from a sequence-based screen of a plasmid metagenomic library from uncultivated marine microorganisms. The properties of FumF protein may be ideal for the industrial production of <smcaps>L</smcaps>-malate under higher temperature conditions. The identification of FumF underscores the potential of marine metagenome screening for novel biomolecules.</p

A missing high-spin molecule in the family of cyano-bridged heptanuclear heterometal complexes, [(LCuII)6FeIII(CN)6]3+, and its CoIII and CrIII analogues, accompanied in the crystal by a novel octameric water cluster

Three isostructural cyano-bridged heptanuclear complexes, [{CuII(saldmen)(H2O)}6{MIII(CN)6}](ClO4)3$\cdotp$8H2O (M = FeIII 2; CoIII, 3; CrIII 4), have been obtained by reacting the binuclear copper(II) complex, [Cu2(saldmen)2(mu-H2O)(H2O)2](ClO4)2$\cdotp$2H2O 1, with K3[Co(CN)6], K4[Fe(CN)6], and, respectively, K3[Cr(CN)6] (Hsaldmen is the Schiff base resulted from the condensation of salicylaldehyde with N,N-dimethylethylenediamine). A unique octameric water cluster, with bicyclo[2,2,2]octane-like structure, is sandwiched between the heptanuclear cations in 2, 3 and 4. The cryomagnetic investigations of compounds 2 and 4 reveal ferromagnetic couplings of the central FeIII or CrIII ions with the CuII ions (JCuFe = +0.87 cm-1, JCuCr = +30.4 cm-1). The intramolecular Cu-Cu exchange interaction in 3, across the diamagnetic cobalt(III) ion, is -0.3 cm-1. The solid-state1H-NMR spectra of compounds 2 and 3 have been investigated