Mutants of chinese hamster cells deficient in thymidylate synthetase

Stable mutants of Chinese hamster V79 cells deficient in thymidylate synthetase (TS; E.C. 2.1.1.45) have been selected from cultures grown in medium supplemented with folinic acid, aminopterin, and thymidine (FAT). After chemical mutagenesis, the frequency of colonies resistant to the “FAT” medium increased more than 100-fold over the spontaneous frequency. The optimal expression time of the mutant phenotype was 5–7 days after mutagen treatment. The recovery of FAT-resistant colonies in the selective medium was not affected by the presence of wild-type cells at a density below 9,000 cells per cm 2 . All 21 mutants tested exhibited thymidine auxotrophy; neither folinic acid nor deoxyuridine could support mutant cell growth. There was no detectable TS activity in all 11 mutants so far examined and only about 50% of wild-type activity in three prototrophic revertants, as measured by whole-cell and cell-free enzyme assays. The apparent Michaelis-Menten constant (K m ) for deoxyuridine-5′-monophosphate and inhibition constant (K i ) for 5-fluorodeoxyuridine-5′-monophosphate, measured by whole-cell enzyme assay, appear to be similar for the wild-type and revertant cell lines. Using 5-fluoro-[6 3 H]-2′-deoxyuridine 5′-monophosphate as active site titrant, the relative amounts of TS in crude cell extract from the parental, revertant, and mutant cells were shown to exist in a 1:0.5:0 ratio. Furthermore, the enzymes from two revertants were more heat labile than that of V79 cells. These properties, taken together, suggest that the FAT-resistant, thymidine auxotrophic phenotype may be the result of a structural gene mutation at the TS locus. The availability of such a mutant facilitates studies on thymidylate stress in relation to DNA metabolism, cell growth, and mutagenesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49874/1/1041200202_ftp.pd

Right for the Right Reason: Training Agnostic Networks

We consider the problem of a neural network being requested to classify images (or other inputs) without making implicit use of a "protected concept", that is a concept that should not play any role in the decision of the network. Typically these concepts include information such as gender or race, or other contextual information such as image backgrounds that might be implicitly reflected in unknown correlations with other variables, making it insufficient to simply remove them from the input features. In other words, making accurate predictions is not good enough if those predictions rely on information that should not be used: predictive performance is not the only important metric for learning systems. We apply a method developed in the context of domain adaptation to address this problem of "being right for the right reason", where we request a classifier to make a decision in a way that is entirely 'agnostic' to a given protected concept (e.g. gender, race, background etc.), even if this could be implicitly reflected in other attributes via unknown correlations. After defining the concept of an 'agnostic model', we demonstrate how the Domain-Adversarial Neural Network can remove unwanted information from a model using a gradient reversal layer.Comment: Author's original versio

A study on the association of the chromosome 12p13 locus with sporadic late-onset alzheimer's disease in Chinese

Recent linkage and association studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to Alzheimer's disease (AD). We attempted to replicate this association in a Chinese data set comprised of 256 AD cases and 264 age-matched normal controls. A total of 14 single nucleotide polymorphisms (SNPs) were examined. Single marker association revealed the two SNPs in NCAPD2 (rs7311174 and rs2072374) as showing nominal significant p values (p = 0.0491 and 0.0116, respectively). Haplotype analysis found LD block one to be significantly associated with AD (global p = 0.0250). Haplotypes CGGATG and CAGTCG were also significantly associated with AD (p = 0.0498 and p = 0.0482, respectively). These genetic analyses provide evidence that the chromosome 12p13 locus is associated with AD in Chinese. © 2009 S. Karger AG, Basel.postprin

A sparse Bayesian learning method for structural equation model-based gene regulatory network inference

Gene regulatory networks (GRNs) are underlying networks identified by interactive relationships between genes. Reconstructing GRNs from massive genetic data is important for understanding gene functions and biological mechanism, and can provide effective service for medical treatment and genetic research. A series of artificial intelligence based methods have been proposed to infer GRNs from both gene expression data and genetic perturbations. The accuracy of such algorithms can be better than those models that just consider gene expression data. A structural equation model (SEM), which provides a systematic framework integrating both types of gene data conveniently, is a commonly used model for GRN inference. Considering the sparsity of GRNs, in this paper, we develop a novel sparse Bayesian inference algorithm based on Normal-Equation-Gamma (NEG) type hierarchical prior (BaNEG) to infer GRNs modeled with SEMs more accurately. First, we reparameterize an SEM as a linear type model by integrating the endogenous and exogenous variables; Then, a Bayesian adaptive lasso with a three-level NEG prior is applied to deduce the corresponding posterior mode and estimate the parameters. Simulations on synthetic data are run to compare the performance of BaNEG to some state-of-the-art algorithms, the results demonstrate that the proposed algorithm visibly outperforms the others. What’s more, BaNEG is applied to infer underlying GRNs from a real data set composed of 47 yeast genes from Saccharomyces cerevisiae to discover potential relationships between genes

The influences of phytohormones on triacylglycerol accumulation in an oleaginous marine diatom Phaeodactylum tricornutum

Environmental stresses such as nitrate deprivation and high light are effective at increasing lipid content in microalgae, but they can also slow down and even stop growth. In this study, the phytohormones methyl jasmonate, salicylic acid, gibberellin, abscisic acid, and ethephon were introduced to cultures of the oleaginous marine diatom Phaeodactylum tricornutum in an attempt to increase growth and lipid production. Single-factor experiments showed that the influences of some of the phytohormones were closely related to their concentrations. Methyl jasmonate, abscisic acid, and salicylic acid promoted P. tricornutum growth and lipid accumulation at certain concentrations. The differing effects of the three phytohormones on P. tricornutum may be related to the respective phytohormone's responsive cis-regulatory elements in the upstream regions of the triacylglycerol (TAG) synthesis genes. Methyl jasmonate, abscisic acid, and salicylic acid were further studied in response surface experiments, through which a 141% increase in TAG production was attained for 10-L cultures of P. tricornutum grown under optimal conditions. This study suggests that some phytohormones can promote P. tricornutum lipid accumulation without hindering growth. It also provides another strategy for improving the production of microalgae for use as biodiesel

KINEMATIC CHARACTERISTICS OF LOWER EXTREMITY DURING 5OM BREATHHOLD OF FIN SWIMMING

The purpose of this study was to determine the kinematic Characteristic of the lower extremity as well as the mono-fin during short distance fin swimming in Chinese fin swimmers. Eight Chinese fin swimmers were asked to perform 50m while holding the breath at maximum effort for three trials. One cycle of fin swimming motion at midway was videotaped. Two-dimensional analysis methods were employed to analyse the movement of fin swimrning. The vertical velocity and vertical acceleration of the fin tail, average velocity oftotal body centre of mass (COM), angular velocity of the thigh, and angular velocity of the shank were calculated and normalised for one cycle of fin swimming. Results showed that the peak value of horizontal velocity of the total body COM occurred when the fin tail reached its maximum downward velocity

Methods for Biomimetic Mineralisation of Human Enamel: A Systematic Review

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Dynamics of Optically Mutual-injected Terahertz Quantum Cascade Lasers

Based on the rate equation model, we study the phase locking and self-mixing properties of optically mutual-injected terahertz quantum cascade lasers. Within the phase-locked range, the laser array works steadily at the same frequency, and the electric field amplitudes are stable. Out of the phase-locked range, the instantaneous frequencies and electric field amplitudes oscillate with time. The spontaneous emission noise of mutual-injected QCLs is higher than that of free-running lasers with the same parameters. Mutual-injected QCLs for self-mixing velocity measurement are also analyzed and simulated. When the array works in the phase-locked range, simulation with a moving target shows that self-mixing signals can be observed from each laser. These results are helpful for further understanding the nonlinear dynamic behaviors of THz QCLs under optical injection and provide theoretical support for the development of self-mixing measurement techniques using QCL arrays