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排序方式: 共有1487条查询结果,搜索用时 15 毫秒
81.
Chemical signals modulate aggressive behavior in mice. For example, male urinary cues enhance aggression against other adults: a resident mouse attacks a male but not a castrated intruder, unless it is anointed with male urine. Our purpose was to understand whether molecules excreted with urine also act as aggression triggers in a different context. Therefore, the effect of urine, or molecules purified from urine, voided by different animals (males or females), was tested on the aggression of male mice against pups. Latency to the first attack, percentage of pups receiving the first attack, and percentage of attacked pups after 5 and 15 min were recorded. At variance with intermale aggression, male urinary chemosignals sprayed on pups reduced infanticide, while female urine did not. Male urine also delayed infanticide when compared to female urine. Pups anointed with low molecular weight dialyzed urine and with the high molecular weight protein fraction were attacked later than controls. Pups anointed with Major Urinary Proteins (MUPs) also were attacked later. The volatiles retained by MUPs act in the same way as adult male urine. MUPs and their ligands did not modify biting of food items. The results show that mice do not perceive male chemosignals as compulsory aggression triggers but rather can consistently and differentially shape their behavior in response to the same molecules according to different contextual events. 相似文献
82.
Identification of potent human anti-IL-1RI antagonist antibodies 总被引:4,自引:0,他引:4
Fredericks ZL Forte C Capuano IV Zhou H Vanden Bos T Carter P 《Protein engineering, design & selection : PEDS》2004,17(1):95-106
Interleukin-1 (IL-1) blockade by IL-1 receptor antagonist benefits some arthritis patients by reducing joint damage. This fact inspired us to develop antagonist human therapeutic antibodies against IL-1R(I) using phage libraries that display single-chain variable fragment (scFv) antibody fragments. Panning libraries against human IL-1R(I) generated 39 unique scFv-phage whose binding to IL-1R(I) was competed by IL-1 ligands. Fifteen of these scFv-phage, identified using IL-1R(I)-binding assays and dissociation rate ranking, were reformatted as scFv-Fc and IgG(4) molecules. The ease of producing antibodies in the scFv-Fc format permitted rapid identification of four lead clones (C10, C13, C14, C15) that inhibit NF-kappaB nuclear translocation induced by IL-1. Reformatting these clones as IgG(4) molecules increased their inhibition potency by =24-fold. C10 IgG(4) is the most potent antagonist of IL-1alpha (26 nM IC(50)) and IL-1beta (18 nM IC(50)) in the NF-kappaB bioassay, although less potent than IL-1ra ( approximately 0.4 nM IC(50)). C10 is the highest affinity clone for human IL-1R(I) (K(D) approximately 60 nM). Flow cytometry indicates that several lead clones bind cell-surface cynomolgus or murine IL-1R(I), characteristics advantageous for preclinical toxicology and efficacy studies. This study demonstrates the utility of scFv-Fc fusion proteins for rapid screening of clones derived from phage libraries to identify antibody leads with therapeutic potential. 相似文献
83.
We present C2 quasi-interpolating schemes with tension properties. The B-splines like functions used in the quasi-interpolanting schemes are parametric cubic curves and their shape can be easily controlled via tension parameters which have an immediate geometric interpretation. Applications to the problem of approximation of curves with shape-constraints are discussed. 相似文献
84.
Poly(ethylene terephthalate) (PET) is one of the most commonly employed polymers in the textile industry. Its relevance as a source of evidence in the reconstruction of criminal cases is nevertheless very limited because the properties and morphologies of fibers from different producers tend to be very similar. By integrating bands, obtained on single fibers by infrared (IR) microscopy, associated with trans and gauche conformation and to the O-H end-groups of the molecules, a method is proposed that can discriminate otherwise similar PET fibers. The absorbancies at 1370 and at 846 cm(-1) relative, respectively, to the gauche and trans conformation, were measured and ratioed. The end-group content was evaluated by ratioing the absorbancies of the signals at 3440 and at 874 cm(-1). Relative standard deviation (R. S. D.) was 1% for repetitive analyses on the same location of the same single fiber. Precision was reduced if the ratios were measured along the length of a single fiber (R. S. D. = 3%) and even further when different fibers of the same sample were examined (R. S. D. varied from 2 to 10%). This simple method can greatly enhance the evidential value of PET fibers by subclassifying them, thus helping the Court to better assess their significance. 相似文献
85.
This paper introduces the computer security domain of anomaly detection and formulates it as a machine learning task on temporal sequence data. In this domain, the goal is to develop a model or profile of the normal working state of a system user and to detect anomalous conditions as long-term deviations from the expected behavior patterns. We introduce two approaches to this problem: one employing instance-based learning (IBL) and the other using hidden Markov models (HMMs). Though not suitable for a comprehensive security solution, both approaches achieve anomaly identification performance sufficient for a low-level focus of attention detector in a multitier security system. Further, we evaluate model scaling techniques for the two approaches: two clustering techniques for the IBL approach and variation of the number of hidden states for the HMM approach. We find that over both model classes and a wide range of model scales, there is no significant difference in performance at recognizing the profiled user. We take this invariance as evidence that, in this security domain, limited memory models (e.g., fixed-length instances or low-order Markov models) can learn only part of the user identity information in which we're interested and that substantially different models will be necessary if dramatic improvements in user-based anomaly detection are to be achieved. 相似文献
86.
Bassarello C Cimino P Bifulco G Boger DL Smith JA Chazin WJ Gomez-Paloma L 《Chembiochem : a European journal of chemical biology》2003,4(11):1188-1193
We report the NMR solution structure of (+)-CPI-indole (CPI, 1,2,8,8a-tetrahydrocyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one), an agent belonging to the CC-1065/duocarmycin family of antitumor compounds. This (+)-CPI-indole structure is covalently bound to d(G(1)ACTAATTGTC(11))-d(G(12)TCAATTAGTC(22)), a synthetic DNA duplex containing a high-affinity binding site. The three-dimensional structure has been determined by several cycles of restrained molecular dynamics calculations with a total of 563 NMR-derived constraints, both in vacuo and by using the generalized Born solvent continuum model. In-depth analysis of the structure of this ligand-DNA complex led to a detailed knowledge of the bound state conformation of the CPI-indole, the most simplified agent related to CC-1065 and duocarmycins, the parent members of a family of extremely potent antitumor compounds. Comparison of the CPI-indole bound conformation with those previously found for (+)-duocarmycin SA (DSA), its unnatural enantiomer (-)-DSA, and the demethoxylated analogue (+)-DSI in their DNA complexes provided additional evidence of the tight correlation between the catalytic effect exerted by DNA on the alkylation reaction and the extent of angular twist between the two planar heteroaromatic subunits of these agents. Additionally, comparison of the structural features of the DNA-bound state of a "naked" ligand, such as CPI-indole, with those of various other duocarmycin agents provided useful information for the interpretation of the observed effects on chemical reactivity of the different substitution patterns at the hemispheres of these types of complex. 相似文献
87.
Douglas D. Gransberg Carla Lopez del Puerto Daniel Humphrey 《Canadian Metallurgical Quarterly》2007,133(6):404-408
Intuitively, there should be a relationship between the size of the design fee for a transportation project and the quality of the resulting design. This study sought that relationship by looking at the fee expressed as a percentage of the construction cost and the final construction cost growth from the engineer’s initial estimate of the construction cost at the time the design contract was awarded. The research team analyzed 31 projects from the Oklahoma Turnpike Authority with a total construction value of $90 million. The projects were divided into road and bridge projects. Based on the results of the analysis, it seems that as the design fee decreases, the absolute percentage of construction cost growth from the engineer’s early estimate increases. The relationship is strongest for bridge projects, which tend to be more technically complex to design than roadway projects. This confirms for U.S. projects the result of an earlier study in Saudi Arabia. This paper concludes that the design fee should be viewed as an investment at a point in time where the ability to impact the project is the highest and can accrue the benefit of reduced cost growth. 相似文献
88.
89.
Portugal is faced with important challenges concerning the definition of policies to achieve energy and environmental targets, taking also into account the economic and social issues. A multi-sectoral economy-energy-environment model has been developed to perform a prospective analysis of the changes in the economic structure and the energy system, as well as to assess the corresponding environmental impacts, providing decision support in policy making. This model is a multi-objective linear programming model that allows for the explicit consideration of distinct axes of evaluation, generally conflicting and non-commensurate, of the merit of distinct policies. The policy recommendations obtained are subject to the inherent uncertainty associated with the model coefficients and, therefore, they may not be robust in face of changes of the input data. The specification of less energy or carbon-intensive technologies is done by considering pollutant/energy coefficients defined as intervals. This analysis is crucial for understanding the role of technology in carbon mitigation efforts and other energy system planning settings, allowing to explore the effects of distinct policies on the total system costs, the fuel and technology mix, and the levels of greenhouse gases and other emissions. 相似文献
90.
Carla F. Fávaro Tatiana B. Santos Paulo H. G. Zarbin 《Journal of chemical ecology》2012,38(9):1124-1132
Agroecus griseus is a serious corn pest in Brazil. Contents of the dorsal abdominal glands (DAGs) in nymphs, and the metathoracic gland (MTG) in adults of this species were characterized and quantified. Compounds found were similar to those of other Pentatomidae species and included aliphatic hydrocarbons, aldehydes, oxo-alkenals, and esters. However, two compounds were found in the MTG that have not been described previously for this family. Mass spectrometry, infrared spectroscopy, and gas chromatographic analysis using coinjection with authentic standards confirmed the identities of the compounds as enantiopure (S)-2-methylbutyl acetate and 3-methyl-2-butenyl acetate. The five nymphal instars showed significantly different ratios of components, mainly between those of the first and later instars. No significant differences were detected in MTG contents between sexes. Gas chromatography (GC) analysis of aeration extracts of males and females showed the presence of a compound released exclusively by males. Gas chromatography – electroantennographic detection (GC-EAD) assays indicated that the male-specific compound is bioactive in females, suggesting the presence of an attractant pheromone. The mass spectrum and infrared data for this compound matched with methyl 2,6,10-trimethyltridecanoate, a sex pheromone component previously detected in the stink bugs, Euschistus heros and E. obscurus. The synthetic standard coeluted with the natural pheromone on two different GC stationary phases, confirming the proposed structure. Y-tube olfactometer assays showed that the synthetic standard was strongly attractive to females, and GC-EAD tests produced responses with antennae from females similar to those of the natural pheromone. 相似文献