Modulation of exploratory behavior in female mice by protein-borne male urinary molecules

Male pheromones are believed to attract females and repel male mice in open field tests but, when tested in more complex environments, they can attract male mice in usually avoided areas. Females were tested in an apparatus with one dark and one light side, in the absence or presence of male urine or the major urinary proteins (MUPs) bearing the natural ligands. Diestrous females were slower in leaving from the dark area when male urine or MUPs were present in it. Estrogen-primed females showed the opposite behavior, with an increase in the same latency. The light-avoidance behavior of prepubertal females, or females reared without males was not influenced by the presence of male chemosignals. The results show that adult female mice can react to MUP-borne volatiles as to adult male urine and use them as cues of male mice, if they were previously exposed to male cues during infancy. MUP-borne molecules are, thus, the olfactory trace of males in the environment and modulate mice exploratory behavior.     

Mixture models for quantitative HIV RNA data

Clinical investigators are increasing their use of quantitative determinations of HIV viral load in their study populations. The distributions of these measures may be highly skewed, left-censored, and with an extra spike below the detection limit of the assay. We recommended use of a mixture model in this situation, with two sets of explanatory covariates. We extend this model to incorporate multiple measures across time, and to employ shared parameters as a way of increasing model efficiency and parsimony. Data from a cohort of HIV-infected men are used to illustrate these features, and simulations are performed to assess the utility of shared parameters.     

Male Urinary Chemosignals Differentially Affect Aggressive Behavior in Male Mice

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.     

Identification of potent human anti-IL-1RI antagonist antibodies

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 相似文献   

Quasi-Interpolants with Tension Properties from and in CAGD

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.     

Forensic analysis of poly(ethylene terephthalate) fibers by infrared spectroscopy

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.     

An Empirical Study of Two Approaches to Sequence Learning for Anomaly Detection

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.     

NMR structure of the (+)-CPI-indole/d(GACTAATTGAC)-d(GTCAATTAGTC) covalent complex

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.     

Relating Cost Growth from the Initial Estimate to Design Fee for Transportation Projects

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.