47 research outputs found

    Ro 04-6790-induced cognitive enhancement: No effect in trace conditioning and novel object recognition procedures in adult male Wistar rats

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    The evidence for cognitively enhancing effects of 5-hydroxytryptamine6 (5-HT6) receptor antagonists such as Ro 04-6790 is inconsistent and seems to depend on the behavioural test variant in use. Trace conditioning holds promise as a behavioral assay for hippocampus-dependent working memory function. Accordingly, Experiment 1 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on associating a noise conditioned stimulus paired with foot shock (unconditioned stimulus) at a 3 or 30 s trace interval in adult male Wistar rats. Contextual conditioning was measured as suppression to the contextual cues provided by the experimental chambers and as suppression to a temporally extended light background stimulus which provided an experimental context. Experiment 2 assessed the effect of Ro 04-6790 (5 and 10 mg/kg i.p.) on recognition memory as tested by the exploration of novel relative to familiar objects in an open arena. In Experiment 1, Ro 04-6790 (5 and 10 mg/kg) was without effect on trace and contextual conditioning. In Experiment 2, there was no indication of the expected improvement under Ro 04-6790 at the same doses previously found to enhance recognition memory as measured in tests of novel object exploration. Thus, there was no evidence that treatment with the 5-HT6 receptor antagonist Ro 04-6790 acted as a cognitive enhancer in either trace conditioning or object recognition procedures. We cannot exclude the possibility that the experimental procedures used in the present study would have been sensitive to the cognitive enhancing effects of Ro 04-6790 in a different dose range, behavioral test variant, or in a different strain of rat. Nonetheless the drug treatment was not ineffective in that object exploration was reduced under 10 mg/kg Ro 04-6790

    Developing manufacturing control software: A survey and critique

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    The complexity and diversity of manufacturing software and the need to adapt this software to the frequent changes in the production requirements necessitate the use of a systematic approach to developing this software. The software life-cycle model (Royce, 1970) that consists of specifying the requirements of a software system, designing, implementing, testing, and evolving this software can be followed when developing large portions of manufacturing software. However, the presence of hardware devices in these systems and the high costs of acquiring and operating hardware devices further complicate the manufacturing software development process and require that the functionality of this software be extended to incorporate simulation and prototyping.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45542/1/10696_2005_Article_BF01328739.pd

    A line-balancing strategy for designing flexible assembly systems

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    We present a rough-cut analysis tool that quickly determines a few potential cost-effective designs at the initial design stage of flexible assembly systems (FASs) prior to a detailed analysis such as simulation. It uses quantitative methods for selecting and configuring the components of an FAS suitable for medium to high volumes of several similar products. The system is organized as a series of assembly stations linked with an automated material-handling system moving parts in a unidirectional flow. Each station consists of a single machine or of identical parallel machines. The methods exploit the ability of flexible hardware to switch almost instantaneously from product to product. Our approach is particularly suitable where the product mix is expected to be stable, since we combine the hardware-configuration phase with the task-allocation phase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45513/1/10696_2004_Article_BF00167513.pd

    UBVRI Light curves of 44 Type Ia supernovae

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    We present UBVRI photometry of 44 Type la supernovae (SNe la) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SNe la to date, nearly doubling the number of well-observed, nearby SNe la with published multicolor CCD light curves. The large sample of [U-band photometry is a unique addition, with important connections to SNe la observed at high redshift. The decline rate of SN la U-band light curves correlates well with the decline rate in other bands, as does the U - B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ∼40% intrinsic scatter compared to the B band

    Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

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    The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

    Mind the gap: the ratio of yolk androgens and antioxidants varies between sons and daughters dependent on paternal attractiveness

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    Females are expected to partition resources between offspring in a context-dependent way to maximise total fitness returns from a reproductive attempt. Female zebra finches (Taeniopygia guttata) vary the allocation of yolk androgens and antioxidants among offspring. Importantly, the balance between androgens and antioxidants in yolks may be more important than their independent absolute amounts in terms of fitness consequences for developing young. Therefore, we tested whether the relative allocation of these two resources in yolks varies according to either the Trivers-Willard, positive or compensatory maternal investment hypothesis. We manipulated male attractiveness using coloured leg bands (red-banded males appear attractive; green-banded males, unattractive) and measured yolk androgens and antioxidants in each egg, egg sex, clutch sex ratio and female condition. While female zebra finches manipulated the balance of androgens and antioxidants within and between clutches in response to mate attractiveness, offspring sex and their own condition, they did not do so in a way that consistently followed any of the hypotheses. Mothers paired with unattractive males allocated a larger antioxidant/androgen ratio to daughters than sons. This pattern was reversed when paired to an attractive male; sons received a larger antioxidant/androgen ratio than daughters. We also found offspring sex ratio decreased with increasing female condition for unattractive males, but not for attractive males. However, without knowing the fitness consequences of the balance of different egg constituents, it is difficult to interpret the patterns consistently in terms of the Trivers-Willard, compensatory and positive investment hypothese

    Mind the gap: the ratio of yolk androgens and antioxidants varies between sons and daughters dependent on paternal attractiveness

    No full text
    Females are expected to partition resources between offspring in a context-dependent way to maximise total fitness returns from a reproductive attempt. Female zebra finches (Taeniopygia guttata) vary the allocation of yolk androgens and antioxidants among offspring. Importantly, the balance between androgens and antioxidants in yolks may be more important than their independent absolute amounts in terms of fitness consequences for developing young. Therefore, we tested whether the relative allocation of these two resources in yolks varies according to either the Trivers-Willard, positive or compensatory maternal investment hypothesis. We manipulated male attractiveness using coloured leg bands (red-banded males appear attractive; green-banded males, unattractive) and measured yolk androgens and antioxidants in each egg, egg sex, clutch sex ratio and female condition. While female zebra finches manipulated the balance of androgens and antioxidants within and between clutches in response to mate attractiveness, offspring sex and their own condition, they did not do so in a way that consistently followed any of the hypotheses. Mothers paired with unattractive males allocated a larger antioxidant/androgen ratio to daughters than sons. This pattern was reversed when paired to an attractive male; sons received a larger antioxidant/androgen ratio than daughters. We also found offspring sex ratio decreased with increasing female condition for unattractive males, but not for attractive males. However, without knowing the fitness consequences of the balance of different egg constituents, it is difficult to interpret the patterns consistently in terms of the Trivers-Willard, compensatory and positive investment hypotheses.</p

    Sex allocation in response to paternal attractiveness in the zebra finch

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    Females mated to attractive males are predicted to produce male-biased broods. Previous studies on zebra finches, Taeniopygia guttata, in which colored leg rings were used to alter male attractiveness, support this hypothesis. However, because molecular sexing techniques were not available, it was not known when during development this bias arose. Also, because both attractive (red-ringed) and unattractive (green-ringed) males were within the same aviary, assortative mating between treatments may have confounded the results. Using two different experimental designs, we tested whether the sex ratio of zebra finch eggs and chicks differed in response to paternal ring color whilst controlling for assortative mating between treatments. In the aviary experiment, birds could interact socially, but all males in an aviary bad the same leg ring color. In the cage experiment, each female was randomly assigned a red- or green-ringed mate, thus also eliminating assortative mating within treatments. Offspring were sexed based on plumage or using a molecular method. The sex ratio at laying did not differ between treatments in either the aviary (n = 313 eggs) or cage (n = 151 eggs) experiments, suggesting that female zebra finches do not manipulate the primary sex ratio in response to their mate's ring color. However, in the cage experiment we found greater male embryonic mortality, in the attractive group, Which resulted in a female-biased sex ratio at sexual maturity, that is, in the opposite direction to that found in previous studies. Possible explanations for the disparity between our results and those of previous studies are considered.</p

    Race, Genetics and Health: An Introduction

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    Health disparities, Race, Ethnicity, Genes, Race-specific illnesses, Race-specific diseases, Individualized medicine, Racialized medicine, BiDil, Pharmacogenetics, Genomics,
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