Generation and reproductive phenotypes of mice lacking estrogen receptor β

Estrogens influence the differentiation and maintenance of reproductive tissues and affect lipid metabolism and bone remodeling. Two estrogen receptors (ERs) have been identified to date, ERα and ERβ. We previously generated and studied knockout mice lacking estrogen receptor α and reported severe reproductive and behavioral phenotypes including complete infertility of both male and female mice and absence of breast tissue development. Here we describe the generation of mice lacking estrogen receptor β (ERβ −/−) by insertion of a neomycin resistance gene into exon 3 of the coding gene by using homologous recombination in embryonic stem cells. Mice lacking this receptor develop normally and are indistinguishable grossly and histologically as young adults from their littermates. RNA analysis and immunocytochemistry show that tissues from ERβ −/− mice lack normal ERβ RNA and protein. Breeding experiments with young, sexually mature females show that they are fertile and exhibit normal sexual behavior, but have fewer and smaller litters than wild-type mice. Superovulation experiments indicate that this reduction in fertility is the result of reduced ovarian efficiency. The mutant females have normal breast development and lactate normally. Young, sexually mature male mice show no overt abnormalities and reproduce normally. Older mutant males display signs of prostate and bladder hyperplasia. Our results indicate that ERβ is essential for normal ovulation efficiency but is not essential for female or male sexual differentiation, fertility, or lactation. Future experiments are required to determine the role of ERβ in bone and cardiovascular homeostasis.

Verb generation in patients with focal frontal lesions: A neuropsychological test of neuroimaging findings

What are the neural bases of semantic memory? Traditional beliefs that the temporal lobes subserve the retrieval of semantic knowledge, arising from lesion studies, have been recently called into question by functional neuroimaging studies finding correlations between semantic retrieval and activity in left prefrontal cortex. Has neuroimaging taught us something new about the neural bases of cognition that older methods could not reveal or has it merely identified brain activity that is correlated with but not causally related to the process of semantic retrieval? We examined the ability of patients with focal frontal lesions to perform a task commonly used in neuroimaging experiments, the generation of semantically appropriate action words for concrete nouns, and found evidence of the necessity of the left inferior frontal gyrus for certain components of the verb generation task. Notably, these components did not include semantic retrieval per se.

Localized Changes in Peroxidase Activity Accompany Hydrogen Peroxide Generation during the Development of a Nonhost Hypersensitive Reaction in Lettuce1

Peroxidase activity was characterized in lettuce (Lactuca sativa L.) leaf tissue. Changes in the activity and distribution of the enzyme were examined during the development of a nonhost hypersensitive reaction (HR) induced by Pseudomonas syringae (P. s.) pv phaseolicola and in response to an hrp mutant of the bacterium. Assays of activity in tissue extracts revealed pH optima of 4.5, 6.0, 5.5 to 6.0, and 6.0 to 6.5 for the substrates tetramethylbenzidine, guaiacol, caffeic acid, and chlorogenic acid, respectively. Inoculation with water or with wild-type or hrp mutant strains of P. s. pv phaseolicola caused an initial decline in total peroxidase activity; subsequent increases depended on the hydrogen donor used in the assay. Guaiacol peroxidase recovered more rapidly in tissues undergoing the HR, whereas changes in tetramethylbenzidine peroxidase were generally similar in the two interactions. In contrast, increases in chlorogenic acid peroxidase were significantly higher in tissues inoculated with the hrp mutant. During the HR, increased levels of Mn2+/2,4-dichlorophenol-stimulated NADH and NADPH oxidase activities, characteristic of certain peroxidases, were found in intercellular fluids and closely matched the accumulation of H2O2 in the apoplast. Histochemical analysis of peroxidase distribution by electron microscopy revealed a striking, highly localized increase in activity within the endomembrane system and cell wall at the sites of bacterial attachment. However, no clear differences in peroxidase location were observed in tissue challenged by the wild-type strain or the hrp mutant. Our results highlight the significance of the subcellular control of oxidative reactions leading to the generation of reactive oxygen species, cell wall alterations, and the HR.

Source and Magnitude of Ammonium Generation in Maize Roots1

Studies with 15N indicate that appreciable generation of NH4+ from endogenous sources accompanies the uptake and assimilation of exogenous NH4+ by roots. To identify the source of NH4+ generation, maize (Zea mays L.) seedlings were grown on 14NH4+ and then exposed for 3 d to highly labeled 15NH4+. More of the entering 15NH4+ was incorporated into the protein-N fraction of roots in darkness (approximately 25%) than in the light (approximately 14%). Although the 14NH4+ content of roots declined rapidly to less than 1 μmol per plant, efflux of 14NH4+ continued throughout the 3-d period at an average daily rate of 14 μmol per plant. As a consequence, cumulative 14NH4+ efflux during the 3-d period accounted for 25% of the total 14N initially present in the root. Although soluble organic 14N in roots declined during the 3-d period, insoluble 14N remained relatively constant. In shoots both soluble organic 14N and 14NH4+ declined, but a comparable increase in insoluble 14N was noted. Thus, total 14N in shoots remained constant, reflecting little or no net redistribution of 14N between shoots and roots. Collectively, these observations reveal that catabolism of soluble organic N, not protein N, is the primary source of endogenous NH4+ generation in maize roots.

Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia.

Working memory refers to the ability of the brain to store and manipulate information over brief time periods, ranging from seconds to minutes. As opposed to long-term memory, which is critically dependent upon hippocampal processing, critical substrates for working memory are distributed in a modality-specific fashion throughout cortex. N-methyl-D-aspartate (NMDA) receptors play a crucial role in the initiation of long-term memory. Neurochemical mechanisms underlying the transient memory storage required for working memory, however, remain obscure. Auditory sensory memory, which refers to the ability of the brain to retain transient representations of the physical features (e.g., pitch) of simple auditory stimuli for periods of up to approximately 30 sec, represents one of the simplest components of the brain working memory system. Functioning of the auditory sensory memory system is indexed by the generation of a well-defined event-related potential, termed mismatch negativity (MMN). MMN can thus be used as an objective index of auditory sensory memory functioning and a probe for investigating underlying neurochemical mechanisms. Monkeys generate cortical activity in response to deviant stimuli that closely resembles human MMN. This study uses a combination of intracortical recording and pharmacological micromanipulations in awake monkeys to demonstrate that both competitive and noncompetitive NMDA antagonists block the generation of MMN without affecting prior obligatory activity in primary auditory cortex. These findings suggest that, on a neurophysiological level, MMN represents selective current flow through open, unblocked NMDA channels. Furthermore, they suggest a crucial role of cortical NMDA receptors in the assessment of stimulus familiarity/unfamiliarity, which is a key process underlying working memory performance.

Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries.

Proteolysis of short N alpha-protected peptide substrates bound to polyoxyethylene-polystyrene beads releases selectively free amino sites in the enzyme-accessible "surface" area. The substantial majority of functional sites in the "interior" of the polymeric support are not reached by the enzyme and remain uncleaved (protected). Subsequent synthesis with two classes of orthogonal protecting groups-N alpha-tert-butyloxycarbonyl (Boc) and N alpha-9-fluorenylmethyloxy-carbonyl (Fmoc)-allows generation of two structures on the same bead. The surface structure is available for receptor interactions, whereas the corresponding interior structure is used for coding. Coding structures are usually readily sequenceable peptides. This "shaving" methodology was illustrated by the preparation of a peptide-encoded model peptide combinatorial library containing 1.0 x 10(5) members at approximately 6-fold degeneracy. From this single library, good ligands were selected for three different receptors: anti-beta-endorphin anti-body, streptavidin, and thrombin, and the binding structures were deduced correctly by sequencing the coding peptides present on the same beads.

Study of plutonium oxide heat generation in a wood moderated container /

The generation of heat due to the radioactive decay of plutonium in the form of plutonium dioxide stored in wooden containers is considered. The results of two experiments in which plutonium dioxide is placed inside wooden blocks and the temperature rise measured at various points is reported. Heat transfer calculations are then performed to show that the data obtained are those which would be expected, i.e., that Fourier's Law adequately describes the situation. The heat build up in a proposed wood moderated shipping container is calculated, using some of the assumptions verified in the described experiments.

Long wave generation by the shoaling and breaking of transient wave groups on a beach

This paper presents new laboratory data on the generation of long waves by the shoaling and breaking of transient-focused short-wave groups. Direct offshore radiation of long waves from the breakpoint is shown experimentally for the first time. High spatial resolution enables identification of the relationship between the spatial gradients of the short-wave envelope and the long-wave surface. This relationship is consistent with radiation stress theory even well inside the surf zone and appears as a result of the strong nonlinear forcing associated with the transient group. In shallow water, the change in depth across the group leads to asymmetry in the forcing which generates significant dynamic setup in front of the group during shoaling. Strong amplification of the incident dynamic setup occurs after short-wave breaking. The data show the radiation of a transient long wave dominated by a pulse of positive elevation, preceded and followed by weaker trailing waves with negative elevation. The instantaneous cross-shore structure of the long wave shows the mechanics of the reflection process and the formation of a transient node in the inner surf zone. The wave run-up and relative amplitude of the radiated and incident long waves suggests significant modification of the incident bound wave in the inner surf zone and, the dominance of long waves generated by the breaking process. It is proposed that these conditions occur when the primary short waves and bound wave are not shallow water waves at the breakpoint. A simple criterion is given to determine these conditions, which generally occur for the important case of storm waves.

Experimental optimization of triangular pulse generation in normal dispersion fiber for all optical processing applications

We experimentally investigate a multi-parameter optimization of conditions for generation of triangular pulses in normal dispersion fiber. We find that triangular pulses suitable for all optical processing applications can be generated for a wide range of input pulse chirps but that triangular pulse quality and stability is improved with increased input pulse chirp.

Comparison of frequency symmetric signal generation from a BPSK input using fiber and semiconductor-based nonlinear elements

This letter compares two nonlinear media for simultaneous carrier recovery and generation of frequency symmetric signals from a 42.7-Gb/s nonreturn-to-zero binary phase-shift-keyed input by exploiting four-wave mixing in a semiconductor optical amplifier and a highly nonlinear optical fiber for use in a phase-sensitive amplifier.

Using architecture models to support the generation and operation of component-based adaptive systems

Modelling architectural information is particularly important because of the acknowledged crucial role of software architecture in raising the level of abstraction during development. In the MDE area, the level of abstraction of models has frequently been related to low-level design concepts. However, model-driven techniques can be further exploited to model software artefacts that take into account the architecture of the system and its changes according to variations of the environment. In this paper, we propose model-driven techniques and dynamic variability as concepts useful for modelling the dynamic fluctuation of the environment and its impact on the architecture. Using the mappings from the models to implementation, generative techniques allow the (semi) automatic generation of artefacts making the process more efficient and promoting software reuse. The automatic generation of configurations and reconfigurations from models provides the basis for safer execution. The architectural perspective offered by the models shift focus away from implementation details to the whole view of the system and its runtime change promoting high-level analysis. © 2009 Springer Berlin Heidelberg.

Multimodal spectral control of a quantum-dot diode laser for THz difference frequency generation

Generation of stable dual and/or multiple longitudinal modes emitted from a single quantum dot (QD) laser diode (LD) over a broad wavelength range by using volume Bragg gratings (VBG's) in an external cavity setup is reported. The LD operates in both the ground and excited states and the gratings give a dual-mode separation around each emission peak of 5 nm, which is suitable as a continuous wave (CW) optical pump signal for a terahertz (THz) photomixer device. The setup also generates dual modes around both 1180m and 1260 nm simultaneously, giving four simultaneous narrow linewidth modes comprising two simultaneous difference frequency pump signals. (C) 2011 American Institute of Physics.

Generation and performance of localised surface plasmons utilising nano-scale structured multi-layered thin films deposited upon D-shaped optical fiber

A new generation of surface plasmonic optical fibre sensors is fabricated using multiple coatings deposited on a lapped section of a single mode fibre. Post-deposition UV laser irradiation using a phase mask produces a nano-scaled surface relief grating structure, resembling nano-wires. The overall length of the individual corrugations is approximately 14 μm with an average full width half maximum of 100 nm. Evidence is presented to show that these surface structures result from material compaction created by the silicon dioxide and germanium layers in the multi-layered coating and the surface topology is capable of supporting localised surface plasmons. The coating compaction induces a strain gradient into the D-shaped optical fibre that generates an asymmetric periodic refractive index profile which enhances the coupling of the light from the core of the fibre to plasmons on the surface of the coating. Experimental data are presented that show changes in spectral characteristics after UV processing and that the performance of the sensors increases from that of their pre-UV irradiation state. The enhanced performance is illustrated with regards to change in external refractive index and demonstrates high spectral sensitivities in gaseous and aqueous index regimes ranging up to 4000 nm/RIU for wavelength and 800 dB/RIU for intensity. The devices generate surface plasmons over a very large wavelength range, (visible to 2 μm) depending on the polarization state of the illuminating light. © 2013 SPIE.

A Method of Context-sensitive Help Generation Using a Task Project

The article presents a new method to automatic generation of help in software. Help generation is realized in the framework of the tool for development and automatic generation of user interfaces based on ontologies. The principal features of the approach are: support for context-sensitive help, automatic generation of help using a task project and an expandable system of help generation.

Networks, space and organisational performance:a study of the determinants of industrial research income generation by universities

This paper examines the extent to which both network structure and spatial factors impact on the organizational performance of universities as measured by the generation of industrial research income. Drawing on data concerning the interactions of universities in the UK with large research and development (R&D)-intensive firms, the paper employs both social network analysis and regression analysis. It is found that the structural position of a university within networks with large R&D-intensive firms is significantly associated with the level of research income gained from industry. Spatial factors, on the other hand, are not found to be clearly associated with performance, suggesting that universities operate on a level playing field across regional environments once other factors are controlled for.