Dreaming of Mother and Home

https://digitalcommons.library.umaine.edu/mmb-vp/4597/thumbnail.jp

Effects of hyperlinks on navigation in virtual environments

Hyperlinks introduce discontinuities of movement to 3-D virtual environments (VEs). Nine independent attributes of hyperlinks are defined and their likely effects on navigation in VEs are discussed. Four experiments are described in which participants repeatedly navigated VEs that were either conventional (i.e. obeyed the laws of Euclidean space), or contained hyperlinks. Participants learned spatial knowledge slowly in both types of environment, echoing the findings of previous studies that used conventional VEs. The detrimental effects on participants' spatial knowledge of using hyperlinks for movement were reduced when a time-delay was introduced, but participants still developed less accurate knowledge than they did in the conventional VEs. Visual continuity had a greater influence on participants' rate of learning than continuity of movement, and participants were able to exploit hyperlinks that connected together disparate regions of a VE to reduce travel time

Ligand-Independent Adenosine A 2B Receptor Constitutive Activity as a Promoter of Prostate Cancer Cell Proliferation s

ABSTRACT Aberrant ligand-independent G protein-coupled receptor constitutive activity has been implicated in the pathophysiology of a number of cancers. The adenosine A 2B receptor (A 2B AR) is dynamically upregulated under pathologic conditions associated with a hypoxic microenvironment, including solid tumors. This, in turn, may amplify ligand-independent A 2B AR signal transduction. The contribution of A 2B AR constitutive activity to disease progression is currently unknown yet of fundamental importance, as the preferred therapeutic modality for drugs designed to reduce A 2B AR constitutive activity would be inverse agonism as opposed to neutral antagonism. The current study investigated A 2B AR constitutive activity in a heterologous expression system and a native 22Rv1 human prostate cancer cell line exposed to hypoxic conditions (2% O 2 ). (4-chlorophenyl)piperazide-1-sulfonyl)phenyl)-1-propylxanthine), mediated a concentration-dependent decrease in baseline cAMP levels in both cellular systems. Proliferation of multiple prostate cancer cell lines was also attenuated in the presence of PSB-603. Importantly, both the decrease in baseline cAMP accumulation and the reduction of proliferation were not influenced by the addition of adenosine deaminase, demonstrating that these effects are not dependent on stimulation of A 2B ARs by the endogenous agonist adenosine. Our study is the first to reveal that wild-type human A 2B ARs have high constitutive activity in both model and native cells. Furthermore, our findings demonstrate that this ligand-independent A 2B AR constitutive activity is sufficient to promote prostate cancer cell proliferation in vitro. More broadly, A 2B AR constitutive activity may have wider, currently unappreciated implications in pathologic conditions associated with a hypoxic microenvironment

Electrically pumped continuous wave quantum dot lasers epitaxially grown on patterned, on-axis (001) Si

High performance III-V lasers at datacom and telecom wavelengths on on-axis (001) Si are needed for scalable datacenter interconnect technologies. We demonstrate electrically injected quantum dot lasers grown on on-axis (001) Si patterned with {111} v-grooves lying in the [110] direction. No additional Ge buffers or substrate miscut was used. The active region consists of five InAs/InGaAs dot-in-a-well layers. We achieve continuous wave lasing with thresholds as low as 36 mA and operation up to 80°C

1.3 μm submilliamp threshold quantum dot micro-lasers on Si

As a promising integration platform, silicon photonics need on-chip laser sources that dramatically improve capability, while trimming size and power dissipation in a cost-effective way for volume manufacturability. Currently, direct heteroepitaxial growth of III–V laser structures on Si using quantum dots as the active region is a vibrant field of research, with the potential to demonstrate low-cost, high-yield, long-lifetime, and high-temperature devices. Ongoing work is being conducted to reduce the power consumption, maximize the operating temperature, and switch from miscut Si substrates toward the so-called exact (001) Si substrates that are standard in microelectronics fabrication. Here, we demonstrate record-small electrically pumped micro-lasers epitaxially grown on industry standard (001) silicon substrates. Continuous-wave lasing up to 100°C was demonstrated at 1.3 μm communication wavelength. A submilliamp threshold of 0.6 mA was achieved for a micro-laser with a radius of 5 μm. The thresholds and footprints are orders of magnitude smaller than those previously reported lasers epitaxially grown on Si

MISCAST : MIssense variant to protein StruCture Analysis web SuiTe

Human genome sequencing efforts have greatly expanded, and a plethora of missense variants identified both in patients and in the general population is now publicly accessible. Interpretation of the molecular-level effect of missense variants, however, remains challenging and requires a particular investigation of amino acid substitutions in the context of protein structure and function. Answers to questions like 'Is a variant perturbing a site involved in key macromolecular interactions and/or cellular signaling?', or 'Is a variant changing an amino acid located at the protein core or part of a cluster of known pathogenic mutations in 3D?' are crucial. Motivated by these needs, we developed MISCAST (missense variant to protein structure analysis web suite; http://miscast.broadinstitute.org/). MISCAST is an interactive and user-friendly web server to visualize and analyze missense variants in protein sequence and structure space. Additionally, a comprehensive set of protein structural and functional features have been aggregated in MISCAST from multiple databases, and displayed on structures alongside the variants to provide users with the biological context of the variant location in an integrated platform. We further made the annotated data and protein structures readily downloadable from MISCAST to foster advanced offline analysis of missense variants by a wide biological community.Peer reviewe

Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants

Interpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variations on protein structure and function being especially challenging. Here we characterize the three-dimensional (3D) amino acid positions affected in pathogenic and population variants from 1,330 disease-associated genes using over 14,000 experimentally solved human protein structures. By measuring the statistical burden of variations (i.e., point mutations) from all genes on 40 3D protein features, accounting for the structural, chemical, and functional context of the variations' positions, we identify features that are generally associated with pathogenic and population missense variants. We then perform the same amino acid-level analysis individually for 24 protein functional classes, which reveals unique characteristics of the positions of the altered amino acids: We observe up to 46% divergence of the class-specific features from the general characteristics obtained by the analysis on all genes, which is consistent with the structural diversity of essential regions across different protein classes. We demonstrate that the function-specific 3D features of the variants match the readouts of mutagenesis experiments for BRCA1 and PTEN, and positively correlate with an independent set of clinically interpreted pathogenic and benign missense variants. Finally, we make our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step toward translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the variants' pathogenicity in terms of the perturbed molecular mechanisms.Peer reviewe

The Non-linear Dynamics of Meaning-Processing in Social Systems

Social order cannot be considered as a stable phenomenon because it contains an order of reproduced expectations. When the expectations operate upon one another, they generate a non-linear dynamics that processes meaning. Specific meaning can be stabilized, for example, in social institutions, but all meaning arises from a horizon of possible meanings. Using Luhmann's (1984) social systems theory and Rosen's (1985) theory of anticipatory systems, I submit equations for modeling the processing of meaning in inter-human communication. First, a self-referential system can use a model of itself for the anticipation. Under the condition of functional differentiation, the social system can be expected to entertain a set of models; each model can also contain a model of the other models. Two anticipatory mechanisms are then possible: one transversal between the models, and a longitudinal one providing the modeled systems with meaning from the perspective of hindsight. A system containing two anticipatory mechanisms can become hyper-incursive. Without making decisions, however, a hyper-incursive system would be overloaded with uncertainty. Under this pressure, informed decisions tend to replace the "natural preferences" of agents and an order of cultural expectations can increasingly be shaped