Suppression of pro-inflammatory cytokine release by selective inhibition of inducible nitric oxide synthase in mucosal explants from patients with ulcerative colitis

Peer reviewe

Visualizing multi-dimensional pareto-optimal fronts with a 3D virtual reality system

In multiobjective optimization, there are several targets that are in conflict, and thus they all cannot reach their optimum simultaneously. Hence, the solutions of the problem form a set of compromised trade-off solutions (a Pareto-optimal front or Pareto-optimal solutions) from which the best solution for the particular problem can be chosen. However, finding that best compromise solution is not an easy task for the human mind. Pareto-optimal fronts are often visualized for this purpose because in this way a comparison between solutions according to their location on the Pareto-optimal front becomes somewhat easier. Visualizing a Pareto-optimal front is straightforward when there are only two targets (or objective functions), but visualizing a front for more than two objective functions becomes a difficult task. In this paper, we introduce a new and innovative method of using three-dimensional virtual reality (VR) facilities to present multi-dimensional Pareto-optimal fronts. Rotation, zooming and other navigation possibilities of VR facilities make easy to compare different trade-off solutions, and fewer solutions need to be explored in order to understand the interrelationships among conflicting objective functions. In addition, it can be used to highlight and characterize interesting features of specific Pareto-optimal solutions, such as whether a particular solution is close to a constraint boundary or whether a solution lies on a relatively steep trade-off region. Based on these additional visual aids for analyzing trade-off solutions, a preferred compromise solution may be easier to choose than by other means

Applying mass spectrometric methods to study androgen biosynthesis and metabolism in prostate cancer

Recent development of gas chromatography and liquid chromatography-tandem mass spectrometry (GC-MS/MS, LC-MS/MS) has provided novel tools to define sex steroid concentrations. These new methods overcome several of the problems associated with immunoassays for sex steroids. With the novel MS-based applications we are now able to measure small concentrations of the steroid hormones reliably and with high accuracy in both body fluids and tissue homogenates. The sensitivity of the tandem mass spectrometry assays allows us also for the first time to reliably measure picomolar or even femtomolar concentrations of estrogens and androgens. Furthermore, due to a high sensitivity and specificity of MS technology, we are also able to measure low concentrations of steroid hormones of interest in the presence of pharmacological concentration of other steroids and structurally closely related compounds. Both of these features are essential for multiple preclinical models for prostate cancer. The MS assays are also valuable for the simultaneous measurement of multiple steroids and their metabolites in small sample volumes in serum and tissue biopsies of prostate cancer patients before and after drug interventions. As a result, novel information about steroid hormone synthesis and metabolic pathways in prostate cancer has been obtained. In our recent studies, we have extensively applied a GC-MS/MS method to study androgen biosynthesis and metabolism in VCaP prostate cancer xenografts in mice. In the present review, we shortly summarize some of the benefits of the GC-MS/MS and novel LC-MS/MS assays, and provide examples of their use in defining novel mechanisms of androgen action in prostate cancer

The Origin And Loss Of Periodic Patterning In The Turtle Shell

The origin of the turtle shell over 200 million years ago greatly modified the amniote body plan, and the morphological plasticity of the shell has promoted the adaptive radiation of turtles. The shell, comprising a dorsal carapace and a ventral plastron, is a layered structure formed by basal endochondral axial skeletal elements (ribs, vertebrae) and plates of bone, which are overlain by keratinous ectodermal scutes. Studies of turtle development have mostly focused on the bones of the shell; however, the genetic regulation of the epidermal scutes has not been investigated. Here, we show that scutes develop from an array of patterned placodes and that these placodes are absent from a soft-shelled turtle in which scutes were lost secondarily. Experimentally inhibiting Shh, Bmp or Fgf signaling results in the disruption of the placodal pattern. Finally, a computational model is used to show how two coupled reaction-diffusion systems reproduce both natural and abnormal variation in turtle scutes. Taken together, these placodal signaling centers are likely to represent developmental modules that are responsible for the evolution of scutes in turtles, and the regulation of these centers has allowed for the diversification of the turtle shell

The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis

Peer reviewe

The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis

Peer reviewe

Attention Drives Synchronization of Alpha and Beta Rhythms between Right Inferior Frontal and Primary Sensory Neocortex

The right inferior frontal cortex (rIFC) is specifically associated with attentional control via the inhibition of behaviorally irrelevant stimuli and motor responses. Similarly, recent evidence has shown that alpha (7–14 Hz) and beta (15–29 Hz) oscillations in primary sensory neocortical areas are enhanced in the representation of non-attended stimuli, leading to the hypothesis that allocation of these rhythms plays an active role in optimal inattention. Here, we tested the hypothesis that selective synchronization between rIFC and primary sensory neocortex occurs in these frequency bands during inattention. We used magnetoencephalography to investigate phase synchrony between primary somatosensory (SI) and rIFC regions during a cued-attention tactile detection task that required suppression of response to uncertain distractor stimuli. Attentional modulation of synchrony between SI and rIFC was found in both the alpha and beta frequency bands. This synchrony manifested as an increase in the alpha-band early after cue between non-attended SI representations and rIFC, and as a subsequent increase in beta-band synchrony closer to stimulus processing. Differences in phase synchrony were not found in several proximal control regions. These results are the first to reveal distinct interactions between primary sensory cortex and rIFC in humans and suggest that synchrony between rIFC and primary sensory representations plays a role in the inhibition of irrelevant sensory stimuli and motor responses.National Institutes of Health (U.S.) (Grant P41RR14075)National Institutes of Health (U.S.) (Grant K25MH072941)National Institutes of Health (U.S.) (Grant K01AT003459)National Institutes of Health (U.S.) (Grant K24AT004095)National Institutes of Health (U.S.) (Grant RO1-NS045130-01)National Institutes of Health (U.S.) (Grant T32GM007484)National Science Foundation (U.S.) (Grant 0316933)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant DGE-1147470

KLEIN: A New Family of Lightweight Block Ciphers

Resource-efficient cryptographic primitives become fundamental for realizing both security and efficiency in embedded systems like RFID tags and sensor nodes. Among those primitives, lightweight block cipher plays a major role as a building block for security protocols. In this paper, we describe a new family of lightweight block ciphers named KLEIN, which is designed for resource-constrained devices such as wireless sensors and RFID tags. Compared to the related proposals, KLEIN has advantage in the software performance on legacy sensor platforms, while in the same time its hardware implementation can also be compact