Melanin granules cluster within supra-nuclear caps in basal keratinocytes (KCs) of the human epidermis, where they protect KC genomic DNA against ultraviolet radiation (UVR) damage. While much is known about melanogenesis in melanocytes (MCs) and a moderate amount about melanin transfer from MC to KC, we know little about the fate of melanin once inside KCs. We recently reported that melanin fate in progenitor KCs is regulated by rare asymmetric organelle movement during mitosis. Here, we explore the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. Short-term cultures of human skin explants were treated with cytochalasin-B and nocodazole to target actin filaments and microtubules, respectively. Treatment effects on melanin distribution were assessed by the Warthin–Starry stain, on centrosome-associated proteins by immunofluorescence microscopy, and on co-localisation with melanin granules by brightfield microscopy. Cytochalasin-B treatment disassembled supra-nuclear melanin caps, while nocodazole treatment moved melanin from the apical to basal KC domain. Centrosome and centriolar satellite-associated proteins showed a high degree of co-localisation with melanin. Thus, once melanin granules are transferred to KCs, their preferred apical distribution appears to be facilitated by coordinated movement of centrosomes and centriolar satellites. This mechanism may control melanin’s strategic position within UVR-exposed KCs. 相似文献
In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo. 相似文献
The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration. 相似文献
Melatonin and resistance exercise alone have been shown to increase the levels of growth hormone (GH). The purpose of this
study was to determine the effects of ingestion of a single dose of melatonin and heavy resistance exercise on serum GH, somatostatin
(SST), and other hormones of the GH/insulin-like growth factor 1 (IGF-1) axis. Physically active males (n = 30) and females
(n = 30) were randomly assigned to ingest either a melatonin supplement at 0.5 mg or 5.0 mg, or 1.0 mg of dextrose placebo.
After a baseline blood sample, participants ingested the supplement and underwent blood sampling every 15 min for 60 min,
at which point they underwent a single bout of resistance exercise with the leg press for 7 sets of 7 reps at 85% 1-RM. After
exercise, participants provided additional blood samples every 15 min for a total of 120 min. Serum free GH, SST, IGF-1, IGFBP-1,
and IGFBP-3 were determined with ELISA. Data were evaluated as the peak pre- and post-exercise values subtracted from baseline
and the delta values analyzed with separate three-way ANOVA (p < 0.05). In males, when compared to placebo, 5.0 mg melatonin
caused GH to increase (p = 0.017) and SST to decrease prior to exercise (p = 0.031), whereas both 0.5 and 5.0 mg melatonin
were greater than placebo after exercise (p = 0.045) and less than placebo for SST. No significant differences occurred for
IGF-1; however, males were shown to have higher levels of IGFBP-1 independent of supplementation (p = 0.004). The 5.0 mg melatonin
dose resulted in higher IGFBP-3 in males (p = 0.017). In conclusion, for males 5.0 mg melatonin appears to increase serum
GH while concomitantly lowering SST levels; however, when combined with resistance exercise both melatonin doses positively
impacts GH levels in a manner not entirely dependent on SST. 相似文献
We present the evolution and current state of the Mr. Racer car racing controller that excelled at the corresponding TORCS competitions of the last years. Although several heuristics and black-box optimization methods are employed, the basic idea of the controller architecture has been to take over many of the mechanisms human racing drivers apply. They learn the track geometry, plan ahead, and wherever necessary, adapt their plans to the current circumstances quickly. Mr. Racer consists of several modules that have partly been adapted and optimized separately, where the final tuning is usually done with respect to a certain racing track during the warmup phase of the TORCS competitions. We also undertake an experimental evaluation that investigates how the controller profits from adding some of the modules to a basic configuration and which modules are most important for reaching the best possible performance. 相似文献
The computation of a six-dimensional density matrix is the crucial step for the evaluation of kinetic energy in electronic structure calculations. For molecules with heavy nuclei, one has to consider a very refined mesh in order to deal with the nuclear cusps. This leads to high computational time and needs huge memory for the computation of the density matrix. To reduce the computational complexity and avoid discretization errors in the approximation, we use mesh-free canonical tensor products in electronic structure calculations. In this paper, we approximate the six-dimensional density matrix in an efficient way and then compute the kinetic energy. Accuracy is examined by comparing our computed kinetic energy with the exact computation of the kinetic energy. 相似文献
This paper explores the limitations of contemporary interface design and offers the potential of more profound forms of interaction by drawing on the rich and much older heritage of interactive art. Whilst HCI design is preoccupied with making the computer more simple to use, installation work, kinetic sculpture, and interactive multimedia art forms have generally been more concerned with the predicament of human/technological negotiation, whilst remaining a salient form of human communication. HCI activity sets out to make the complex systems of computing easy to understand and use, whilst interactive art often uses simple technology to make complex, inspiring and esoteric statements and experiences. In many ways the more simple and 'low resolution' the technology the more immersive, acute and intimate the experience. 'Low resolution' examples such as telephone-sex-lines are explored alongside more immersive systems, such as biofeedback interfaces, and other interactive experiments drawn from the 'technic' strand of art history. 相似文献
Conventionally drought severity is assessed based on drought indices. Recently the Reconnaissance Drought Index (RDI) was
proposed to assess drought severity based on the precipitation to potential evapotranspiration ratio (P/PET). In this paper
RDI is studied as a bivariate index under a set of assumptions and simplifications. The paper presents a simple computational
procedure for estimating the P/PET ratio for selected reference periods varying from 3 to 12 months, for any return period
of drought. Alternatively, based on this procedure, the severity of any drought episode is rationally assessed. A bivariate
probability analysis is employed based on the assumption that P and PET values are normally distributed and often negatively
correlated. Examples for the application of the proposed procedure are presented using data from several meteorological stations
in Greece. It is shown that the assumption of normality of both P and PET holds for long periods at all examined stations. 相似文献
Managing the resources in a large Web serving system requires knowledge of the resource needs for service requests of various types. In order to investigate the properties of Web traffic and its demand, we collected measurements of throughput and CPU utilization and performed some data analyses. First, we present our findings in relation to the time-varying nature of the traffic, the skewness of traffic intensity among the various types of requests, the correlation among traffic streams, and other system-related phenomena. Then, given such nature of web traffic, we devise and implement an on-line method for the dynamic estimation of CPU demand.
Assessing resource needs is commonly performed using techniques such as off-line profiling, application instrumentation, and kernel-based instrumentation. Little attention has been given to the dynamic estimation of dynamic resource needs, relying only on external and high-level measurements such as overall resource utilization and request rates. We consider the problem of dynamically estimating dynamic CPU demands of multiple kinds of requests using CPU utilization and throughput measurements. We formulate the problem as a multivariate linear regression problem and obtain its basic solution. However, as our measurement data analysis indicates, one is faced with issues such as insignificant flows, collinear flows, space and temporal variations, and background noise. In order to deal with such issues, we present several mechanisms such as data aging, flow rejection, flow combining, noise reduction, and smoothing. We implemented these techniques in a Work Profiler component that we delivered as part of a broader system management product. We present experimental results from using this component in scenarios inspired by real-world usage of that product. 相似文献