264 research outputs found

    Surface nanoscale axial photonics: Robust fabrication of high quality factor microresonators

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    Recently introduced Surface Nanoscale Axial Photonics (SNAP) makes it possible to fabricate high Q-factor microresonators and other photonic microdevices by dramatically small deformation of the optical fiber surface. To become a practical and robust technology, the SNAP platform requires methods enabling reproducible modification of the optical fiber radius at nanoscale. In this Letter, we demonstrate super-accurate fabrication of high Q-factor microresonators by nanoscale modification of the optical fiber radius and refractive index using the CO2 laser and the UV excimer laser beam exposures. The achieved fabrication accuracy is better than 2 angstroms in variation of the effective fiber radius

    UVB-induced nuclear translocation of TC-PTP by AKT/14-3-3σ axis inhibits keratinocyte survival and proliferation

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    Understanding protein subcellular localization is important to determining the functional role of specific proteins. T-cell protein tyrosine phosphatase (TC-PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C-terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45) is mainly localized to the cytoplasm in keratinocytes and it is translocated to the nucleus following UVB irradiation. Here, we report that TC45 is translocated by an AKT/14-3-3σ-mediated mechanism in response to UVB exposure, resulting in increased apoptosis and decreased keratinocyte proliferation. We demonstrate that UVB irradiation increased phosphorylation of AKT and induced nuclear translocation of 14-3-3σ and TC45. However, inhibition of AKT blocked nuclear translocation of TC45 and 14-3-3σ. Site-directed mutagenesis of 14-3-3σ binding sites within TC45 showed that a substitution at Threonine 179 (TC45/T179A) effectively blocked UVB-induced nuclear translocation of ectopic TC45 due to the disruption of the direct binding between TC45 and 14-3-3σ. Overexpression of TC45/T179A in keratinocytes resulted in a decrease of UVB-induced apoptosis which corresponded to an increase in nuclear phosphorylated STAT3, and cell proliferation was higher in TC45/T179A-overexpressing keratinocytes compared to control keratinocytes following UVB irradiation. Furthermore, deletion of TC45 NLSII blocked its UVB-induced nuclear translocation, indicating that both T179 and NLSII are required. Taken together, our findings suggest that AKT and 14-3-3σ cooperatively regulate TC45 nuclear translocation in a critical step of an early protective mechanism against UVB exposure that signals the deactivation of STAT3 in order to promote keratinocyte cell death and inhibit keratinocyte proliferation

    The effectiveness of manual stretching in the treatment of plantar heel pain: a systematic review

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    Background: Plantar heel pain is a commonly occurring foot complaint. Stretching is frequently utilised as a treatment, yet a systematic review focusing only on its effectiveness has not been published. This review aimed to assess the effectiveness of stretching on pain and function in people with plantar heel pain. Methods: Medline, EMBASE, CINAHL, AMED, and The Cochrane Library were searched from inception to July 2010. Studies fulfilling the inclusion criteria were independently assessed, and their quality evaluated using the modified PEDro scale. Results: Six studies including 365 symptomatic participants were included. Two compared stretching with a control, one study compared stretching to an alternative intervention, one study compared stretching to both alternative and control interventions, and two compared different stretching techniques and durations. Quality rating on the modified Pedro scale varied from two to eight out of a maximum of ten points. The methodologies and interventions varied significantly between studies, making meta-analysis inappropriate. Most participants improved over the course of the studies, but when stretching was compared to alternative or control interventions, the changes only reached statistical significance in one study that used a combination of calf muscle stretches and plantar fascia stretches in their stretching programme. Another study comparing different stretching techniques, showed a statistically significant reduction in some aspects of pain in favour of plantar fascia stretching over calf stretches in the short term. Conclusions: There were too few studies to assess whether stretching is effective compared to control or other interventions, for either pain or function. However, there is some evidence that plantar fascia stretching may be more effective than Achilles tendon stretching alone in the short-term. Appropriately powered randomised controlled trials, utilizing validated outcome measures, blinded assessors and long-term follow up are needed to assess the efficacy of stretching

    The role of T-cell protein tyrosine phosphatase in epithelial carcinogenesis

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    T-cell protein tyrosine phosphatase (TC-PTP, encoded by PTPN2) is a non-receptor PTP that is mostly highly expressed in hematopoietic tissues. TC-PTP modulates a variety of physiological functions including cell cycle progression, cell survival and proliferation, and hematopoiesis through tyrosine dephosphorylation of its target substrates, such as EGFR, JAK1, JAK3, STAT1, and STAT3. Studies with whole or tissue-specific loss of TC-PTP function transgenic mice have shown that TC-PTP has crucial roles in the regulation of the immune response, insulin signaling, and oncogenic signaling. More recently, generation of epidermal-specific TC-PTP-deficient mice for use in multistage skin carcinogenesis bioassays demonstrated that TC-PTP suppresses skin tumor formation by negatively regulating STAT3 and AKT signaling. Further investigation showed that TC-PTP also minimizes UVB-induced epidermal cell damage by promoting apoptosis through the negative regulation of Flk-1/JNK signaling. These findings provide major evidence for a tumor suppressive function for TC-PTP against environment-induced skin cancer. Here, we will discuss TC-PTP, its substrates, and its functions with an emphasis on its role in skin carcinogenesis

    Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development

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    Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2fl/fl) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP deficiency also resulted in a significant increase in epidermal thickness and hyperproliferation following exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis showed that both phosphorylated STAT3 and phosphorylated AKT expressions were significantly increased in epidermis of TC-PTP-deficient mice compared to control mice following TPA treatment. Inhibition of STAT3 or AKT reversed the effects of TC-PTP deficiency on apoptosis and proliferation. Finally, TC-PTP knockout mice showed a shortened latency of tumorigenesis and significantly increased numbers of tumors during two-stage skin carcinogenesis. Our findings reveal that TC-PTP has potential as a novel target for the prevention of skin cancer through its role in the regulation of STAT3 and AKT signaling

    Soliton dragging in discrete and distributed amplifiers

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    The authors introduce erbium-doped fibre amplifiers (EDFA) into soliton-dragging logic gates (SDLG) to improve their performance in terms of switching energy, fan-out and tolerance to timing jitter. In particular, they experimentally and numerically examine the frequency shifts associated with soliton dragging for orthogonally polarized pulses interacting in discrete and distributed amplifiers. The authors show that EDFA asymmetrize the interaction between pulses, leading to a frequency shift even when pulses completely walk through each other. The gain can increase the fan-out and/or reduce the switching energy, while proper positioning of the amplifier can loosen the timing restrictions for SDLG. We find reasonable agreement between calculations and measurements in the discrete amplifier case. However, discrepancies for the distributed amplifier case may result from non-uniform gain profiles along the length of the amplifier.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48863/2/qs930501.pd

    Effectiveness of calf muscle stretching for the short-term treatment of plantar heel pain: a randomised trial

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    BACKGROUND: Plantar heel pain is one of the most common musculoskeletal disorders of the foot and ankle. Treatment of the condition is usually conservative, however the effectiveness of many treatments frequently used in clinical practice, including stretching, has not been established. We performed a participant-blinded randomised trial to assess the effectiveness of calf muscle stretching, a commonly used short-term treatment for plantar heel pain. METHODS: Ninety-two participants with plantar heel pain were recruited from the general public between April and June 2005. Participants were randomly allocated to an intervention group that were prescribed calf muscle stretches and sham ultrasound (n = 46) or a control group who received sham ultrasound alone (n = 46). The intervention period was two weeks. No participants were lost to follow-up. Primary outcome measures were 'first-step' pain (measured on a 100 mm Visual Analogue Scale) and the Foot Health Status Questionnaire domains of foot pain, foot function and general foot health. RESULTS: Both treatment groups improved over the two week period of follow-up but there were no statistically significant differences in improvement between groups for any of the measured outcomes. For example, the mean improvement for 'first-step' pain (0–100 mm) was -19.8 mm in the stretching group and -13.2 mm in the control group (adjusted mean difference between groups -7.9 mm; 95% CI -18.3 to 2.6). For foot function (0–100 scale), the stretching group improved 16.2 points and the control group improved 8.3 points (adjusted mean difference between groups 7.3; 95% CI -0.1 to 14.8). Ten participants in the stretching group experienced an adverse event, however most events were mild to moderate and short-lived. CONCLUSION: When used for the short-term treatment of plantar heel pain, a two-week stretching program provides no statistically significant benefit in 'first-step' pain, foot pain, foot function or general foot health compared to not stretching
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