Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb?

The etiology of alopecia areata (AA), a putative autoimmune disease characterized by sudden hair loss, has remained obscure. It is not understood, how the characteristic inflammatory infiltrate that selectively attacks anagen hair follicles in AA is generated. We hypothesize that this reflects an unexplored form of autoimmunity, a cytotoxic T cell attack on rhythmically synthesized autoantigens normally sequestered by a lack or very low level of MHC class I (MHC I)-expression, and suggest the following mechanism of AA pathogenesis: Microtrauma, neurogenic inflammation, or microbial antigens cause a localized breakdown of MHC I-"negativity" in the proximal anagen hair bulb via proinflammatory cytokines. This exposes autoantigens derived from melanogenesis-related proteins (MRP-DP), which are only generated during anagen, and triggers two successive waves of autoimmune responses: CD8+ cytotoxic T cells initiate AA after recognizing MRP-DP abnormally presented by MHC I molecules on hair matrix melanocytes and/or keratinocytes; a secondary attack, carried by CD4+ T cells and antigen presenting cells, is then mounted against MHC class II--presented additional autoantigens exposed by damaged melanocytes and keratinocytes. The latter causes most of the follicular damage, and extrafollicular disease, and depends greatly on the immunogenetic background of affected individuals. This unifying hypothesis explains the clinical heterogeneity and all salient features of AA, and argues that only the unlikely coincidence of multiple predisposing events triggers AA. The suppression of MHC I--expression and synthesis of MRP in the hair bulb, and the "tolerization" of MRP-DP autoreactive CD8+ T cells may be promising strategies for treating AA

Nuclear proto-oncogene products transactivate the human papillomavirus type 16 promoter.

Human papillomavirus (HPV) type 16 and 18 viral genomes are frequently detected in cervical and penile cancer biopsies. Although this strongly suggests a prominent role for HPV infection in the development of genital cancer, other genetic or environmental factors are also involved. Genital cancer is postulated to result from loss of cellular control functions, which leads to an unregulated expression of HPV oncogenic proteins. In our study, we determined the trans-activating properties of nuclear proto-oncogene proteins c-Fos, c-Jun and c-Myc on P97 enhancer/promoter activity of HPV16. Using a CAT-reporter construct containing the HPV16 enhancer/promoter element, we investigated the trans-activating effects of c-Fos, c-Jun, c-Myc, and E2 in cervical HT-3 cells. c-Fos and c-Jun overexpression resulted in a 3.3- and 3.1-fold up-regulation of CAT activity. Only 2-fold induction was determined by co-transfection with c-myc and the viral transcription factor E2. Based on these findings, we investigated the expression of HPV DNA (16 and 18) as well as nuclear proto-oncogenes (c-fos, c-jun and c-myc) in nine cervical cancers by in situ hybridisation. In six out of nine carcinomas, HPV16 and/or HPV18 DNA was detectable. All tumours showed an intense and homogeneous expression of c-fos and c-jun mRNA, while the signal for c-myc was detectable only in four specimens. These data suggest that deregulation of nuclear proto-oncogene expression may contribute to an overexpression of HPV-derived oncogenic proteins (E6 and E7), which is generally hypothesised to be an important step in the malignant transformation of HPV-associated tumours

Nonlinear vertical oscillations of a particle in a sheath of a rf discharge

A new simple method to measure the spatial distribution of the electric field in the plasma sheath is proposed. The method is based on the experimental investigation of vertical oscillations of a single particle in the sheath of a low-pressure radio-frequency discharge. It is shown that the oscillations become strongly nonlinear and secondary harmonics are generated as the amplitude increases. The theory of anharmonic oscillations provides a good qualitative description of the data and gives estimates for the first two anharmonic terms in an expansion of the sheath potential around the particle equilibrium.Comment: 11 pages, 4 figure

Electron power absorption dynamics in capacitive radio frequency discharges driven by tailored voltage waveforms in CF4

The power absorption dynamics of electrons and the electrical asymmetry effect in capacitive radio-frequency plasmas operated in CF4 and driven by tailored voltage waveforms are investigated experimentally in combination with kinetic simulations. The driving voltage waveforms are generated as a superposition of multiple consecutive harmonics of the fundamental frequency of 13.56 MHz. Peaks/valleys and sawtooth waveforms are used to study the effects of amplitude and slope asymmetries of the driving voltage waveform on the electron dynamics and the generation of a DC self-bias in an electronegative plasma at different pressures. Compared to electropositive discharges, we observe strongly different effects and unique power absorption dynamics. At high pressures and high electronegativities, the discharge is found to operate in the drift-ambipolar (DA) heating mode. A dominant excitation/ionization maximum is observed during sheath collapse at the edge of the sheath which collapses fastest. High negative-ion densities are observed inside this sheath region, while electrons are confined for part of the RF period in a potential well formed by the ambipolar electric field at this sheath edge and the collapsed (floating potential) sheath at the electrode. For specific driving voltage waveforms, the plasma becomes divided spatially into two different halves of strongly different electronegativity. This asymmetry can be reversed electrically by inverting the driving waveform. For sawtooth waveforms, the discharge asymmetry and the sign of the DC self-bias are found to reverse as the pressure is increased, due to a transition of the electron heating mode from the α-mode to the DA-mode. These effects are interpreted with the aid of the simulation results

Effect of gas properties on the dynamics of the electrical slope asymmetry effect in capacitive plasmas : comparison of Ar, H2 and CF4

Tailored voltage excitation waveforms provide an efficient control of the ion energy (through the electrical asymmetry effect) in capacitive plasmas by varying the 'amplitude' asymmetry of the waveform. In this work, the effect of a 'slope' asymmetry of the waveform is investigated by using sawtooth-like waveforms, through which the sheath dynamic can be manipulated. A remarkably different discharge dynamic is found for Ar, H2, and CF4 gases, which is explained by the different dominant electron heating mechanisms and plasma chemistries. In comparison to Argon we find that the electrical asymmetry can even be reversed by using an electronegative gas such as CF4. Phase resolved optical emission spectroscopy measurements, probing the spatiotemporal distribution of the excitation rate show excellent agreement with the results of particle-in-cell simulations, confirming the high degree of correlation between the excitation rates with the dominant heating mechanisms in the various gases. It is shown that, depending on the gas used, sawtooth-like voltage waveforms may cause a strong asymmetry

Ion energy distribution functions behind the sheaths of magnetized and non magnetized radio frequency discharges

The effect of a magnetic field on the characteristics of capacitively coupled radio frequency discharges is investigated and found to be substantial. A one-dimensional particle-in-cell simulation shows that geometrically symmetric discharges can be asymmetrized by applying a spatially inhomogeneous magnetic field. This effect is similar to the recently discovered electrical asymmetry effect. Both effects act independently, they can work in the same direction or compensate each other. Also the ion energy distribution functions at the electrodes are strongly affected by the magnetic field, although only indirectly. The field influences not the dynamics of the sheath itself but rather its operating conditions, i.e., the ion flux through it and voltage drop across it. To support this interpretation, the particle-in-cell results are compared with the outcome of the recently proposed ensemble-in-spacetime algorithm. Although that scheme resolves only the sheath and neglects magnetization, it is able to reproduce the ion energy distribution functions with very good accuracy, regardless of whether the discharge is magnetized or not

Sensitive detection of sodium in a flame using parametric four-wave mixing and seeded parametric four-wave mixing

Two-photon resonant parametric four-wave mixing and a newly developed variant called seeded parametric four-wave mixing are used to detect trace quantities of sodium in a flame. Both techniques are simple, requiring only a single laser to generate a signal beam at a different wavelength which propagates collinearly with the pump beam, allowing efficient signal recovery. A comparison of the two techniques reveals that seeded parametric four-wave mixing is more than two orders of magnitude more sensitive than parametric four-wave mixing, with an estimated detection sensitivity of 5 x 10(9) atoms/cm(3). Seeded parametric four-wave mixing is achieved by cascading two parametric four-wave mixing media such that one of the parametric fields generated in the first high-density medium is then used to seed the same four-wave mixing process in a second medium in order to increase the four-wave mixing gain. The behavior of this seeded parametric four-wave mixing is described using semiclassical perturbation theory. A simplified small-signal theory is found to model most of the data satisfactorily. However, an anomalous saturationlike behavior is observed in the large signal regime. The full perturbation treatment, which includes the competition between two different four-wave mixing processes coupled via the signal field, accounts for this apparently anomalous behavior

The 2017 Plasma Roadmap: Low temperature plasma science and technology

Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges.I Adamovich et al 2017 J. Phys. D: Appl. Phys. 50 32300