Алмазные фотоприемники ультрафиолетового диапазона

Изготовлены и исследованы планарные алмазные «солнечно-слепые» фотоприемники УФ-диапазона. Приведено теоретическое обоснование принципов работы и экспериментальные параметры фотоприемников в фоторезистивном и фотодиодном режимах

Reconciling Longitudinal Naive T-Cell and TREC Dynamics during HIV-1 Infection

<div><p>Naive T cells in untreated HIV-1 infected individuals have a reduced T-cell receptor excision circle (TREC) content. Previous mathematical models have suggested that this is due to increased naive T-cell division. It remains unclear, however, how reduced naive TREC contents can be reconciled with a gradual loss of naive T cells in HIV-1 infection. We performed longitudinal analyses in humans before and after HIV-1 seroconversion, and used a mathematical model to investigate which processes could explain the observed changes in naive T-cell numbers and TRECs during untreated HIV-1 disease progression. Both CD4⁺ and CD8⁺ naive T-cell TREC contents declined biphasically, with a rapid loss during the first year and a much slower loss during the chronic phase of infection. While naive CD8⁺ T-cell numbers hardly changed during follow-up, naive CD4⁺ T-cell counts continually declined. We show that a fine balance between increased T-cell division and loss in the peripheral naive T-cell pool can explain the observed short- and long-term changes in TRECs and naive T-cell numbers, especially if T-cell turnover during the acute phase is more increased than during the chronic phase of infection. Loss of thymic output, on the other hand, does not help to explain the biphasic loss of TRECs in HIV infection. The observed longitudinal changes in TRECs and naive T-cell numbers in HIV-infected individuals are most likely explained by a tight balance between increased T-cell division and death, suggesting that these changes are intrinsically linked in HIV infection.</p></div

Maraviroc Intensification Improves Endothelial Function in Abacavir-Treated Patients, an Open-Label Randomized Cross-Over Pilot Study

<p>Article full text</p> <p>The full text of this article can be found here </p><p><b><u>https://link.springer.com/article/10.1007/s40121-016-0115-0</u></b></p> <p>Provide enhanced content for this article</p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p>Other enhanced features include, but are not limited to:</p> <ul> <li>Slide decks</li> <li>Videos and animations</li> <li>Audio abstracts</li> <li>Audio slides</li> </ul

Parameter values used to describe the average TREC content and naive T-cell dynamics during HIV infection under the conservative assumption that thymic output and the average TREC content of recent thymic emigrants is not affected.

<p>Parameter values used to describe the average TREC content and naive T-cell dynamics during HIV infection under the conservative assumption that thymic output and the average TREC content of recent thymic emigrants is not affected.</p

Predicted naive T-cell and TREC-content dynamics if HIV increases T-cell division and loss rates.

<p>Simulation results of naive T-cell counts (in black) and average TREC contents (in red) for an individual infected by HIV at the age of 30, assuming that the naive T-cell division rate increased according to the constraints described in Supplemental Methods. Left panels show the short-term dynamics while right panels show the long-term dynamics. Panel a shows the results for CD8⁺ T cells, Panels b and c for CD4⁺ T cells. In panel c, we have modeled the effect of increased turnover during the acute phase of infection, by using a 5-fold higher value of both <i>d</i> and <i>p</i> during the first 6 months of infection compared to the later stage of infection. For CD4⁺ T cells (panels b and c) we plotted the upper and lower bounds on the parameter constraints (denoted by the solid lines (<i>k</i>_<i>p</i> = <i>k</i>_<i>d</i> and <i>k</i>_<i>p</i> = <i>d(k</i>_<i>d</i><i>—1)/p+1</i>, see Supplemental Methods) as well as an intermediate case (denoted by the dashed lines (<i>k</i>_<i>d</i><<i>k</i>_<i>p</i>< <i>d(k</i>_<i>d</i><i>—1)/p+1</i>) assuming that the thymic output and the average number of TREC per RTE are not changed after HIV infection (i.e. <i>k</i>_<i>s</i> = 1 and <i>k</i>_c = 1). <u>Parameters</u>: Panel a: before infection <i>σ</i>_<i>0</i> = 1.09×10¹⁰ cells/year, <i>h</i> = 1.5×10¹¹cells, <i>d</i> = 0.109/year, <i>c</i> = 0.25 and <i>ν</i> = 0.05/year; after infection: <i>d</i> = 1.314/year and <i>p</i> = 1.300/year. Panels b and c: before infection <i>σ</i>_<i>0</i> = 3.65×10¹⁰ cells/year, <i>h</i> = 3.2×10¹¹, <i>d</i> = 0.183/year, <i>c</i> = 0.25 and <i>ν</i> = 0.05/year; after infection: <i>d</i> = 0.548/year, <i>p</i> = 0.498, 0.510 or 0.532/year. Panel c: <i>d</i> = 2.740/year, <i>p</i> = 2.490, 2.550 or 2.660/year during the first six months of infection.</p

Increase of percentage of Ki67⁺ among CD4⁺ T cells (A), naive (CD45RA⁺CD27⁺CCR7⁺) CD4⁺ T cells (B); total CD4⁺Ki67⁺ cell counts (C) and naive CD4⁺Ki67⁺ cell counts (D) for INSPIRE Study (Study II) depending of the dose.

<p>Observed median percentage of Ki67⁺ among CD4⁺ T cells by group: placebo (crosses), 10 µg/kg (triangles), 20 µg/kg (squares) and 30 µg/kg (diamonds). Red arrows indicate IL-7 administration. Error bars and other statistical analyses are provided in Levy et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003630#pcbi.1003630-Levy2" target="_blank">[30]</a>.</p

Total and naive CD4⁺ and CD8⁺ T-cell dynamics over seroconversion and during HIV infection.

<p>Total CD4⁺ T-cell counts (a), total CD8⁺ T-cell counts (b), naive CD4⁺ T-cell counts (c) and naive CD8⁺ T-cell counts (d) per μl of blood over seroconversion and during untreated HIV infection. Longitudinal data are connected by straight lines (n = 18), while cross-sectional data are denoted by open circles. The pre-seroconversion measurements (“Pre”) were measured between 2.8 and 11.4 years pre-seroconversion; since the change in T-cell numbers in healthy individuals is negligible in such a period of time, we used these measurements as the best estimate of the T-cell numbers at the moment of seroconversion. Cross-sectional data were collected during acute (n = 7) and chronic HIV infection (n = 27) as well as during progression to AIDS (n = 16) and were compared to age-matched healthy controls (n = 38). The p-values for the declines in phase I and phase II are given in the figure, while the difference between cross-sectional data from healthy and HIV-infected subjects are marked by an asterisk if the p-value<0.05.</p

Dose-dependent increase of total CD4⁺ T cell count (A) and naive (CD45RA⁺CD27⁺CCR7⁺) CD4⁺ T cell count (B) for INSPIRE Study (Study II).

<p>Observed median count in cells/µL by group: placebo (crosses), 10 µg/kg (triangles), 20 µg/kg (squares) and 30 µg/kg (diamonds). Red arrows indicate IL-7 administration. Error bars and other statistical analyses are provided in Levy et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003630#pcbi.1003630-Levy2" target="_blank">[30]</a>.</p

Characteristics of phase I/II trials and patients included from each study.

<p>* Patients with complete cycles used for the model.</p><p>** Median (Interquartile range).</p><p>Na: Not applicable.</p

Estimates of the “best” model for total CD4⁺ and naive CD4⁺ T-cell dynamics in Study II (INSPIRE Study).

<p>Bold-italic numbers represent significant IL-7 effects. Standard-errors are given between brackets. Parameters for the other models and other studies are presented in Supplemental Materials.</p><p>* Standard-deviation of random effect.</p><p>Note that the random effects were on the log-transformed parameter and not on the natural scale.</p