Understanding vaginal and rectal HIV transmission and protective cellular and molecular mechanisms is critical for designing new prevention strategies, including those required for an effective ...vaccine. The determinants of protection against HIV infection are, however, poorly understood. Increasing evidence suggest that innate immune defenses may help protect mucosal surfaces from HIV transmission in highly exposed, uninfected subjects. More recent studies suggest that systemically administered type 1 interferon protects against simian immunodeficiency virus infection of macaques. Here we hypothesized that topically applied type 1 interferons might stimulate vaginal innate responses that could protect against HIV transmission. We therefore applied a recombinant human type 1 interferon (IFN-β) to the vagina of rhesus macaques and vaginally challenged them with pathogenic simian/human immunodeficiency virus (SHIV). Vaginal administration of IFN-β resulted in marked local changes in immune cell phenotype, increasing immune activation and HIV co-receptor expression, yet provided significant protection from SHIV acquisition as interferon response genes were also upregulated. These data suggest that protection from vaginal HIV acquisition may be achieved by activating innate mucosal defenses.
Nowadays, the vibration analysis of rotating machine signals is a well-established methodology, rooted on powerful tools offered, in particular, by the theory of cyclostationary (CS) processes. Among ...them, the squared envelope spectrum (SES) is probably the most popular to detect random CS components which are typical symptoms, for instance, of rolling element bearing faults. Recent researches are shifted towards the extension of existing CS tools – originally devised in constant speed conditions – to the case of variable speed conditions. Many of these works combine the SES with computed order tracking after some preprocessing steps. The principal object of this paper is to organize these dispersed researches into a structured comprehensive framework. Three original features are furnished. First, a model of rotating machine signals is introduced which sheds light on the various components to be expected in the SES. Second, a critical comparison is made of three sophisticated methods, namely, the improved synchronous average, the cepstrum prewhitening, and the generalized synchronous average, used for suppressing the deterministic part. Also, a general envelope enhancement methodology which combines the latter two techniques with a time-domain filtering operation is revisited. All theoretical findings are experimentally validated on simulated and real-world vibration signals.
•The squared envelope spectrum is a benchmark technique for bearing diagnosis.•Critical comparison between existing envelope enhancement techniques.•Revisiting a general envelope enhancement methodology.•Experimental validation on simulated and real vibration signals.
In rotating machinery vibration analysis, the synchronous average is perhaps the most widely used technique for extracting periodic components. Periodic components are typically related to gear ...vibrations, misalignments, unbalances, blade rotations, reciprocating forces, etc. Their separation from other random components is essential in vibration-based diagnosis in order to discriminate useful information from masking noise. However, synchronous averaging theoretically requires the machine to operate under stationary regime (i.e. the related vibration signals are cyclostationary) and is otherwise jeopardized by the presence of amplitude and phase modulations. A first object of this paper is to investigate the nature of the nonstationarity induced by the response of a linear time-invariant system subjected to speed varying excitation. For this purpose, the concept of a cyclo-non-stationary signal is introduced, which extends the class of cyclostationary signals to speed-varying regimes. Next, a “generalized synchronous average’’ is designed to extract the deterministic part of a cyclo-non-stationary vibration signal—i.e. the analog of the periodic part of a cyclostationary signal. Two estimators of the GSA have been proposed. The first one returns the synchronous average of the signal at predefined discrete operating speeds. A brief statistical study of it is performed, aiming to provide the user with confidence intervals that reflect the "quality" of the estimator according to the SNR and the estimated speed. The second estimator returns a smoothed version of the former by enforcing continuity over the speed axis. It helps to reconstruct the deterministic component by tracking a specific trajectory dictated by the speed profile (assumed to be known a priori).The proposed method is validated first on synthetic signals and then on actual industrial signals. The usefulness of the approach is demonstrated on envelope-based diagnosis of bearings in variable-speed operation.
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•Separation of deterministic from random vibration signals is crucial.•The synchronous average is one of the tools most used for this purpose.•An extension of the synchronous average is proposed to cyclo-non-stationary signals.•Application on simulated and actual industrial signals.
SiGe for channel material has been explored as a major technology element after the introduction of FINFET into CMOS technology 1-4. Research on long channel FETs and discrete short channel FETs ...demonstrated benefits in mobility 1-4 and reliability 2. Given the disruption that SiGe FIN brings, every aspect associated with SiGe FIN needs to be carefully studied towards technology insertion. In this paper, we report the latest SiGe-based FINFET CMOS technology development. CMOS FINFETs with Si-FIN nFET and SiGe-FIN pFET is demonstrated as a viable technology solution for both server and mobile applications at 10nm node and beyond.
Heightened proliferation and death of T lymphocytes may play a key role in human immunodeficiency virus (HIV) pathogenesis; however, the mechanism that mediates this effect and the phenotype of the ...proliferating T cells have not been clearly determined. We assessed S-phase cell frequencies and phenotype by ex vivo bromodeoxyuridine incorporation and flow-cytometric analysis in a group of 35 HIV-infected individuals. Frequencies of S-phase T cells were increased in HIV disease and were related to plasma HIV RNA levels but not to CD4 cell, total T cell, or total lymphocyte counts. S-phase cells were phenotypically defined as “central memory” cells (CD45RO+CD62L+CCR7+). Although activated (CD38+), S-phase cells lacked CD69 expression, rarely expressed CD25, and were not overrepresented among HIV-specific cells, as might have been expected if these cells had recently been activated by HIV antigens. Thus, in HIV infection, central memory T cells may be highly susceptible to bystander mechanisms of immune activation, leading to S-phase entry
•hBD-3 activates PBMC to secrete IFN-γ and kill target cells in mDC and NK dependent fashion.•TLR1, TLR2 and CCR2 are expressed on both mDC and NK cells and are involved in hBD-3 mediated ...activity.•hBD-3 activates NK cells, mDC, and likely facilitates mDC-NK interactions.
We previously showed that human beta defensin-3 (hBD-3) activates mDC via TLR1/2. Here we investigated the effects of hBD-3 on NK cell activation state and effector functions. We observed that hBD-3 activates PBMC to secrete IFN-γ and kill K562 and HUH hepatoma target cells in an NK dependent fashion, and both TLR1/2 and CCR2 are involved. TLR1, TLR2 and CCR2 were expressed on NK cells, and in purified NK culture experiments we observed hBD-3 to directly act on NK cells, resulting in CD69 upregulation and IFNγ secretion. We also observed mDC-hBD-3 enhanced NK cytolytic activity and IFNγ production. These results implicate hBD-3 in its ability to directly activate NK cells and increase NK cell effector function, as well as promote mDC-dependent NK activity. HBD-3 may therefore act as a mediator of innate cell interactions that result in bridging of innate and adaptive immunity.
In this paper, for the first time we demonstrate that horizontally stacked gate-all-around (GAA) Nanosheet structure is a good candidate for the replacement of FinFET at the 5nm technology node and ...beyond. It offers increased W eff per active footprint and better performance compared to FinFET, and with a less complex patterning strategy, leveraging EUV lithography. Good electrostatics are reported at L g =12nm and aggressive 44/48nm CPP (Contacted Poly Pitch) ground rules. We demonstrate work function metal (WFM) replacement and multiple threshold voltages, compatible with aggressive sheet to sheet spacing for wide stacked sheets. Stiction of sheets in long-channel devices is eliminated. Dielectric isolation is shown on standard bulk substrate for sub-sheet leakage control. Wrap-around contact (WAC) is evaluated for extrinsic resistance reduction.
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