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Human cytomegalovirus (HCMV) is a ubiquitous human pathogen that can cause severe disease in immunocompromised individuals, transplant recipients, and to the developing foetus during pregnancy. There is no protective vaccine currently available, and with only a limited number of antiviral drug options, resistant strains are constantly emerging. Successful completion of HCMV replication is an elegant feat from a molecular perspective, with both host and viral processes required at various stages. Remarkably, HCMV and other herpesviruses have protracted replication cycles, large genomes, complex virion structure and complicated nuclear and cytoplasmic replication events. In this review, we outline the 10 essential stages the virus must navigate to successfully complete replication. As each individual event along the replication continuum poses as a potential barrier for restriction, these essential checkpoints represent potential targets for antiviral development.

We investigated hybrid inorganic-organic solar cells combining monocrystalline n-type silicon (n-Si) and a highly conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS). The build-in potential, photo- and dark saturation current at this hybrid interface are monitored for varying n-Si doping concentrations. We corroborate that a high build-in potential forms at the hybrid junction leading to strong inversion of the n-Si surface. By extracting work function and valence band edge of the polymer from ultraviolet photoelectron spectroscopy, a band diagram of the hybrid n-Si/PEDOT:PSS heterojunction is presented. The current-voltage characteristics were analyzed using Schottky and abrupt pn-junction models. The magnitude as well as the dependence of dark saturation current on n-Si doping concentration proves that the transport is governed by diffusion of minority charge carriers in the n-Si and not by thermionic emission of majorities over a Schottky barrier. This leads to a comprehensive explanation of the high observed open-circuit voltages of up to 634 mV connected to high conversion efficiency of almost 14%, even for simple planar device structures without antireflection coating or optimized contacts. The presented work clearly shows that PEDOT:PSS forms a hybrid heterojunction with n-Si behaving similar to a conventional pn-junction and not, like commonly assumed, a Schottky junction.

The defects and subsurface damages induced by crystal growth and micro/nano-machining have a significant impact on the functional performance of machined products. Raman spectroscopy is an efficient, powerful, and non-destructive testing method to characterize these defects and subsurface damages. This paper aims to review the fundamentals and applications of Raman spectroscopy on the characterization of defects and subsurface damages in micro/nano-machining. Firstly, the principle and several critical parameters (such as penetration depth, laser spot size, and so on) involved in the Raman characterization are introduced. Then, the mechanism of Raman spectroscopy for detection of defects and subsurface damages is discussed. The Raman spectroscopy characterization of semiconductor materials’ stacking faults, phase transformation, and residual stress in micro/nano-machining is discussed in detail. Identification and characterization of phase transformation and stacking faults for Si and SiC is feasible using the information of new Raman bands. Based on the Raman band position shift and Raman intensity ratio, Raman spectroscopy can be used to quantitatively calculate the residual stress and the thickness of the subsurface damage layer of semiconductor materials. The Tip-Enhanced Raman Spectroscopy (TERS) technique is helpful to dramatically enhance the Raman scattering signal at weak damages and it is considered as a promising research field.

Human Cytomegalovirus (HCMV) infects over half the world's population, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion maturation, we analysed HCMV virions using proteomics, and identified a significant proportion of host exosome constituents. To validate this acquisition, we characterized exosomes released from uninfected cells, and demonstrated that over 99% of the protein cargo was subsequently incorporated into HCMV virions during infection. This suggested a common membrane origin, and utilization of host exosome machinery for virion assembly and egress. Thus, we selected a panel of exosome proteins for knock down, and confirmed that loss of 7/9 caused significantly less HCMV production. Saliently, we report that VAMP3 is essential for viral trafficking and release of infectious progeny, in various HCMV strains and cell types. Therefore, we establish that the host exosome pathway is intrinsic for HCMV maturation, and reveal new host regulators involved in viral trafficking, virion envelopment, and release. Our findings underpin future investigation of host exosome proteins as important modulators of HCMV replication with antiviral potential.

Protein secretion is generally mediated by a series of distinct pathways in bacteria. Recently, evidence of a novel bacterial secretion pathway involving a bacteriophage-related protein has emerged. TcdE, a holin-like protein encoded by toxigenic isolates of Clostridioides difficile, mediates the release of the large clostridial glucosylating toxins (LCGTs), TcdA and TcdB, and TpeL from C. perfringens uses another holin-like protein, TpeE, for its secretion; however, it is not yet known if TcdE or TpeE secretion is specific to these proteins. It is also unknown if other members of the LCGT-producing clostridia, including Paeniclostridium sordellii (previously Clostridium sordellii), use a similar toxin-release mechanism. Here, we confirm that each of the LCGT-producing clostridia encode functional holin-like proteins in close proximity to the toxin genes. To characterise the respective roles of these holin-like proteins in the release of the LCGTs, P. sordellii and its lethal toxin, TcsL, were used as a model. Construction and analysis of mutants of the P. sordellii tcsE (holin-like) gene demonstrated that TcsE plays a significant role in TcsL release. Proteomic analysis of the secretome from the tcsE mutant confirmed that TcsE is required for efficient TcsL secretion. Unexpectedly, comparative sample analysis showed that TcsL was the only protein significantly altered in its release, suggesting that this holin-like protein has specifically evolved to function in the release of this important virulence factor. This specificity has, to our knowledge, not been previously shown and suggests that this protein may function as part of a specific mechanism for the release of all LCGTs.

In this paper, we propose a temperature sensor based on a 4H-SiC CMOS oscillator circuit and that is able to operate in the temperature range between 298 K and 573 K. The circuit is developed on Fraunhofer IISB’s 2 μm 4H-SiC CMOS technology and is designed for a bias voltage of 20 V and an oscillation frequency of 90 kHz at room temperature. The possibility to relate the absolute temperature with the oscillation frequency is due to the temperature dependency of the threshold voltage and of the channel mobility of the transistors. An analytical model of the frequency-temperature dependency has been developed and is used as a starting point for the design of the circuit. Once the circuit has been designed, numerical simulations are performed with the Verilog-A BSIM4SiC model, which has been opportunely tuned on Fraunhofer IISB’s 2 μm 4H-SiC CMOS technology, and their results showed almost linear frequency-temperature characteristics with a coefficient of determination that was higher than 0.9681 for all of the bias conditions, whose maximum is 0.9992 at a VDD = 12.5 V. Moreover, we considered the effects of the fabrication process through a Monte Carlo analysis, where we varied the threshold voltage and the channel mobility with different values of the Gaussian distribution variance. For example, at VDD = 20 V, a deviation of 17.4% from the nominal characteristic is obtained for a Gaussian distribution variance of 20%. Finally, we applied the one-point calibration procedure, and temperature errors of +8.8 K and −5.8 K were observed at VDD = 15 V.

The composition of Van-der-Waals heterostructures is conclusively determined using a hybrid evaluation scheme of data acquired by optical microspectroscopy. This scheme deploys a parameter set comprising both change in reflectance and wavelength shift of distinct extreme values in reflectance spectra. Furthermore, the method is supported by an accurate analytical model describing reflectance of multilayer systems acquired by optical microspectroscopy. This approach allows uniquely for discrimination of 2D materials like graphene and hexagonal boron nitride (hBN) and, thus, quantitative analysis of Van-der-Waals heterostructures containing structurally very similar materials. The physical model features a transfer-matrix method which allows for flexible, modular description of complex optical systems and may easily be extended to individual setups. It accounts for numerical apertures of applied objective lenses and a glass fiber which guides the light into the spectrometer by two individual weighting functions. The scheme is proven by highly accurate quantification of the number of layers of graphene and hBN in Van-der-Waals heterostructures. In this exemplary case, the fingerprint of graphene involves distinct deviations of reflectance accompanied by additional wavelength shifts of extreme values. In contrast to graphene, the fingerprint of hBN reveals a negligible deviation in absolute reflectance causing this material being only detectable by spectral shifts of extreme values.

The antigen presentation molecule MHC class I related protein-1 (MR1) is best characterized by its ability to present bacterially derived metabolites of vitamin B2 biosynthesis to mucosal-associated invariant T-cells (MAIT cells). Through in vitro human cytomegalovirus (HCMV) infection in the presence of MR1 ligand we investigate the modulation of MR1 expression. Using coimmunoprecipitation, mass spectrometry, expression by recombinant adenovirus and HCMV deletion mutants we investigate HCMV gpUS9 and its family members as potential regulators of MR1 expression. The functional consequences of MR1 modulation by HCMV infection are explored in coculture activation assays with either Jurkat cells engineered to express the MAIT cell TCR or primary MAIT cells. MR1 dependence in these activation assays is established by addition of MR1 neutralizing antibody and CRISPR/Cas-9 mediated MR1 knockout. Here we demonstrate that HCMV infection efficiently suppresses MR1 surface expression and reduces total MR1 protein levels. Expression of the viral glycoprotein gpUS9 in isolation could reduce both cell surface and total MR1 levels, with analysis of a specific US9 HCMV deletion mutant suggesting that the virus can target MR1 using multiple mechanisms. Functional assays with primary MAIT cells demonstrated the ability of HCMV infection to inhibit bacterially driven, MR1-dependent activation using both neutralizing antibodies and engineered MR1 knockout cells. This study identifies a strategy encoded by HCMV to disrupt the MR1:MAIT cell axis. This immune axis is less well characterized in the context of viral infection. HCMV encodes hundreds of proteins, some of which regulate the expression of antigen presentation molecules. However the ability of this virus to regulate the MR1:MAIT TCR axis has not been studied in detail.

Over 50% of the world’s population is infected with Human Cytomegalovirus (HCMV). HCMV is responsible for serious complications in the immuno-compromised and is a leading cause of congenital birth defects. The molecular function of many HCMV proteins remains unknown, and a deeper understanding of the viral effectors that modulate virion maturation is required. In this study, we observed that UL34 is a viral protein expressed with leaky late kinetics that localises to the nucleus during infection. Deletion of UL34 from the HCMV genome (ΔUL34) did not abolish the spread of HCMV. Instead, over >100-fold fewer infectious virions were produced, so we report that UL34 is an augmenting gene. We found that ΔUL34 is dispensable for viral DNA replication, and its absence did not alter the expression of IE1, MCP, gB, UL26, UL83, or UL99 proteins. In addition, ΔUL34 infections were able to progress through the replication cycle to form a viral assembly compartment; however, virion maturation in the cytoplasm was abrogated. Further examination of the nucleus in ΔUL34 infections revealed replication compartments with aberrant morphology, containing significantly less assembled capsids, with almost none undergoing subsequent maturation. Therefore, this work lays the foundation for UL34 to be further investigated in the context of nuclear organization and capsid maturation during HCMV infection.