Multivariable stability analysis of position-controlled payloads to support shrink in semiconductor manufacturing

This paper addresses the challenge of ever-smaller structures in the semiconductor industry and the resulting requirements for high-performance mechatronic systems, especially wafer scanners, in lithography processes in the context of mechatronic system design and analysis. As a result, the development of sophisticated methods for modeling, control, and analysis of control systems has become necessary. To meet this need, advanced analysis methods of multivariable control systems are investigated, in particular the combination of classical stability analysis methods like the Nyquist criteria and use of Individual Channel Analysis and Design (ICAD) methods. For this purpose, the requirements for the analysis of multivariable control systems are summarized and put in the context of classical methods of system analysis, for example, the use of Nyquist methods to evaluate the stability of the control loop. Subsequently, the paper provides a rationale for why the use of Single-Input Single-Output (SISO) methods to assess stability and robustness is not sufficient and how these can be extended to Multiple-Input Multiple Output (MIMO) methods to meet the requirements. A set of tailored Nyquist-like MIMO analysis methods are theoretically derived, including the ICAD method and classical Nyquist stability analysis and its use in the analysis of multivariable control system is explained. A coupling ratio parameter, quantifying the coupling of multivariable systems, is derived from the extended ICAD method. The iterative design process is explained, which allows conclusions to be drawn about individual system parameters and how to optimize them to achieve high performance. To compare the methods, a model of a mechanical payload with variable eigenfrequencies is derived. Subsequently, the suitability of the respective method for multivariable stability analysis is tested in different system configurations. In conclusion, this paper provides insight into the analysis of stability and robustness of multivariable control systems and presents the challenges and opportunities of using these advanced methods to design high-performance mechatronics in the context of increasing requirements due to the shrink in semiconductor manufacturing. This provides a valuable contribution to the design of high-performance mechatronic systems

The attenuated pseudorabies virus vaccine strain Bartha K61 : a brief review on the knowledge gathered during 60 years of research

Pseudorabies virus (PRV) is a member of the alphaherpesvirus subfamily of the herpesviruses and is the causative agent of Aujeszky's disease in pigs, causing respiratory, neurological, and reproductive symptoms. Given the heavy economic losses associated with Aujeszky's disease epidemics, great efforts were made to develop efficacious vaccines. One of the best modified live vaccines to this day is the attenuated Bartha K61 strain. The use of this vaccine in extensive vaccination programs worldwide has assisted considerably in the eradication of PRV from the domesticated pig population in numerous countries. The Bartha K61 strain was described in 1961 by Adorjan Bartha in Budapest and was obtained by serial passaging in different cell cultures. Ever since, it has been intensively studied by several research groups, for example, to explore its efficacy as a vaccine strain, to molecularly and mechanistically explain its attenuation, and to use it as a retrograde neuronal tracer and as a vector vaccine. Given that the Bartha K61 vaccine strain celebrates its 60th birthday in 2021 with no sign of retirement, this review provides a short summary of the knowledge on its origin, characteristics, and use as a molecular tool and as a vaccine

Proteome Analysis of Swine Macrophages after Infection with Two Genotype II African Swine Fever Isolates of Different Pathogenicity

Since the introduction of a highly pathogenic genotype II isolate of the African swine fever virus (ASFV) into Georgia in 2007, African swine fever (ASF) has gone panzootic. Outbreaks have been reported in Europe, Asia and, more recently, Latin America. Thus, ASFV has become a major threat to the pig industry worldwide, as broadly applicable vaccines are not available. While the majority of ASFV strains show high virulence in domestic pigs and wild boar, variations within the ASFV genome have resulted in the emergence of attenuated strains with low or moderate virulence. However, the molecular basis of the differences in virulence has not yet been discovered. To reveal virulence-associated protein expression patterns, we analysed the proteomes of the natural target cells of ASFV, primary porcine macrophages, after infection with two genotype II ASFV strains displaying high (Armenia 2008) and moderate (Estonia 2014) virulence using quantitative mass spectrometry. Very similar expression patterns were observed for the viral genes, and any differences were limited to the deletions within the Estonia 2014 genome. In addition to the canonical ASFV proteins, twelve novel protein products from recently described transcripts were confirmed in both isolates. Pathway analyses showed that both isolates evoked a similar host proteome response, despite their difference in virulence. However, subtle differences in the manipulation of the proteins involved in the proinflammatory response mediated by the MAPK14/p38 signalling cascade were observe

Chemosensory properties of murine nasal and cutaneous trigeminal neurons identified by viral tracing

BACKGROUND: Somatosensation of the mammalian head is mainly mediated by the trigeminal nerve that provides innervation of diverse tissues like the face skin, the conjunctiva of the eyes, blood vessels and the mucouse membranes of the oral and nasal cavities. Trigeminal perception encompasses thermosensation, touch, and pain. Trigeminal chemosensation from the nasal epithelia mainly evokes stinging, burning, or pungent sensations. In vitro characterization of trigeminal primary sensory neurons derives largely from analysis of complete neuronal populations prepared from sensory ganglia. Thus, functional properties of primary trigeminal afferents depending on the area of innervation remain largely unclear. RESULTS: We established a PrV based tracing technique to identify nasal and cutaneous trigeminal neurons in vitro. This approach allowed analysis and comparison of identified primary afferents by means of electrophysiological and imaging measurement techniques. Neurons were challenged with several agonists that were reported to exhibit specificity for known receptors, including TRP channels and purinergic receptors. In addition, TTX sensitivity of sodium currents and IB4 binding was investigated. Compared with cutaneous neurons, a larger fraction of nasal trigeminal neurons showed sensitivity for menthol and capsaicin. These findings pointed to TRPM8 and TRPV1 receptor protein expression largely in nasal neurons whereas for cutaneous neurons these receptors are present only in a smaller fraction. The majority of nasal neurons lacked P2X(3 )receptor-mediated currents but showed P2X(2)-mediated responses when stimulated with ATP. Interestingly, cutaneous neurons revealed largely TTX resistant sodium currents. A significantly higher fraction of nasal and cutaneous afferents showed IB4 binding when compared to randomly chosen trigeminal neurons. CONCLUSION: In conclusion, the usability of PrV mediated tracing of primary afferents was demonstrated. Using this technique it could be shown that compared with neurons innervating the skin nasal trigeminal neurons reveal pronounced chemosensitivity for TRPM8 and TRPV1 channel agonists and only partially meet properties typical for nociceptors. In contrast to P2X(3 )receptors, TRPM8 and TRPV1 receptors seem to be of pronounced physiological relevance for intranasal trigeminal sensation

Human Herpesvirus-6 Induces MVB Formation, and Virus Egress Occurs by an Exosomal Release Pathway

The final envelopment of most herpesviruses occurs at Golgi or post-Golgi compartments, such as the trans Golgi network (TGN); however, the final envelopment site of human herpesvirus 6 (HHV-6) is uncertain. In this study, we found novel pathways for HHV-6 assembly and release from T cells that differed, in part, from those of alphaherpesviruses. Electron microscopy showed that late in infection, HHV-6-infected cells were larger than uninfected cells and contained many newly formed multivesicular body (MVB)-like compartments that included small vesicles. These MVBs surrounded the Golgi apparatus. Mature virions were found in the MVBs and MVB fusion with plasma membrane, and the release of mature virions together with small vesicles was observed at the cell surface. Immunoelectron microscopy demonstrated that the MVBs contained CD63, an MVB/late endosome marker, and HHV-6 envelope glycoproteins. The viral glycoproteins also localized to internal vesicles in the MVBs and to secreted vesicles (exosomes). Furthermore, we found virus budding at TGN-associated membranes, which expressed CD63, adaptor protein (AP-1) and TGN46, and CD63 incorporation into virions. Our findings suggest that mature HHV-6 virions are released together with internal vesicles through MVBs by the cellular exosomal pathway. This scenario has significant implications for understanding HHV-6's maturation pathway

Ultrastructural analysis of sequential Cyprinid herpesvirus 3 morphogenesis in vitro

Cyprinid herpesvirus 3 (CyHV-3) is an alloherpesvirus, and it is the aetiological agent of koi herpesvirus disease. Although the complex morphogenic stages of the replication cycle of CyHV-3 were shown to resemble that of other members of the Herpesvirales, detailed analysis of the sequence and timing of these events was not definitively determined. This study describes these features through a time course using cyprinid cell cultures (KF-1 and CCB) infected with CyHV-3 (KHV isolate, H361) and analysed by transmission electron microscopy. Rapid viral entry was noted, with high levels of intracellular virus within 1–4 h post-infection (hpi). Intranuclear capsid assembly, paracrystalline array formation and primary envelopment of capsids occurred within 4 hpi. Between 1 and 3 days post-infection (dpi), intracytoplasmic secondary envelopment occurred, as well as budding of infectious virions at the plasma membrane. At 5–7 dpi, the cytoplasm contained cytopathic vacuoles, enveloped virions within vesicles, and abundant non-enveloped capsids; also there was frequent nuclear deformation. Several morphological features are suggestive of inefficient viral assembly, with production of non-infectious particles, particularly in KF-1 cells. The timing of this alloherpesvirus morphogenesis is similar to other members of the Herpesvirales, but there may be possible implications of using different cell lines for CyHV-3 propagation

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

Epidemiology of Bluetongue Virus Serotype 8, Germany

In Germany, bluetongue disease had not been reported before 2006. During August 2006–August 2008, >24,000 bluetongue virus serotype 8 infections were reported, most (20,635) in 2007. In 2006 and 2007, respectively, case-fatality rates were 6.4% and 13.1% for cattle and 37.5% and 41.5% for sheep. Vaccination in 2008 decreased cases

Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

α-Herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sites

α-Herpesviruses constitute closely related neurotropic viruses, including herpes simplex virus in man and pseudorabies virus (PRV) in pigs. Peripheral sensory neurons, such as trigeminal ganglion (TG) neurons, are predominant target cells for virus spread and lifelong latent infections. We report that in vitro infection of swine TG neurons with the homologous swine α-herpesvirus PRV results in the appearance of numerous synaptophysin-positive synaptic boutons (varicosities) along the axons. Nonneuronal cells that were juxtaposed to these varicosities became preferentially infected with PRV, suggesting that varicosities serve as axonal exit sites for the virus. Viral envelope glycoprotein D (gD) was found to be necessary and sufficient for the induction of varicosities. Inhibition of Cdc42 Rho GTPase and p38 mitogen-activated protein kinase signaling pathways strongly suppressed gD-induced varicosity formation. These data represent a novel aspect of the cell biology of α-herpesvirus infections of sensory neurons, demonstrating that virus attachment/entry is associated with signaling events and neuronal changes that may prepare efficient egress of progeny virus