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Vaccination against human cytomegalovirus (CMV) infection remains high priority. A recombinant form of a protein essential for CMV entry, glycoprotein B (gB), demonstrated partial protection in a clinical trial (NCT00299260) when delivered with the MF59 adjuvant. Although the antibody titre against gB correlated with protection poor neutralising responses against the 5 known antigenic domains (AD) of gB were evident. Here, we show that vaccination of CMV seronegative patients induces an antibody response against a region of gB we term AD-6. Responses to the polypeptide AD-6 are detected in >70% of vaccine recipients yet in <5% of naturally infected people. An AD-6 antibody binds to gB and to infected cells but not the virion directly. Consistent with this, the AD-6 antibody is non-neutralising but, instead, prevents cell-cell spread of CMV in vitro. The discovery of AD-6 responses has the potential to explain part of the protection mediated by gB vaccines against CMV following transplantation. A gB/MF59 vaccine candidate for human cytomegalovirus (HCMV) provided partial protection in organ transplant patients. Here, the authors identify antibody responses in trial participants that target virally infected cells to control cell-to-cell spread of HCMV, providing a potential mechanism for the observed protection. [ABSTRACT FROM AUTHOR]

Tunable electromagnets and corresponding devices, such as magnetic lenses or stigmators, are the backbone of high-energy charged particle optical instruments, such as electron microscopes, because they provide higher optical power, stability, and lower aberrations compared to their electric counterparts. However, electromagnets are typically macroscopic (super-)conducting coils, which cannot generate swiftly changing magnetic fields, require active cooling, and are structurally bulky, making them unsuitable for fast beam manipulation, multibeam instruments, and miniaturized applications. Here, we present an on-chip microsized magnetic charged particle optics realized via a self-assembling micro-origami process. These micro-electromagnets can generate alternating magnetic fields of about ±100 mT up to a hundred MHz, supplying sufficiently large optical power for a large number of charged particle optics applications. That particular includes fast spatiotemporal electron beam modulation such as electron beam deflection, focusing, and wave front shaping as required for stroboscopic imaging. Electron beam manipulation is important for their application in microscopes, lithography instruments, and colliders. Here the authors report a wafer scale, self-assembled, microcoil electrically-driven magnetic charge particle optic device that can be implemented into different configurations for controlling of electron beams. [ABSTRACT FROM AUTHOR]

Ras-driven tumorigenesis is assumed to depend on Raf for ERK activation and proliferation; yet, an in vivo requirement for Raf as MEK/ERK activator in this setting has not been demonstrated to date. Here, we show that epidermis-restricted B-Raf ablation restrains the onset and stops the progression of established Ras-driven tumors by limiting MEK/ERK activation and proliferation. Concomitant elimination of B-Raf and Raf-1 enforces the abrupt regression of established tumors owing to the decrease in ERK activation and proliferation caused by B-Raf ablation combined with the ERK-independent increase in Rho-dependent kinase (Rok) signaling and differentiation triggered by Raf-1 inactivation. Thus, B-Raf and Raf-1 have non-redundant functions in Ras-driven tumorigenesis. Of note, Raf kinase inhibitors achieve impressive results in melanomas harboring oncogenic BRAF, but are ineffective against Ras-driven tumors; moreover, therapy-related skin tumors driven by a paradox ERK activation as well as primary and acquired resistance have been reported. Our results suggest that therapies targeting both Raf kinase-dependent and -independent pathways may be effective against a broader range of malignancies and reduce the risks of adverse effects and/or resistance. [ABSTRACT FROM AUTHOR]

The epidermis is the outermost layer of the body and protects it from environmental insults. This crucial function is sustained by a continuous process of self-renewal involving the carefully balanced proliferation and differentiation of progenitor cells constantly replacing the mature cells at the surface of the epidermis. Genetic changes in the signalling pathways controlling keratinocyte proliferation and differentiation disrupt this balance and lead to pathological changes including carcinogenesis. This review discusses the role of Ras, an oncogene critically involved in the development of skin neoplasia, and its downstream effector Raf in epidermal homeostasis and tumourigenesis. In particular, we will focus on the recently established role of Raf-1 as the decisive element that, by restraining keratinocyte differentiation, allows the development and maintenance of Ras-driven tumours. [ABSTRACT FROM AUTHOR]

Ceramic injection molding (CIM) has become a standard process in the ceramics industry in the last 20 years. Components such as alumina inserts for water taps or water pump seals have become affordable since they are being produced in millions of pieces. High performance ceramics with submicron or even nanoscale structural features are well known from material science. Due to the difficult processing properties of such ultrafine powders, nanocomposites produced by CIM are not yet commercially available. Many nanocomposite ceramics with extremely attractive properties as extreme hardness, toughness and strength are only applied in high-price niche applications due to their high manufacturing cost which is determined by low turnover hot-pressing or spark plasma sintering (SPS) processes and difficult and cost intensive hard machining operations. A commercial breakthrough to a broader range of applications can only be achieved if near-net-shape manufacturing of such parts becomes possible. For complex shapes injection molding based on thermoplastic feedstocks seems very attractive. In this study the feasibility of net-shape thermoplastic forming of nanocomposite ZTA was tested in comparison to state-of-the-art micro and submicronscale ZTA. Although ultrafine powders have become available and affordable their processing is still challenging. Compounding these powders into feedstocks with high solid content and suitable rheological properties is considerably more difficult than with standard recipes and grain sizes, but becomes possible if high torque mixing e.g. in a twin screw extruder is applied. The rheological properties of the feedstocks was investigated by capillary rheometry. The differences in rheological behaviour between micro- and nanocomposites of zirconia toughened alumina (ZTA) and the effect on the microstructures and mechanical properties are shown. Testing samples were produced by CIM and extrusion. Such ZTA feedstocks can be processed on standard injection molding machines without modifying the equipment. Thermoplastic extrusion of thin wall tubes was also carried out. The main difficulties identified in nanocomposite feedstocks were the very narrow ranges of composition and processing parameters which have to be exactly complied to in order to avoid binder segregation, warping and microstructural defects in the sintered part. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor (FGF) signaling can bypass the requirement for estrogen receptor (ER) activation in the growth of ER-positive (ER+) breast cancer cells. Fibroblast growth factor-1 stimulation leads to phosphorylation of the adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT-1) on C-terminal tyrosine residues, whereas it is constitutively bound through its N-terminal phosphotyrosine-binding domain (PTB) to FGF receptors (FGFRs). By expressing the PTB domain of SNT-1 (SNT-1 PTB) in an inducible manner in an ER+ breast carcinoma line, ML20, we asked whether we could uncouple FGFR activation from its downstream signaling components and abrogate FGF-1-induced antiestrogen-resistant growth. Induction of SNT-1 PTB resulted in a significant decrease of FGF-1-dependent tyrosine phosphorylation of endogenous SNT-1, strong inhibition of complex formation between SNT-1, Gab-1 and Sos-1, and reduced activation of Ras, mitogen-activated protein kinase (MAP kinase), and Akt. SNT-1 PTB also inhibited the phosphorylation of p70S6K on Thr421/Ser424 and Ser411, which may result from the abrogation of MAP kinase activity. Moreover, we also observed a decreased phosphorylation of the MAP kinase-independent site Thr389. This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Collectively these results suggest that SNT-1 plays a pivotal role in FGF-dependent activation of the Ras-MAP kinase, PI-3 kinase, and mTOR pathways in these cells. Fibroblast growth factor-1 dependent colony formation of ML20 cells in media containing the pure antiestrogen ICI 182,780 was also markedly inhibited upon induction of SNT-1 PTB, suggesting that blockade of FGFR–SNT-1 interactions might abrogate FGF-mediated antiestrogen resistance in breast cancers.Oncogene (2006) 25, 6003–6014. doi:10.1038/sj.onc.1209592; published online 8 May 2006 [ABSTRACT FROM AUTHOR]

Objective: To determine the value of procalcitonin (PCT) monitoring in transplant patients receiving pan-T-cell antibody therapy.Design: Retrospective clinical study.Setting: A collaborative study between the Institute of Medical Immunology, the Department of Nephrology and Internal Intensive Care, both Charite, Humboldt University Berlin, and the Department of Laboratory Medicine, Friedrichshain Hospital, Berlin, Germany.Patients and Interventions: Thirty-one patients were included in the study: 8 kidney transplant patients with acute rejection episodes, 5 receiving OKT3 monoclonal antibody therapy, 3 receiving steroid bolus therapy; 21 patients undergoing renal transplantation, 11 receiving ATG perioperatively, 10 without ATG administration; 2 patients undergoing renal transplantation and receiving anti-IL-2R mAb.Measurements and Results: Procalcitonin (PCT) and tumor necrosis factor (TNF) alpha plasma levels were measured in infection-free transplant patients treated with the pan-T-cell antibodies ATG or OKT3. We found PCT plasma concentrations up to 600 ng/ml (reference < 0.5 ng/ ml), which are comparable to those seen in severe sepsis. Increases in TNF-alpha plasma levels preceded the rises in PCT. After peaking on day 1 of therapy the PCT plasma concentrations returned to normal values independently of further antibody administration. In contrast, steroid bolus therapy or anti-interleukin 2 receptor mAb administration did not increase plasma PCT or TNF-alpha levels.Conclusions: PCT monitoring for evaluating infectious complications in kidney transplant patients must be very careful during pan-T-cell antibody therapy. [ABSTRACT FROM AUTHOR]

Angiopoietin-1 (Ang1) has been shown to act as an angiogenic promoter in embryonic angiogenesis by promoting vascular branching, pericyte recruitment and endothelial survival. We have investigated the role of Ang1 in tumour neovascularization under clinical conditions and in animal models. The expression of Ang1 in clinical breast cancer specimens was analysed by using laser-capture microdissection and reverse transcriptase-linked polymerase chain reaction (RT-PCR) on RNA isolated from the samples. Despite the expression of Ang1 in many human breast cancer cell lines, the gene was expressed in only three of 21 breast cancer clinical specimens, even though its receptor, Tie2, is abundant in the vasculature of all of these tumours. Ang1 was then overexpressed in a human breast cancer cell line (MCF-7) on its own and in conjunction with FGF1, an angiogenic factor shown to be able to increase the tumorigenicity of MCF-7 cells. High concentrations of Ang1 were produced in the conditioned media of the transfected cells (range 156-820 ng ml[SUP-1]). However, in contrast to its physiological role as promoter of angiogenesis, overexpression of Ang1 did not enhance tumour growth, but instead caused up to a 3-fold retardation of tumour growth (P = 0.003). [ABSTRACT FROM AUTHOR]

By means of gas chromatographic and mass spectroscopic methods, and combined GC-electroantennogram and electrosensillogram techniques, ( E)-11-hexadecenal and (10 E, 12 E)-10,12-hexadecadienal [( E,E)-bombykal is also the main constituent of the pheromone of the silver-striped hawk-moth Hippotion celerio. The biological activity of the substances was demonstrated with electroantennogram and single cell recording, and the physiological efficacy of the different hexadecadienal isomers compared. [ABSTRACT FROM AUTHOR]

The Neotropical species Pachycondyla marginata conducts well-organized predatory raids on the termite species Neocapritermes opacus and frequently emigrates to new nest sites. During both activities the ants employ chemical trail communication. The trail pheromone orginates from the pygidial gland. Among the substances identified in the pygidial gland secretions, only citronellal was effective as a trail pheromone. Isopulegol elicited an increase in locomotory activity in the ants and may function as a synergist recruitment signal. The chemical signal is enhanced by a shaking display performed by the recruiting ant. [ABSTRACT FROM AUTHOR]

Both linear and non-linear viscoelasticity experiments have been performed in semi-dilute micellar aqueous solutions of ethanediyl-α,ω-bis (dodecylmethylammonium bromide) as a function of solution chloride (NaCl) concentration. The results suggest that both linear and non-linear properties are affected by the electrostatic interactions. In particular, the plateau modulus G′ and the ratio σ/ G′, where σ represents the plateau value in a stress-shear rate experiment, are enhanced as the electrostatic interactions are screened by addition of salt. The zero-shear viscosity is lowered upon addition of NaCl, due likely to an exchange of the Cl ions with the Br counterions. [ABSTRACT FROM AUTHOR]

By means of gas chromatography, gas chromatographic coupled mass spectrometry, trail-following experiments and electrophysiological recordings from worker antennae, the major trail pheromone components from the hindgut of the formicine species Camponotus atriceps and C. floridanus were identified as 3,5-dimethyl-6-(1′-methylpropyl)-tetrahydropyran-2-one and nerolic acid, respectively. The Dufour's gland contents of both species, investigated by gas chromatographic coupled mass spectrometry, show significant differences. [ABSTRACT FROM AUTHOR]

Copyright of Physik der Kondensierten Materie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Physik der Kondensierten Materie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Physik der Kondensierten Materie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A hallmark of vascular disease is the inappropriate proliferative and synthetic behaviour of vascular smooth muscle cells. This phenotypically immature behaviour arises as a consequence of the myocytes undergoing phenotypic conversion and/or clonal proliferation of a 'fetal' type of smooth muscle cell preexisting in the vessel wall. De-differentiation and initiation of proliferation is not only induced by endothelial desquamation and acute exposure of smooth muscle cells to platelet-derived mitogens, but also occurs in the uninjured blood vessel. Therefore normal components of the blood vessel are implicit in the pathological process. These include vasoconstrictor peptides, growth factor peptides and extracellular matrix molecules. In vitro and in vivo experimentation has indicated that while some of these compounds individually are only mild stimulators of smooth muscle proliferative metabolism, they may act synergistically to induce robust responses. Here we discuss the effects of the vasoconstrictor peptide angiotensin II, which can be locally generated within the vessel wall itself, on the expression of extracellular matrix molecules in vitro and in vivo. We focus on the angiotensin II-modulated expression of extracellular matrix glycoproteins, e.g. thrombospondin, tenascin, fibronectin and laminin. [ABSTRACT FROM AUTHOR]

Decades of techno-economic energy policymaking and research have meant evidence from the Social Sciences and Humanities (SSH)-including critical reflections on what changing a society's relation to energy (efficiency) even means-have been underutilised. In particular, (i) the SSH have too often been sidelined and/or narrowly pigeonholed by policymakers, funders, and other decision-makers when driving research agendas, and (ii) the setting of SSH-focused research agendas has not historically embedded inclusive and deliberative processes. The aim of this paper is to address these gaps through the production of a research agenda outlining future SSH research priorities for energy efficiency. A Horizon Scanning exercise was run, which sought to identify 100 priority SSH questions for energy efficiency research. This exercise included 152 researchers with prior SSH expertise on energy efficiency, who together spanned 62 (sub-)disciplines of SSH, 23 countries, and a full range of career stages. The resultant questions were inductively clustered into seven themes as follows: (1) Citizenship, engagement and knowledge exchange in relation to energy efficiency; (2) Energy efficiency in relation to equity, justice, poverty and vulnerability; (3) Energy efficiency in relation to everyday life and practices of energy consumption and production; (4) Framing, defining and measuring energy efficiency; (5) Governance, policy and political issues around energy efficiency; (6) Roles of economic systems, supply chains and financial mechanisms in improving energy efficiency; and (7) The interactions, unintended consequences and rebound effects of energy efficiency interventions. Given the consistent centrality of energy efficiency in policy programmes, this paper highlights that well-developed SSH approaches are ready to be mobilised to contribute to the development, and/or to understand the implications, of energy efficiency measures and governance solutions. Implicitly, it also emphasises the heterogeneity of SSH policy evidence that can be produced. The agenda will be of use for both (1) those new to the energy-SSH field (including policyworkers), for learnings on the capabilities and capacities of energy-SSH, and (2) established energy-SSH researchers, for insights on the collectively held futures of energy-SSH research., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)