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In this work, an alternative attempt to motivate the Many-Worlds Interpretation (MWI) is undertaken. The usual way of arguing for MWI mostly revolves around how it might solve the measurement problem in a more straightforward and concise manner than rival interpretations. However, here an effort is made to defend MWI in an indirect manner, namely via repeated case discrimination and a process of ‘conceptual elimination’. That is, it will be argued that its major rivals, with QBism and Relational Quantum-Mechanics being among the most noteworthy ones, either face conceptual incoherence or conceptually collapse into a variant of MWI. Finally, it is argued that hidden-variable theories face severe challenges when being applied to Quantum Field Theory such that appropriate modifications may lead back to MWI, thereby purportedly leaving MWI as the only viable option.

Interferometry reveals quantized changes in the angular momentum of neutrons that have been ‘twisted’ by passage through a spiral staircase structure. Orbital angular momentum control in neutron optics Orbital angular momentum is a quantized degree of freedom exploited in many applications. The photon orbital angular momentum has been used in fundamental tests of quantum mechanics and imaging and the electron orbital angular momentum has proven useful for determining the chirality of crystals. But the phenomenon had not previously been demonstrated in neutrons. Here Dmitry Pushin and colleagues show how to control orbital angular momentum states in a neutron beam through the use of macroscopic spiral phase plates. After applying this 'twist' to an input neutron beam, the quantized orbital angular momentum of neutrons is characterized by neutron interferometry. In contrast to photons and electrons, neutrons are massive particles, hence this result could open important new perspectives for testing quantum mechanics with massive observables. In addition, the neutron orbital angular momentum could enable new approaches for neutron scattering techniques. The quantized orbital angular momentum (OAM) of photons 1 offers an additional degree of freedom and topological protection from noise. Photonic OAM states have therefore been exploited in various applications 2 , 3 ranging from studies of quantum entanglement and quantum information science 4 , 5 , 6 , 7 to imaging 8 , 9 , 10 , 11 , 12 . The OAM states of electron beams 13 , 14 , 15 have been shown to be similarly useful, for example in rotating nanoparticles and determining the chirality of crystals 16 , 17 , 18 , 19 . However, although neutrons—as massive, penetrating and neutral particles—are important in materials characterization, quantum information and studies of the foundations of quantum mechanics, OAM control of neutrons has yet to be achieved. Here, we demonstrate OAM control of neutrons using macroscopic spiral phase plates that apply a ‘twist’ to an input neutron beam. The twisted neutron beams are analysed with neutron interferometry. Our techniques, applied to spatially incoherent beams, demonstrate both the addition of quantum angular momenta along the direction of propagation, effected by multiple spiral phase plates, and the conservation of topological charge with respect to uniform phase fluctuations. Neutron-based studies of quantum information science 20 , 21 , the foundations of quantum mechanics 22 , 23 , and scattering and imaging 24 of magnetic, superconducting and chiral materials have until now been limited to three degrees of freedom: spin, path and energy. The optimization of OAM control, leading to well defined values of OAM, would provide an additional quantized degree of freedom for such studies.

Spin-orbit coupling of light has come to the fore in nanooptics and plasmonics, and is a key ingredient of topological photonics and chiral quantum optics. We demonstrate a basic tool for incorporating analogous effects into neutron optics: the generation and detection of neutron beams with coupled spin and orbital angular momentum. The ³He neutron spin filters are used in conjunction with specifically oriented triangular coils to prepare neutron beams with lattices of spin-orbit correlations, as demonstrated by their spin-dependent intensity profiles. These correlations can be tailored to particular applications, such as neutron studies of topological materials.

Quantification theories assume that numbers govern and steer a policy field or an organisation. In order to steer successfully, however, the local interpretation of numbers takes centre stage as the meaning of numbers - and thus the way how actors respond to them - varies between systems or sectors. Empirically, this article reviews how a German university makes sense of political numbers and their implicit steering signals, and how quantification alters its organisational structures and reshapes the roles of academics. The article analyses the translation process distinguishing between three levels: the political discourse on university reform; the organisational adaptations; and the effects they have on the professional academic role. The article finds that the university has highly differentiated strategies to respond to the 'governance by numbers,' and that it has established independent number-based steering systems. We also find that such differentiation of programmes makes the university management more flexible, helping it deal with anticipated goal conflicts and unwanted allocative effects, but it also places serious strain on - and potentially overburns - the coordination provided by the university's central administration. We also find that academics have started to align their behavioural strategies towards fulfilling their organisational goals and that they tend to deviate from professional expectations. Discussing these differentiated strategies, this article shows how the differentiation of governance approaches also contributes to the university becoming an 'organisational actor.' These preliminary findings suggest the need for and potential direction of further investigations.

Mast cells (MCs) are tissue resident cells of hemopoietic origin and are critically involved in allergic diseases. MCs bind IgE by means of their high-affinity receptor for IgE (FcεRI). The FcεRI belongs to a family of multi-chain immune recognition receptors and is activated by cross-linking in response to multivalent antigens (Ags)/allergens. Activation of the FcεRI results in immediate release of preformed granular substances (e.g. histamine, heparin, and proteases), generation of arachidonic acid metabolites, and production of pro-inflammatory cytokines. The FcεRI shows a remarkable, bell-shaped dose-response behavior with weak induction of effector responses at both low and high (so-called supra-optimal) Ag concentrations. This is significantly different from many other receptors, which reach a plateau phase in response to high ligand concentrations. To explain this unusual dose-response behavior of the FcεRI, scientists in the past have drawn parallels to so-called precipitin curves resulting from titration of Ag against a fixed concentration of antibody (Ab) in solution (a.k.a. Heidelberger curves). Thus, for high, supra-optimal Ag concentrations one could assume that every IgE-bound FcεRI formed a monovalent complex with “its own Ag”, thus resulting in marginal induction of effector functions due to absence of receptor cross-linking. However, this was never proven to be the case. More recently, careful studies of FcεRI activation and signaling events in MCs in response to supra-optimal Ag concentrations have suggested a molecular explanation for the descending part of this bell-shaped curve. It is obvious now that extensive FcεRI/IgE/Ag clusters are formed and inhibitory molecules and signalosomes are engaged in response to supra-optimal cross-linking (amongst them the Src family kinase Lyn and the inositol-5′-phosphatase SHIP1) and they actively down-regulate MC effector responses. Thus, the analysis of MC signaling triggered by supra-optimal crosslinking holds great potential for identifying novel targets for pharmacologic therapeutic intervention to benefit patients with acute and chronic allergic diseases.

Methods to prepare and characterize neutron helical waves carrying orbital angular momentum (OAM) were recently demonstrated at small-angle neutron scattering (SANS) facilities. These methods enable access to the neutron orbital degree of freedom which provides new avenues of exploration in fundamental science experiments as well as in material characterization applications. However, it remains a challenge to recover phase profiles from SANS measurements. We introduce and demonstrate a novel neutron interferometry technique for extracting phase information that is typically lost in SANS measurements. An array of reference beams, with complementary structured phase profiles, are put into a coherent superposition with the array of object beams, thereby manifesting the phase information in the far-field intensity profile. We demonstrate this by resolving petal-structure signatures of helical wave interference for the first time: an implementation of the long-sought recovery of phase information from small-angle scattering measurements. Introduction of structured neutron waves carrying orbital angular momentum (OAM) in small-angle neutron scattering experiments provides novel approaches to the characterisation of material properties. Here the authors demonstrate the retrieval of phase information in far-field intensity profiles by means of an interferometric technique using helical neutron waves.

Repurposing existing, clinically approved, antiviral drugs as COVID-19 therapeutics is a rapid way to help combat the SARS-CoV-2 pandemic. Interferons (IFNs) usually form part of the body’s natural innate immune defenses against viruses, and they have been used with partial success to treat previous new viral threats, such as HIV, hepatitis C virus, and Ebola virus. Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a recently emerged respiratory coronavirus that has infected >23 million people worldwide with >800,000 deaths. Few COVID-19 therapeutics are available, and the basis for severe infections is poorly understood. Here, we investigated properties of type I (β), II (γ), and III (λ1) interferons (IFNs), potent immune cytokines that are normally produced during infection and that upregulate IFN-stimulated gene (ISG) effectors to limit virus replication. IFNs are already in clinical trials to treat COVID-19. However, recent studies highlight the potential for IFNs to enhance expression of host angiotensin-converting enzyme 2 (ACE2), suggesting that IFN therapy or natural coinfections could exacerbate COVID-19 by upregulating this critical virus entry receptor. Using a cell line model, we found that beta interferon (IFN-β) strongly upregulated expression of canonical antiviral ISGs, as well as ACE2 at the mRNA and cell surface protein levels. Strikingly, IFN-λ1 upregulated antiviral ISGs, but ACE2 mRNA was only marginally elevated and did not lead to detectably increased ACE2 protein at the cell surface. IFN-γ induced the weakest ISG response but clearly enhanced surface expression of ACE2. Importantly, all IFN types inhibited SARS-CoV-2 replication in a dose-dependent manner, and IFN-β and IFN-λ1 exhibited potent antiviral activity in primary human bronchial epithelial cells. Our data imply that type-specific mechanisms or kinetics shape IFN-enhanced ACE2 transcript and cell surface levels but that the antiviral action of IFNs against SARS-CoV-2 counterbalances any proviral effects of ACE2 induction. These insights should aid in evaluating the benefits of specific IFNs, particularly IFN-λ, as repurposed therapeutics. IMPORTANCE Repurposing existing, clinically approved, antiviral drugs as COVID-19 therapeutics is a rapid way to help combat the SARS-CoV-2 pandemic. Interferons (IFNs) usually form part of the body’s natural innate immune defenses against viruses, and they have been used with partial success to treat previous new viral threats, such as HIV, hepatitis C virus, and Ebola virus. Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2.

Signaling proteins in eukaryotes usually comprise a catalytic domain coupled to one or several interaction domains, such as SH2 and SH3 domains. An additional class of proteins critically involved in cellular communication are adapter or scaffold proteins, which fulfill their purely non-enzymatic functions by organizing protein–protein interactions. Intriguingly, certain signaling enzymes, e.g., kinases and phosphatases, have been demonstrated to promote particular cellular functions by means of their interaction domains only. In this review, we will refer to such a function as \"the adapter function of an enzyme\". Though many stories can be told, we will concentrate on several proteins executing critical adapter functions in cells of the immune system, such as Bruton´s tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), and SH2-containing inositol phosphatase 1 (SHIP1), as well as in cancer cells, such as proteins of the rat sarcoma/extracellular signal-regulated kinase (RAS/ERK) mitogen-activated protein kinase (MAPK) pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors. Thereby, we are highlighting the need to develop pharmacological approaches, such as proteolysis-targeting chimeras (PROTACs), that eliminate the entire protein, and thus both enzymatic and adapter functions of the signaling protein. We also review how genetic knock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.