גבול (Border)

This paper is a reexamination of the concept of the geopolitical border through a critical analysis of prevalent conceptualizations of borders, as they are articulated in the fields of geopolitics, political theory and international relations. Suggesting that thinking of borders as the derivative of territorial definitions disregards the dependency of territoriality and sovereign space on the praxes of border making, this paper offers an analytic distinction between normative articulations of borders and the border as a political practice. This distinction enables the identification of partial and incoherent border making processes. Consequently, the creation of borders can be analyzed as an effect of a multiplicity of performative praxes, material, juridical and otherwise discursive, that operate in relation to the management of space and attribute it with geopolitical distinctions. Furthermore, the paper suggests that these praxes, which appear in dispersed sites and in a wide variety of loci, are intrinsically linked to different spatial practices of population management, of governmentality. Thus, I offer a reading of borders as a praxis which manages binary differentiations of matrixes of governmentality, which create schisms in the population as a totality, through the deployment of the evocation of sovereignty as the legitimizing source of this differentiation or for the means necessary for its sustainment.

Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors

The role of proteases in viral infection of the lung is poorly understood. Thus, we examined matrix metalloproteinases (MMPs) and cathepsin proteases in respiratory syncytial virus (RSV)-infected mouse lungs. RSV-induced gene expression for MMPs -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, and -28 and cathepsins B, C, E, G, H, K, L1, S, W, and Z in the airways of Friend leukemia virus B sensitive strain mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β-deficient mice were exposed to RSV. Mavs-deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13, and -28 and cathepsins C, G, K, S, W, and Z. In lung epithelial cells, retinoic acid-inducible gene-1 (RIG-I) was identified as the major RIG-I-like receptor required for RSV-induced protease expression via MAVS. Overexpression of RIG-I or treatment with interferon-β in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV-infected mice.

miR-31 Dysregulation in Cystic Fibrosis Airways Contributes to Increased Pulmonary Cathepsin S Production

Rationale:
Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to lung inflammation via degradation of antimicrobial proteins, such as lactoferrin and members of the β-defensin family.

Objectives:
In this study, we investigated the hypothesis that airway epithelial cells are a source of CTSS, and mechanisms underlying CTSS expression in the CF lung.

Methods:
Protease activity was determined using fluorogenic activity assays. Protein and mRNA expression were analyzed by ELISA, Western blotting, and reverse-transcriptase polymerase chain reaction.Measurements and Main Results: In contrast to neutrophil elastase, CTSS activity was detectable in 100% of CF BAL fluid samples from patients without Pseudomonas aeruginosa infection. In this study, we identified epithelial cells as a source of pulmonary CTSS activity with the demonstration that CF airway epithelial cells express and secrete significantly more CTSS than non-CF control cells in the absence of proinflammatory stimulation. Furthermore, levels of the transcription factor IRF-1 correlated with increased levels of its target gene CTSS. We discovered that miR-31, which is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels with concomitant knockdown of CTSS expression and secretion.

Conclusions:
The miR-31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung disease and may open up new avenues for exploration in the search for an effective therapeutic target.

(Dis‑)Harmony in movement: effects of musical dissonance on movement timing and form

While the origins of consonance and dissonance in terms of acoustics, psychoacoustics and physiology have been debated for centuries, their plausible effects on movement synchronization have largely been ignored. The present study aims to address this by investigating whether, and if so how, consonant/dissonant pitch intervals affect the spatiotemporal properties of regular reciprocal aiming movements. We compared movements synchronized either to consonant or to dissonant sounds, and showed that they were differently influenced by the degree of consonance of the sound presented. Interestingly, the difference was present after the sound stimulus was removed. In this case, the performance measured after consonant sound exposure was found to be more stable and accurate, with a higher percentage of information/movement coupling (tau-coupling) and a higher degree of movement circularity when compared to performance measured after the exposure to dissonant sounds. We infer that the neural resonance representing consonant tones leads to finer perception/action coupling which in turn may help explain the prevailing preference for these types of tones.

Movement and Perceptual Strategies to Intercept Virtual Sound Sources

To intercept a moving object, one needs to be in the right place at the right time. In order to do this, it is necessary to pick up and use perceptual information that specifies the time to arrival of an object at an interception point. In the present study, we examined the ability to intercept a laterally moving virtual sound object by controlling the displacement of a sliding handle and tested whether and how the interaural time difference (ITD) could be the main source of perceptual information for successfully intercepting the virtual object. The results revealed that in order to accomplish the task, one might need to vary the duration of the movement, control the hand velocity and time to reach the peak velocity (speed coupling), while the adjustment of movement initiation did not facilitate performance. Furthermore, the overall performance was more successful when subjects employed a time-to-contact (tau) coupling strategy. This result shows that prospective information is available in sound for guiding goal-directed actions.

Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.

Laser-engineered dissolving microneedle arrays for protein delivery: potential for enhanced intradermal vaccination

OBJECTIVES: We aimed to highlight the utility of novel dissolving microneedle (MN)-based delivery systems for enhanced transdermal protein delivery. Vaccination remains the most accepted and effective approach in offering protection from infectious diseases. In recent years, much interest has focused on the possibility of using minimally invasive MN technologies to replace conventional hypodermic vaccine injections.

METHODS: The focus of this study was exploitation of dissolving MN array devices fabricated from 20% w/w poly(methyl vinyl ether/maleic acid) using a micromoulding technique, for the facilitated delivery of a model antigen, ovalbumin (OVA).

KEY FINDINGS: A series of in-vitro and in-vivo experiments were designed to demonstrate that MN arrays loaded with OVA penetrated the stratum corneum and delivered their payload systemically. The latter was evidenced by the activation of both humoral and cellular inflammatory responses in mice, indicated by the production of immunoglobulins (IgG, IgG1, IgG2a) and inflammatory cytokines, specifically interferon-gamma and interleukin-4. Importantly, the structural integrity of the OVA following incorporation into the MN arrays was maintained.

CONCLUSION: While enhanced manufacturing strategies are required to improve delivery efficiency and reduce waste, dissolving MN are a promising candidate for 'reduced-risk' vaccination and protein delivery strategies.

Transcriptional response of T cells to IFN-alpha:changes induced in IFN-alpha-sensitive and resistant cutaneous T cell lymphoma

Interferon-alpha (IFN-alpha) therapy is commonly used in the treatment of neoplastic and autoimmune diseases, including cutaneous T cell lymphoma (CTCL). However, the IFN-alpha response is unpredictable, and the IFN-alpha cell targets and pathways are only partially understood. To delineate the molecular mechanisms of IFN-alpha activity, gene expression profiling was performed in a time-course experiment of both IFN-alpha sensitive and IFN-alpha-resistant variants of a CTCL cell line. These experiments revealed that IFN-alpha is responsible for the regulation of hundreds of genes in both variants and predominantly involves genes implicated in signal transduction, cell cycle control, apoptosis, and transcription regulation. Specifically, the IFN-alpha response of tumoral T cells is due to a combination of induction of apoptosis in which TNFSF10 and HSXIAPAF1 may play an important role and cell cycle arrest achieved by downregulation of CDK4 and CCNG2 and upregulation of CDKN2C and tumor suppressor genes (TSGs). Resistance to IFN-alpha appears to be associated with failure to induce IRF1 and IRF7 and deregulation of the apoptotic signals of HSXIAPAF1, TRADD, BAD, and BNIP3. Additionally, cell cycle progression is heralded by upregulation of CDC25A and CDC42. A critical role of NF-kappaB in promoting cell survival in IFN-alpha-resistant cells is indicated by the upregulation of RELB and LTB.

Chemistry and Distribution of Daughter Species in the Circumstellar Envelopes of O-Rich AGB Stars

Context. Thanks to the advent of Herschel and ALMA, new high-quality observations of molecules present in the circumstellar envelopes of asymptotic giant branch (AGB) stars are being reported that reveal large differences from the existing chemical models. New molecular data and more comprehensive models of the chemistry in circumstellar envelopes are now available.
Aims: The aims are to determine and study the important formation and destruction pathways in the envelopes of O-rich AGB stars and to provide more reliable predictions of abundances, column densities, and radial distributions for potentially detectable species with physical conditions applicable to the envelope surrounding IK Tau.
Methods: We use a large gas-phase chemical model of an AGB envelope including the effects of CO and N2 self-shielding in a spherical geometry and a newly compiled list of inner-circumstellar envelope parent species derived from detailed modeling and observations. We trace the dominant chemistry in the expanding envelope and investigate the chemistry as a probe for the physics of the AGB phase by studying variations of abundances with mass-loss rates and expansion velocities.
Results: We find a pattern of daughter molecules forming from the photodissociation products of parent species with contributions from ion-neutral abstraction and dissociative recombination. The chemistry in the outer zones differs from that in traditional PDRs in that photoionization of daughter species plays a significant role. With the proper treatment of self-shielding, the N → N2 and C+→ CO transitions are shifted outward by factors of 7 and 2, respectively, compared with earlier models. An upper limit on the abundance of CH4 as a parent species of (≲2.5 × 10-6 with respect to H2) is found for IK Tau, and several potentially observable molecules with relatively simple chemical links to other parent species are determined. The assumed stellar mass-loss rate, in particular, has an impact on the calculated abundances of cations and the peak-abundance radius of both cations and neutrals: as the mass-loss rate increases, the peak abundance of cations generally decreases and the peak-abundance radius of all species moves outwards. The effects of varying the envelope expansion velocity and cosmic-ray ionization rate are not as significant.

Induction and antagonism of antiviral responses in respiratory syncytial virus-infected pediatric airway epithelium.

Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well- differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs that was mediated in part by secreted factors, including interferon lambda-1 (IFNλ1)/IL-29. In contrast, type I interferons were not detected following RSV infection of WD-PBECs., Interferon (IFN) responses in RSV-infected WD-PBECs reflected those in lower airway samples from RSV-hospitalized infants. In view of the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD-PBECs before or after infection abrogated RSV replication. Interestingly, IL-29 demonstrated prophylactic, but not therapeutic, potential against RSV. The absence of therapeutic potential reflected effective RSV antagonism of IFN-mediated antiviral responses in infected cells. Our data are consistent with RSV non-structural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with concomitant reduced expression of antiviral effector molecules, such as MxA/B. Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC cultures. Importantly, our study provides the rationale to further explore IL-29 as a novel RSV prophylactic.

Ultraviolet emission lines of Si II in cool star and solar spectra

Recent atomic physics calculations for Si II are employed within the CLOUDY modelling code to analyse Hubble Space Telescope (HST) STIS ultraviolet spectra of three cool stars, β Geminorum, α Centauri A and B, as well as previously published HST/GHRS observations of α Tau, plus solar quiet Sun data from the High Resolution Telescope and Spectrograph. Discrepancies found previously between theory and observation for line intensity ratios involving the 3s²3p ²PJ-3s3p^{2 4}P^J' intercombination multiplet of Si II at ~ 2335 Å are significantly reduced, as are those for ratios containing the 3s²3p ²PJ-3s3p^{2 2}DJ ~ transitions at ~1816 Å. This is primarily due to the effect of the new Si II transition probabilities. However, these atomic data are not only very different from previous calculations, but also show large disagreements with measurements, specifically those of Calamai et al. for the intercombination lines. New measurements of transition probabilities for Si II are hence urgently required to confirm (or otherwise) the accuracy of the recently calculated values. If the new calculations are confirmed, then a long-standing discrepancy between theory and observation will have finally been resolved. However, if the older measurements are found to be correct, then the agreement between theory and observation is simply a coincidence and the existing discrepancies remain.