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This study aims to analysing the exclusively phraseological occurrency of some adjectives taken from German. This phenomenon reffers to the isolation of words and lexical forms out of linguistical and extralinguistical causes, in phraseological sintagmas. Firstly, we will briefly present the main directions in the research of this isolated lexemes. Then, we will analyse the linguistical features specific to these linguistical facts, using as exemples some of the German adjectives.
Ongoing and predicted global change makes understanding and predicting species’ range shifts an urgent scientific priority. Here, we provide a synthetic perspective on the so far poorly understood effects of interspecific interactions on range expansion rates. We present theoretical foundations for how interspecific interactions may modulate range expansion rates, consider examples from empirical studies of biological invasions and natural range expansions as well as process-based simulations, and discuss how interspecific interactions can be more broadly represented in process-based, spatiotemporally explicit range forecasts. Theory tells us that interspecific interactions affect expansion rates via alteration of local population growth rates and spatial displacement rates, but also via effects on other demographic parameters. The best empirical evidence for interspecific effects on expansion rates comes from studies of biological invasions. Notably, invasion studies indicate that competitive dominance and release from specialized enemies can enhance expansion rates. Studies of natural range expansions especially point to the potential for competition from resident species to reduce expansion rates. Overall, it is clear that interspecific interactions may have important consequences for range dynamics, but also that their effects have received too little attention to robustly generalize on their importance. We then discuss how interspecific interactions effects can be more widely incorporated in dynamic modeling of range expansions. Importantly, models must describe spatiotemporal variation in both local population dynamics and dispersal. Finally, we derive the following guidelines for when it is particularly important to explicitly represent interspecific interactions in dynamic range expansion forecasts: if most interacting species show correlated spatial or temporal trends in their effects on the target species, if the number of interacting species is low, and if the abundance of one or more strongly interacting species is not closely linked to the abundance of the target species.
Background: Aviscumine, a recombinant plant protein, is an immune modulator that induces ribotoxic stress at the 28S ribosomal RNA subunit. In this way cytokine release and T-cell responses are enhanced. This phase II trial was conducted to test the efficacy and safety of aviscumine in patients with systemically pre-treated metastatic melanoma stage IV.
Methods: A total of 32 patients with progressive stage IV melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial. All patients had an ECOG performance status of 0 or 1. Patients received 350 ng aviscumine twice weekly by subcutaneous injection until progression. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was assessed as adverse events (AEs). Tumor response was assessed every eight weeks and survival of patients was followed up to one year after the end of therapy. Thirty one patients (intent-to-treat population (ITT)) were assessed for efficacy; safety was assessed in the whole population.
Results: One patient achieved a partial response (PR) and 10 patients showed stable disease/no change (SD). The median progression-free survival (mPFS) was 63 days (95% CI 57–85) and median overall survival (mOS) was 335 days (95% CI 210–604). In total 210 treatment-emergent adverse events were recorded. Grade 1 or 2 AEs occurred in 72% of patients and were mostly application-site effects such as pruritus Grade 3–4 treatment-emergent drug-related adverse events occurred in 9% of patients.
Conclusion: These results suggest that aviscumine may have a clinical impact in patients with previously treated metastatic melanoma and provide rationale for further clinical evaluation of this agent. In the light of effective new immune checkpoint blockers it might be a candidate for combinations with these agents.
To understand what makes some species successful invaders, it is critical to quantify performance differences between native and introduced regions, and among populations occupying a broad range of environmental conditions within each region. However, these data are not available even for the world’s most notorious invasive species. Here we introduce the Global Garlic Mustard Field Survey, a coordinated distributed field survey to collect performance data and germplasm from a single invasive species: garlic mustard (Alliaria petiolata) across its entire distribution using minimal resources. We chose this species for its ecological impacts, prominence in ecological studies of invasion success, simple life history, and several genetic and life history attributes that make it amenable to experimental study. We developed a standardised field survey protocol to estimate population size (area) and density, age structure, plant size and fecundity, as well as damage by herbivores and pathogens in each population, and to collect representative seed samples. Across four years and with contributions from 164 academic and non-academic participants from 16 countries in North America and Europe thus far, we have collected 45,788 measurements and counts of 137,811 plants from 383 populations and seeds from over 5,000 plants. All field data and seed resources will be curated for release to the scientific community. Our goal is to establish A. petiolata as a model species for plant invasion biology and to encourage large collaborative studies of other invasive species.
Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage.
Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME.
Als Rudolf Kassner Anfang Dezember 1900 nach zehnmonatigem Aufenthalt in Frankreich in die väterliche Wiener Wohnung nahe der Karlskirche zurückkehrt, lässt er knapp vier Wochen verstreichen, ehe er sich am 4. Januar 1901 brieflich bei Houston Stewart Chamberlain in Erinnerung bringt. Wie manchen anderen "geehrten und geschätzten Geistern" hatte er dem Autor des bewunderten Buchs "Die Grundlagen des neunzehnten Jahrhunderts" sein zu Jahrhundertbeginn bei Eugen Diederichs in Leipzig erschienenes Erstlingswerk "Die Mystik, die Künstler und das Leben" vom Verlag zusenden lassen und nach längerer Wartezeit am 13. Mai 1900 begeisterte Zustimmung erfahren. Noch in der ersten Januardekade 1901 betritt er das hochgelegene "Studierzimmer" in der Blümelgasse 17 und wird als "junger Schriftsteller und Gelehrter von seltener Begabung" sofort in den engeren Freundeskreis aufgenommen. Hier lernt er im Spätherbst desselben Jahres Hermann Graf Keyserling kennen. Der führt ihn nicht nur bei Hugo von Hofmannsthal in Rodaun ein, sondern auch in den "internationalen Salon der Fürstin Marie von Thurn und Taxis" in der Wiener Victorgasse 5a. Die erste Begegnung Kassners mit dem Fürstenpaar findet vermutlich Anfang 1902 statt, da die Fürstin "selten mit ihrem Train vor Weihnachten aus Lautschin" nach Wien "übersiedelt". Genauere Belege fehlen; doch dürfte der Besuch in eine gewisse zeitliche Nähe zum Treffen mit Hofmannsthal zu rücken sein, das für den 4. Dezember 1901 bezeugt ist. Die überlieferte Korrespondenz setzt im Frühjahr 1902 ein. Sie erstreckt sich über mehr als drei Jahrzehnte und liest sich, trotz erheblicher Lücken, die aus anderen Quellen, nicht zuletzt dem Briefwechsel zwischen der Fürstin und Rainer Maria Rilke, zu erschließen sind, als Dokument einer Lebensfreundschaft, die von ungeteilter, liebevoll verehrender Hochachtung getragen ist.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.
The morphology of presynaptic specializations can vary greatly ranging from classical single-release-site boutons in the central nervous system to boutons of various sizes harboring multiple vesicle release sites. Multi-release-site boutons can be found in several neural contexts, for example at the neuromuscular junction (NMJ) of body wall muscles of Drosophila larvae. These NMJs are built by two motor neurons forming two types of glutamatergic multi-release-site boutons with two typical diameters. However, it is unknown why these distinct nerve terminal configurations are used on the same postsynaptic muscle fiber. To systematically dissect the biophysical properties of these boutons we developed a full three-dimensional model of such boutons, their release sites and transmitter-harboring vesicles and analyzed the local vesicle dynamics of various configurations during stimulation. Here we show that the rate of transmission of a bouton is primarily limited by diffusion-based vesicle movements and that the probability of vesicle release and the size of a bouton affect bouton-performance in distinct temporal domains allowing for an optimal transmission of the neural signals at different time scales. A comparison of our in silico simulations with in vivo recordings of the natural motor pattern of both neurons revealed that the bouton properties resemble a well-tuned cooperation of the parameters release probability and bouton size, enabling a reliable transmission of the prevailing firing-pattern at diffusion-limited boutons. Our findings indicate that the prevailing firing-pattern of a neuron may determine the physiological and morphological parameters required for its synaptic terminals.