104 research outputs found
Principle and design of pseudo-natural products
Natural products (NPs) are a significant source of inspiration towards the discovery of new bioactive compounds based on novel molecular scaffolds. However, there are currently only a small number of guiding synthetic strategies available to generate novel NP-inspired scaffolds, limiting both the number and types of compounds accessible. In this Perspective, we discuss a design approach for the preparation of biologically relevant small-molecule libraries, harnessing the unprecedented combination of NP-derived fragments as an overarching strategy for the synthesis of new bioactive compounds. These novel ‘pseudo-natural product’ classes retain the biological relevance of NPs, yet exhibit structures and bioactivities not accessible to nature or through the use of existing design strategies. We also analyse selected pseudo-NP libraries using chemoinformatic tools, to assess their molecular shape diversity and properties. To facilitate the exploration of biologically relevant chemical space, we identify design principles and connectivity patterns that would provide access to unprecedented pseudo-NP classes, offering new opportunities for bioactive small-molecule discovery
Sharp bounds on 2m/r for static spherical objects
Sharp bounds are obtained, under a variety of assumptions on the eigenvalues
of the Einstein tensor, for the ratio of the Hawking mass to the areal radius
in static, spherically symmetric space-times.Comment: We changed a footnote in which an earlier result of H\aa{}kan
Andr\'{e}asson was not described correctl
Guided by Evolution: Biology-Oriented Synthesis of Bioactive Compound Classes
Biology-oriented-synthesis (BIOS), is a chemocentric approach to identifying structurally novel molecules as tools for chemical biology and medicinal chemistry research. The vast chemical space cannot be exhaustively covered by synthetic chemistry. Thus, methods which reveal biologically relevant portions of chemical space are of high value. Guided by structural conservation in the evolution of both proteins and natural products, BIOS classifies bioactive compound classes in a hierarchical manner based on molecular architecture and bioactivity. Biologically relevant scaffolds inspire and guide the synthesis of BIOS libraries, which calls for the development of suitable synthetic methodologies. These compound collections have enriched biological relevance, leading to the discovery of bioactive small molecules. These potent and selective modulators allow the study of complex biological pathways and may serve as starting points for drug discovery programs. Thus, BIOS can also be regarded as a hypothesis-generating tool, guiding the design and preparation of novel, bioactive molecular scaffolds. This review elaborates the principles of BIOS and highlights selected examples of their application, which have in turn created future opportunities for the expansion of BIOS and its combination with fragment-based compound discovery for the identification of biologically relevant small molecules with unprecedented molecular scaffolds
Distribution of surficial sediments in the Southern Evoikos and Petalioi Gulfs, Greece
A series of 123 surficial sediment samples from the Southern Evoikos and Petalioi Gulfs was studied for grain-size properties, carbonate content and mineralogical composition. Distribution of the sediments revealed two sedimentary provinces. The first concerns the Southern Evoikos Gulf, characterised by silty sediments with relatively low carbonate content. Quartz, feldspars, micas, clay and carbonate minerals are the major mineralogical components of the sediments. These sediments are the result of the Asopos River supply during Holocene and they contribute to the formation of smooth bottom morphology. The second province concerns the Petalioi Gulf (Northern and Southern), where the surficial sediments are mainly sandy and characterised by very high carbonate content. Their mineralogical composition reflects the lithology of the drainage basin. Since the modern terrigenous solid supply is limited, these sediments are not considered as products of recent sedimentation, but older deposits (relict sands). Their presence at such depths is justified by sea-level fluctuations and their preservation is due to the low sedimentation rate in the Petalioi Gulf, in combination with the strong hydrodynamic status of the area
Guided by Evolution: Biology-Oriented Synthesis of Bioactive Compound Classes
Biology-oriented-synthesis (BIOS), is a chemocentric approach to identifying structurally novel molecules as tools for chemical biology and medicinal chemistry research. The vast chemical space cannot be exhaustively covered by synthetic chemistry. Thus, methods which reveal biologically relevant portions of chemical space are of high value. Guided by structural conservation in the evolution of both proteins and natural products, BIOS classifies bioactive compound classes in a hierarchical manner based on molecular architecture and bioactivity. Biologically relevant scaffolds inspire and guide the synthesis of BIOS libraries, which calls for the development of suitable synthetic methodologies. These compound collections have enriched biological relevance, leading to the discovery of bioactive small molecules. These potent and selective modulators allow the study of complex biological pathways and may serve as starting points for drug discovery programs. Thus, BIOS can also be regarded as a hypothesis-generating tool, guiding the design and preparation of novel, bioactive molecular scaffolds. This review elaborates the principles of BIOS and highlights selected examples of their application, which have in turn created future opportunities for the expansion of BIOS and its combination with fragment-based compound discovery for the identification of biologically relevant small molecules with unprecedented molecular scaffolds
Supercritical biharmonic equations with power-type nonlinearity
The biharmonic supercritical equation , where and
, is studied in the whole space as well as in a
modified form with as right-hand-side with an additional
eigenvalue parameter in the unit ball, in the latter case together
with Dirichlet boundary conditions. As for entire regular radial solutions we
prove oscillatory behaviour around the explicitly known radial {\it singular}
solution, provided , where
is a further critical exponent, which was introduced in a recent work by
Gazzola and the second author. The third author proved already that these
oscillations do not occur in the complementing case, where .
Concerning the Dirichlet problem we prove existence of at least one singular
solution with corresponding eigenvalue parameter. Moreover, for the extremal
solution in the bifurcation diagram for this nonlinear biharmonic eigenvalue
problem, we prove smoothness as long as
Pseudo Natural Products—Chemical Evolution of Natural Product Structure
Pseudo‐natural products (PNPs) combine natural product (NP) fragments in novel arrangements not accessible by current biosynthesis pathways. As such they can be regarded as non‐biogenic fusions of NP‐derived fragments. They inherit key biological characteristics of the guiding natural product, such as chemical and physiological properties, yet define small molecule chemotypes with unprecedented or unexpected bioactivity. We iterate the design principles underpinning PNP scaffolds and highlight their syntheses and biological investigations. We provide a cheminformatic analysis of PNP collections assessing their molecular properties and shape diversity. We propose and discuss how the iterative analysis of NP structure, design, synthesis, and biological evaluation of PNPs can be regarded as a human‐driven branch of the evolution of natural products, that is, a chemical evolution of natural product structure
HIGH-RESOLUTION GEOMORPHOLOGICAL MAPPING OF THE SHALLOW CONTINENTAL SHELF WEST OF THE KAVALA BAY, NORTH AEGEAN
Σημαντικές γεωμορφολογικές δομές του ρηχού τμήματος της υφαλοκρηπίδας δυτικά του Κόλπου της Καβάλας χαρτογραφήθηκαν χρησιμοποιώντας τα δεδομένα από μια υδρογραφική αποτύπωση (τον Ιούνιο 2014) 320 ναυτικών μιλίων, η οποία περιελάμβανε υψηλής διακριτικότητας πολυδεσμική βαθυμετρική καταγραφή και διασκόπηση πυθμένα με σεισμική ανάκλαση. Αναγνωρίστηκε ένα σύστημα ρηγμάτων αποτελούμενο από ένα σετ δυο κυρίων κανονικών ρηγμάτων (καταγεγραμμένο μήκος και μετρημένο κατακόρυφο άλμα αυτών: 12 χλμ, 5 χλμ και > 40 μ, 25 μ, αντίστοιχα,) με έντονη επιφανειακή εκδήλωση στο θαλάσσιο πυθμένα, καθώς και τρία δευτερεύοντα ρήγματα νότια των κύριων ρηγμάτων, τα οποία φανερώνουν συνιζηματογενή τεκτονισμό. Η εντυπωσιακή διαφορά στις υφές των ιζημάτων που καλύπτουν αφενός το υποκείμενο ρηξιτέμαχος του βορειότερου κυρίου ρήγματος και αφετέρου την οροφή του νοτιότερου κυρίου ρήγματος δείχνει τη σημαντική επίδραση του τεκτονισμού στις ιζηματολογκές διεργασίες της περιοχής μελέτης. Όσον αφορά τις υπάρχουσες γεωμορφές, οι περισσότερο ενδιαφέρουσες είναι εκείνες των αμμωδών θινών στο βορειοανατολικό τμήμα της περιοχής μελέτης, ευρισκόμενες σε βάθη από 25 μ μέχρι τουλάχιστον 65 μ. Οι μεγάλες διαστάσεις τους καθώς και ο προσανατολισμός τους ως προς την ακτογραμμή υποδηλώνουν ως μηχανισμό σχηματισμού τους την δράση ισχυρών πυθμιαίων ρευμάτωνProminent geomorphological features of the shallow continental shelf west of the Kavala Bay (Loutra Eleftheron-Nea Peramos) were mapped using the data from a hydrographic survey (June 2014) of 320 nautical miles during which high resolution multibeam bathymetry and seismic-reflection subbottom profiling were carried out simultaneously. A fault zone comprised by a set of two primary sigmoidal gravity faults (recorded lengths and measured offsets: 12 km, 5 km and > 40 m, 25 m, respectively), with distinct expression on the seabed, and three other secondary gravity faults situated southern of the major faults, revealing synsedimentary tectonics, was identified. The striking difference between the texture of the footwall block sediments of the northern major fault and the texture of the sediments occupying the deep hanging wall block of the southern major fault emphasizes the impact of local tectonics on the sedimentary evolution of the study area. Concerning the observed bedforms, the most interesting were the sand dunes occurring at depths from 25 m to 65 m at least and occupying the northeast part of the study area. Their large dimensions and orientation in relation to the coastline position imply as a mechanism for their formation intense bottom-current activity
Santorini volcano as a potential Martian analogue: The Balos Cove Basalts
The interpretation of geologic processes on Mars from sparse meteorite, remote sensing and rover data is influenced by knowledge gained from well-characterized terrestrial analogues. This calls for detailed study of candidate terrestrial analogues and comparison of their observable features to those encountered on the surface of Mars. We evaluated the mineralogical, geochemical, and physical properties of the Balos cove basalts (BCB) from the island of Santorini and compared them to Martian meteorites, Mars rover surface measurements, and other verified Martian analogues obtained from the International Space Analogue Rockstore (ISAR). Twenty rock samples were collected from the Balos cove area based on their freshness, integrity, and basaltic appearance in the field. Optical microscopy of BCB revealed a pilotaxitic to trachytic texture, with olivine and clinopyroxenephenocrysts in a fine groundmass of olivine, clinopyroxene, plagioclase, magnetite, and devitrified glass. All major minerals show normal zoning, including calcic plagioclase (An_(78–85) at the core and An_(60–76) at the rim), augite (En_(36-48)Wo_(41-44)Fs_(11–21)), and olivine (Fo_(74–88)). The dominant bands in the infrared-attenuated total reflectance (IR-ATR) spectra from BCB can be assigned to olivine (~875 cm−1), calcic plagioclase (~1130 cm^(−1)), and augite (~970 cm^(−1)). The whole-rock chemical compositions and mineralogy of the BCB are similar to published analyses of typical olivine-phyric shergottites and basalts and basaltic materials analyzed in Gusev and Gale craters on Mars. BCB porosity is in the range of 7–15% and is similar to the porosities of the ISAR samples. Although no terrestrial rock is ever a perfect match to Martian compositions, the differences in mineralogy and geochemistry between BCB and some classes of Martian samples are relatively subtle and the basalts of Santorini are as close a match as other accepted Mars basalt analogues. The Santorini site offers excellent field logistics that, together with the petrology of the outcrop, makes it a valuable locality for testing and calibration deployments, field training, and other activities related to current and future Mars exploration
A new critical curve for the Lane-Emden system
We study stable positive radially symmetric solutions for the Lane-Emden
system in , in , where .
We obtain a new critical curve that optimally describes the existence of such
solutions.Comment: 13 pages, 1 figur
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