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UNIONS: The Ultraviolet Near-infrared Optical Northern Survey
Full text linkThe Ultraviolet Near-Infrared Optical Northern Survey (UNIONS) is a “collaboration of collaborations” that is using the Canada–France–Hawai’i Telescope, the Pan-STARRS telescopes, and the Subaru Observatory to obtain ugriz images of a core survey region of 6250 deg2 of the northern sky. The 10σ point source depth of the data, as measured within a 2″ diameter aperture, are [u, g, r, i, z] = [23.7, 24.5, 24.2, 23.8, 23.3] in AB magnitudes. UNIONS is addressing some of the most fundamental questions in astronomy, including the properties of dark matter, the growth of structure in the Universe from the very smallest galaxies to large-scale structure, and the assembly of the Milky Way. It is set to become a major ground-based legacy survey for the northern hemisphere for the next decade, and it provides an essential northern complement to the static-sky science of the Vera C. Rubin Observatory’s Legacy Survey of Space and Time. UNIONS supports the core science mission of the Euclid space mission by providing the data necessary in the northern hemisphere for the calibration of the wavelength dependence of the Euclid point-spread function and derivation of photometric redshifts in the North Galactic Cap. This region contains the highest quality sky for Euclid, with low backgrounds from the zodiacal light, stellar density, extinction, and emission from Galactic cirrus. Here, we describe the UNIONS survey components, science goals, data products, and the current status of the overall program
The dwarf stellar mass function in different environments and the lack of a generic missing dwarfs problem in ΛCDM
Full text linkWe combine deep photometric data in the COSMOS and XMM-LSS fields with high-resolution cosmological hydrodynamical simulations to explore two key questions: (1) how does the galaxy stellar mass function, particularly in the dwarf (Mstar < 10^9.5 MSun ) regime, vary with environment, defined as distance from the large-scale structure (LSS) traced by nodes and filaments in the cosmic web? (2) is there a generic 'missing dwarfs' problem in LambdaCDM predictions when all environments - and not just satellites around Milky Way like galaxies - are considered? The depth of the observational data used here enables us to construct complete, unbiased samples of galaxies, down to Mstar ~ 10^7 MSun and out to z ~ 0.4. Strong environmental differences are found for the galaxy stellar mass function when considering distance from LSS. As we move closer to LSS, the dwarf mass function becomes progressively flatter and the knee of the mass function shifts to larger stellar masses, both of which result in a higher ratio of massive to dwarf galaxies. While the stellar mass functions from the three simulations (NewHorizon, TNG50 and FIREbox) considered here do not completely agree across the dwarf regime, there is no evidence of a generic missing dwarfs problem in the context of LambdaCDM, akin to the results of recent work that demonstrates that there is no missing satellites problem around Galactic analogues
Visualising Sentient Place: An Artist’s Study of Figure and Place through the Relationship of Francis Bacon's Paintings with his Reece Mews Studio
Full text linkThis thesis looks at the human figure as place, taking the example of the artist Francis Bacon
and his studio at 7 Reece Mews, London, to understand how an artist can visualise ‘placed
experience.’ Bacon said, “I am very influenced by places – by the atmosphere of a room.” I
take this as a starting point to challenge the accepted ‘caged’ reading of his work. I argue
that Bacon’s oeuvre grew out of initial ideas in his work as an interior designer, to question
how the human figure can be pictured. His ‘sensitivity to places’ informed Bacon’s work and
when he finally entered Reece Mews, aged 52, his work changed to reflect his own
experience and milieu. Through a focus on edges in painting, considering the philosophy of
Place by Edward S Casey, and Jeff Malpas, I outline how Bacon’s studio became intrinsic to
his working process, due to the ‘chaotic’ detritus he collected around him, which allowed
him to bypass ‘willed’ authorship, so he became “a vessel through which an image took
shape.” The images that this extended self (or reversed self) created at Reece Mews lead to
several late “figure paintings without figures,” where the body-figure is replaced with the
place-figure. An image of the human figure as place; sentient place
GC-GAT: Multimodal Vehicular Trajectory Prediction Using Graph Goal Conditioning and Cross-Context Attention
Full text linkPredicting future trajectories of surrounding vehicles heavily relies on what contextual information is given to a motion prediction model. The context itself can be static (lanes, regulatory elements, etc) or dynamic (traffic participants). This letter presents a lane graph-based motion prediction model that first predicts graph-based goal proposals and later fuses them with cross attention over multiple contextual elements. We follow the famous encoder-interactor-decoder architecture where the encoder encodes scene context using lightweight Gated Recurrent Units, the interactor applies cross-context attention over encoded scene features and graph goal proposals, and the decoder regresses multimodal trajectories via Laplacian Mixture Density Network from the aggregated encodings. Using cross-attention over graph-based goal proposals gives robust trajectory estimates since the model learns to attend to future goal-relevant scene elements for the intended agent. We evaluate our work on nuScenes motion prediction dataset, achieving state-of-the-art results
Synthesis of Bisquinolines, Napthythyridines and Pyronaridine to Elucidate the Mechanism of Antimalarial Drug Action
Full text linkIn recent years Plasmodium falciparum has become resistant to many clinically used antimalarial agents. This reinforces the need to develop Novel antimalarial drugs.
This study details the synthesis of improved antimalarials based on bisquinolines. The synthesised molecules were studied for their potential activity, both in silico and in-vitro and in an attempt to understand the structural determinants of their antimalarial activity. Further in-vivo studies were performed on a variety of quinoline based compounds to determine their possible mode/s of action, possibly associated with their interaction with haem and haem derived complexes.
The synthesis of various bisquinolines, and consequently, the development of an extra thermodynamic pharmacophore model that has allowed identification of a potent, soluble, orally bioavailable antimalarial bisquinoline, meta-quine (N,N-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in-vivo (oral ID50 25 μmol/kg) and multidrug-resistant Plasmodium falciparum K1 in-vitro (0.17 μM). Meta-quine shows strong affinity for the putative antimalarial receptor, haem at pH7.4 in aqueous DMSO.
In an effort to find compounds superior to meta-quine, the de-halogeno-amination/SNAr Displacement reaction in N-methylpyrollidinone was used to construct both a fluorinated analogue of RO 47-7737, and an inactive 4-aminoquinoline/ mefloquine hybrid, and observed lack of antimalarial activity of this compound against Plasmodium berghei infection in mice. The latter Structure determined by X-ray crystallography, revealed hydrogen bonding to solvent (methanol).
The site and order of protonation of these quinolines was investigated using quantum mechanics calculations (Courtesy of Prof Drew, Reading University). Results suggested that protonation was impeded at the endocyclic nitrogen in mefloquine due to electronic rather than steric factors and the molecule was protonated preferentially at the piperidine side chain in Mefloquine. In contrast, both mono- and bis-4-aminoquinolines were protonated at the endocyclic quinoline nitrogen. This suggested that trifluoromethyl groups buttressing the endocyclic quinolinyl nitrogen was detrimental to 4-aminoquinoline receptor binding, but not quinoline methanols; suggesting that these two classes of molecules act by different mechanisms/binding modes within the acidic vacuole of Plasmodia.
4-Hydroxy-1,5-naphthyridine (SN 13,639), a key intermediate in the production of certain azasubstituted antimalarials, is normally synthesised by a multistep route comprising cyclization, de-esterification and decarboxylation. An unexpected and direct formation of 4-hydroxy-1,5-naphthyridine by Gould-Jacob cyclization in refluxing diphenyl ether was found.
This occurred under microwave conditions, to produce ethyl 4-hydroxy-1,5-naphthyridine-3-carboxylate, which spontaneously underwent a rare retro-fries rearrangement to form 4-hydroxy-1,5-naphthyridine, which also identified the transition state involved. The product was unambiguously characterised by X-ray crystallography and 2D-NMR experiments. Various adducts and solvated forms were examined by DFT experiments.
An examination of the large downfield shifts observed for the molecule in TFA-d were rationalised by proposing protonation at N-5 accompanied by the formation of a novel hydrogen bonded complex with the solvent. Similar interactions may occur between naphthyridines and the acidic side chain of the haem receptor. Although antimalarial activity of 4-hydroxy-1,5-naphthyridine is weak against multi-drug resistant strains of Plasmodia, the compound allows rapid access to various known antimalarial naphthyridines and could act as fluorescent probe of drug action.
Pyronaridine (4-[(7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino]-2,6-bis[(pyrrolidin-1-yl)methyl]phenol). The first European synthesis of pyronaridine 4-(7-Chloro-2-methoxy-benzo[b][1,5]naphthyridin-10-ylamino)-2,6-bis-pyrrolidin-1-ylmethyl-phenol (15), a potent antimalarial, from commercially available starting materials, namely 2,4-dichlorobenzoic acid and 2-methoxy-5- aminopyridine. The copper mediated Ullmann synthesis of 4-chloro-2-(methoxy-3-pyridylamino) benzoic acid in n-pentanol was accompanied by the formation of its pentyl ester complicating isolation and purification.
An alternative Ullmann-Goldberg procedure was developed using DMF, both successfully replaced the n-pentanol and also produced the pyridylamino-benzoic acid under anhydrous, oxygen free, conditions, in which cyclodehydration was followed by dehydrochlorination using anhydrous POCl3, the desired product 7,10-dichloro-2-methoxy-benzo [b][1,5] naphthyridine was accompanied by an unexpected (and undesired) trichlorinated product in which the methoxy group had been displaced to form 2,7,10-trichloro-benzo [b][1,5] naphthyridine.
The trichlorinated molecule was the dominant product (>50%) if the reaction was continued beyond four hours as confirmed by GC-MS spectrometry. Subsequent SNAr reaction whereby the halogen situated at the 10 position in 7,10-dichloro-2-methoxy-benzo [b][1,5] naphthyridine was displaced by p-aminophenol produced 4-(7-chloro-2-methoxy-benzo[b][1,5]naphthyridin-10-yl(amino)-phenol as a bright yellow solid, as opposed to a brown solid as reported by Zheng et al. (1982). The presence of oxygen during the reflux period proved detrimental and rapidly oxidized the material to various compounds including a red-brown product identified as the corresponding quinone-imine. The target substance was produced by refluxing the air sensitive 4-(2,7-dichloro-benzo [b][1,5] naphthyridin-10-ylamino)-phenol with excess pyrrolidine and aqueous formaldehyde (Mannich Reaction) under argon.
Pyronaridine was isolated as a moderately air sensitive free base using flash column chromatography on silica developed with methanol: ammonia (9:1, v/v under argon), and proved identical to an authentic sample when examined by a variety of analytical techniques (NMR, HRMS, HPLC-MS and TLC). The solid was, however, stable as the known yellow tetraphosphate salt. Hence, a superior, enhanced reliable synthetic procedure, but lower in overall yield (9-19%), when compared to the original method (33%) published in the Chinese language (Zheng et al. 1982) has been developed. Our spectroscopic (NMR and accurate MS) confirms that the published structure coincides with the data presented herein. The biological activity of pyronaridine, pyracrine and the aromatic head group was determined in-vivo.
The side chain/head group was completely inactive at the doses tested whereas both pyracrine and pyronaridine were highly active against the Plasmodium berghei drug sensitive strain N/13/1A/4/20 and are suitable for further development
Constraints on Primordial Magnetic Fields from the Lyman-α forest
Full text linkWe present the first constraints on primordial magnetic fields from the Lyman-α forest using full cosmological hydrodynamic simulations. At the scales and redshifts probed by the data, the flux power spectrum is extremely sensitive to the extra power induced by primordial magnetic fields in the linear matter power spectrum, at a scale that we parametrize with k_{peak}. We rely on a set of more than a quarter million flux models obtained by varying thermal and reionization histories and cosmological parameters. We find a hint of extra power that is well fitted by the primordial magnetic field model with B∼0.2 nG, corresponding to k_{peak}∼20 Mpc^{-1}. However, when applying very conservative assumptions on the modeling of the noise, we obtain a 3σ C.L. lower limit k_{peak}>30 Mpc^{-1}, which translates into the tightest bounds on the strength of primordial intergalactic magnetic fields: B<0.30 nG (for a fixed, nearly scale-invariant n_{B}=-2.9)
Exact Analytical Solutions for Static Response of Helical Single-Walled Carbon Nanotubes Using Nonlocal Euler–Bernoulli Beam Theory
Full text linkThis study presents an exact analytical investigation into the static response of helical single-walled carbon nanotube (SWCNT) beams based on Eringen’s differential nonlocal elasticity theory, which captures nanoscale effects arising from interatomic interactions. A key contribution of this work is the derivation of the governing equations for helical SWCNT beams, based on the nonlocal Euler–Bernoulli theory, followed by their exact analytical solution using the initial value method. To the best of the authors’ knowledge, this represents the first closed-form formulation for such complex nanostructures using this theoretical framework of nonlocal elasticity theory. The analysis considers both cantilevered and clamped–clamped boundary conditions, under various concentrated force and moment loadings applied at the ends and midpoint of the helical beam. Displacements and rotational components are expressed in the Frenet frame, enabling direction-specific evaluation of the deformation behaviour. Parametric studies are conducted to investigate the influence of geometric parameters—such as the winding angle (α) and aspect ratio (R/d) and the nonlocal parameter (R/γ). Results show that nonlocal elasticity theory consistently predicts higher displacements and rotations than the classical local theory, revealing its importance for accurate modelling of nanoscale structures. The proposed analytical framework serves as a benchmark reference for the modelling and design of nanoscale helical structures such as nano-springs, actuators, and flexible nanodevices
The Role of Myocyte Extracellular Vesicles in Inducing Apoptosis of Murine Lung Cancer CMT64/61 Cells
Full text linkExtracellular vehicles (EVs) are a heterogeneous group of particles ranging from 15 nm to 1000 nm in diameter, released by almost every cell type, including tumours. These vesicles contain a complex cargo, including protein, lipid and nucleic acids, which reflect the status of the cell of origin. Increasing evidence suggests that EVs play an important role in intercellular communication, both locally and systemically, by transferring their cargo between cells and inducing phenotypical and functional changes in recipient cells. In cancer, the pro-tumourigenic role of EVs is well established; however, their capability as an anti-tumourigenic agent is still emerging. This study identified a novel anti-tumourigenic role of skeletal muscle (C2C12) derived EVs towards highly metastatic lung carcinoma cells (CMT 64/61).
Skeletal muscle is a rare site for malignant metastasis and the mechanism underling the rarity of this phenomenon has remained elusive. The data obtained in this study indicated that myocyte EVs at low concentration, up to 200 μg/ml, exert cytotoxic effects on lung carcinoma cells, whilst having no effect on normal fibroblast cells (NIH 3T3). Myocyte EVs induced morphological changes in carcinoma cell mitochondria, decreased mitochondrial membrane potential leading to increased caspase 3 and 9 activity and apoptosis. A significant % of apoptosis, 34.8%, was exerted by 200 μg/ml of myocyte EVs within 48 h. No significant apoptosis was seen in non-carcinoma cells. Cell cycle analysis revealed that myocyte EVs mediated carcinoma cell proliferation suppression via cell cycle arrest at S phase. Transwell migration assay indicated a dose dependent reduction in carcinoma cell migration towards the microenvironment containing myocyte EVs.
To further explore the possible protein cargo that exert above effects, proteomics analysis was conducted on myocyte EVs. Scaffold software identified 29 upregulated proteins in myocyte EVs and interestingly, STRING and KEGG analysis on these proteins identified 3 possible pathways that could exert cytotoxic, apoptotic and cytostatic effects on carcinoma cells.
Proteins including Cathepsin L1, Cathepsin B and Cathepsin D, involved in Lysosome and Apoptosis pathway whilst Decorin, Thrombospondin-1 and Cathepsin L1 in Proteoglycan in cancer pathway. While all of these proteins may contribute to the effects observed in carcinoma cells, Decorin (DCN) seemed a promising target due its already known anti-tumourigenic properties. Together these results indicate that skeletal muscle derived EVs function as an anti-tumourigenic agent; hence identifies as a potential therapeutic agent in the treatment of metastatic lung carcinoma
Contrasting Behavioural and Biochemical Characteristics of Normal and Spontaneously α‐Synuclein‐Deficient Mice Treated With MPTP
Full text linkα‐Synuclein is the primary toxic constituent of Lewy bodies, but its exact function under homeostatic conditions remains elusive. To better understand the role of α‐synuclein, we compared two C57BL sub‐strains: the normal α‐synuclein‐expressing J6 and the α‐synuclein‐deficient J6‐OlaHSD, for behavioural, dopaminergic and glial integrity in substantia nigra (SN) and caudate putamen (CPu) before and after 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) treatment. After MPTP treatment, J6 mice showed significant weight loss (−7% by Day 10), whereas OlaHSD mice maintained stable body weight. At baseline, J6 mice exhibited 33% higher locomotor activity but 38% more thigmotaxis, and 33% less endurance on the Rotarod test than OlaHSD mice. Loss of tyrosine hydroxylase‐positive neurons was similar in OlaHSD (−40%) and J6 mice (−34%). J6 mice had double the SN GFAP‐ir cells of J6‐OlaHSD, a difference that was unchanged by MPTP treatment. In the CPu, MPTP increased GFAP‐ir cells in both strains, but Iba1‐ir cells significantly increased only in MPTP‐treated OlaHSD mice, compared to J6 strain. We further compared the biochemical signatures using Raman micro‐spectroscopy. The Raman spectra of the freshly cut SN sections showed a greater shift in the α‐helix to β‐sheet protein conformation ratio in MPTP‐induced J6 mice, likely due to the absence of the Snca1 gene in OlaHSD mice. These findings suggest that the absence of α‐synuclein plays a subtle role in the behavioural and neurochemical differences but has no significant effect on dopaminergic neurotransmission. It is therefore concluded that the presence of α‐synuclein is important for non‐dopaminergic behaviours such as anxiety‐like behaviours and regulation of body weight. Under toxic challenge, gliosis in the SN and CPu may be regulated by α‐synuclein. This study also emphasises the utility of Raman spectroscopy as a potential tool for identifying subtle protein conformation differences in mice with and without Snca1
Neue Forschungsperspektiven auf die Handlungsfähigkeit salafistischer Frauen
Full text linkPublic and academic debate about Salafi women is often characterized by extremes: they are either portrayed as oppressed victims or uncritically as empowered actors. However, a new research perspective based on extensive studies reveals a much more nuanced reality. This article summarizes previous research and presents new empirical findings