A transitional disk around an intermediate mass star in the sparse population of the Orion OB1 Association

We present a detailed study of the disk around the intermediate mass star SO 411, aiming to explain the spectral energy distribution of this star. We show that this is a transitional disk truncated at $\sim$11 au, with $\sim$0.03 lunar masses of optically thin dust inside the cavity. Gas also flows through the cavity, since we find that the disk is still accreting mass onto the star, at a rate of $\sim 5x10^{-9}$ Msun/yr. Until now, SO 411 has been thought to belong to the $\sim$3 Myr old {$\sigma$} Orionis cluster. However, we analyzed the second Gaia Data Release in combination with kinematic data previously reported, and found that SO 411 can be associated with an sparse stellar population located in front of the {$\sigma$} Orionis cluster. If this is the case, then SO 411 is older and even more peculiar, since primordial disks in this stellar mass range are scarce for ages $>$5 Myr. Analysis of the silicate 10$\mu$m feature of SO 411 indicates that the observed feature arises at the edge of the outer disk, and displays a very high crystallinity ratio of $\sim$0.5, with forsterite the most abundant silicate crystal. The high forsterite abundance points to crystal formation in non-equilibrium conditions. The PAH spectrum of SO 411 is consistent with this intermediate state between the hot and luminous Herbig Ae and the less massive and cooler T Tauri stars. Analysis of the 7.7$\mu$m PAH feature indicates that small PAHs still remain in the SO 411 disk.Comment: Accepted in the Astrophysical Journal (17 pages, 9 Figures

Lanthanoid complexes of tetrazolyl-functionalised Calix[4]arenes

Syntheses of the bis-, tris- and tetra-tetrazolato calix[4]arene ligands were performed from their corresponding nitrile derivatives. Mono-nuclear lanthanoid complexes were characterised in the presence of triethylamine, while addition of aqueous ammonium acetate resulted in the formation of an unprecedented discrete linear nineteen lanthanoid hydroxo cluster (Ln19). It was found the length of the cluster could be altered to an Ln12 structure, while retaining an identical cluster motif, by simply replacing ammonium acetate with ammonium benzoate

Structure of the lectin mannose 6-phosphate receptor homology (MRH) domain of glucosidase II an enzyme that regulates glycoprotein folding quality control in the endoplasmic reticulum

Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and the glucose added by UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GIIα subunit and a regulatory GIIβ subunit. GIIβ participates in the endoplasmic reticulum localization of GIIα and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIβ MRH domain by NMR spectroscopy. It adopts a β-barrel fold similar to that of other MRH domains, but its binding pocket is the most shallow known to date as it accommodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIβ but not in other MRHs that influences GII glucose trimming activity.Fil: Olson, Linda J.. Medical College Of Wisconsin; Estados UnidosFil: Orsi, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alculumbre, Solana G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Peterson, Francis C.. Medical College Of Wisconsin; Estados UnidosFil: Stigliano, Ivan Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Parodi, Armando Jose A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: D'alessio, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires; ArgentinaFil: Dahms, Nancy M.. Medical College Of Wisconsin; Estados Unido

LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome

SPINK5, encoding the putative multi-domain serine protease inhibitor LEKTI, was recently identified as the defective gene in the severe autosomal recessive ichthyosiform skin condition, Netherton syndrome (NS). Using monoclonal and polyclonal antibodies, we show that LEKTI is a marker of epithelial differentiation, strongly expressed in the granular and uppermost spinous layers of the epidermis, and in differentiated layers of stratified epithelia. LEKTI expression was also demonstrated in normal differentiated human primary keratinocytes (HK) through detection of a 145 kDa full-length protein and a shorter isoform of 125 kDa. Both proteins are N-glycosylated and rapidly processed in a post-endoplasmic reticulum compartment into at least three C-terminal fragments of 42, 65 and 68 kDa, also identified in conditioned media. Processing of the 145 and 125 kDa precursors was prevented in HK by treatment with a furin inhibitor. In addition, in vitro cleavage of the recombinant 145 kDa precursor by furin generated C-terminal fragments of 65 and 68 kDa, further supporting the involvement of furin in LEKTI processing. In contrast, LEKTI precursors and proteolytic fragments were not detected in differentiated HK from NS patients. Defective expression of LEKTI in skin sections was a constant feature in NS patients, whilst an extended reactivity pattern was observed in samples from other keratinizing disorders, demonstrating that loss of LEKTI expression in the epidermis is a diagnostic feature of NS. The identification of novel processed forms of LEKTI provides the basis for future functional and structural studies of fragments with physiological relevanc

Stringent Limits on the Polarized Submillimeter Emission from Protoplanetary Disks

We present arcsecond-resolution Submillimeter Array (SMA) polarimetric observations of the 880 um continuum emission from the protoplanetary disks around two nearby stars, HD 163296 and TW Hydrae. Although previous observations and theoretical work have suggested that a 2-3% polarization fraction should be common for the millimeter continuum emission from such disks, we detect no polarized continuum emission above a 3-sigma upper limit of 7 mJy in each arcsecond-scale beam, or <1% in integrated continuum emission. We compare the SMA upper limits with the predictions from the exploratory Cho & Lazarian (2007) model of polarized emission from T Tauri disks threaded by toroidal magnetic fields, and rule out their fiducial model at the ~10-sigma level. We explore some potential causes for this discrepancy, focusing on model parameters that describe the shape, magnetic field alignment, and size distribution of grains in the disk. We also investigate related effects like the magnetic field strength and geometry, scattering off of large grains, and the efficiency of grain alignment, including recent advances in grain alignment theory, which are not considered in the fiducial model. We discuss the impact each parameter would have on the data and determine that the suppression of polarized emission plausibly arises from rounding of large grains, reduced efficiency of grain alignment with the magnetic field, and/or some degree of magnetic field tangling (perhaps due to turbulence). A poloidal magnetic field geometry could also reduce the polarization signal, particularly for a face-on viewing geometry like the TW Hya disk. The data provided here offer the most stringent limits to date on the polarized millimeter-wavelength emission from disks around young stars.Comment: 15 pages, 6 figures, accepted for publication in Ap

Recyclable calix[4]arene–lanthanoid luminescent hybrid materials with color-tuning and color-switching properties

Inorganic–organic hybrid materials combine the properties of both components providing functionality with a wide range of potential applications. Phase segregation of the inorganic and organic components is a common challenge in these systems, which is overcome here by copolymerizing a metal-free calixarene ionophore and methyl methacrylate. A lanthanoid ion is then added using a swelling–deswelling procedure. The resulting luminescent hybrid materials can be made to emit any required color, including white light, by loading with an appropriate mixture of lanthanoids. The gradation of the emitted color can also be finely adjusted by changing the excitation wavelength. The polymer monolith can be recycled to emit a different color by swelling with a solution containing a different lanthanoid ion. This methodology is flexible and has the potential to be extended to many different ionophores and polymer matrices

Ionophoric properties of a tetra-tetrazole functionalised calix[4]arene

© 2015 Taylor & Francis. The synthesis and characterisation of p-t-butylcalix[4]arene functionalised at the lower rim with four tetrazole moieties is reported. The macrocycle is found to be a poorer ionophore for lanthanoid cations than the bis-tetrazole-substituted analogue. Solution-phase photophysical studies strongly suggested that the cations interacted only weakly with the calixarene ligand. A mixed sodium/triethylammonium salt of the calixarene ligand was crystallised in the presence of lanthanoid cations and structurally characterised. Strong intramolecular interactions are hypothesised to be the cause of the observed behaviour

Hydrated Lanthanoid Complexes of 5-(2'-Pyridyl)tetrazole Formed in the Presence of Dimethyl Sulfoxide

Reaction of DMSO solvates of lanthanoid nitrates or perchlorates with 5-(2'-pyridyl)tetrazole (pytz) and triethylamine in organic solvents resulted in the unexpected crystallization of hydrates, rather than DMSO solvates. This was confirmed by the structural characterization of [Eu(pytz)3(H2O)3]. Decreasing the metal:ligand ratio in the reaction mixture resulted in the crystallization of a complex salt formulated as [Y(pytz)2(H2O)4](pytz).(Hpytz).4H2O; once again DMSO was absent from the product. Interestingly, the omission of base from one reaction resulted in the serendipitous crystallization of Hpytz in a zwitterionic form, unlike the neutral ligand structure reported previously

Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis

Background: Neoadjuvant use of immune checkpoint inhibitors (ICIs) before liver resection results in pathological tumour regression in patients with hepatocellular carcinoma. We aimed to describe the characteristics of pathological responses after preoperative ICI therapy for hepatocellular carcinoma and to evaluate the association between the depth of tumour regression and relapse-free survival. Methods: In this cross-trial, patient-level analysis, we performed a pooled analysis of data from patients with hepatocellular carcinoma receiving ICI therapy before liver resection as part of a global collaborative consortium (NeoHCC) of five phase 1 and 2 clinical trials and standardised observational protocols conducted in 12 tertiary referral centres across the USA, UK, and Taiwan. Eligible patients were adults (aged ≥18 years) diagnosed with hepatocellular carcinoma by tissue core biopsy before treatment initiation, a Liver Imaging Reporting and Data System score of 5 on imaging, or both, with an Eastern Cooperative Oncology Group performance status score of 0-1, and no extrahepatic spread or previous ICI treatment. Pathological response was measured as the percentage of non-viable tumour in the resected surgical specimen, with major pathological response corresponding to at least 70% tumour regression and pathological complete response corresponding to 100% tumour regression. We correlated pathological response with radiological overall response using RECIST criteria (version 1.1) and relapse-free survival, and evaluated the threshold of tumour regression that could be optimally associated with relapse-free survival. Findings: At data cutoff on Jan 31, 2024, 111 patients were included in the study, of whom data on pathological response were available for 104 (94%) patients. Patients received treatment from Oct 5, 2017, to Nov 15, 2023, mostly ICI combinations (76 [69%]), for a median of 1·4 months (IQR 0·7-2·9). 87 (78%) patients were men and 24 (22%) were women. Most patients had underlying viral chronic liver disease (73 [66%]) and Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (61 [55%]), without portal vein thrombosis (87 [78%]). We observed major pathological response in 33 (32%) patients and pathological complete response in 19 (18%) patients. Radiological overall response was associated with major pathological response, with 23 (74%) of 31 patients with radiological response showing major pathological response compared with ten (14%) of 73 patients without radiological response (p&lt;0·0001). However, ten (30%) of 33 major pathological responses were not predicted by radiological response. After a median follow-up of 27·2 months (95% CI 22·3-32·1), median relapse-free survival for the whole cohort was 43·6 months (95% CI 28·3-not evaluable). Relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable-not evaluable] vs 28·3 months [12·8-43·8]; hazard ratio 0·26 [0·10-0·66]; p=0·0024) and in patients with pathological complete response than in those who did not have a pathological complete response (NR [95% CI not evaluable-not evaluable] vs 32·8 months [15·0-50·5]; 0·19 [0·05-0·78]; p=0·010). Unbiased recursive partitioning of the cohort for the risk of relapse, death, or both identified a threshold of 90% as the optimal cutoff of pathological tumour regression to predict improved relapse-free survival. Interpretation: The extent of tumour regression following neoadjuvant ICI therapy could identify patients with improved relapse-free survival following liver resection. The threshold of at least 90% tumour regression should be validated for its surrogate role for relapse-free survival in phase 3 randomised controlled trials. Funding: None