Chandra Study of Young Stellar Objects in the NGC 1333 Star-forming Cloud

NGC 1333, a highly active star formation region within the Perseus molecular cloud complex, has been observed with the ACIS-I detector on board the Chandra X-ray Observatory. In our image with a sensitivity limit of ~ 1e28 erg/s, we detect 127 X-ray sources, of which, 95 are known cluster members. The X-ray luminosity function of the discovered YSO population spans a range of 1e28-3.2e31 erg/s in the 0.5-8 keV band. Comparison with K-band source counts indicates that we detect all of the known cluster members with K < 12, and about half of members with K > 12. We detect seven X-ray emitting YSOs which drive optically visible jets as well as one deeply embedded object that has not been detected in near-IR observations. The presence or absence of an outflows does not appear to produce any difference in X-ray properties of YSOs. We also find no systematic differences in X-ray luminosity distributions between two complete subsamples of CTTs and WTTs. That suggests that there is no difference in the astrophysical mechanism of WTT and CTT X-ray emission production. Additional results include: the X-ray emission from two late-B stars which illuminate the reflection nebula originates from unresolved late-type companions; two T Tauri stars are discovered as previously unknown components of visual binaries; and the X-ray counterpart of SVS 16 has the column density much lower than that expected from near-IR photometry and thus its X-ray luminosity is not anomalously high, as has been previously suggested.Comment: 53 pages, 14 figures, 3 tables. To appear in the Astrophysical Journal; scheduled for 2002, ApJ, 575 (August 10th). High quality copy available at ftp://ftp.astro.psu.edu/pub/gkosta/ngc1333

Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis

A Novel Substrate-Based HIV-1 Protease Inhibitor Drug Resistance Mechanism

BACKGROUND: HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resistant HIV protease variants. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. We investigated whether HIV could yet again find a way to become less susceptible to these novel inhibitors. METHODS AND FINDINGS: We have performed in vitro selection experiments using a novel PI with an increased genetic barrier (RO033-4649) and demonstrated selection of three viruses 4- to 8-fold resistant to all PI compared to wild type. These PI-resistant viruses did not have a single substitution in the viral protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three resistant viruses. These changes, when introduced in a reference strain, conferred PI resistance. The mechanism leading to PI resistance is enhancement of the processing efficiency of the altered substrate by wild-type protease. Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical isolates demonstrated the presence of these NC/p1 cleavage site mutations in some clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%, and codon 437 substitutions in 10%). Moreover, these cleavage site substitutions were highly significantly associated with reduced susceptibility to PI in clinical isolates lacking primary protease mutations. Furthermore, we used data from a clinical trial (NARVAL, ANRS 088) to demonstrate that these NC/p1 cleavage site changes are associated with virological failure during PI therapy. CONCLUSIONS: HIV can use an alternative mechanism to become resistant to PI by changing the substrate instead of the protease. Further studies are required to determine to what extent cleavage site mutations may explain virological failure during PI therapy

Technology for a Mid-IR Flagship Mission to Characterize Earth-like Exoplanets

The exploration of Earth-like exoplanets will be enabled at mid-infrared wavelengths through technology and engineering advances in nulling interferometry and precision formation flying. Nulling interferometry provides the dynamic range needed for the detection of biomarkers. Formation flying provides the angular resolution required in the mid-infrared to separately distinguish the spectra of planets in multi-planet systems. The flight performance requirements for nulling have been met and must now be validated in a flight-like environment. Formation-flying algorithms have been demonstrated in the lab and must now be validated in space. Our proposed technology program is described

Marine Biodiversity in South Africa: An Evaluation of Current States of Knowledge

Continental South Africa has a coastline of some 3,650 km and an Exclusive Economic Zone (EEZ) of just over 1 million km2. Waters in the EEZ extend to a depth of 5,700 m, with more than 65% deeper than 2,000 m. Despite its status as a developing nation, South Africa has a relatively strong history of marine taxonomic research and maintains comprehensive and well-curated museum collections totaling over 291,000 records. Over 3 million locality records from more than 23,000 species have been lodged in the regional AfrOBIS (African Ocean Biogeographic Information System) data center (which stores data from a wider African region). A large number of regional guides to the marine fauna and flora are also available and are listed

The SPIRITS Sample of Luminous Infrared Transients: Uncovering Hidden Supernovae and Dusty Stellar Outbursts in Nearby Galaxies

We present a systematic study of the most luminous (M IR [Vega magnitudes] brighter than −14) infrared (IR) transients discovered by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) between 2014 and 2018 in nearby galaxies (D 12) show multiple, luminous IR outbursts over several years and have directly detected, massive progenitors in archival imaging. With analyses of extensive, multiwavelength follow-up, we suggest the following possible classifications: five obscured core-collapse supernovae (CCSNe), two erupting massive stars, one luminous red nova, and one intermediate-luminosity red transient. We define a control sample of all optically discovered transients recovered in SPIRITS galaxies and satisfying the same selection criteria. The control sample consists of eight CCSNe and one Type Iax SN. We find that 7 of the 13 CCSNe in the SPIRITS sample have lower bounds on their extinction of 2 < A V < 8. We estimate a nominal fraction of CCSNe in nearby galaxies that are missed by optical surveys as high as ${38.5}_{-21.9}^{+26.0} \%$ (90% confidence). This study suggests that a significant fraction of CCSNe may be heavily obscured by dust and therefore undercounted in the census of nearby CCSNe from optical searches

The SPIRITS sample of Luminous Infrared Transients: Uncovering Hidden Supernovae and Dusty Stellar Outbursts in Nearby Galaxies

We present a systematic study of the most luminous (M IR [Vega magnitudes] brighter than −14) infrared (IR) transients discovered by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) between 2014 and 2018 in nearby galaxies (D 12) show multiple, luminous IR outbursts over several years and have directly detected, massive progenitors in archival imaging. With analyses of extensive, multiwavelength follow-up, we suggest the following possible classifications: five obscured core-collapse supernovae (CCSNe), two erupting massive stars, one luminous red nova, and one intermediate-luminosity red transient. We define a control sample of all optically discovered transients recovered in SPIRITS galaxies and satisfying the same selection criteria. The control sample consists of eight CCSNe and one Type Iax SN. We find that 7 of the 13 CCSNe in the SPIRITS sample have lower bounds on their extinction of 2 < A V < 8. We estimate a nominal fraction of CCSNe in nearby galaxies that are missed by optical surveys as high as 38.5^(+26.0)_(-21.9)% (90% confidence). This study suggests that a significant fraction of CCSNe may be heavily obscured by dust and therefore undercounted in the census of nearby CCSNe from optical searches