Monte Carlo likelihood inference for missing data models

We describe a Monte Carlo method to approximate the maximum likelihood estimate (MLE), when there are missing data and the observed data likelihood is not available in closed form. This method uses simulated missing data that are independent and identically distributed and independent of the observed data. Our Monte Carlo approximation to the MLE is a consistent and asymptotically normal estimate of the minimizer $\theta^*$ of the Kullback--Leibler information, as both Monte Carlo and observed data sample sizes go to infinity simultaneously. Plug-in estimates of the asymptotic variance are provided for constructing confidence regions for $\theta^*$. We give Logit--Normal generalized linear mixed model examples, calculated using an R package.Comment: Published at http://dx.doi.org/10.1214/009053606000001389 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Perspectives Provided by Leopard and Other Cat Genomes: How Diet Determined the Evolutionary History of Carnivores, Omnivores, and Herbivores

Recent advances in genome sequencing technologies have enabled humans to generate and investigate the genomes of wild species. This includes the big cat family, such as tigers, lions, and leopards. Adding the first high quality leopard genome, we have performed an in-depth comparative analysis to identify the genomic signatures in the evolution of felid to become the top predators on land. Our study focused on how the carnivore genomes, as compared to the omnivore or herbivore genomes, shared evolutionary adaptations in genes associated with nutrient metabolism, muscle strength, agility, and other traits responsible for hunting and meat digestion. We found genetic evidence that genomes represent what animals eat through modifying genes. Highly conserved genetically relevant regions were discovered in genomes at the family level. Also, the Felidae family genomes exhibited low levels of genetic diversity associated with decreased population sizes, presumably because of their strict diet, suggesting their vulnerability and critical conservation status. Our findings can be used for human health enhancement, since we share the same genes as cats with some variation. This is an example how wildlife genomes can be a critical resource for human evolution, providing key genetic marker information for disease treatment

A young double stellar cluster in a HII region, emerging from its parent molecular cloud

We report the properties of a new young double stellar cluster in the region towards IRAS 07141-0920 contained in the HII region Sh2-294. High-resolution optical UBVRI and Halpha images, near-infrared JHKs and H2 filter images were used to make photometric and morphological studies of the point sources and the nebula seen towards Sh2-294. The optical images reveal an emission nebula with very rich morphological details, composed mainly of UV scattered light and of Halpha emission. Contrasting with the bright parts of the nebula, opaque, elongated patches are seen. Our optical photometry confirms that the illuminator of the nebula is likely to be a B0.5V star located at a distance of about 3.2 kpc. Our near-IR images reveal an embedded cluster, extending for about 2 pc and exhibiting sub-clustering: a denser, more condensed, sub-cluster surrounding the optical high-mass B0.5V illuminator star; and a more embedded, optically invisible, sub-cluster located towards the eastern, dark part of the nebula and including the luminous MSX source G224.1880+01.2407, a massive protostellar candidate that could be the origin of jets and extended features seen at 2.12 micron. The double cluster appears to be clearing the remaining molecular material of the parent cloud, creating patches of lower extinction and allowing some of the least reddened members to be detected in the optical images. We find 12 MS and 143 PMS members using 3 different methods: comparison with isochrones in optical colour-magnitude diagrams, detection of near-IR excess, and presence of Halpha emission. The most massive star fits a 4 Myr post-MS isochrone. The age of the optically selected PMS population is estimated to be 7-8 Myr. The IR-excess population shows sub-clustering on scales as small as 0.23 pc and is probably much younger.Comment: 15 pages, 16 figure

Proteomic analysis of the response of the plant growth-promoting bacterium Pseudomonas putida UW4 to nickel stress

<p>Abstract</p> <p>Background</p> <p>Plant growth-promoting bacteria can alleviate the inhibitory effects of various heavy metals on plant growth, via decreasing levels of stress-induced ethylene. However, little has been done to detect any mechanisms specific for heavy metal resistance of this kind of bacteria. Here, we investigate the response of the wild-type plant growth-promoting bacterium <it>Pseudomonas putida </it>UW4 to nickel stress using proteomic approaches. The mutant strain <it>P. putida </it>UW4/AcdS^-, lacking a functional 1-aminocyclopropane-1-carboxylic acid deaminase gene, was also assessed for its response to nickel stress.</p> <p>Results</p> <p>Two dimensional difference in-gel electrophoresis (DIGE) was used to detect significantly up- or down- regulated proteins (<it>p </it>< 0.05, | ratio | > 1.5) in <it>P. putida </it>in response to the presence of 2 mM Ni. Out of a total number of 1,702 proteins detected on the analytical gels for <it>P. putida </it>UW4, the expression levels of 82 (4.82%) proteins increased significantly while the expression of 81 (4.76%) proteins decreased significantly. Of 1,575 proteins detected on the analytical gels for <it>P. putida </it>UW4/AcdS^-, the expression levels of 74 (4.70%) proteins increased and 51 (3.24%) proteins decreased significantly. Thirty-five proteins whose expression was altered were successfully identified by mass spectrometry and sequence comparisons with related species. Nineteen of the identified proteins were detected as differentially expressed in both wild-type and mutant expression profiles.</p> <p>Conclusion</p> <p>Functional assessment of proteins with significantly altered expression levels revealed several mechanisms thought to be involved in bacterial heavy metal detoxification, including general stress adaptation, anti-oxidative stress and heavy metal efflux proteins. This information may contribute to the development of plant growth-promoting bacteria mediated phytoremediation processes.</p

Variant WWTR1 gene fusions in epithelioid hemangioendothelioma-A genetic subset associated with cardiac involvement

The genetic hallmark of epithelioid hemangioendothelioma (EHE) is a recurrent WWTR1-CAMTA1 fusion, which is present in most cases bearing a conventional histology. A subset of cases is characterized by a distinct morphology and harbors instead a YAP1-TFE3 fusion. Nevertheless, isolated cases lack these canonical fusions and remain difficult to classify. Triggered by an index case of a left atrial mass in a 76-year-old female with morphologic features typical of EHE, but which showed an WWTR1-MAML2 fusion by targeted RNA sequencing, we searched our files for similar cases displaying alternative WWTR1 fusions. A total of 6 EHE cases were identified with variant WWTR1 fusions, four of them presenting within the heart. There were 3 females and 3 males, with a wide age range at diagnosis (21–76 years, mean 62, median 69). The 4 cardiac cases occurred in older adults (mean age of 72, equal gender distribution), three involved the left atrium and one the right ventricle. One case presented in the vertebral bone and one in pelvic soft tissue. Microscopically, all tumors had morphologic features within the spectrum of classic EHE; two of the cases appeared overtly malignant. All cases were tested by FISH and 4 were investigated by targeted RNA sequencing. Two tumors harbored WWTR1-MAML2 fusions, one WWTR1-ACTL6A, and in 3 cases no WWTR1 partner was identified. Of the 4 patients with follow-up, 2 died of disease, one was alive with lung metastases, and the only patient free of disease was s/p resection of a T11 vertebral mass. Our findings report on additional genetic variants involving WWTR1 rearrangements, with WWTR1-MAML2 being a recurrent event, in a small subset of EHE, which appears to have predilection for heart

Epithelioid hemangioma of bone harboring FOS and FOSB gene rearrangements:A clinicopathologic and molecular study

The diagnosis of epithelioid hemangioma (EH) remains challenging due to its rarity, worrisome histologic features and locally aggressive clinical and radiographic presentation. Especially in the bone, EH can be misdiagnosed as a malignant vascular neoplasm due its lytic, often destructive or multifocal growth, as well as atypical morphology. The discovery of recurrent FOS and FOSB gene fusions in the pathogenesis of most EH has strengthened its stand-alone classification, distinct from other malignant epithelioid vascular lesions, such as epithelioid hemangioendothelioma or angiosarcoma. In this study we investigate a group of molecularly confirmed skeletal EH by the presence of FOS or FOSB gene rearrangements to better define its clinical and pathologic characteristics within a homogenous molecular subset. The cohort included 38 patients (25 males, 13 females), with a mean age at diagnosis of 38 years (range, 4–75). Regional, multifocal presentation was noted in 10 cases. Only six cases were correctly recognized as EH by the referring institutions, while most were misdiagnosed as other vascular tumors. Of the 17 patients with follow-up data available, 5 patients (29%) developed local recurrence after marginal en bloc excision (n = 3) or curettage (n = 2). Local recurrence-free survival rates were 84% at 3 years and 38% at 5 years. No metastasis or disease-related death was identified. Imaging studies exhibited no specific features, showing cortical bone destruction and soft-tissue extension in 14 (38%) cases. FOS gene rearrangements were detected in 28 (74%) of cases, while FOSB rearrangements in 10 (26%) cases. Our results highlight the significant challenges encountered in establishing a correct diagnosis exclusive of the molecular testing, mainly due to its overlap to other malignant epithelioid vascular tumors. Skeletal EH emerges as a genetically defined locally aggressive vascular neoplasm, with a high rate of local recurrence, but lacking the propensity for distant spread