Instrumental Variables, Errors in Variables, and Simultaneous Equations Models: Applicability and Limitations of Direct Monte Carlo

A Direct Monte Carlo (DMC) approach is introduced for posterior simulation in the Instrumental Variables (IV) model with one possibly endogenous regressor, multiple instruments and Gaussian errors under a flat prior. This DMC method can also be applied in an IV model (with one or multiple instruments) under an informative prior for the endogenous regressor's effect. This DMC approach can not be applied to more complex IV models or Simultaneous Equations Models with multiple endogenous regressors. An Approximate DMC (ADMC) approach is introduced that makes use of the proposed Hybrid Mixture Sampling (HMS) method, which facilitates Metropolis-Hastings (MH) or Importance Sampling from a proper marginal posterior density with highly non-elliptical shapes that tend to infinity for a point of singularity. After one has simulated from the irregularly shaped marginal distri- bution using the HMS method, one easily samples the other parameters from their conditional Student-t and Inverse-Wishart posteriors. An example illustrates the close approximation and high MH acceptance rate. While using a simple candidate distribution such as the Student-t may lead to an infinite variance of Importance Sampling weights. The choice between the IV model and a simple linear model un- der the restriction of exogeneity may be based on predictive likelihoods, for which the efficient simulation of all model parameters may be quite useful. In future work the ADMC approach may be extended to more extensive IV models such as IV with non-Gaussian errors, panel IV, or probit/logit IV

Transit timing variation analysis of the low-mass brown dwarf KELT-1 b

We investigate whether there is a variation in the orbital period of the short-period brown dwarf-mass KELT-1 b, which is one of the best candidates to observe orbital decay. We obtain 19 high-precision transit light curves of the target using six different telescopes. We add all precise and complete transit light curves from open databases and the literature, as well as the available Transiting Exoplanet Survey Satellite (TESS) observations from sectors 17 and 57, to form a transit timing variation (TTV) diagram spanning more than 10 yr of observations. The analysis of the TTV diagram, however, is inconclusive in terms of a secular or periodic variation, hinting that the system might have synchronized. We update the transit ephemeris and determine an informative lower limit for the reduced tidal quality parameter of its host star of Q ′⋆>(8.5±3.9)×106 assuming that the stellar rotation is not yet synchronized. Using our new photometric observations, published light curves, the TESS data, archival radial velocities, and broadband magnitudes, we also update the measured parameters of the system. Our results are in good agreement with those found in previous analyses

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Times of Minima of Some Eclipsing Binaries

We present new times of minima in the light curves of some eclipsing binarie

Proteostasis Dysregulation in Pancreatic Cancer

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), has a dismal 5-year survival rate of less than 5%. Radical surgical resection, in combination with adjuvant chemotherapy, provides the best option for long-term patient survival. However, only approximately 20% of patients are resectable at the time of diagnosis, due to locally advanced or metastatic disease. There is an urgent need for the identification of new, specific, and more sensitive biomarkers for diagnosis, prognosis, and prediction to improve the treatment options for pancreatic cancer patients. Dysregulation of proteostasis is linked to many pathophysiological conditions, including various types of cancer. In this review, we report on findings relating to the main cellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, in pancreatic cancer. The expression of several components of the proteolytic network, including E3 ubiquitinligases and deubiquitinating enzymes, are dysregulated in PDAC, which accounts for approximately 90% of all pancreatic malignancies. In the future, a deeper understanding of the emerging role of proteostasis in pancreatic cancer has the potential to provide clinically relevant biomarkers and new strategies for combinatorial therapeutic options to better help treat the patients.Peer reviewe