Spontaneous Expulsion of a Biliary Stent via the abdominal wall: A rare complication: Case Report

We report a rare complication of a biliary stent inserted via endoscopic retrograde cholangio-pancreatography (ERCP) for benign biliary disease in a 60 years-old female presented with abdominal pain and a tender left iliac fossa (LIF) mass. She had change of the colour of the skin over the hypogastric region. Crepitus was felt in the subcutaneous tissue. Surgical drainage of the abscess was undertaken. A black, 14-cm biliary stent was found in the centre of the necrotic tissue. The patient, thereafter, made an uneventful recovery and the LIF mass disappeared. The wound was closed with secondary sutures about three weeks later, and complete healing was achieved thereafter. Here we discuss this rare complication. Keywords: Biliary stent migration, colonic perforation, abdominal mass, large bowel obstruction, abdominal wall abscess, ERCP complication. Sudan Journal of Medical Sciences Vol. 3 (3) 2008: pp. 255-25

A search for technosignatures from 14 planetary systems in the Kepler field with the Green Bank Telescope at 1.15-1.73 GHz

Analysis of Kepler mission data suggests that the Milky Way includes billions of Earth-like planets in the habitable zone of their host star. Current technology enables the detection of technosignatures emitted from a large fraction of the Galaxy. We describe a search for technosignatures that is sensitive to Arecibo-class transmitters located within ~420 ly of Earth and transmitters that are 1000 times more effective than Arecibo within ~13 000 ly of Earth. Our observations focused on 14 planetary systems in the Kepler field and used the L-band receiver (1.15-1.73 GHz) of the 100 m diameter Green Bank Telescope. Each source was observed for a total integration time of 5 minutes. We obtained power spectra at a frequency resolution of 3 Hz and examined narrowband signals with Doppler drift rates between +/-9 Hz/s. We flagged any detection with a signal-to-noise ratio in excess of 10 as a candidate signal and identified approximately 850 000 candidates. Most (99%) of these candidate signals were automatically classified as human-generated radio-frequency interference (RFI). A large fraction (>99%) of the remaining candidate signals were also flagged as anthropogenic RFI because they have frequencies that overlap those used by global navigation satellite systems, satellite downlinks, or other interferers detected in heavily polluted regions of the spectrum. All 19 remaining candidate signals were scrutinized and none were attributable to an extraterrestrial source.Comment: 15 pages, 5 figures, accepted for publication in the Astronomical Journa

Thermally driven spin injection from a ferromagnet into a non-magnetic metal

Creating, manipulating and detecting spin polarized carriers are the key elements of spin based electronics. Most practical devices use a perpendicular geometry in which the spin currents, describing the transport of spin angular momentum, are accompanied by charge currents. In recent years, new sources of pure spin currents, i.e., without charge currents, have been demonstrated and applied. In this paper, we demonstrate a conceptually new source of pure spin current driven by the flow of heat across a ferromagnetic/non-magnetic metal (FM/NM) interface. This spin current is generated because the Seebeck coefficient, which describes the generation of a voltage as a result of a temperature gradient, is spin dependent in a ferromagnet. For a detailed study of this new source of spins, it is measured in a non-local lateral geometry. We developed a 3D model that describes the heat, charge and spin transport in this geometry which allows us to quantify this process. We obtain a spin Seebeck coefficient for Permalloy of -3.8 microvolt/Kelvin demonstrating that thermally driven spin injection is a feasible alternative for electrical spin injection in, for example, spin transfer torque experiments

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

Targeted Mutation Detection in Advanced Breast Cancer Using MammaSeq Identifies RET as a Potential Contributor to Breast Cancer Metastasis

The lack of any reported breast cancer specific diagnostic NGS tests inspired the development of MammaSeq, an amplicon based NGS panel built specifically for use in advanced breast cancer. In a pilot study to define the clinical utility of the panel, 46 solid tumor samples, plus an additional 14 samples of circulating-free DNA (cfDNA) from patients with advanced breast cancer were sequenced and analyzed using the OncoKB precision oncology database. We identified 26 clinically actionable variants (levels 1-3) annotated by the OncoKB precision oncology database, distributed across 20 out of 46 solid tumor cases (40%), and 4 clinically actionable mutations distributed across 4 samples in the 14 cfDNA sample cohort (29%). The mutation allele (MAF) frequencies of ESR1-D538G and FOXA1-Y175C mutations correlated with CA.27.29 levels in patient-matched blood, indicating that MAF may be a reliable marker for disease burden. Interestingly, 4 of the mutations found in metastatic samples occurred in the gene RET, an oncogenic receptor tyrosine kinase. In an orthogonal study, the lab has recently identified RET as one of the most recurrently upregulated genes in breast cancer brain metastases. Interestingly, the ligand for RET is the family of glial-cell derived neurotrophic factors (GDNF), a growth factor secreted by glial cells of the central nervous system. This lead to the hypothesis that RET overexpression facilitates breast cancer brain metastasis in response to the high levels of GDNF, while RET activating point mutations increase metastatic capacity without specific organ tropism. While the effect of GDNF treatment on proliferation in 2D was limited, in ultra-low attachment (ULA) plates we saw a significant increase in anchorage independent growth of MCF-7 cells. To determine if GDNF acts as a chemoattractant for RET positive BrCa cells, we utilized a transwell migration assay, with GDNF as the sole chemoattractant. When RET was overexpressed, there was a visual increase in cell migration. Together, these studies demonstrate the clinical feasibility of using MammaSeq to detect clinically actionable mutations in breast cancer patients, and provides provisional data supporting the investigation of RET signaling as a potentially targetable mediator of breast cancer brain metastasis

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

ExoMol line lists - XLIV. IR and UV line list for silicon monoxide (SiO)

A new silicon monoxide (28Si16O) line list covering infrared, visible and ultraviolet regions called SiOUVenIR is presented. This line list extends the infrared EBJT ExoMol line list by including vibronic transitions to the A 1Π and E 1Σ+ electronic states. Strong perturbations to the A 1Π band system are accurately modelled through the treatment of 6 dark electronic states: C 1Σ−, D 1Δ, a 3Σ+, b 3Π, e 3Σ− and d 3Δ. Along with the X 1Σ+ ground state, these 9 electronic states were used to build a comprehensive spectroscopic model of SiO using a combination of empirical and ab initio curves, including the potential energy (PE), spin-orbit (SO), electronic angular momentum (EAM) and (transition) dipole moment curves. The ab initio PE and coupling curves, computed at the multireference configuration interaction (MRCI) level of theory, were refined by fitting their analytical representations to 2617 experimentally derived SiO energy levels determined from 97 vibronic bands belonging to the X–X, E–X and A–X electronic systems through the MARVEL procedure. 112 observed forbidden transitions from the C–X, D–X, e–X, and d–X bands were assigned using our predictions, and these could be fed back into the MARVEL procedure. The SiOUVenIR line list was computed using published ab initio transition dipole moments for the E–X and A–X bands; the line list is suitable for temperatures up to 10 000 K and for wavelengths longer than 140 nm. SiOUVenIR is available from www.exomol.com and the CDS database

ExoMol line lists - XLIV. IR and UV line list for silicon monoxide (SiO)

A new silicon monoxide (28Si16O) line list covering infrared, visible and ultraviolet regions called SiOUVenIR is presented. This line list extends the infrared EBJT ExoMol line list by including vibronic transitions to the A 1Π and E 1Σ+ electronic states. Strong perturbations to the A 1Π band system are accurately modelled through the treatment of 6 dark electronic states: C 1Σ−, D 1Δ, a 3Σ+, b 3Π, e 3Σ− and d 3Δ. Along with the X 1Σ+ ground state, these 9 electronic states were used to build a comprehensive spectroscopic model of SiO using a combination of empirical and ab initio curves, including the potential energy (PE), spin-orbit (SO), electronic angular momentum (EAM) and (transition) dipole moment curves. The ab initio PE and coupling curves, computed at the multireference configuration interaction (MRCI) level of theory, were refined by fitting their analytical representations to 2617 experimentally derived SiO energy levels determined from 97 vibronic bands belonging to the X–X, E–X and A–X electronic systems through the MARVEL procedure. 112 observed forbidden transitions from the C–X, D–X, e–X, and d–X bands were assigned using our predictions, and these could be fed back into the MARVEL procedure. The SiOUVenIR line list was computed using published ab initio transition dipole moments for the E–X and A–X bands; the line list is suitable for temperatures up to 10 000 K and for wavelengths longer than 140 nm. SiOUVenIR is available from www.exomol.com and the CDS database