150 research outputs found
Understanding high pressure hydrogen with a hierarchical machine-learned potential
The hydrogen phase diagram has a number of unusual features which are
generally well reproduced by density functional calculations. Unfortunately,
these calculations fail to provide good physical insights into why those
features occur. In this paper, we parameterize a model potential for molecular
hydrogen which permits long and large simulations. The model shows excellent
reproduction of the phase diagram, including the broken-symmetry Phase II, an
efficiently-packed phase III and the maximum in the melt curve. It also gives
an excellent reproduction of the vibrational frequencies, including the maximum
in the vibrational frequency and negative thermal expansion. By
detailed study of lengthy molecular dynamics, we give intuitive explanations
for observed and calculated properties. All solid structures approximate to
hexagonal close packed, with symmetry broken by molecular orientation. At high
pressure, Phase I shows significant short-ranged correlations between molecular
orientations. The turnover in Raman frequency is due to increased coupling
between neighboring molecules, rather than weakening of the bond. The liquid is
denser than the close-packed solid because, at molecular separations below
2.3\AA, the favoured relative orientation switches from
quadrupole-energy-minimising to steric-repulsion-minimising. The latter allows
molecules to get closer together, without atoms getting closer but this cannot
be achieved within the constraints of a close-packed layer
On single-crystal neutron-diffraction in DACs: quantitative structure refinement of light elements on SNAP and TOPAZ
Whole transcriptome sequencing identifies tumor-specific mutations in human oral squamous cell carcinoma
Zollinger-Ellison syndrome associated with neurofibromatosis type 1: a case report
BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with characteristic features of skin and central nervous system involvement. Gastrointestinal involvement is rare, but the risk of malignancy development is considerable. Zollinger-Ellison syndrome is caused by gastrin-secreting tumors called gastrinomas. Correct diagnosis is often difficult, and curative treatment can only be achieved surgically. CASE PRESENTATION: A 41-year-old female affected by neurofibromatosis type 1 presented with a history of recurrent epigastric soreness, diarrhea, and relapsing chronic duodenal ulcer. Her serum fasting gastrin level was over 1000 pg/mL. An abdominal CT scan revealed a 3 × 2-cm, well-enhanced mass adjacent to the duodenal loop. She was not associated with multiple endocrine neoplasia type 1. Operative resection was performed and gastrinoma was diagnosed by immunohistochemical staining. The serum gastrin level decreased to 99.1 pg/mL after surgery, and symptoms and endoscopic findings completely resolved without recurrences. CONCLUSION: Gastrinoma is difficult to detect even in the general population, and hence symptoms such as recurrent idiopathic peptic ulcer and diarrhea in neurofibromatosis type 1 patients should be accounted for as possibly contributing to Zollinger-Ellison syndrome
Selection-Independent Generation of Gene Knockout Mouse Embryonic Stem Cells Using Zinc-Finger Nucleases
Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10−6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells
The prognostic value of Foxp3+ tumor-infiltrating lymphocytes in patients with glioblastoma
Awareness of visceral leishmaniasis and its relationship to canine infection in riverside endemic areas in Northeastern Brazil
Identification and development of a functional marker from 6-SFT-A2 associated with grain weight in wheat
Liver architecture, cell function, and disease.
The liver is an organ consisting of the largest reticulo-endothelial cell network in the body and playing an important role in host defense against invading microorganisms. The organ is comprised of parenchymal cells and many different types of non-parenchymal cells, all of which play a significant role. Even biliary epithelial cells are not only the target in autoimmune liver diseases but also have central role in orchestrating several immune cells involved in both innate and acquired immunity. Tissue damage caused by various agents results in inflammation, necrosis, fibrosis, and, eventually, distortion of normal hepatic architecture, cirrhosis, and functional deterioration
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