Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

OBJECTIVE: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis. METHODS: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy < or = 3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects. RESULTS: Patients with Barrett's esophagus had significantly increased acid reflux time (p < 0.01-0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (p < 0.01-0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis. CONCLUSION: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

Hands‐On CFD Educational Interface for Engineering Courses and Laboratories

This study describes the development, implementation, and evaluation of an effective curriculum for students to learn computational fluid dynamics (CFD) in introductory and intermediate undergraduate and introductory graduate level courses/laboratories. The curriculum is designed for use at different universities with different courses/laboratories, learning objectives, applications, conditions, and exercise notes. The common objective is to teach students from novice to expert users who are well prepared for engineering practice. The study describes a CFD Educational Interface for hands‐on student experience, which mirrors actual engineering practice. The Educational Interface teaches CFD methodology and procedures through a step‐by‐step interactive implementation automating the CFD process. A hierarchical system of predefined active options facilitates use at introductory and intermediate levels, encouraging self‐learning, and eases transition to using industrial CFD codes. An independent evaluation documents successful learning outcomes and confirms the effectiveness of the interface for students in introductory and intermediate fluid mechanics courses.     

Use of a Molecular Switch Probe to Activate or Inhibit GIRK1 Heteromers In Silico Reveals a Novel Gating Mechanism

G protein-gated inwardly rectifying K⁺ (GIRK) channels form highly active heterotetramers in the body, such as in neurons (GIRK1/GIRK2 or GIRK1/2) and heart (GIRK1/GIRK4 or GIRK1/4). Based on three-dimensional atomic resolution structures for GIRK2 homotetramers, we built heterotetrameric GIRK1/2 and GIRK1/4 models in a lipid bilayer environment. By employing a urea-based activator ML297 and its molecular switch, the inhibitor GAT1587, we captured channel gating transitions and K⁺ ion permeation in sub-microsecond molecular dynamics (MD) simulations. This allowed us to monitor the dynamics of the two channel gates (one transmembrane and one cytosolic) as well as their control by the required phosphatidylinositol bis 4-5-phosphate (PIP₂). By comparing differences in the two trajectories, we identify three hydrophobic residues in the transmembrane domain 1 (TM1) of GIRK1, namely, F87, Y91, and W95, which form a hydrophobic wire induced by ML297 and de-induced by GAT1587 to orchestrate channel gating. This includes bending of the TM2 and alignment of a dipole of two acidic GIRK1 residues (E141 and D173) in the permeation pathway to facilitate K⁺ ion conduction. Moreover, the TM movements drive the movement of the Slide Helix relative to TM1 to adjust interactions of the CD-loop that controls the gating of the cytosolic gate. The simulations reveal that a key basic residue that coordinates PIP₂ to stabilize the pre-open and open states of the transmembrane gate flips in the inhibited state to form a direct salt-bridge interaction with the cytosolic gate and destabilize its open state.     

Large-scale synthesis of centrifugally spun tantalum oxynitride fiber electrocatalysts for hydrogen evolution reaction

Tantalum oxynitride (TaO_xN_1−x) fibers were synthesized and evaluated for their electrocatalytic hydrogen activity using an in-house developed centrifugal spinning setup. By tailoring the composition of the spinning solution and optimizing collector distance and rotation speed of the spinneret, bead-free TaO_xN_1−x fibers with a diameter of 800 nm were obtained. The fibers were structurally characterized through phase and elemental analysis, confirming the formation of monoclinic TaO_xN_1−x with clear splitting of the X-ray photoelectron spectroscopy peaks indicating Ta was in +5 oxidation state. The resulting oxynitride fibers exhibited superior electrocatalytic performance with low overpotentials (250 mV) to generate 10 mA/cm² compared to Ta₂O₅ oxide fibers. Interestingly, the enhanced activity of oxynitride fibers was observed to be suppressed in basic medium due to the high oxophilicity of tantalum ions and a negative Gibbs adsorption-free energy, leading to poisoning of the active sites. This work demonstrates a facile pathway for the fabrication of high-performance electrocatalysts, based on TaO_xN_1−x fibers, from a cost-effective and energy-efficient centrifugal spinning technique.     

Algorithm selection for SMT

International Journal on Software Tools for Technology Transfer - This paper presents MachSMT, an algorithm selection tool for Satisfiability Modulo Theories (SMT) solvers. MachSMT supports the...     

Inhibiting Erastin-Induced Ferroptotic Cell Death by Purine-Based Chelators

Ferroptosis is a cell death event caused by increased lipid peroxidation leading to iron-dependent oxidative stress and is associated with a wide variety of diseases. In recent years, ferroptosis inhibition has emerged as a novel strategy to target different pathologies. Here, we report the synthesis of two purine derivatives, 1 and 2 , for iron chelation strategy and evaluate their potency to inhibit erastin-induced ferroptosis. Both compounds showed efficient iron chelation in solution as well as in cellular environment. The crystal structure of the purine derivatives with iron demonstrated a 2 : 1 (ligand to metal center) stoichiometry for iron and purine derivative complexation. The synthesized compounds also decrease the reactive oxygen species concentration in cell cultures. Compound 2 showed better potency towards the prevention of ferroptotic cell death as compared to commercially available iron chelator in the erastin-induced ferroptosis cell culture model. Such purine analogues are potential functional scaffolds for the development of target molecules for ferroptosis inhibition.     

Fabrication of CeO2 microspheres by internal gelation process using flow-focusing droplet generator

Sphere-pac fuel is an alternative nuclear fuel technology in which microspheres of two or more sizes are utilized to fill the cladding tube in place of the more conventional single-size fuel pellets. This provides leeway for adjusting the fuel pellet packing density and resulting cladding tube porosity. The current investigation makes use of a flow-focusing droplet generator made from stainless steel (S.S.) 316 L, with a channel internal diameter (I.D.) of 0.5, 0.8, 1, and 3 mm. These microspheres were supposed to be of actinide oxide but here, cerium has been chosen as a surrogate of plutonium. Detailed information about the flow-focusing droplet generator, internal gelation process, and sphere-pac fuel has been provided. The size and size distribution of ceria microspheres were investigated by varying the flow rates of the continuous and dispersed phase. The characterization of ceria microspheres has been conducted using techniques such as scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Brunauer–Emmett–Teller (BET) analyses. The size of prepared monodisperse microspheres was controlled precisely (within ±2%) in the range of 498–2888 μm using four S.S. 316 L flow-focusing droplet generators with channel I.D. 0.5, 0.8, 1, and 3 mm, respectively, and the coefficient of variation of the size distribution was found to be less than 2%.     

Modelling temperature dynamics of the SAGD process in an oil reservoir by the discovery of parametric partial differential equations

Many chemical and industrial processes are complex, and the dynamics of such processes cannot be explained using a partial differential equation (PDE) or a system of PDEs with constant coefficients. Parametric PDEs, that is, PDEs with their coefficients varying across time or space, are utilized for this purpose. The non-availability of data at all spatial locations and partially available process knowledge add to the complexity of modelling such processes. This paper proposes a framework to discover parametric PDEs using data-driven and hybrid modelling approaches with the temperature dynamics of steam-assisted gravity drainage (SAGD) process in an oil reservoir as the system under study. We utilize an ensemble of 200 realizations of the temperature dynamics generated using the variogram for the PDE discovery. Permeability, which is one of the oil reservoir's petrophysical properties, is used to develop the hybrid models. We infer that utilizing partial process knowledge aids in improving the model's accuracy.     

Buried Metal Silicon-on-Insulator Junctionless Transistor for Low Power CMOS Logic Circuits

Silicon - This paper deals with an innovative structure of silicon-on-insulator junctionless transistor (SOIJLT) by incorporating a buried metal layer of proper work-function which creates the...     

A Novel Surfactant with Short Hydrophobic Head and Long Hydrophilic Tail Generates Vesicles with Unique Structural Feature

Surfactant molecules typically have a long hydrophobic tail and a short hydrophilic head group. It remains unexplored if surfactants can have a short hydrophobic head group and a long hydrophilic tail. Designing such surfactants is a challenge as a lengthy hydrophilic tail would completely solubilize the molecules. In this context, herein, the Fmoc-functionalized Gly-Pro-Hyp (GPO) tripeptide repeat-based molecule (Fm-GPO) with fluorenyl moiety as a short hydrophobic head and peptide as a long hydrophilic tail is demonstrated as a reverse surfactant at physiological pH, for the first time. π–π stacking of the fluorenyl moieties and intermolecular hydrogen bonding between the peptide chains with extended polyproline-II structure promoted the self-assembly into spherical vesicles with a unique feature of a large hydrophilic area in the interior and exterior of the bilayer. The current Fm-GPO system offers a new class of surfactants with unique features that can aid in the design of drug-loaded vehicles, which can be target-specific as the peptide chain can be manipulated with different functional ultra-short peptide sequences.