BACKGROUND: Isolated injury to the superior mesenteric vein (SMV) caused by blunt abdominal trauma is rare but often lethal, especially in pediatric patients. Due to the low incidence of SMV injuries, there are no universal guidelines for its diagnosis and treatment. The diagnosis is made using either computed tomography (CT) or intraoperative exploration. Primary vascular repair is recommended. CASE REPORT: A 10-year-old girl was transferred to a trauma center after a high-energy motor vehicle collision. Under the diagnosis of acute abdomen with hemoperitoneum, the patient underwent urgent laparotomy, 34 min after admission to the hospital. A complete laceration of the SMV trunk was observed. Definitive vascular repair of the transected SMV was performed. An interposition graft from the internal jugular vein was used with a good postoperative course. CONCLUSION: This case report demonstrates that definitive vascular repair of the SMV reduces the risk of intestinal ischemia and should be performed in cases where ligation presents a real threat to small bowel viability. In cases of severe SMV injury, the internal jugular vein is a high-quality and easily accessible graft.
- MeSH
- Child MeSH
- Accidents, Traffic MeSH
- Lacerations * surgery etiology MeSH
- Laparotomy methods MeSH
- Humans MeSH
- Tomography, X-Ray Computed MeSH
- Abdominal Injuries * complications surgery diagnosis MeSH
- Vascular System Injuries * surgery etiology diagnosis MeSH
- Wounds, Nonpenetrating * complications surgery diagnosis MeSH
- Mesenteric Veins * injuries surgery diagnostic imaging MeSH
- Vascular Surgical Procedures methods MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step of glycolysis, committing glucose to conversion into cellular energy. PFK1 is highly regulated to respond to the changing energy needs of the cell. In bacteria, the structural basis of PFK1 regulation is a textbook example of allostery; molecular signals of low and high cellular energy promote transition between an active R-state and inactive T-state conformation, respectively. Little is known, however, about the structural basis for regulation of eukaryotic PFK1. Here, we determine structures of the human liver isoform of PFK1 (PFKL) in the R- and T-state by cryoEM, providing insight into eukaryotic PFK1 allosteric regulatory mechanisms. The T-state structure reveals conformational differences between the bacterial and eukaryotic enzyme, the mechanisms of allosteric inhibition by ATP binding at multiple sites, and an autoinhibitory role of the C-terminus in stabilizing the T-state. We also determine structures of PFKL filaments that define the mechanism of higher-order assembly and demonstrate that these structures are necessary for higher-order assembly of PFKL in cells.
- MeSH
- Adenosine Triphosphate * metabolism MeSH
- Allosteric Regulation MeSH
- Cryoelectron Microscopy MeSH
- Phosphofructokinase-1 * metabolism chemistry genetics MeSH
- Glycolysis MeSH
- Liver enzymology metabolism MeSH
- Protein Conformation MeSH
- Humans MeSH
- Models, Molecular MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
This study investigates the factors modulating the reactivity of 5'-deoxyadenosyl (5'dAdo ̇) radical, a potent hydrogen atom abstractor that forms in the active sites of radical SAM enzymes and that otherwise undergoes a rapid self-decay in aqueous solution. Here, we compare hydrogen atom abstraction (HAA) reactions between native substrates of radical SAM enzymes and 5'dAdo ̇ in aqueous solution and in two enzymatic microenvironments. With that we reveal that HAA efficiency of 5'dAdo ̇ is due to (i) the in situ formation of 5'dAdo ̇ in a pre-ordered complex with a substrate, which attenuates the unfavorable effect of substrate:5'dAdo ̇ complex formation, and (ii) the prevention of the conformational changes associated with self-decay by a tight active-site cavity. The enzymatic cavity, however, does not have a strong effect on the HAA activity of 5'dAdo ̇. Thus, we performed an analysis of in-water HAA performed by 5'dAdo ̇ based on a three-component thermodynamic model incorporating the diagonal effect of the free energy of reaction, and the off-diagonal effect of asynchronicity and frustration. To this aim, we took advantage of the straightforward relationship between the off-diagonal thermodynamic effects and the electronic-structure descriptor - the redistribution of charge between the reactants during the reaction. It allows to access HAA-competent redox and acidobasic properties of 5'dAdo ̇ that are otherwise unavailable due to its instability upon one-electron reduction and protonation. The results show that all reactions feature a favourable thermodynamic driving force and tunneling, the latter of which lowers systematically barriers by ∼2 kcal mol-1. In addition, most of the reactions experience a favourable off-diagonal thermodynamic contribution. In HAA reactions, 5'dAdo ̇ acts as a weak oxidant as well as a base, also 5'dAdo ̇-promoted HAA reactions proceed with a quite low degree of asynchronicity of proton and electron transfer. Finally, the study elucidates the crucial and dual role of asynchronicity. It directly lowers the barrier as a part of the off-diagonal thermodynamic contribution, but also indirectly increases the non-thermodynamic part of the barrier by presumably controlling the adiabatic coupling between proton and electron transfer. The latter signals that the reaction proceeds as a hydrogen atom transfer rather than a proton-coupled electron transfer.
Objective.This study aims to assess the composition of scattered particles generated in proton therapy for tumors situated proximal to some titanium (Ti) dental implants. The investigation involves decomposing the mixed field and recording Linear Energy Transfer (LET) spectra to quantify the influence of metallic dental inserts located behind the tumor.Approach.A therapeutic conformal proton beam was used to deliver the treatment plan to an anthropomorphic head phantom with two types of implants inserted in the target volume (made of Ti and plastic, respectively). The scattered radiation resulted during the irradiation was detected by a hybrid semiconductor pixel detector MiniPIX Timepix3 that was placed distal to the Spread-out Bragg peak. Visualization and field decomposition of stray radiation were generated using algorithms trained in particle recognition based on artificial intelligence neural networks (AI NN). Spectral sensitive aspects of the scattered radiation were collected using two angular positions of the detector relative to the beam direction: 0° and 60°.Results.Using AI NN, 3 classes of particles were identified: protons, electrons & photons, and ions & fast neutrons. Placing a Ti implant in the beam's path resulted in predominantly electrons and photons, contributing 52.2% of the total number of detected particles, whereas for plastic implants, the contribution was 65.4%. Scattered protons comprised 45.5% and 31.9% with and without metal inserts, respectively. The LET spectra were derived for each group of particles identified, with values ranging from 0.01 to 7.5 keVμm-1for Ti implants/plastic implants. The low-LET component was primarily composed of electrons and photons, while the high-LET component corresponded to protons and ions.Significance.This method, complemented by directional maps, holds the potential for evaluating and validating treatment plans involving stray radiation near organs at risk, offering precise discrimination of the mixed field, and enhancing in this way the LET calculation.
- MeSH
- Phantoms, Imaging * MeSH
- Humans MeSH
- Linear Energy Transfer * MeSH
- Neural Networks, Computer MeSH
- Radiotherapy Planning, Computer-Assisted methods MeSH
- Prostheses and Implants MeSH
- Proton Therapy * methods instrumentation MeSH
- Scattering, Radiation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
As is the case with batch-based tableting processes, continuous tablet manufacturing can be conducted by direct compression or with a granulation step such as dry or wet granulation included in the production procedure. In this work, continuous manufacturing tests were performed with a commercial tablet formulation, while maintaining its original material composition. Challenges were encountered with the feeding performance of the API during initial tests which required designing different powder pre-blend compositions. After the pre-blend optimization phase, granules were prepared with a roller compactor. Tableting was conducted with the granules and an additional brief continuous direct compression run was completed with some ungranulated mixture. The tablets were assessed with off-line tests, applying the quality requirements demanded for the batch-manufactured product. Chemical maps were obtained by Raman mapping and elemental maps by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Large variations in both tablet weights and breaking forces were observed in all tested samples, resulting in significant quality complications. It was suspected that the API tended to adhere to the process equipment, accounting for the low API content in the powder mixture and tablets. These results suggest that this API or the tablet composition was unsuitable for manufacturing in a continuous line; further testing could be continued with different materials and changes in the process.
Experimental and theoretical foundations for femtosecond time-resolved circular dichroism (TRCD) spectroscopy of excitonic systems are presented. In this method, the system is pumped with linearly polarized light and the signal is defined as the difference between the transient absorption spectrum probed with left and with right circularly polarized light. We present a new experimental setup with a polarization grating as key element to generate circularly polarized pulses. Herein the positive (negative) first order of the diffracted light is left-(right-)circularly polarized and serves as a probe pulse in a TRCD experiment. The grating is capable of transferring ultrashort broadband pulses ranging from 470 nm to 720 nm into two separate beams with opposite ellipticity. By applying a specific chopping scheme we can switch between left and right circular polarizations and detect transient absorption (TA) and TRCD spectra on a shot-to-shot basis simultaneously. We perform experiments on a squaraine polymer, investigating excitonic dynamics, and we develop a general theory for TRCD experiments of excitonically coupled systems that we then apply to describe the experimental data in this particular example. At a magic angle of 54.7° between the pump-pulse polarization and the propagation direction of the probe pulse, the TRCD and TA signals become particularly simple to analyze, since the orientational average over random orientations of complexes factorizes into that of the interaction with the pump and the probe pulse, and the intrinsic electric quadrupole contributions to the TRCD signal average to zero for isotropic samples. Application of exciton theory to linear absorption and to linear circular dichroism spectra of squaraine polymers reveals the presence of two fractions of polymer conformations, a dominant helical conformation with close interpigment distances that are suggested to lead to short-range contributions to site energy shifts and excitonic couplings of the squaraine molecules, and a fraction of unfolded random coils. Theory demonstrates that TRCD spectra of selectively excited helices can resolve state populations that are practically invisible in TA spectroscopy due to the small dipole strength of these states. A qualitative interpretation of TRCD and TA spectra in the spectral window investigated experimentally is offered. The 1 ps time component found in these spectra is related to the slow part of exciton relaxation obtained between states of the helix in the low-energy half of the exciton manifold. The dominant 140 ps time constant reflects the decay of excited states to the electronic ground state.
- Publication type
- Journal Article MeSH
With the use of proton-NMR and powder XRD (XRPD) studies, the suitability of specific Au-focused electron beam induced deposition (FEBID) precursors has been investigated with low electron energy, structure, excited states and resonances, structural crystal modifications, flexibility, and vaporization level. 4,5-Dichloro-1,3-diethyl-imidazolylidene trifluoromethyl gold(I) is a compound that is a uniquely designed precursor to meet the needs of focused electron beam-induced deposition at the nanostructure level, which proves its capability in creating high purity structures, and its growing importance in other AuImx and AuClnB (where x and n are the number of radicals, B = CH, CH3, or Br) compounds in the radiation cancer therapy increases the efforts to design more suitable bonds in processes of SEM (scanning electron microscopy) deposition and in gas-phase studies. The investigation performed of its powder shape using the XRPD XPERT3 panalytical diffractometer based on CoKα lines shows changes to its structure with change in temperature, level of vacuum, and light; the sensitivity of this compound makes it highly interesting in particular to the radiation research. Used in FEBID, though its smaller number of C, H, and O atoms has lower levels of C contamination in the structures and on the surface, it replaces these bonds with C-Cl and C-N bonds that have lower bond-breaking energy. However, it still needs an extra purification step in the deposition process, either H2O, O2, or H jets.
- Publication type
- Journal Article MeSH
Stray radiation produced by ultra-high dose-rates (UHDR) proton pencil beams is characterized using ASIC-chip semiconductor pixel detectors. A proton pencil beam with an energy of 220 MeV was utilized to deliver dose rates (DR) ranging from conventional radiotherapy DRs up to 270 Gy/s. A MiniPIX Timepix3 detector equipped with a silicon sensor and integrated readout electronics was used. The chip-sensor assembly and chipboard on water-equivalent backing were detached and immersed in the water-phantom. The deposited energy, particle flux, DR, and the linear energy transfer (LET(Si)) spectra were measured in the silicon sensor at different positions both laterally, at different depths, and behind the Bragg peak. At low-intensity beams, the detector is operated in the event-by-event data-driven mode for high-resolution spectral tracking of individual particles. This technique provides precise energy loss response and LET(Si) spectra with radiation field composition resolving power. At higher beam intensities a rescaling of LET(Si) can be performed as the distribution of the LET(Si) spectra exhibits the same characteristics regardless of the delivered DR. The integrated deposited energy and the absorbed dose can be thus measured in a wide range. A linear response of measured absorbed dose was obtained by gradually increasing the delivered DR to reach UHDR beams. Particle tracking of scattered radiation in data-driven mode could be performed at DRs up to 0.27 Gy/s. In integrated mode, the saturation limits were not reached at the measured out-of-field locations up to the delivered DR of over 270 Gy/s. A good agreement was found between measured and simulated absorbed doses.
- MeSH
- Silicon MeSH
- Linear Energy Transfer MeSH
- Proton Therapy * methods MeSH
- Protons MeSH
- Radiometry * methods MeSH
- Water MeSH
- Publication type
- Journal Article MeSH
Two dimensional (2D) nanomaterials display properties with significant biological utility (e.g., antimicrobial activity). In this study, MXene-functionalized graphene (FG) nanocomposites with Ti3C2T x in varying ratios (FG : Ti3C2T x , 25 : 75%, 50 : 50%, and 75 : 25%) were prepared and characterized via scanning electron microscopy, scanning electron microscopy-energy dispersive X-ray (SEM-EDX), high-resolution transmission electron microscopy (HRTEM), and zeta potential analysis. Their cytotoxicity was assessed using immortalized human keratinocytes (HaCaT) cells at three different timepoints, and antibacterial activity was assessed using Gram-positive Methicillin resistant Staphylococcus aureus, MRSA, and Gram-negative neuro-pathogenic Escherichia coli K1 (E. coli K1) in vitro. The nanomaterials and composites displayed potent antibacterial effects against both types of bacteria and low cytotoxicity against HaCaT cells at 200 μg mL-1, which is promising for their utilization for biomedical applications.
- Publication type
- Journal Article MeSH
BACKGROUND: The spatially varying mechanical properties in finite element models of bone are most often derived from bone density data obtained via quantitative computed tomography. The key step is to accurately and efficiently map the density given in voxels to the finite element mesh. METHODS: The density projection is first formulated in least-squares terms and then discretized using a continuous and discontinuous variant of the finite element method. Both discretization variants are compared with the nodal and element approaches known from the literature. FINDINGS: In terms of accuracy in the L2 norm, energy distance and efficiency, the discontinuous zero-order variant appears to be the most advantageous. The proposed variant sufficiently preserves the spectrum of density at the edges, while keeping computational cost low. INTERPRETATION: The continuous finite element method is analogous to the nodal formulation in the literature, while the discontinuous finite element method is analogous to the element formulation. The two variants differ in terms of implementation, computational cost and ability to preserve the density spectrum. These differences cannot be described and measured by known indirect methods from the literature.
- MeSH
- Finite Element Analysis MeSH
- Bone and Bones * diagnostic imaging MeSH
- Bone Density MeSH
- Humans MeSH
- Tomography, X-Ray Computed * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
