Maximum Change Research Articles

Construction of multilayered gene circuits using de-novo-designed synthetic transcriptional regulators in cell-free systems

BackgroundDe-novo-designed synthetic transcriptional regulators have great potential as the genetic parts for constructing complex multilayered gene circuits. The design flexibility afforded by advanced nucleic acid sequence design tools vastly expands the repertoire of regulatory elements for circuit design. In principle, the design space of synthetic regulators should allow for the construction of regulatory circuits of arbitrary complexity; still, the orthogonality and robustness of such components have not been fully elucidated, thereby limiting the depth and width of synthetic circuits.ResultsIn this work, we systematically explored the design strategy of synthetic transcriptional regulators, termed switchable transcription terminators. Specifically, by redesigning key sequence domains, we created a high-performance switchable transcription terminator with a maximum fold change of 283.11 upon activation by its cognate input RNA. Further, an automated design algorithm was developed for these elements to improve orthogonality for a complex multi-layered circuit construction. The resulting orthogonal switchable transcription terminators could be used to construct a three-layer cascade circuit and a two-input three-layer OR gate.ConclusionsWe demonstrated a practical strategy for designing standardized regulatory elements and assembling modular gene circuits, ultimately laying the foundation for the streamlined construction of complex synthetic gene circuits.

Crystal structure, magnetic property and cryogenic magnetocaloric effect of Gd4Al2O9 aluminate

Developing magnetic materials with excellent magnetocaloric effect (MCE) is a vital prerequisite for practical magnetic refrigeration (MR) applications. Herein, a single-phased polycrystalline Gd4Al2O9 compound was fabricated using the co-precipitation method, and its structure, magnetic property together with magnetocaloric performance were investigated. The Gd4Al2O9 compound was found to crystallize in the monoclinic structure space group P21/c with lattice parameters a = 7.4852 Å, b = 10.5561 Å, c = 11.1774 Å, β = 108.95° and V=835.3107 Å3, and the constituent elementals had valence states of Gd3+, Al3+ and O2−. Excellent comprehensive MCE performance was observed for the Gd4Al2O9 compound in low-temperature regions. The obtained values of maximal magnetic entropy change, temperature-averaged entropy change (3 K) and relative cooling power under the magnetic flux density change of 0–7 T are 26.31 J/kg·K, 25.09 J/kg·K and 317.05 J/kg. The Gd4Al2O9 compound shows impressive comprehensive MCE performances compared with some recently reported rare earth-based MR materials with prominent performances, meaning that it is a suitable candidate material for low-temperature MR applications.

Structure, Optical Properties and Magnetocaloric Effects in Gd3Fe5O12 Garnet Synthesized by Solid State Method

In this work, gadolinium iron garnet (Gd3Fe5O12) was synthesized using the solid-state ceramic method. The structural analysis, confirmed through Rietveld refinement, indicated the formation of a single-phase garnet structure. Scanning electron microscopy studies revealed uniform grain size and homogeneity in the sintered material, while UV-vis absorption studies showed a peak at 300 nm, indicating strong ultraviolet interaction and an optical band gap of 3.64 eV, suggesting optoelectronic potential. The fluorescence emission spectrum shows a band at 435 nm, while the excitation spectrum exhibits bands at 275 and 360 nm. The magnetic measurements demonstrated Gd ion ordering at low temperatures, with a compensation temperature around 290 K. Arrott plots confirmed the second-order magnetic phase transition. Importantly, Gd3Fe5O12 exhibited both normal and inverse magnetocaloric effects, with a maximum magnetic entropy change of 1.05 J kg–1 K–1 at 230 K under 9 T magnetic field. These properties indicate Gd3Fe5O12 material as a promising candidate for magnetic refrigeration and optoelectronic applications.

Discovery of a blood-based miRNA signature that can predict onset of active tuberculosis among household contacts of TB patients

BackgroundNon-sputum based predictive biomarkers capable of identifying individuals with high risk of progression to active tuberculosis (TB) are critical for global TB control. MicroRNAs (miRNAs) are significant regulators involved in TB pathogenesis and hence we aimed to identify a miRNA signature capable of predicting progression to TB disease.MethodsWe compared the differential miRNA expression profile of QuantiFERON supernatants of TB Progressors, defined as healthy household contacts (HHCs) of TB patients, who developed active TB disease during a 2-year follow-up period, and Non-progressors defined as HHCs from the same longitudinal cohort who did not develop TB disease during the entire follow-up period, using the nanostring nCounter platform. Receiver Operator Characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the identified miRNA biomarkers, followed by random forest analysis to determine the best predictive model.ResultsWe identified 30 differentially regulated miRNAs between the two groups. Of these, hsa-miR-585-3p and hsa-miR-92a-3p were up-regulated with a maximum fold change of 1.74 and 1.71 respectively, while hsa-miR-223-3p and hsa-miR-451a were down-regulated by −2.05 and −2.04 fold respectively. Random forest analysis revealed that hsa-miR-181a-5p, hsa-miR-204-5p, hsa-miR-197-3p, hsa-miR-92a-3p, hsa-miR-451a, hsa-miR-24-3p, and hsa-miR-487a-3p exhibited 100% accuracy in identifying Progressors. This panel of 7 miRNAs demonstrated excellent diagnostic performance characteristics with 100% sensitivity and specificity.ConclusionWe propose that the identified miRNA signature has the potential to serve as a very useful tool for early identification of individuals who bear the highest risk of progression to TB, so that they can be targeted for timely intervention.

Worse arterial pressure reservoir capacity is associated with exacerbated hemodynamic response to capnogram changes and more labile intraoperative cardiopulmonary-metabolic coupling

Abstract Background The apparent promise of capnography as a cardiac monitor based on the coupled cardiopulmonary response to metabolic changes remains hampered by inconsistent results in studies investigating previous correlations between hemodynamics (e.g.cardiac output) and end-tidal CO2 (EtCO2).(1,2,3) Excess pressure (Pexcess), a dynamic sub-component of pressure waveform representing pressure beyond buffering capacity (reservoir pressure) of elastic large arteries, strongly correlates with aortic flow in humans, suggesting the Pexcess as a promising tool for non-invasive hemodynamic monitoring.(4,5) Purpose We aimed to clarify potential cofounders and pathophysiological mechanisms modifying the EtCO2-arterial hemodynamic coupling, by analysing the intra-operative temporal relations of paired reservoir-excess and capnogram parameters Methods In 190 patients with normal pre-operative pulmonary function tests who underwent non-cardiac surgery, simultaneous capnogram and intra-arterial pressure signals were analysed off-line. Signal windows (>2 minutes) of maximum and minimum mean arterial pressure were autoidentified, the capnogram and pressure signals were averaged into a single representative cycle, to extract reservoir-excess pressure and capnogram parameters (EtCO2, expiratory slope, alpha slope, and plateau slope) accordingly.(6,7) Arterial reservoir capacity (ARC) was defined as Preservoir/Pexcess, which was used to stratify patients into quartiles. Relationships between maximum changes in capnogram and pressure parameters were analysed (Figure 1). Results The ΔEtCO2 and ΔPa mean were correlated significantly in all groups. In patients with the highest ARC (Q4), Pexcess remained unaltered in response to ΔEtCO2 (r:0.095 p:0.545), unlike other subgroups with significant positive correlations. In Q4 (the highest ARC group), the increment in Preservoir was the main cause of ΔPa in relation to ΔEtCO2. In contrast, the ΔEtCO2 - ∆Pexcess relationship was most pronounced in the group with the poorest ARC (r:0.634 p:0.005), underlying the significance of the pressure reservoir behaviour as a determinant of metabolic oscillations in arterial hemodynamics, even though the changes in ΔEtCO2 were equivalent.(Figure 2) Conclusion(s) Worse arterial pressure reserve capacity is associated with an exacerbated hemodynamic response to capnogram changes and a more labile cardiopulmonary-metabolic coupling, characterised by a pronounced increase in excess pressure in response to increased EtCO2 in patients with low ARC. Substantial Pa alterations accompanying EtCO2 changes had opposite drivers in low and high ARC groups (predominant augmentation of Preservoir vs Pexcess). Utilisation of the capnogram for cardiac hemodynamic monitoring is substantially affected by ARC, hence it should be considered while developing capnogram-based monitoring indices.Figure 1.Methodology and example casesFigure 2.Main results

Acute hemodynamic effect of oral ketones in patients with acutely decompensated heart failure and low cardiac output syndrome: a prospective randomized study.

Abstract Background Preliminary studies showed positive inotropic effect of mild ketosis in patients with heart failure with reduced ejection fraction (HFrEF). Purpose To evaluate the acute hemodynamic effect of oral administration of beta-hydroxybutyrate (OHB) in patients with HFrEF and low cardiac output syndrome. Methods Patients with acutely decompensated HFrEF treated with inotropic therapy were randomized (1:1) to enteral bolus of OHB (25g of OHB monoester in 65 ml of solution; H.V.M.N Ketone Ester, H.V.M.N, USA) administered three times with 3-hour intervals or to euvolemic placebo. The serum concentration of OHB, biochemical markers, and invasive hemodynamics (Swan-Ganz catheter with continuous thermodilution) were repeatedly measured before and during 24 hours after administration of OHB. The primary endpoint was the maximum change in cardiac index (CI). Results The study included 20 patients with decompensated HFrEF (age: 57 ± 8 years; left ventricular ejection fraction: 21 ± 4%; non-ischemic cardiomyopathy: 16 [80%], median INTERMACS class: 3 [IQR 2 - 4]), who were treated with milrinone (0.5 ± 0.1 ug/kg/min, n=18) or levosimendan (0.1 ug/kg/min up to 25 mg, n=2). Patients in the OHB group (n = 10) did not differ from the placebo group (n = 10) in baseline clinical, biochemical, hemodynamic or echocardiographic characteristics. Baseline OHB concentration was normal (<0.6 mmol/L) in all patients. Administration of OHB increased serum concentration from 0.3 ± 0.2 mmol/L to a maximum of 2.4 ± 0.7 mmol/L (<0.001). Concentrations of OHB peaked at 1.5 ± 0.5 hours after administration of each OHB drink, and the maximum concentration was achieved at 4.1 ± 2.5 hours (Figure 1). No changes in OHB concentration were observed in the placebo group. In both study groups, there was a significant increase of CI at 3 hours compared to baseline, but the increase was significantly greater in the OHB group (OHB: 3.2 ± 0.6 vs. 2.1 ± 0.4 L/min/m2; placebo: 2.3 ± 0.4 vs. 2.0 ± 0.3 L/min/m2; both p<0.001 compared to baseline; p < 0.001 for OHB vs. placebo at 3 hours). The maximum relative increase of CI was 60 ± 24% in the OHB group (p <0.001) and 18 ± 8% in the placebo group (p< 0.01). The change of CI correlated with the change of OHB concentration in the OHB group (r = 0.58, p<0.001) but not in the placebo group (r = 0.1, p = 0.3). The changes in CI were not related to heart rate or concentration of norepinephrine, which did not change significantly throughout the study in both groups. Conclusion Oral administration of OHB leads to a significant temporary increase in myocardial contractility. This novel therapeutic concept might be a promising adjunction to inotropic support in patients with decompensated HFrEF.

Optimizing Room‐Temperature Thermoelectric and Magnetocaloric Performance via Constructing Multi‐Scale Interfacial Phases in LaFeSi/BiSbTe Thermo‐Electro‐Magnetic Refrigeration Materials

AbstractFabricating a thermo‐electro‐magnetic material that exhibits simultaneously excellent magnetocaloric (MC) and thermoelectric (TE) performance is challenging since the interfacial reaction causes severe deterioration of MC and TE performance. In this work, a construction of multi‐scale interfaces in LaFe10.4Co0.8Si1.8/Bi0.5Sb1.5Te3 (LFS/BST) composites is realized by adopting a low‐temperature high‐pressure sintering strategy. It is revealed in the atomic‐scale that the interfacial reaction between LFS and BST leads to the formation of (Fe,Co)(Sb,Te)2 micro‐grains and LaTe2 nano‐grains, and the latter form low‐mismatch phase boundaries with LFS matrix. Benefiting from the multi‐scale interfacial phases, excellent MC performance of LFS is preserved alongside a minor impact on TE properties, e.g., a peak zT of 1.04 and a small decrease of 3.0% in relative cooling power are achieved in the 2%LFS/BST composite. Compared with other thermo‐electro‐magnetic materials, a good trade‐off between MC and TE performance is realized in LFS/BST composites with simultaneously high MC and TE performance. The 20%LFS/BST composite exhibits a room‐temperature zT of 0.46 with large maximum magnetic entropy change and relative cooling power of 0.81 J kg−1 K−1 and 44.83 J kg−1, respectively. This work provides an effective material design for developing the all‐solid‐state MC/TE hybrid refrigeration technique.

Magnetocaloric and Magnetostrictive Properties of the Tb(Co,In)<sub>2</sub> Laves Phases

Multicomponent polycrystalline TbInxCo2–x (with х = 0–0.2) solid solutions are prepared for the first time, and their crystal structure and magnetic, magnetocaloric, and magnetostrictive properties are studied. X-ray diffraction patterns taken at room temperature demonstrate mainly the presence of the cubic C15 Laves phase in all samples. As the indium content increases to x = 0.1, the lattice parameter is found to increase; the further increase in the indium content to х = 0.2 leads to a decrease in the lattice parameter. In this case, the Curie temperature TC monotonically increases to 245 K. The isotheral magnetic entropy change ΔSmag is calculated in accordance with magnetic measurements using the thermodynamic Maxwell’s relation. At a magnetic field change from 0 to 1.8 T, the maximum entropy change monotonically decreases and, for composition with x = 0.2, is 1.8 J/(kg∙К). As the indium content increases to x = 0.05, the volume magnetostriction increases. The further increase in the indium concentration leads to the decrease in the peak values and their shift to high temperatures.

Effect of obstruction ratio rate of change gradients on the deflagration characteristics of H2-Air premixed gases

To investigate the effect of the gradient of obstruction ratio change rate on the H2-Air premixed gas combustion explosion in the semi-confined space, Fluent software is used to simulate the explosion flame, turbulent turning and pressure wave coupling process under the conditions of obstacles with different obstruction ratios change rate. The results indicate that as the obstruction ratio's rate of change increases, flame propagation speed decreases, while pressure peak and pressure change rate increase. The flame front becomes sharper, and a positive change in obstruction ratio more significantly affects flame shape and speed than a negative change. At obstruction ratio change rates of −0.3 and −0.2, the flame front area and peak area reach their maximum values. At a change rate of 0.3, the pressure peak is 232 kPa, and the maximum pressure change is 126 kPa/ms, indicating the explosion intensity reaches its peak.

Modified throughput ninhydrin method for the qualitative assessment of dietary protein absorption in pig plasma

Abstract Background Protein maldigestion and malabsorption lead to malnutrition and are a feature of exocrine pancreatic insufficiency (EPI). Although it is the current standard, measurement of nitrogen in stool to assess protease activity is indirect. Up to 80% of hydrolysed proteins appear in blood in the form of peptides so we developed a method to measure peptide-derived amino acids in plasma as a relevant measure of proteolysis, verified its accuracy, precision, and linearity, and validated it in a porcine model. Materials and Methods We modified a ninhydrin method. Large proteins were eliminated from plasma with 10 kDa-cut-off centrifugal filters. Free and total amino acids were measured in permeate before and after its hydrolysis. Peptide-derived amino acids were quantified by subtracting free amino acids from total amino acids. We verified the method in vitro and by comparing results in healthy and EPI pigs. Results The accuracy of the analysis was close to 100%, with excellent precision (mean relative standard deviation for low, medium and high amino acid levels = 0.88%) and with stringent linearity (r2=0.986, %RE =5.23). The high-throughput ninhydrin method detected levels of peptide-derived amino acids in vivo with maximal changes seen approximately 2 hours postprandially in young pigs. The AUC and Cmax were significantly higher in healthy compared to EPI pigs (p = 0.0026 and p = 0.0037, respectively). Conclusions The high-throughput ninhydrin method is a sensitive, reliable, and practical method for the estimation of dietary peptide-derived amino acids. This assay endpoint could serve as a direct biomarker of protein digestion and absorption.

Finite element study of stress distribution in medial UKA under varied lower limb alignment

Knee osteoarthritis (KOA) has a high incidence among the elderly, significantly impacting their quality of life and overall health. Medial unicompartmental knee arthroplasty (UKA) is an excellent choice for treating knee single-compartment lesions, and lower limb alignment has a profound impact on medial UKA. To explore the influence of different lower limb alignments on medial UKA. In this study, we selected MR and CT data of healthy adult male knee joints to establish a complete finite element analysis (FEA) model of the knee joint. After validation, we established a finite element model of medial UKA. Subsequently, we created 60 sets of FEA models with different lower limb alignments to analyze the impact of different lower limb alignments on medial UKA. A vertical load of 1000 N was applied to the FEA models with different lower limb alignments. During the process of shifting the Mikulicz line from the midpoint of the knee joint towards the medial side, the lower limb load was primarily concentrated on the medial compartment. The stress values of the lateral meniscus, tibial cartilage, and femoral cartilage gradually decreased. ROI (region of interest) 1 and ROI 2 showed the maximum principal strain changes, while ROI 3 and ROI 4 exhibited less pronounced fluctuations, with the maximum principal strain roughly proportionally increased. During the process of shifting the Mikulicz line towards the lateral side from the midpoint of the knee joint, the stress on the lateral compartment increased observably. ROI 1, ROI 2, ROI 3, and ROI 4 showed decreased maximum principal strains, approximately inversely proportional changes, but the overall reduction was relatively small. Different lower limb alignments have a profound impact on the short- and long-term joint function after UKA. When the Mikulicz line is 10 mm inside the midpoint of the knee joint or slightly outside, there is a relatively lower risk of tibial component fractures, lower stress on the lateral compartment, and lower load on the prosthesis. During medial UKA, measures such as bone resection and prosthesis selection should be taken to ensure that the Mikulicz line is in the ideal position.

Excellent Magnetocaloric Properties near 285 K of Amorphous Fe88Pr6Ce4B2 Ribbon

A novel amorphous Fe88Pr6Ce4B2 ribbon with better magnetocaloric properties near 285 K is reported in the present work. The Fe88Pr6Ce4B2 ribbon exhibits a typical second-order ferromagnetic–paramagnetic transition near its Curie temperature (Tc, ~284 K), with a maximum magnetic entropy change (−ΔSmpeak) of ~4.15 J/(kg × K) under 5 T and a maximum adiabatic temperature rise (ΔTad) of ~2.57 K under 5 T, both of which are almost the largest amongst the iron-based metallic glasses with Tc = 285 ± 10 K. The high −ΔSmpeak enables several amorphous hybrids with table-like −ΔSm–T curves to be synthesized by appropriately proportioning the Fe88Pr6Ce4B2 ribbon and other amorphous ribbons with different Tc. The larger average −ΔSm and effective refrigeration capacity, as well as the appropriate temperature range, make the two amorphous hybrids potential candidates for use as refrigerants in household magnetic air conditioners.

Magnetic properties and magnetocaloric effect in thiospinel Fe1-xCuxCr2S4 (x = 0.0, 0.5) compounds

In this study, we investigate the magnetic and magnetocaloric properties of Cr-based spinel sulphides Fe1-xCuxCr2S4 (x = 0.0 and x = 0.5). The magnetic transition temperature of FeCr2S4 (176 K) increases to 330 K when 50 % of Fe in FeCr2S4 structure is substituted with Cu. Temperature-dependent Zero-Field-Cooled (ZFC) and Field-Cooled (FC) magnetic moment measurements show a paramagnetic (PM) to ferrimagnetic (FiM) phase transition in our samples. Magnetocaloric properties were investigated through magnetization isotherm measurements. The maximum magnetic entropy change values are −2.78 J/kg. K and −2.11 J/kg. K under 5 T magnetic field, for x = 0 and x = 0.5 in Fe1-xCuxCr2S4, respectively. Analysis of phenomenological universal curves and Arrott plots indicate a second-order magnetic transition for both compounds. Consequently, Fe0.5Cu0.5Cr2S4 emerges as a promising candidate for magnetic refrigeration applications due to its considerable high magnetic entropy change and its proximity to room temperature transition.

Diagnostic Value of Magnetocardiography to Detect Abnormal Myocardial Perfusion: A Pilot Study.

Magnetocardiography (MCG) is a novel non-invasive technique that detects subtle magnetic fields generated by cardiomyocyte electrical activity, offering sensitive detection of myocardial ischemia. This study aimed to assess the ability of MCG to predict impaired myocardial perfusion using single-photon emission computed tomography (SPECT). A total of 112 patients with chest pain underwent SPECT and MCG scans, from which 65 MCG output parameters were analyzed. Using least absolute shrinkage and selection operator (LASSO) regression to screen for significant MCG variables, three machine learning models were established to detect impaired myocardial perfusion: random forest (RF), decision tree (DT), and support vector machine (SVM). The diagnostic performance was evaluated based on the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Five variables, the ratio of magnetic field amplitude at R-peak and positive T-peak (RoART+), R and T-peak magnetic field angle (RTA), maximum magnetic field angle (MAmax), maximum change in current angle (CCAmax), and change positive pole point area between the T-wave beginning and peak (CPPPATbp), were selected from 65 automatic output parameters. RTA emerged as the most critical variable in the RF, DT, and SVM models. All three models exhibited excellent diagnostic performance, with AUCs of 0.796, 0.780, and 0.804, respectively. While all models showed high sensitivity (RF = 0.870, DT = 0.826, SVM = 0.913), their specificity was comparatively lower (RF = 0.500, DT = 0.300, SVM = 0.100). Machine learning models utilizing five key MCG variables successfully predicted impaired myocardial perfusion, as confirmed by SPECT. These findings underscore the potential of MCG as a promising future screening tool for detecting impaired myocardial perfusion. ChiCTR2200066942, https://www.chictr.org.cn/showproj.html?proj=187904.

Thermodynamic analysis of the inverse electrocaloric effect in ferroelectric thin films

Abstract Inverse electrocaloric (i-EC) effect occurs in ferroelectrics when the applied electric field aligns anti-parallel to polarization. In this study, the dependence of the i-EC effect on temperature and misfit strain is formulated and applied to clamped BaTiO3 thin films using the Landau–Ginzburg–Devonshire formalism. It is found that an interplay exists between the pyroelectric coefficient and the maximum possible inverse electric field. We demonstrate that the temperature change is strongly dependent on the inverse field amplitude and is maximal at lower temperatures away from the ferroelectric-paraelectric transition for a given misfit strain. Such an outcome is opposite to the direct electrocaloric effect, where it is desirable to remain near the transition temperature for the maximum electrocaloric temperature change. The fact that the i-EC effect can be maximum at lower temperatures could allow for the potential tailoring of this effect in strained films at moderate temperatures for device applications.

Electrode Materials for NO Electroreduction Based on Dithiolene Metal–Organic Frameworks: A Theoretical Study

To quickly and efficiently screen catalytic materials with both activity and selectivity for the nitric oxide reduction reaction (NORR), we adopted a strategy that considers the activity of the side reaction hydrogen evolution reaction (HER) first. It can be seen that Fe3(THT)2 (THT = triphenylene-2,3,6,7,10,11-hexathiol) has extremely excellent HER activity, with a Gibbs free energy change (ΔG) of 0.007 eV. Based on the relationship between ΔG and theoretical exchange current density, all TM3(THT)2 can be divided into two regions: one is the absolute values of ΔG greater than 1 eV, the other is the absolute values of ΔG greater than 0 eV and less than 1eV. Obviously, the candidates with the absolute values of ΔG greater than 1 eV have poor HER performance, but this precisely provides the possibility of obtaining NORR catalytic materials with both excellent selectivity and activity. Subsequent calculation results show that the maximum ΔG change of the rate-determining step of Ta3(THT)2 is unexpectedly only 0.05 eV. Therefore, Ta3(THT)2 may be regarded as the NORR catalytic material with both excellent performance and selectivity. Based on the electron transfer and partial density of states (PDOS) analysis, it can be seen that Ta plays a crucial role in the activation stage of NO. The approach that considers the activity of the side reaction HER first may provide a new idea for rapidly screening highly selective and active NORR catalysts.

Frozen and unfrozen moisture content estimation in coral calcareous sand during artificial freezing

In tropical areas where coral calcareous sands are prevalent, artificial freezing techniques are frequently employed during construction. However, the fundamental thermodynamic behaviors and moisture dynamics of calcareous sands under freezing conditions are poorly understood. Therefore, we conducted laboratory tests and developed a numerical model to capture the total moisture, liquid water, and ice contents of calcareous sand during artificial freezing. The thermal fiber Bragg grating (T − FBG) and frequency − domain reflectometry methods were used in the study. Freezing characteristic curves were quantitatively analyzed with taking into account the initial moisture content and ambient temperature. The results indicate that T − FBG effectively estimates the total moisture content in unfrozen and frozen calcareous sand, as well as ice content in frozen soil, with less than 0.029 m3/m3 error. Ice melting induced by T − FBG heating is affected by the initial moisture content, heating duration, power, and ambient temperature. However, the maximum change is below 0.008 m3/m3, which is negligible. The van Genuchten model accurately describes the liquid moisture–temperature relationship of unsaturated calcareous sand, with an R2 exceeding 0.98. The residual–initial moisture content relationship follows a quadratic function. During freezing, the temperature reduction aligns with the Kozlowski model, and the liquid moisture–temperature relationship follows a cubic polynomial function.

Effects of Eu3+ doping on the structural, magnetocaloric effect and critical behavior of Ruddlesden-Popper compounds La1.4-xEuxSr1.6Mn2O7 (0 ≤ x ≤ 0.1)

The effects of Eu3+ doping on the structural and magnetocaloric effect of Ruddlesden-Popper compounds La1.4-xEuxSr1.6Mn2O7 (0 ≤ x ≤ 0.1) were investigated. The X-ray diffraction and infrared spectroscopy confirmed that La1.4-xEuxSr1.6Mn2O7 compounds exhibited the tetragonal lattice symmetry (I4/mmm) of the Ruddlesden-Popper phase. The crystal structure of La1.4-xEuxSr1.6Mn2O7 compounds distorted and phase separated as the amount of Eu3+ doping varied. The magnetization-temperature curves demonstrated that La1.4-xEuxSr1.6Mn2O7 compounds display a notable transition temperature attributed to its anisotropic exchange coupling. The maximum magnetic entropy changes (−ΔSMmax) of La1.4-xEuxSr1.6Mn2O7(x = 0, 0.075, and 0.1) compounds are 2.82, 3.12 and 3.40 J/(kg·K) at the 5 T applied magnetic field. Meanwhile, its relative cooling power (RCP) was 186.37, 207.42 and 242.54 J/kg, respectively. The critical behavior of La1.4-xEuxSr1.6Mn2O7 (0≤x≤0.1) compounds was analyzed around Tc, and it was found that the critical index (β = 0.413, γ = 1.020, δ = 3.038) is essentially in line with the mean field theory.

Phase 2 Trial of Vosoritide Use in Patients with Hypochondroplasia: A Pharmacokinetic/ Pharmacodynamic Analysis.

Vosoritide is a C-type natriuretic peptide (CNP) analog that binds its receptor on chondrocytes, promoting growth by inhibiting the ERK1/2-MAPK pathway. We previously reported the results of a Phase II study in children with hypochondroplasia. Vosoritide led to an average increase in annualized growth velocity (AGV) of 1.81 cm/year and gain of 0.36 in height SD over 12 months. We present here the pharmacokinetic/ pharmacodynamic (PK/PD) data from this study and examine the correlations between these parameters and growth outcomes. We conducted a Phase II trial of daily subcutaneous vosoritide (15 mcg/kg/day) in 24 prepubertal subjects with hypochondroplasia (12 females, mean age 5.9+/-2.3 years, mean height -3.29+0.68 SD). Plasma vosoritide levels were assayed using an electrochemiluminescence assay. Pharmacodynamic markers including serum collagen X biomarker (CXM) and urine cGMP production were measured at Day 1, Month 6 and Month 12 visits. Pearson correlations and regression analyses were performed between PK and PD parameters and growth outcomes. Vosoritide PK parameters were similar to those previously reported in patients with achondroplasia. CXM levels increased from a baseline mean of 22.5±6.5 to 41.6±15.9 ng/ml after 12 months of treatment (p < 0.0001). Urine cGMP increased within 1 hour and peaked at 2 hours after injection. The mean AUC for cGMP production was not significantly different at each study visit. The maximum change in cGMP AUC correlated with PK AUC ((r=0.46, p=0.0001). However, drug exposure, as measured by average PK AUC, did not correlate with any growth outcome. CXM levels correlated with the prior 6-month interval height velocity (partial correlation coefficient=0.40, p=0.0048). However, change in CXM did not correlate with change in height velocity or change in height SD during treatment. Vosoritide treatment showed improvement in AGV and height SD in children with hypochondroplasia. PK analysis indicates that drug exposure was correlated to global CNP activity as measured by urine cGMP but did not correlate with growth outcomes. More studies are needed to identify specific patient characteristics that can predict response to therapy and clinical outcomes.

Carbon ion beam dosimetry in magnetic fields using Farmer-type ionization chambers of different radii: measurements and simulations

Objective.To investigate magnetic field effects on the dose distribution and ionization chambers response in carbon ion reference fields and determine magnetic field correction factors for chambers of different volumes.Approach.The response of six Farmer-type chambers with varying radii (1-6 mm, termed as R1-R6) was measured in magnetic fields up to 1 T in 0.1 T increments using an experimental electromagnet and compared with Monte Carlo simulations. Chamber readings were measured in the entrance region of a monoenergetic carbon ion beam of 390.75 MeV u-1. A lower energy of 200.28 MeV u-1was applied to chamber R3 for comparison. Polarity and recombination corrections were investigated for the R3 chamber. The local dose change induced by the magnetic field was calculated by Monte Carlo, which together with change of the chamber's response, was used to calculate the final magnetic field correction factors.Main results.The dependence of the chamber response on the magnetic field was non-linear and volume-dependent. Maximum changes ranged from 0.30% (R4) to 0.62% (R5) at 0.2 T. For R3, the response for the lower energy was systematically decreased by 0.2% in the range of 0.2 T to 0.7 T. No significant effect of the magnetic field on polarity and ion recombination correction was found. The maximum variation of the local dose was found to be (0.03 ± 0.08) % at 0.2 T for beam energy of 390.75 MeV u-1. Magnetic field correction factors for the different chambers ranged from 0.28% (R4) to 0.60% (R5).Significance.This study provides the first detailed analysis of chambers' response to magnetic flux densities of up to 1 T using chambers of different radii and comparison with simulations. By combining the chamber response alterations with local dose changes magnetic field correction factors were calculated for all six chambers, including the commercial Farmer-type chamber.