Successive Injections Research Articles

Peri-levator Betamethasone Versus Triamcinolone Injection in Management of Thyroid Eye Disease-related Upper Eyelid Retraction Without Proptosis.

To compare the efficacy of peri-levator injection of both betamethasone and triamcinolone in the management of thyroid eye disease-related upper eyelid retraction without proptosis. This prospective, double-blind, randomized clinical trial was conducted at Assiut University Hospital, Upper Egypt in the period between December 2021 and October 2023. The study included 47 patients (56 eyes) and was divided into 2 groups. In group A, 1 ml betamethasone was injected into the peri-levator area, while in group B, 1 ml triamcinolone was injected. The injection was repeated every month for up to 5 injections if there was an improvement in margin reflex distance 1 (MRD1). The injection was stopped if MRD1 reached the normal value or if 2 successive injections caused no improvement in MRD1. The postinjection outcome was divided into: 1) effective if MRD1 reached the normal ≤4.5 mm; 2) partially effective if MRD1 was improved but did not reach the normal; and 3) ineffective if there was no improvement in MRD1. The follow up ranged from 6 to 20 months. In group A, the injection was effective in 26 eyes (92.9%) and partially effective in 2 eyes (7.1%). In group B, the injection was effective in 17 eyes (60.7%), partially effective in 6 eyes (21.4%), and ineffective in 5 eyes (17.9%). The mean number of injections was significantly lower in group A than in group B: 1.61 ± 0.50 versus 2.36 ± 1.16. This study results suggest that betamethasone is more effective with a smaller number of injections than triamcinolone in the management of thyroid eye disease-related upper eyelid retraction.

Chronological Management of Adjuvant Effect for Optimized mRNA Vaccine Inspired by Natural Virus Infection.

The efficacy and safety of mRNA vaccines both rely on a fine-tuning of specific humoral and cellular immune responses. Instead of adjustments in vaccine component, we proposed a concept of chronological management of adjuvant effect to modulate the adaptive immune potency and preference inspired by natural virus infection. By simulating type I interferon expression dynamics during viral infection, three vaccine strategies employing distinct exposure sequences of adjuvant and mRNA have been developed, namely Precede, Coincide, and Follow. Follow, the strategy of adjuvant administration following mRNA, effectively suppressed tumor progression, which was attributed to enhanced mRNA translation, augmented p-MHC I expression, and elevated CD8+ T cell response. Meanwhile, Follow exhibited improved biosafety, characterized by reduced incidences of cardiac and liver toxicity, owing to its alteration to the vaccination microenvironment between successive injections. Our strategy highlights the importance of fine-tuning adjuvant effect dynamics in optimizing mRNA vaccines for clinical application.

Geochemical characteristics and genesis of niobium–yttrium–fluorine granite pegmatite from Hmrat El Sorwhyia area, North Eastern Desert, Egypt

The granite pegmatites of Hmrat El Sorwhyia, situated in the northern Egyptian-Nubian Shield, are predominantly hosted within the central areas of syenogranitic bodies, with limited occurrences noted along the marginal sites. The Hmrat El Sorwhyia granitic pegmatites represent a notable example of rare-metal mineralisation. This study introduces novel bulk- rock compositions, including major, trace, and rare earth elements, to investigate and constrain the origin and mechanisms influencing the genesis of the Hmrat El Sorwhyia granitic pegmatites and their rare-metal mineralisation. The studied pegmatites exhibit diverse morphologies, featuring lenticular pockets that contain the highest radioelement concentrations. The maximum (equivalent uranium) eU value is 760 ppm while the maximum (equivalent thorium) eTh value is 5552 ppm. These pegmatites have granitic composition and peraluminous characteristics, indicative of A-type affinity associated with post-collisional tectonic settings, and are categorised as niobium–yttrium–fluorine-type pegmatites. The formation of granite pegmatites through fractional crystallisation during the late-stage magmatic processes involved the concentration of U, Th, rare earth elements, Zr, Y, and Nb. This concentration facilitated the crystallisation of thorite, uranothorite, columbite, cerianite, and zircon. Additionally, assimilation-fractional crystallisation mechanisms led to the exchange of accessory phases between successive injections of pegmatite and the surrounding wallrock, resulting in variable mineral concentrations. These open-system processes were responsible for the development of these pegmatites.

Оценка нестабильности последовательных впрыскиваний топливной аппаратуры дизелей

The issues of uneven cyclic feed in sequential injections by diesel fuel equipment are considered, which is directly related to solving the problem of ensuring the quality of operation of engines of various types and purposes when operating at low loads and rotational speeds. The special importance of solving these problems from the standpoint of ensuring fuel efficiency, environmental pollution, solving issues of engine reliability and improving their operational properties was noted. The features of the formation of residual fuel pressure in the high-pressure pipeline are revealed. The periodic fluctuations of the cyclic feed and injection parameters from cycle to cycle are estimated. A study of possible options for the operation of fuel equipment in low fuel supply modes has been carried out. Based on the analysis, a criterion for evaluating the instability of successive injection cycles for diesel fuel equipment during its operation in various modes has been introduced. By studying numerical examples, the conditions of unstable fuel supply processes in successive injections of various characteristic modes are determined. The criterion determines the quality of the fuel equipment of marine diesel engines and diesel generators in terms of ensuring a minimum stable idle speed and the possibility of ensuring stable reduced fuel supplies. The variability of fuel supply processes in sequential feeds is the cause of increased exchange processes of electric power flow during parallel operation of diesel alternators and reduces the performance characteristics of diesels for various purposes when operating in partial modes. In the process of carrying out development work, scientific research and during the refinement of diesels, the instability criterion allows us to assess the quality of the fuel equipment precisely in partial modes. This is of particular importance for diesel engines of fishing vessels operating for a long time at shared loading modes and low idle speeds, as well as for engines of the tugboat fleet and auxiliary diesel generator sets of all types of facilities used.

Cyclin-dependent kinase 5 as a potential therapeutic target to alleviate high glucose-induced podocyte apoptosis and hyperglycemia-induced renal injury in mice.

Hyperglycemia is a risk factor for impaired renal function, including cellular metabolic disturbance, apoptosis, inflammation, and histologic lesion. This study aims to investigate the potential therapeutic targeting of cyclin-dependent kinase 5 (Cdk5) in hyperglycemia-induced podocyte dysfunction and renal damage. Cell viability and apoptosis of podocytes were assessed through CCK-8 and TUNEL staining, respectively, following exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with Cdk5 inhibitors (trans-resveratrol, myricetin, salvianolic acid A, and BML-259). Diabetic mice were established by intraperitoneal injection of freshly streptozotocin (STZ), which was given at a dose of 35 mg/kg in five successive injections. Additionally, histochemical staining was employed to evaluate the morphologic lesion of the kidney. Cdk5 was found to be activated by HG stimulation both in vitro and in vivo. Notably, the inhibition of Cdk5 effectively mitigated the podocyte dysfunction induced by HG, including growth inhibition, membrane damage, and apoptosis. The compounds Trans-resveratrol, myricetin, salvianolic acid A, and BML-259 exhibited low binding energy values of -8.032 kcal/mol, -8.693 kcal/mol, -8.743 kcal/mol, and -10.952 kcal/mol, respectively, indicating strong and stable binding affinity between these candidates and Cdk5. The results of in vivo experimental analysis demonstrate that Cdk5 inhibitors, namely trans-resveratrol, myricetin, salvianolic acid A, and BML-259, confer protection against tubular and glomerular lesions induced by hyperglycemia. Both myricetin and BML-259 exhibit comparable protective effects on renal injury by inhibiting Cdk5.

Archaeal community composition as key driver of H2 consumption rates at the start-up of the biomethanation process

The performance of hydrogen consumption by various inocula derived from mesophilic anaerobic digestion plants was evaluated under ex situ biomethanation. A panel of 11 mesophilic inocula was operated at a concentration of 15 gVS.L−1 at a temperature of 35 °C in batch system with two successive injections of H2:CO2 (4:1 mol:mol). Hydrogen consumption and methane production rates were monitored from 44 h to 72 h. Hydrogen consumption kinetics varies significantly based on the inoculum origin, with no accumulation of volatile fatty acids. Microbial community analyses revealed that microbial indicators such as the increase in Methanosarcina sp. abundance and the increase of the Archaea/Bacteria ratio were associated to high initial hydrogen consumption rates. The improvement in the hydrogen consumption rate between the two injections was correlated with the enrichment in hydrogenotrophic methanogens. This work provides new insights into the early response of microbial communities to hydrogen injection and on the microbial structures that may favor their adaptation to the biomethanation process.

Ultrastable Anion Radicals in Ligand-Dimerized Frameworks for Self-Accumulated Electrochemiluminescence.

Electrochemiluminescence (ECL) is a light-emitting process that occurs via an annihilation reaction among energetic radical intermediates, whose stabilities determine the ECL efficiency. In this study, a ligand-dimerized metal-organic framework (MOF) with ultrastable anion radical is designed as an efficient nanoemitter for self-accumulated ECL. Due to the nonplanar structure of perylene diimide (PDI) derivate, two PDI ligands in the framework form a J-dimer unit with a vertical distance of ∼5.74 Å. In cathodic scanning, the ligand-dimerized MOF demonstrates three-step ECL emissions with a gradual increase in ECL intensity. Unlike the decrease in the PDI ligand, the self-accumulated ECL of the MOF was observed with 16.8-fold enhancement due to the excellent stability of radical intermediates in frameworks. Electron paramagnetic resonance demonstrated the ultrastability of free radicals in the designed frameworks, with 82.2% remaining even after one month of storage. Density functional theory calculations supported that PDI dimerization was energetically favorable upon successive electron injection. Moreover, the ECL wavelength is 610 nm, corresponding to the emission of excited dimers. The radical-stabilized reticular nanoemitters open up a new platform for decoding the fundamentals of self-accumulated ECL systems.

Successive data injection in conditional quantum GAN applied to time series anomaly detection

AbstractClassical GAN architectures have shown interesting results for solving anomaly detection problems in general and for time series anomalies in particular, such as those arising in communication networks. In recent years, several quantum GAN (QGAN) architectures have been proposed in the literature. When detecting anomalies in time series using QGANs, huge challenges arise due to the limited number of qubits compared to the size of the data. To address these challenges, a new high‐dimensional encoding approach, named Successive Data Injection (SuDaI) is proposed. In this approach, SuDaI explores a larger portion of the quantum state, compared to the conventional angle encoding method used predominantly in the literature. This is achieved through repeated data injections into the quantum state. SuDaI encoding allows the authors to adapt the QGAN for anomaly detection with network data of a much higher dimensionality than with the existing known QGANs implementations. In addition, SuDaI encoding applies to other types of high‐dimensional time series and can be used in contexts beyond anomaly detection and QGANs, opening up therefore multiple fields of application.

Liposomal factor VIII as an efficient pharmaceutical system for the treatment of hemophilia.

Currently, the most important treatment approach for hemophilia type A is recombinant Factor VIII. However, due to its low retention time in the blood, the patients usually need successive injections. In addition, neutralization of injected proteins by antibodies complicates treatment. We examined the prolongation of the persistence time of injectable FVIII in the blood and the potential effects on survival using promising PEGylated liposomes (PEGLip) utilizing hydrogenated soy phosphatidylcholine (HSPC, Tm= 54.5 ºC) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC, Tm= - 2 ºC). Nanoliposomes with different percentages of PEG (3% and 5%) were obtained via the thin film hydration procedure and extrusion. Liposomal FVIII formulation was prepared and characterization was done. The results revealed that the formulations are in the 80-120 nm range with uniform dispersion, which was confirmed using transmission electron microscopy (TEM) imaging. The phase transition temperature (Tm) of the liposomes was obtained by differential scanning calorimetry (DSC). With an attachment efficacy of approximately 87%, proteins bind non-covalently yet with a strong affinity to the exterior of PEGLip. The final formulations underwent additional examination. No significant change was observed in size, charge, and PDI between the FVIII-conjugated liposomal formulations and their liposomal nanoparticles. The selected formulations were injected into BALB/c mice. The circulation time and potential clotting effectiveness of PEGLip-FVIII are vastly improved over free protein, in non-hemophilic mice. The obtained results showed that using phospholipids with high Tm (HSPC) can improve the hemostatic efficiency of liposomes more than phospholipids with low Tm (POPC).

How Injection History Can Affect Hydraulic Fracturing–Induced Seismicity: Insights from Downhole Monitoring at Preston New Road, United Kingdom

ABSTRACT In August 2019, a multistage hydraulic fracturing (HF) operation was carried out at Preston New Road, United Kingdom. HF caused abundant seismic activity that culminated with an ML 2.9 event. The seismic activity was recorded by a downhole array of 12 sensors located in a nearby monitoring well. About 55,556 events were detected and located in real time during the operation by a service company. In this study, we first improve the number of detections by applying template matching and later calculate the moment magnitude of the associated earthquakes. Then we show that by separately analyzing the periods during and immediately after injection, distinct patterns can be identified. We observe an increase in the delay and decrease in amplitude of peak seismicity during subsequent phases of injection. After injection, the seismicity decay can be described by the Omori–Utsu law. The decay rate tends to slow with each successive injection, in particular during the later injection stages. In addition, the frequency–magnitude distribution evolves from a tapered distribution (lack of large events) to a bilinear distribution (excess of large events). This evolution is gradual, with the corner magnitude increasing with each injection. We interpret these patterns as the result of the combined effect of two factors: (1) the stimulated volume becoming increasingly aseismic and (2) the gradual increase in its size, which increases the probability of triggered events on preexisting faults. More generally, these patterns suggest that seismic activity during injection is strongly influenced by the injection history and is modulated by local conditions such as stress state, fault structure, and permeability.

Simultaneous detection of CA-125 and mesothelin by gold nanoparticles in surface plasmon resonance

The early-stage diagnosis and monitoring of disease evolution is still one of the most challenging tasks in the field of cancer research. Several research have been driven toward the discovery of new cancer biomarkers as well as to the development of biosensors able to detect these biomarkers with high specificity and sensitivity. Many types of cancer have been detected at an advanced stage and, in particular, epithelial ovarian cancer (EOC) has a high incidence of diagnosis in the metastatic stage. This cancer is considered as the most aggressive type of gynecological cancer with a 5-year survival and until now, no specific biomarkers have been identified. Nevertheless, some studies have indicated that mesothelin, a protein overexpressed by tumour cells in the ovary, interacts with the CA-125 biomarker present in the blood system accelerating the metastatic process. Therefore, the simultaneous presence of CA-125 and mesothelin in the blood during the evolution of EOC could be used to diagnose this disease before the metastasis. Therefore, with this motivation, this work aimed at the development of a biosensor capable of simultaneously detecting mesothelin and CA-125 at low concentrations. A biosensor based on the surface plasmon resonance imaging (SPRi) technique was developed and gold nanoparticles (AuNPs) were used in order to enhance the sensitivity. The study analysed successive injections of the biomarkers CA-125 and mesothelin, both in solution (analytical range of 9–120 nM). The limits of detection were obtained for CA-125 and mesothelin, being of 3.03 nM and 13.62 nM, respectively. The biosensor detected mesothelin at a concentration close to the cutoff point for EOC (3 nM) and was able to detect the biomarker CA-125 at 9 nM. Furthermore, the biosensor interacted preferentially and simultaneously with the biomarkers CA-125 and mesothelin incubated in fetal bovine serum. Finally, the use of AuNPs increased the sensor signal for CA-125 detection compared to its direct detection and showed greater selectivity for both biomarkers. Therefore, the biosensor has important characteristics that allow testing with real samples. In a future project, it could be applied in the research of diagnosis and prognosis of EOC.

Unraveling Mechanisms of Highly Efficient Yet Stable Electrochemiluminescence from Quantum Dots.

With CdSe/CdS/ZnS core/shell/shell quantum dots (QDs) as the model system, time- and potential-resolved spectroelectrochemical measurements are successfully applied for studying the general mechanisms and kinetics of electrochemiluminescence (ECL) generation. The rate constant of electron injection from the cathode into a QD to form a negatively charged QD (QD-) increases monotonically from -0.88 V to -1.2 V (vs Ag/AgCl). Mainly due to the deep LUMO of the QDs, the resulting QD- as the key intermediate for ECL generation is structurally stable and possesses very slow spontaneous deionization channels. The latter (the main non-ECL channels) are usually 3-4 orders of magnitude slower than the rate constant of the successive hole injection from an active co-reactant into a QD-. The kinetic studies quantify the internal ECL quantum yield of ideal QD ECL emitters to be nearly identical to that of photoluminescence, which is near unity for the current system. Identification of the key intermediate, discovery of the related elementary steps, and determination of all rate constants not only establish a general framework for understanding ECL generation but also offer basic design rules for ECL emitters.

Ultra-hydrophobic biomimetic transparent bilayer thin film deposited by atmospheric pressure plasma

An open-air atmospheric pressure plasma was used to deposit ultrahydrophobic bilayer coatings. The plasma set-up was tuned, allowing the successive injection in the post-discharge of two monomers. To the best of our knowledge, no study describes the successive deposition by atmospheric plasma of two precursors, which could work in synergy and allow designing composite coatings of high added value. In this study, two liquid precursors were chosen for the deposition of single and bilayer coatings: (i) hexamethyldisiloxane (HMDSO) and (ii) 1H,1H,2H,2H-perfluorooctyltriethoxysilane (pFOTES). Single layer coatings (HMDSO and pFOTES) as well as bilayer coating (HMDSO/pFOTES) were analysed using multiscale techniques: Scanning Electron Microscopy (SEM), profilometer, Atomic Force Microscopy (AFM), Fourier-Transformed Infrared Spectroscopy (FTIR), Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) and drop shape analysis. The bilayer system (HMDSO/pFOTES), resulting from the successive deposition of HMDSO and pFOTES precursors, was confirmed by ToF-SIMS characterization while contact angle measurements highlighted the ultrahydrophobic property of the bilayer: water was fully repelled, with a zero contact angle hysteresis. This resulted from the combination of the multiscale roughnesses of the HMDSO-based and pFOTES based layers, combined with the intrinsic hydrophobicity of the pFOTES layer.

CFD-DEM simulation of aggregation and growth behaviors of fluid-flow-driven migrating particle in porous media

Particle migration with liquid flow is a fundamental problem during the highly efficient development of oil and gas. In this study, the aggregation and growth behaviors of fluid-flow-driven fine particles at the pore scale are investigated by considering their successive injection and migration process based on CFD-DEM. The particle aggregation and growth behaviors within porous media are obtained, by which the particle aggregation growth affects hydraulic properties and the risk of pore clogging are explored. Several experiments of particle injection were also conducted to verify the accuracy of the numerical model. Both simulation results and experimental phenomena illustrate that fine particle are prone to aggregate near the inlet and bottom wall with a discontinuous concentration, and the calculated instantaneous velocities of particle are larger at the outlet and near the wall affected by the deviation of pore size and position. The three modes of migration, aggregation and growth of particles due the successive invasion and deposition are captured at pores, and are mainly divided into independent and dependent growth behaviors based on the presence or absence of deposited particles before the arrival of new-injected particles. Results highlight the effect of injected fluid velocity, fluid viscosity and fine particle concentration on the particle migration and aggregation behaviors and its dependency with the risk of pore clogging, so as to provide theoretical guidance to the prevention of pore clogging in engineering applications.

Diapirs of crystal-rich slurry explain granite emplacement temperature and duration

The mechanism, temperature, and timescale of granite intrusion remain controversial, with wide-ranging implications for understanding continental growth, differentiation, rheology, and deformation dynamics. In this paper we present a method for determining intrusion emplacement temperature and timescale using the characteristics of the surrounding metamorphic aureole, and apply it to the Skiddaw granite in northern England. The estimated emplacement timescale (0.1–2 Myr) implies magma transport velocities of 1–100 mm/year. At the absent or low melt fractions relevant to our estimated emplacement temperature (580–650 ^{circ }C), such velocities are incompatible with pluton formation by successive injections through dykes. Instead, our results indicate the intrusion of a diapir of crystal-rich slurry, solidifying before emplacement, with a rheology governed by the solid crystals. The emplacement depth is likely to be governed by the depth-dependent rheology of the surrounding rocks, occurring close to the brittle-ductile transition. The wider implications of our results relate to (1) the appreciation that much of the chemical and textural characteristics of plutons may relate to pre-emplacement crystallisation at depth, passively transported to higher crustal levels, and (2) an explanation of the difficulty of seismically imaging active plutonism.

Experimental Study: The Effect of Pore Shape, Geometrical Heterogeneity, and Flow Rate on the Repetitive Two-Phase Fluid Transport in Microfluidic Porous Media.

Geologic subsurface energy storage, such as porous-media compressed-air energy storage (PM-CAES) and underground hydrogen storage (UHS), involves the multi-phase fluid transport in structurally disordered or heterogeneous porous media (e.g., soils and rocks). Furthermore, such multi-phase fluid transport is likely to repeatedly occur due to successive fluid injections and extractions, thus, resulting in cyclic drainage-imbibition processes. To complement our preceding study, we conducted a follow-up study with microfluidic pore-network devices with a square solid shape (Type II) to further advance our understanding on the effect of the pore shape (aspect ratio, Type I: 5-6 > Type II: ~1), pore-space heterogeneity (coefficient of variation, COV = 0, 0.25, and 0.5), and flow rates (Q = 0.01 and 0.1 mL/min) on the repetitive two-phase fluid flow in general porous media. The influence of pore shape and pore-space heterogeneity were observed to be more prominent when the flow rate was low (e.g., Q = 0.01 mL/min in this study) on the examined outcomes, including the drainage and imbibition patterns, the similarity of those patterns between repeated steps, the sweep efficiency and residual saturation of the nonwetting fluid, and fluid pressure. On the other hand, a higher flow rate (e.g., Q = 0.1 mL/min in this study) appeared to outweigh those factors for the Type II structure, owing to the low aspect ratio (~1). It was also suggested that the flow morphology, sweep efficiency, residual saturation, and required pressure gradient may not severely fluctuate during the repeated drainage--imbibition processes; instead, becoming stabilized after 4-5 cycles, regardless of the aspect ratio, COV, and Q. Implications of the study results for PM-CAES and UHS are discussed as a complementary analysis at the end of this manuscript.

Genesis of the mafic impact melt rock in the northwest sector of the Vredefort Dome, South Africa

AbstractGenesis and emplacement of Vredefort Granophyre, the impact melt rock exposed on the Vredefort Dome, the erosional remnant of the central uplift of the Vredefort impact structure, South Africa, have long been debated. This debate was recently reinvigorated by the discovery that besides the previously known felsic variety of >66 wt% SiO2, a second, somewhat more mafic phase of <66 wt% SiO2 occurs along a Granophyre dike on farms Kopjeskraal and Eldorado in the northwest sector of the dome. Two hypotheses have been put forward to explain the genesis and emplacement of this second phase: (1) successive injections of impact melt into extensional fractures opened in the course of central uplift formation/crater modification, with melts of distinct compositions derived from a differentiating impact melt body in the crater, and (2) generation of the more mafic phase as a product of admixture/assimilation of a mafic country rock component, either the so‐called epidiorite of possible Ventersdorp Supergroup affiliation or the Dominion Group meta‐lava (DGL), to Felsic Granophyre. In the latter model, contamination with mafic country rock would have occurred during downward intrusion and stoping into and below the crater floor. The so‐called Mafic Granophyre has previously only ever been sampled on a single site (Farm Kopjeskraal). In this study, samples of Granophyre occurring along the southerly extension of this dike on farm Rensburgdrif, and from a second dike on the Rietkuil property further southwest were investigated by field work, and petrographic, geochemical, and isotopic analysis. The mafic phase indeed occurs in the interior of the dike at Rensburgdrif, and also on Rietkuil. New geochemical and Sr‐Nd isotope data support the hypothesis that the Mafic Granophyre composition represents a mixture between Felsic Granophyre and a mafic country rock. A 20% admixture of epidiorite or DGL to Felsic Granophyre provides an excellent match for the chemical composition of the Mafic Granophyre. The Sr‐Nd isotope data indicate that this admixture likely involved the epidiorite component rather than DGL. Together with earlier Sr‐Nd‐Os‐Se isotopic data, and other geochemical data, these results further support formation of the Mafic Granophyre by local assimilation/admixture of epidiorite to Felsic Granophyre.

Thermal-gas-chemical method for oil production intensification in low-temperature reservoirs

A method is proposed for developing an oil deposit based on low-temperature oil oxidation as a result of initiating an exothermic reaction and subsequent injection of oxygen-containing gas into the reservoir. In the proposed method, which includes successive injection of aqueous solutions of potassium salt and sulfuric acid into the well, light oil or gas condensate is injected into the deposit before injection of the aqueous acid solution. Further, after injection of an aqueous solution of sulfuric acid into the formation, air is pumped with further pushing with water. In the method, a 16% aqueous solution of potassium dichromate is used as an aqueous solution of potassium salt. The application of the proposed technology led to an increase in the temperature in the reservoir above 200 °C and an increase in the displacement efficiency up to 19.7%. Keywords: thermal chemical treatment; production stimulation; low-temperature reservoir; enhanced oil recovery; low temperature oxidation; oil displacement.

A rate-of-injection model for predicting single and double injection with or without fusion.

Models used to predict the instantaneous injected fuel mass are of varied interest in automotive applications, including for providing inputs to CFD calculations or for engine control. While multiple injection strategies are now commonly used in diesel engines, the overall approach may be susceptible to injection fusion, which is defined as two successive injections that are partly or totally coupled due to the short time interval between each event. In this work, a new model to predict the instantaneous mass flow rate from a diesel injector is proposed based on the analytical solution of a first-order linear dynamic system exposed to an impulsion. Experiments are also conducted to quantify the main injection characteristics of a solenoid indirect-action injector under different injection pressures, backpressures and injection durations, representing a total of 33 different conditions. From these results, a model is proposed and validated against experimental data using a single injection strategy. Then, the model is enhanced to predict split injection with and without injection fusion. Successful comparisons are realized between the model and the experiment. The model is then used to successfully simulate a piezoelectric injector experiencing different levels of fusion available in the literature so as to illustrate the universality of the proposed approach.

Long-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer’s disease

BackgroundBrain-directed immunotherapy is a promising strategy to target amyloid-β (Aβ) deposits in Alzheimer’s disease (AD). In the present study, we compared the therapeutic efficacy of the Aβ protofibril targeting antibody RmAb158 with its bispecific variant RmAb158-scFv8D3, which enters the brain by transferrin receptor-mediated transcytosis.MethodsAppNL−G−F knock-in mice received RmAb158, RmAb158-scFv8D3, or PBS in three treatment regimens. First, to assess the acute therapeutic effect, a single antibody dose was given to 5 months old AppNL−G−F mice, with evaluation after 3 days. Second, to assess the antibodies’ ability to halt the progression of Aβ pathology, 3 months old AppNL−G−F mice received three doses during a week, with evaluation after 2 months. Reduction of RmAb158-scFv8D3 immunogenicity was explored by introducing mutations in the antibody or by depletion of CD4+ T cells. Third, to study the effects of chronic treatment, 7-month-old AppNL−G−F mice were CD4+ T cell depleted and treated with weekly antibody injections for 8 weeks, including a final diagnostic dose of [125I]RmAb158-scFv8D3, to determine its brain uptake ex vivo. Soluble Aβ aggregates and total Aβ42 were quantified with ELISA and immunostaining.ResultsNeither RmAb158-scFv8D3 nor RmAb158 reduced soluble Aβ protofibrils or insoluble Aβ1-42 after a single injection treatment. After three successive injections, Aβ1-42 was reduced in mice treated with RmAb158, with a similar trend in RmAb158-scFv8D3-treated mice. Bispecific antibody immunogenicity was somewhat reduced by directed mutations, but CD4+ T cell depletion was used for long-term therapy. CD4+ T cell-depleted mice, chronically treated with RmAb158-scFv8D3, showed a dose-dependent increase in blood concentration of the diagnostic [125I]RmAb158-scFv8D3, while concentration was low in plasma and brain. Chronic treatment did not affect soluble Aβ aggregates, but a reduction in total Aβ42 was seen in the cortex of mice treated with both antibodies.ConclusionsBoth RmAb158 and its bispecific variant RmAb158-scFv8D3 achieved positive effects of long-term treatment. Despite its ability to efficiently enter the brain, the benefit of using the bispecific antibody in chronic treatment was limited by its reduced plasma exposure, which may be a result of interactions with TfR or the immune system. Future research will focus in new antibody formats to further improve Aβ immunotherapy.