Higher Dissociation Rate Research Articles

Exploring the potential of end-capping acceptor designing on highly soluble and efficient Schiff-based Hole-Transporting materials for High-Efficiency perovskite solar cells

Photovoltaic materials, especially perovskite solar cells (PSCs) are promising candidates for rising global energy demands. Here, five phenothiazine-based hole-transporting materials (AZOM1, AZOM2, AZOM3, AZOM4, and AZOM5) are designed by Schiff base chemistry with A-π-D-π-A framework for PSCs. We executed density functional theory calculations to explore the electronic, photo-physical, photovoltaic, and charge-transporting properties of the studied hole-transporting materials (HTMs). Our results indicate that AZOM1-AZOM5 HTMs possess more negativeHOMO energies (−5.64 to − 5.49 eV), lower bandgaps, and superior solubility as compared to Spiro-OMeTAD (HOMO energy = − 4.47 eV) and reference AZO-II (HOMO energy = − 4.68 eV), which enhanced their hole extraction and open-circuit photo-voltage (VOC). The transition density matrix and hole-electron distribution analyses show that AZOM1- AZOM5 molecules have ultrafast charge transmission, low overlapping between holes and electrons, and a higher dissociation rate than the Spiro-OMeTAD and AZO-II HTMs. The designed HTMs have smaller exciton binding energies than the Spiro-OMeTAD and AZO-II, allowing electron-hole pairs to dissociate into positive and negative charges smoothly. AZOM1-AZOM5 HTMs have higher hole charge transfer integral than the AZO-II, facilitating high hole mobility in PSCs. All designed HTMs have higher VOC (1.49 to 1.64 V) and lower energy losses (0.63 to 1.03 eV) than the Spiro-OMeTAD and AZO-II HTMs. Moreover, the AZOM1-AZOM5 HTMs demonstrated deeper HOMO energies, high solubility, more stability, and high open-circuit photo-voltages than the recently reported HTMs at “MPW1PW91/6-31G (d, p)” level of theory. Overall, the AZOM1-AZOM5 HTMs are very effective in boosting the solubility, charge-transporting ability, and efficiency of PSCs.

Copper dynamics in vineyard topsoils as affected by the supply of aerated compost tea: Insights from a batch experiment

Aerated compost teas (ACTs) are rich in soluble humic substances (SHS) that have high affinity for metals, notably Cu. Using a batch experiment, we measured the extent to which two ACTs altered Cu dynamics in vineyard topsoils one day and 21 days after their addition. Soils were extracted with 0.01 M KCl, and total Cu concentration, free Cu ion fraction and size distribution of Cu ligands were measured in the extraction solution to assess the impact of ACT on the mobility of Cu. Diffusive gradient in thin film (DGT) measurements were carried out to assess the effect of ACT on Cu bioavailability, and the dissociation rate of Cu-SHS complexes was measured. The results revealed that ACT increased the mobility of Cu from a factor 1.2 to 5.8 depending on the soil, the ACT and the incubation time. Cu mobilization was associated with an increase in absorbance at 254 nm and a decrease in the free Cu ion fraction in the KCl extract. Associated with the strong agreement between the size distribution of SHS and that of Cu ligands in the KCl extract of soils treated with ACT, these results showed that Cu was mobilized through complexation by the SHS present in ACTs. A fraction of the SHS supplied with ACTs sorbed onto the soil constituents, notably in calcareous soils where this fraction reached 86% for ACT B. Between 15% and 50% of the SHS remaining in solution degraded between day one and day 21 under the presumed action of microflora. This explains why the Cu mobilization efficiency of ACTs was on average lower in calcareous soils than in non-calcareous soils, and decreased with time. Lastly, ACT increased the bioavailability of Cu in soils from a factor 1.3 to 4.2, due to the relatively high dissociation rate of Cu-SHS complexes.

Cerebellar atrophy in genetic epileptic encephalopathies: A cohort study and a systematic review

ObjectiveTo analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). MethodsThis research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. ResultsThe cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. ConclusionCerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.

Abstract 6318: Development of an anti-PD-L1 CAR T therapeutic treating advanced gastric cancer with enhanced efficacy and lower off-tumor activities

Abstract Purpose: Driven by a relentless unmet need with unsatisfied cancer therapy, we aimed to develop chimeric antigen receptor T-cell (CAR-T) therapy for targeting advanced gastric cancer (AGC) expressing PD-L1. We constructed a 2nd generation CAR lentiviral vector expressing a unique anti-PD-L1 scFv with moderate affinity (VaxCAR001) in order to compare scFvs derived from Avelumab or Atezolizumab. This project focused on the efficacy and safety of PD-L1 CAR-Ts, which are affected by their binding affinity and dissociation with the target protein, PD-L1 during the treatment period. Methods and Results: The findings of this study revealed significant differences among PD-L1-targeting CAR-T cells with different affinities and dissociations. VaxCAR001 cells, showing intermediate affinity, demonstrated a higher CD8 ratio (up to 78% compared to 58% in Avelumab-derived and 45% in Atezolizumab-derived CAR-T), reduced expression of inhibitory markers including Tim-3, LAG-3, and TIGIT, (8%, 39% and 13% in VaxCAR001 vs 35%, 55% and 42 % in Avelumab, 19%, 51% and 34% in Atezolizumab scFv-derived CAR-T, respectively) and more sustained cytotoxicity. Notably, it maintained strong cytotoxicity even one month after production, while the Avelumab or Atezolizumab ScFv-derived CAR-T cells did not. In multicellular spheroid 3D co-culture with CAR T cells, VaxCAR001 exhibited superior infiltration into the core of spheroid and induced higher CAR-T-mediated killing for 3D tumor spheroids as indicated by LDH assay (68%, 800% increased than Avelumab or Atezolizumab scFv-derived CAR-T). Moreover, in an MSI-high AGC mouse model, treatment with VaxCAR001 cells resulted in a significant reduction in tumor size and prolonged survival until the end of the study period. On the other hand, treatment with the Avelumab or Atezolizumab scFv-derived CAR-T cells led to high mortality, with most mice succumbing within three weeks after CAR-T cell injection, suggesting an on-target off-tumor effect. Conclusion: This study demonstrates that VaxCAR001 cells bearing intermediate affinity and high dissociation rate for target PD-L1 showed the superior killing of PD-L expressing tumor cells in vitro and in vivo and manifested better safety profiles, as compared to CAR-T cells bearing scFv derived from commercial anti-PD-L1 targeting monoclonal antibodies such as avelumab and atezolizumab. VaxCAR001 revealed extended cytotoxicity, enhanced infiltration into tumor spheroids, and greater tumor size reduction in in vivo models. Importantly, it also demonstrated superior safety profiles, as evidenced by reduced expression of inhibitory markers and fewer off-tumor adverse effects. These findings would accelerate the clinical stage developments as an effective and safer treatment strategy against AGC. Citation Format: Minwoo Baek, Jae-In Yu, Eun-Ji Choi, Yeojin Lim, Jiwon Yang, Se-Ryeong Choi, Yoonjoo Choi, Mihwa Kim, Joon Haeng Rhee, Je-Jung Lee. Development of an anti-PD-L1 CAR T therapeutic treating advanced gastric cancer with enhanced efficacy and lower off-tumor activities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6318.

Impact of acetamide, 1,2,4-triazole, and 1-dodecyl-2-pyrrolidinone on carbon dioxide hydrate growth: Application in carbon dioxide capture and sequestration

Gas hydrates have served as the focal point of research from a sustainable engineering perspective, due to their specific applications in diverse scientific areas including carbon dioxide (CO2) gas storage, carbon capture, and sequestration (CCS). However, improved kinetics of CO2 hydrate formation will render the development of technologies for CCS. In this context, it should be mentioned that under the seafloor, low temperature and high pressure prevail, which makes the sequestration of gaseous CO2 in the form of solid hydrates plausible. In this study, both formation and dissociation kinetics of CO2 hydrates have been investigated in the presence of aqueous solutions of three CO2-philic additives, namely, acetamide, 1,2,4-triazole, and non-ionic surfactant 1-dodecyl-2-pyrrolidinone (DDP) with varying concentrations (0.5, 1, 2, and 4 wt%) at 274.55 K and 3.6 MPa in a 1.4 L stirred tank reactor. These chemicals having high binding energies with CO2, draw the dissolved CO2 molecules towards the hydrate cages by strongly interacting with them. Moreover, DDP can enhance the rate of gas dissolution by lowering the surface tension at the gas-water interface and altering the contact angle. All the additives exhibited considerable improvements in gas uptake than pure water, with 0.5 wt% DDP showing the most substantial promoting effect as it increased the moles of CO2 uptake and water-to-hydrate conversion by 55%. Likewise, about a 28% rise in these metrics was observed with 0.5 wt% acetamide and 2 wt% of 1,2,4-triazole. Furthermore, a reduction of 80% was observed in t90 with 0.5 wt% of DDP. The positive impacts of DDP and acetamide were highest at a lower concentration of 0.5 wt%, signifying their economic feasibility. The dissociation studies conducted on the CO2 hydrates up to 293.15 K demonstrated high dissociation rates, thus faster CO2 recovery for further use. This study conclusively shows that the additives might be used as equitable kinetic promoters for the CO2 hydrate relevant to CCS.

Shame-induced dissociation: An experimental study of experiential avoidance.

The study experimentally investigated shame-induced dissociation, and to what extent that process was associated with exposure to childhood maltreatment. Using a shame-related script-driven imagery paradigm and mirror-viewing task, 50 female participants from the community recalled two shame-related and two neutral autobiographical memories, after which they listened to recordings of themselves retelling the narratives looking in a mirror or at a black curtain (i.e., mirror-viewing task). Shame-related memories compared to neutral memories resulted in higher rates of dissociation. The relationship between shame and dissociation was significantly moderated by experiential avoidance or avoidance of unwanted cognitive and affective reactions. In contrast to previous research, looking in the mirror and childhood maltreatment severity did not predict dissociative responses. The strong relationship between shame and dissociation suggests the importance of monitoring patients' affect and behavior when revisiting shame-related memories, to not reinforce dissociative reactions and inadvertently foster treatment resistance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Rational design of TGFbRII dominant negative armored GPC3 CAR-T cells for the treatment of hepatocellular carcinoma

Abstract Chimeric antigen receptor (CAR)-T therapy has yielded impressive clinical results in hematological malignancies and it is a promising approach for solid tumor treatment. However, toxicity is a concern hampering its broader use. In selecting a lead CAR-T candidate against the oncofetal antigen glypican 3 (GPC3), we employed a strategy to manage the toxicity profile by lead selecting a single-chain variable fragment with reduced affinity characterized by a high dissociation rate. Compared to a high-affinity construct, the low-affinity CAR maintained cytotoxic function but showed reduced toxicity in a mouse model of hepatocellular carcinoma (HCC). The HCC microenvironment is rich of the immunosuppressive cytokine TGFβ, prompting us to armor the low affinity GPC3 CAR-T cells with a dominant-negative TGFβRII (TGFβRIIDN). In vitro, expression of TGFβRIIDN nearly abolished TGFβ-induced SMAD2/3 phosphorylation and reduced suppression of IL-2 and IFNg production. In a xenograft model of a human TGFβ highHCC, armored CAR-T cells had 10/10 complete responders (CR) while the unarmored CAR-T had 4/10 CRs. In four TGFβ highpatient-derived xenograft models armored CAR-T cells achieved 60–90% tumor growth inhibition (TGI) while the unarmored CAR-T achieved no significant TGI. The armored CAR-T cells infiltrated TGFβ highHCC tumors more abundantly than their unarmored counterparts and expressed lower levels of immune checkpoint markers PD1 and LAG3. In line with these observations, we detected significantly more IFNg at peak response, confirming in vivo functional superiority of TGFβRIIDN armored CAR-T therapy. These data support the clinical development of AZD5851, GPC3 CAR-T armored with TGFβRIIDN.

Feel-Own-Move: a psychomotor therapy program for victims of intimate partner violence living in shelter homes. Feasibility and effects on mental health, bodily dissociation, and quality of life.

Intimate partner violence (IPV) is a worldwide concern, impacting victims' mental health, physical health, and quality of life. High rates of posttraumatic stress disorder (PTSD), depression, anxiety, bodily dissociation, and somatic symptoms have been found in victims of IPV, with an important impact on the chronicity of impairments and on the outcomes of psychological interventions. Therapeutic interventions available in shelter homes for victims are scarce in addressing their body-mind needs therefore asking for better empirical research. Thus, the aim of this study was to evaluate the feasibility and effects of Feel-Own-Move (FOM), an 8-week psychomotor therapy program for victims of IPV, on their mental health, levels of bodily dissociation, and general quality of life. A within-subject repeated measures design was used to evaluate the intervention effects, and feasibility results were analyzed. Seventeen women completed the program (mean age 42.8 years, range 21-64). Results showed a significant decrease in levels of bodily dissociation, with FOM having a large effect size. The intervention also had a large effect size at increasing the environment domain of quality of life, although no statistically significant differences were found. FOM ended with excellent rates of reach, adherence, acceptability, and satisfaction. A positive retention rate was also found. In conclusion, FOM seems to be a feasible psychomotor therapy intervention for female victims of IPV living in shelters. Importantly, this program showed to be effective in reducing bodily dissociation among participants, which is suggested to prospectively contribute to their mental health and quality of life.

A STUDY OF THE Ti-Mn REDOX COUPLE FOR REDOX FLOW BATTERY BASED ON COMSOL

In this study, the distribution of overpotential, dissociation rate, electrode potential, current density, and comparison of dissociation rate with Vanadium ion is proposed to examine for a Titanium Manganese Redox Flow Battery (TMRFB). TMRFB can be a solution in the current condition of energy scarcity and environmental pollution due to its high capacity and ecofriendly characteristics. Rather with the more expensive vanadium redox flow batteries, Mn-based flow batteries have gained appeal due to their inexpensive cost and high energy density. This study shows that the Ti4+/ Ti3+ and Mn3+/Mn2+ ions have higher dissociation rate at the membrane and lower at the inlet where the velocity of the electrolyte flow is higher; The membrane undergoes more oxidation-reduction reactions, therefore the electrolyte flow rate is crucial in the redox flow cell; Furthermore, our study finds that as electrode thickness is compressed, current density and electrode potential are enhanced while overpotential is lowered; comparison with vanadium redox battery it is found that Ti-Mn shows greater dissociation rate than Vanadium ions. The model's equations are solved by using the finite-element approach in COMSOL Multiphysics software. The reaction is modeled using an electrolyte-electrode interface connection. Dissociation rate shows that the oxidation-reduction reaction occurs with less potential at the membrane. Battery performance can be increased by optimizing the electrolyte flow rate. Electrode compression increases conductivity and battery performance.

Kinetic and molecular insight into immunoglobulin G binding to immobilized recombinant protein A of different orientations

Mechanistic understanding of immunoglobulin G (IgG) binding to protein A is crucial for the design and development of high-performance protein A chromatography. In this work, the IgG binding domain (Z) of protein A from Staphylococcus aureus was genetically modified by introducing a cysteine residue at the N-terminus (Cys-Z) or a cysteine-lysine dipeptide at the C-terminus (Z-Cys), and the two ligands were used to unravel the IgG binding mechanism by means of binding kinetics and different single molecule measurements. Surface plasma resonance (SPR) measurement of the binding kinetics of mouse myeloma IgG2a (mIgG2a) to the two ligands indicated that oriented ligand immobilization significantly increased the association rate constant of mIgG2a, and Z-Cys had the highest binding affinity to mIgG2a among the three ligands (Cys-Z, Z-Cys and Z). This was attributed to the synergistic contribution of the high association rate constant and low dissociation rate constant to mIgG2a. Furthermore, quartz crystal microbalance with energy dissipation monitoring (QCM-D) measurement provided the maximum adsorption densities of IgGs on the Z-Cys-immobilized chip as zeta potentials of IgGs were nearly zero. The QCM-D investigation revealed that the adsorbed layer was dependent on ligand type and density, and IgG. Moreover, Z-Cys and Cys-Z induced IgG binding in flipped orientations, as evidenced by the antigen-antibody reaction. Finally, rectangular DNA origami tiles were introduced to analyze the molecular orientation of adsorbed IgG. Single-molecule imaging showed that mIgG2a was associated with flexible Z-Cys on the tiles predominantly in side-on and end-on orientations. The research has provided molecular insight into the binding mechanism of IgG molecules at liquid–solid interfaces and would help design new protein A-based ligands and high-capacity adsorbents.

Reinforcing DNA Supramolecular Hydrogel with Polymeric Multiple-Unit Linker

Reinforcing DNA Supramolecular Hydrogel with Polymeric Multiple-Unit Linker

Improvement of SI engine combustion with ammonia as fuel: Effect of ammonia dissociation prior to combustion

Although recent studies have shown the possibility of running ‘standard’ spark-ignition engines with pure ammonia, the operating range remains limited mainly due to the unfavorable characteristics of ammonia for premixed combustion and often requires the addition of a complementary fuel such as H2 to extend it. As the best way to add H2 is to crack ammonia directly on-board, this paper focuses on the impact of the upstream cracking level of ammonia on the performance and emissions of a single cylinder spark ignition engine. Experiments were performed over several equivalence ratios, dissociation rates and load conditions. It is confirmed that only a slight rate of ammonia dissociation (10%) upstream of the combustion considerably enhances the engine's operating range thanks to a better combustion stability. In terms of pollutant emissions, the partial dissociation of ammonia, especially for slightly lean mixtures induces a very clear trade-off between high NOx and high unburned ammonia level for high and low ammonia dissociation rates, respectively. Therefore, cracking NH3 does not only improve the operating range of ammonia-fueled spark ignition engines but can also help to reduce NH3. However, to reach the same engine output work, higher ammonia fuel consumption will be necessary since the global system efficiency is lower using fuel dissociation. In addition, the global warming effect is increased with dissociation level since a higher level of N2O is generated by the hydrogen contribution.

Double amplification upon immuno-gold nanoparticles promoted trace measurement of ricin by biolayer interferometry

The upsurge of biotoxin threat worldwide stressed challenges in the first response to date. Implementing sensitive, specific, and rapid sensing methods is very worthwhile. An emerging optical sensing technique, biolayer interferometry (BLI), has the merits of real-time, fluidics-free, label-free detection, shows its great potential for highly sensitive measurement of biotoxins via a simple, fast and straightforward way. In this article, we contributed a double amplification strategy upon immuno-gold nanoparticles (immunoGNPs) in BLI, which promoted a measurement of trace ricin based on the modified monoclonal antibodies sandwiched sensing mode. ImmunoGNPs fuel signal amplification by a three-fold action: the enhanced differential interference pattern, multivalent binding effect, and improved intrinsic nanozyme catalytic activity. Under a complete optimization, the sensitivity was 1000-fold improved in comparison with the direct immunoassay, with the limit of detection as low as 5 pM (0.3 ng/mL) and a linear range reaching three orders of magnitude. All the whole measurement procedures were completed within 15 min. Moreover, with the aid of GNPs, mAb with low affinity and high dissociation rate can provide sensitivity as good as mAb with high affinity and low dissociation rate, revealed multivalent binding effect by enhancing avidity several orders of magnitude via reducing the dissociation rate constant. It supported a feasible way to rescue mAb with weak affinity dominated by a fast dissociation behavior in the sensing field. We also proved the applicability of this BLI assay in practical samples such as crude biotoxins and intoxicated human plasma.

The Influence of Magnetic Field on Newly Designed Oxyhydrogen and Hydrogen Production by Water Electrolysis

Herein, new prototypes of a dry cell and an H2 generator are designed to produce hydrogen and HHO (oxyhydrogen) gas, and the effect of a magnetic field on both systems is examined. Experiments are conducted in both systems; a 3.5% potassium hydroxide electrolyte is chosen because it is an alkaline type of solution with a high dissociation rate. NdFeB magnets with magnetic fluxes of 1.2 and 1.6 T are added to both systems to reveal the effect of the Lorentz force on gas production. The flow rates of HHO gas in the productions under 1.2 and 1.6 T in the HHO system are 680 and 730 ml min−1, respectively. These values show that the flow velocities were 15.4% (1.2 T) and 23% (1.6 T) greater, respectively than the values recorded without a magnetic field (MF). Additionally, the percentage of hydrogen production increased by 4% for 1.2 T and 11% for 1.6 T compared to the measured value without the MF. In addition, production costs are calculated for both systems in the study: the energy required to obtain the same flow rate as the comparison examples in the literature was lower.

Optimization of Pichia pastoris Expression System for High-Level Production of Margatoxin.

Margatoxin (MgTx) is a high-affinity blocker of voltage-gated potassium (Kv) channels. It inhibits Kv1.1–Kv1.3 ion channels in picomolar concentrations. This toxin is widely used to study physiological function of Kv ion channels in various cell types, including immune cells. Isolation of native MgTx in large quantities from scorpion venom is not affordable. Chemical synthesis and recombinant production in Escherichia coli need in vitro oxidative refolding for proper disulfide bond formation, resulting in a very low yield of peptide production. The Pichia pastoris expression system offers an economical approach to overcome all these limitations and gives a higher yield of correctly refolded recombinant peptides. In this study, improved heterologous expression of recombinant MgTx (rMgTx) in P. pastoris was obtained by using preferential codons, selecting the hyper-resistant clone against Zeocin, and optimizing the culturing conditions. About 36 ± 4 mg/L of >98% pure His-tagged rMgTx (TrMgTx) was produced, which is a threefold higher yield than has been previously reported. Proteolytic digestion of TrMgTx with factor Xa generated untagged rMgTx (UrMgTx). Both TrMgTx and UrMgTx blocked the Kv1.2 and Kv1.3 currents (patch-clamp) (K d for Kv1.2 were 64 and 14 pM, and for Kv1.3, 86 and 50 pM, respectively) with comparable potency to the native MgTx. The analysis of the binding kinetics showed that TrMgTx had a lower association rate than UrMgTx for both Kv1.2 and Kv1.3. The dissociation rate of both the analogues was the same for Kv1.3. However, in the case of Kv1.2, TrMgTx showed a much higher dissociation rate with full recovery of the block than UrMgTx. Moreover, in a biological functional assay, both peptides significantly downregulated the expression of early activation markers IL2R and CD40L in activated CD4+ TEM lymphocytes whose activation was Kv1.3 dependent. In conclusion, the authors report that the Pichia expression system is a powerful method to produce disulfide-rich peptides, the overexpression of which could be enhanced noticeably through optimization strategies, making it more cost-effective. Since the presence of the His-tag on rMgTx only mildly altered the block equilibrium and binding kinetics, recombinant toxins could be used in ion channel research without removing the tag and could thus reduce the cost and time demand for toxin production.

Activated N-methyl-D-aspartate receptor ion channels detected in focal epilepsy with [18 F]GE-179 positron emission tomography.

Imaging activated glutamate N-methyl-D-aspartate receptor ion channels (NMDAR-ICs) using positron emission tomography (PET) has proved challenging due to low brain uptake, poor affinity and selectivity, and high metabolism and dissociation rates of candidate radioligands. The radioligand [18 F]GE-179 is a known use-dependent marker of NMDAR-ICs. We studied whether interictal [18 F]GE-179 PET would detect foci of abnormal NMDAR-IC activation in patients with refractory focal epilepsy. Ten patients with refractory focal epilepsy and 18 healthy controls had structural magnetic resonance imaging (MRI) followed by a 90-min dynamic [18 F]GE-179 PET scan with simultaneous electroencephalography (EEG). PET and EEG findings were compared with MRI and previous EEGs. Standard uptake value (SUV) images of [18 F]GE-179 were generated and global gray matter uptake was measured for each individual. To localize focal increases in uptake of [18 F]GE-179, the individual SUV images were interrogated with statistical parametric mapping in comparison to a normal database. Additionally, individual healthy control SUV images were compared with the rest of the control database to determine their prevalence of increased focal [18 F]GE-179 uptake. Interictal [18 F]GE-179 PET detected clusters of significantly increased binding in eight of 10 patients with focal epilepsy but none of the controls. The number of clusters of raised [18 F]GE-179 uptake in the patients with epilepsy exceeded the focal abnormalities revealed by the simultaneously recorded EEG. Patients with extensive clusters of raised [18 F]GE-179 uptake showed the most abnormal EEGs. Detection of multiple foci of abnormal NMDAR-IC activation in 80% of our patients with refractory focal epilepsy using interictal [18 F]GE-179 PET could reflect enhanced neuronal excitability due to chronic seizure activity. This indicates that chronic epileptic activity is associated with abnormal NMDAR ion channel activation beyond the initial irritative zones. [18 F]GE-179 PET could be a candidate marker for identifying pathological brain areas in patients with treatment-resistant focal epilepsy.

Negative Symptoms Management in Schizophrenia

Clinicians often overlook the presence of negative symptoms in treating schizophrenia. The burden borne by patients, families, and society is quite heavy. These symptoms not only have high costs, but also affect the functional prognosis in independence and socializing. There is a need for adequate therapy of negative symptoms of schizophrenia which can improve the patient’s quality of life. Negative symptoms are characterized by blunt affect, alogia, avolition, anhedonia, and asociality. Knowing the difference between the primary and secondary types of negative symptoms of schizophrenia can bring big impact on the therapy. The primary type of negative symptoms is an integral part of schizophrenia, while the secondary one is caused by external conditions of schizophrenia, such as depression. Management of negative symptoms of schizophrenia includes psychopharmaceuticals and non-psychopharmaceuticals. Atypical antipsychotics remain the drug of choice due to their affinity not only to D2 receptor, but also to serotonin, glutamate, histamine, α adrenergic, and muscarinic receptors. In addition, the higher dissociation rate of D2 receptors of atypical antipsychotics allow for minimal motor side effect. Cariprazine has been approved by The Food and Drug Associaton and The European Medicines Agency to treat primary and persistent negative symptoms due to its minimal side effect. Non-pharmacological therapies such as Cognitive Behavioral Therapy (CBT) and Motivation and Engagement Training (MOVE) can optimize the treatment efficacy. These therapies will enhance the cognitive improvement, adaptation, and social skill development of the patients.

An exergy-based energy efficiency analysis on gas production from gas hydrates reservoir by brine stimulation combined depressurization method

Before performing commercial scale production of natural gas hydrates (NGHs), it is inevitable to estimate the productivity, production period, optimal operation parameters, and further evaluate the technical and economic feasibilities of NGHs field production. The dissociation of gas hydrates is an endothermic process. This needs to compensate additional energy, such as chemical energy, geothermal energy and electricity, etc., in order to keep high dissociation rate. Exergy is a basic parameter that used for various energy systems as a potential tool for design, analysis and optimization. This work provided an exergy analysis method to evaluate the economic efficiency of NGHs exploitation process by brine stimulation combined depressurization method. The input data including cumulative volume of gas production, mass of water production and gas-to-water ratio was obtained by the numerical simulation of TOUGH + HYDRATE. Through the exergy analysis, the total productivity and production period could be determined. These have rarely been reported. The influences of operation parameters, such as well spacing, injection temperature and injection rate of brine on net exergy production were investigated for guiding the set of optimal operating conditions. Since the cost may be one of the biggest challenges for NGHs production, this work suggests making full use of all kinds low-level energy sources to improve energy efficiency, such as brine with high concentration produced by desalination, tidal energy, wind energy, etc.

The impact of childhood trauma on the emergence and development of dissociative disorders

Dissociative experiences are common both in children and adults. Their frequency and severity range from normal dissociation to pathological fragmentation of identity. High rates of dissociation and Dissociative Disorders have been documented in both community and clinical samples. Trauma, especially chronic trauma, plays an essential role in the development and long-term presence of dissociative symptoms. During overwhelming and often traumatic experiences dissociation protects the individual by psychological detachment from the unbearable reality. Chronic dissociative experiences might cause severe disintegration of the individual’s mental experience. The Trauma Model suggests that dissociation is a psychobiological response which enables survival during and after the traumatic event. The Developmental Model is based on an assumption that disturbed attachment, especially early interpersonal trauma, might lead to the development of severe dissociation in children and adolescents, often lasting into adulthood. Diagnostic systems include three diagnoses that deal with the specific relationship between trauma and dissociation. Two of these diagnoses have been recognized recently - Complex PTSD (ICD-11) and the Dissociative Subtype of PTSD (DSM-5); one has already been established - the Dissociative Identity Disorder. Patients with Dissociative Disorders suffer from a range of symptoms. The most severe symptoms include chronic suicidal ideation and frequent suicide attempts. Therefore, researchers and clinicians should routinely assess dissociation in their everyday practice. In patients with Dissociative Disorders, the main treatment goal is the integration of their mental experience.

One-step efficient non-hydrogen conversion of cellulose into γ-valerolactone over AgPW/CoNi@NG composite

One-step efficient conversion of cellulose into value-added γ-valerolactone (GVL) is of great interest because it not only integrates complex tandem reactions in one-step, but also does not need additional hydrogen sources. To achieve this goal, it is crucial to fabricate high-performance catalyst that can accelerate both hydrolysis of cellulose and further transformation of generated stoichiometric levulinic acid (LA) and formic acid (FA) into GVL. CoNi nanoparticles encapsulated in N-doped thin graphene shell gave GVL yield as high as 55.9 % at 200 °C combined with Ag+-exchanged heteropolyacid (AgPW). This composite catalyst is highly resistant to the corrosion of LA and FA, and hence shows high catalytic stability. LA-adsorption FTIR spectra and DFT calculations indicate that LA and FA can penetrate through shell graphene layers into core CoNi sites via cracks. Compared to H2, FA can much more rapidly reduce LA because of its low dissociation energy barrier and high dissociation rate.