Cross-validation of a non-invasive positron detector to measure the arterial input function for pharmacokinetic modelling in dynamic positron emission tomography

Kinetic modeling of positron emission tomography (PET) data can assess index rate of uptake, metabolism and predict disease progression more accurately than conventional static PET. However, it requires knowledge of the time-course of the arterial blood radioactivity concentration, called the arterial input function (AIF). The gold standard to acquire the AIF is by invasive means. The purpose of this study was to validate a previously developed dual readout scintillating fiber-based non-invasive positron detector, hereinafter called non-invasive detector (NID), developed to determine the AIF for dynamic PET measured from the human radial artery. The NID consisted of a 3 m long plastic scintillating fiber with each end coupled to a 5 m long transmission fiber followed by a silicon photomultiplier. The scintillating fiber was enclosed inside the grooves of a plastic cylindrical shell. Two sets of experiments were performed to test the NID against a previously validated microfluidic positron detector. A closed-loop microfluidic system combined with a wrist phantom was used. During the first experiment, the three PET radioisotopes ¹⁸F, ¹¹C and ⁶⁸Ga were tested. After optimizing the detector, a second series of tests were performed using only ¹⁸F and ¹¹C. The maximum pulse amplitude to electronic noise ratio was 52 obtained with ¹¹C. Linear regressions showed a linear relation between the two detectors. These preliminary results show that the NID can accurately detect positrons from a patient’s wrist and has the potential to non-invasively measure the AIF during a dynamic PET scan. The accuracy of these measurements needs to be determined.     

Identification and synthesis of an efficient multivalent E. coli heat labile toxin inhibitor __ A dynamic combinatorial chemistry approach

A polymer based dynamic combinatorial library (DCL) was generated through condensation between aldehyde functionalized linear poly(glycidol) (APG) and galactose containing acylhydrazide derivatives. Pentameric E. coli heat labile enterotoxin B subunit (LTB) was subsequently applied to the DCL as external stimulus, resulting in amplification of a specific acylhydrazone side chain that was further used for the synthesis of a multivalent LTB inhibitor. In the in vitro biological evaluation, this inhibitor exhibited strong inhibition properties as well as low cytotoxicity.     

Dynamic modeling for shear stress induced ATP release from vascular endothelial cells

A dynamic model is proposed for shear stress induced adenosine triphosphate (ATP) release from endothelial cells (ECs). The dynamic behavior of the ATP/ADP concentration at the endothelial surface by viscous shear flow is investigated through simulation studies based on the dynamic ATP release model. The numerical results demonstrate that the ATP/ADP concentration against time at endothelium-fluid interface predicted by the dynamic ATP release model is more consistent with the experimental observations than that predicted by previous static ATP release model.     

Amidohydrolase Process: Expanding the use of l-N-carbamoylase/N-succinyl-amino acid racemase tandem for the production of different optically pure l-amino acids

A bienzymatic system comprising an N-succinylamino acid racemase from Geobacillus kaustophilus CECT4264 (GkNSAAR) and an enantiospecific l-N-carbamoylase from Geobacillus stearothermophilus CECT43 (BsLcar) has been developed. This biocatalyst has been able to produce optically pure natural and non-natural l-amino acids starting from racemic mixtures of N-acetyl-, N-formyl- and N-carbamoyl-amino acids by dynamic kinetic resolution. The fastest conversion rate was found with N-formyl-amino acids, followed by N-carbamoyl- and N-acetyl-amino acids, and GkNSAAR proved to be the limiting step of the system due to its lower specific activity. Metal ion cobalt was essential for the activity of the biocatalyst and the system was optimally active when Co²⁺ was added directly to the reaction mixture. The optimum pH for the biocatalyst proved to be 8.0, for both N-formyl- and N-carbamoyl-amino acid substrates, whereas optimum temperature ranges were 45–55 °C for N-formyl-amino acids and 55–70 °C for N-carbamoyl-derivatives. The bienzymatic system was equally efficient in converting aromatic and aliphatic substrates. Total conversion was also achieved using high substrate concentrations (100 and 500 mM) with no noticeable inhibition. This “Amidohydrolase Process” enables the production of both natural and non-natural l-amino acids from a broad substrate spectrum with yields of over 95%.     

Musculoskeletal model choice influences hip joint load estimations during gait

The prevalence of musculoskeletal modeling studies investigating hip contact forces and the number of models used to conduct such investigations has increased in recent years. However, the consistency between models remain unknown and differences in model predicted hip contact forces between studies are difficult to distinguish from natural inter-individual differences. The purpose of this study was therefore to evaluate differences in hip joint contact forces during gait between four OpenSim models. These models included the generic models gait2392 and the Arnold Lower Limb Model, as well as the hip specific models hip2372 and London Lower Limb Model. Data from four individuals who have had a total hip replacement with instrumented hip implants performing slow, normal, and fast walking trials were taken from the HIP98 database to evaluate the various models effectiveness at estimating hip loads. Muscle forces were estimated using static optimization and hip contact forces were calculated using the JointReaction analysis in OpenSim. Results indicated that, for gait, the hip specific London Lower Limb Model consistently predicted peak push-off hip joint contact forces with lower magnitude and timing errors compared to the other models. Likewise, root mean square error values were lowest and correlation coefficients were highest for the London Lower Limb Model. These results suggest that the London Lower Limb Model is the most appropriate model for investigations focused on hip joint loading.     

Chromatin reorganization and endogenous auxin/cytokinin dynamic activity during somatic embryogenesis of cultured cotton cell

We conducted a systematic assessment and comparative study on the biochemical and cellular characteristics of cultured cotton cells during the entire process of somatic embryogenesis (SE). All staged cultures were widely investigated in this assay. Cell and tissue ectogenesis manipulation combined with flow cytometry (FCM) was employed to cellular study during the whole totipotency process of dedifferentiation and redifferentiation. We identified two phases of chromatin decondensation during the dedifferentiation and redifferentiation. At the same time, sharp increase in the ratio of indoleacetic acid (IAA), isopentenyladenosine group (iPAs) at the same stage of cell dedifferentiation and redifferentiation process serve as distinct biochemical maker of dedifferentiation and SE initiation with the unique feature. Our results suggest the two phases of chromatin reorganization associated with endogenous auxin/cytokinin dynamic activity may underlie dedifferentiation and redifferentiation during the entire SE process in cotton.     

蝰蛇咬伤治疗期间肾功能指标动态变化分析

目的分析蝰蛇咬伤治疗期间患者肾功能指标的变化情况。方法对近10年来我院收住院治疗的219例蝰蛇咬伤患者的临床资料进行收集整理,将符合本文动态观察要求的28例患者的资料进行分析。结果 28例患者的3项肾功能指标在第2、3次检测时均为快速上升,在第3次检测时均值达到高峰,第4次检测时均开始下降,到第6、7次检测时均基本降至正常水平。结论蝰蛇咬伤患者治疗期间肾功能损害呈动态变化,且3项肾功能指标均值升高和降低均有较好的相关性。     

SPR and ITC determination of the kinetics and the thermodynamics of bivalent versus monovalent sugar ligand–lectin interactions

A kinetic study of the interaction of bivalent and monovalent sugar ligands with a lectin was undertaken with the aid of surface plasmon resonance (SPR) method. The study involved a series of bivalent α-d-mannopyranoside containing sugar ligands, with systematic variation in the distance between the sugar ligands. The detailed kinetic studies showed that bivalent ligands underwent a faster association (k _on) and a slower dissociation (k _off) of the ligand–lectin complexes, in comparison to the monovalent ligand–lectin complexes. The kinetic constants were complemented further by assessing the thermodynamic parameters with the aid of isothermal titration calorimetry (ITC). The initiation of cross-linking of ligand–lectin interactions emerge from the early stages of the complexation. The dynamic light scattering (DLS) and the transmission electron microscopy (TEM) techniques allowed judging the sizes and morphologies of the complex in the solution and solid states, respectively.     

Development of bifunctional biosensors for sensing and dynamic control of glycolysis flux in metabolic engineering

Glycolysis is the primary metabolic pathway in all living organisms. Maintaining the balance of glycolysis flux and biosynthetic pathways is the crucial matter involved in the microbial cell factory. Few regulation systems can address the issue of metabolic flux imbalance in glycolysis. Here, we designed and constructed a bifunctional glycolysis flux biosensor that can dynamically regulate glycolysis flux for overproduction of desired biochemicals. A series of positive-and negative-response biosensors were created and modified for varied thresholds and dynamic ranges. These engineered glycolysis flux biosensors were verified to be able to characterize in vivo fructose-1,6-diphosphate concentration. Subsequently, the biosensors were applied for fine-tuning glycolysis flux to effectively balance the biosynthesis of two chemicals: mevalonate and N-acetylglucosamine. A glycolysis flux-dynamically controlled Escherichia coli strain achieved a 111.3 g/L mevalonate titer in a 1L fermenter.