Notes

Chopping the Gordian Knot: Identifiability involving anaplerotic tendencies throughout Corynebacterium glutamicum by means of (12) C-metabolic flux analysis.
56). After ACLR, older age and a decrease in the thickness change ratio of the superficial area of the infrapatellar fat pad appear to affect post-operative AKP after 6 months.To achieve visual space constancy, our brain remaps eye-centered projections of visual objects across saccades. Here, we measured saccade trajectory curvature following the presentation of visual, auditory, and audiovisual distractors in a double-step saccade task to investigate if this stability mechanism also accounts for localized sounds. We found that saccade trajectories systematically curved away from the position at which either a light or a sound was presented, suggesting that both modalities are represented in eye-centered oculomotor centers. Importantly, the same effect was observed when the distractor preceded the execution of the first saccade. These results suggest that oculomotor centers keep track of visual, auditory and audiovisual objects by remapping their eye-centered representations across saccades. Furthermore, they argue for the existence of a supra-modal map which keeps track of multi-sensory object locations across our movements to create an impression of space constancy.Acoustic phased arrays are capable of steering and focusing a beam of sound via selective coordination of the spatial distribution of phase angles between multiple sound emitters. Constrained by the principle of reciprocity, conventional phased arrays exhibit identical transmission and reception patterns which limit the scope of their operation. This work presents a controllable space-time acoustic phased array which breaks time-reversal symmetry, and enables phononic transition in both momentum and energy spaces. By leveraging a dynamic phase modulation, the proposed linear phased array is no longer bound by the acoustic reciprocity, and supports asymmetric transmission and reception patterns that can be tuned independently at multiple channels. A foundational framework is developed to characterize and interpret the emergent nonreciprocal phenomena and is later validated against benchmark numerical experiments. The new phased array selectively alters the directional and frequency content of the incident signal and imparts a frequency conversion between different wave fields, which is further analyzed as a function of the imposed modulation. The space-time acoustic phased array enables unprecedented control over sound waves in a variety of applications ranging from ultrasonic imaging to non-destructive testing and underwater SONAR telecommunication.Although extremely low-frequency electric fields (ELF-EF) have been utilised for therapeutic purposes, the biological effect and the underlying mechanism of ELF-EF have not been elucidated. Here, we developed a mouse model of immobilisation-induced increase in glucocorticoid (GC) to evaluate the effect of ELF-EF. Mice were exposed to 50-Hz 10 kV/m EF via a parallel plate electrode and immobilised as needed. The ELF-EF suppressed the immobilisation-induced increase in blood GC level. Here, the results of 32 tests using the model were pooled and analysed. The suppressive effect of ELF-EF on immobilisation-induced increase in GC was reproduced, and the GC level was slightly higher in the ELF-EF-treated mice than in the sham-controlled mice, a novel observation. The immobilisation-induced increase in lactate dehydrogenase, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase, markers of tissue damage, was suppressed by co-treatment with EF in the biochemical tests using the same plasma sample. DCycloserine In the metabolome analysis, the changes in corticosterones, leukotrienes, and hydroxyeicosatetraenoic acids, markers of inflammation, showed a pattern similar to that of the plasma GC level. Thus, ELF-EF suppresses the stress response that causes an increase in the GC level and slightly promotes GC production in the absence of stress. Moreover, the suppressive effect of ELF-EF on induced stress response might be involved in stress-induced tissue damage or inflammation in immobilised mice. Overall, the model and the data help explore the biological effect of ELF-EF and explain the stress-relieving effect of EF. They would be useful in determining the medical applications of EF in humans and animals.Sustained disturbances are relevant for environmental biotechnology as they can lead to alternative stable states in a system that may not be reversible. Here, we tested the effect of a sustained organic loading alteration (food-to-biomass ratio, FM, and carbon-to-nitrogen ratio, CN) on activated sludge bioreactors, focusing on the stability of nitrification and nitrifiers. Two sets of replicate 5-L sequencing batch reactors were operated at different, low and high, FM (0.19-0.36 mg COD/mg TSS/d) and CN (3.5-6.3 mg COD/mg TKN) conditions for a period of 74 days, following 53 days of sludge acclimation. Recovery and resilience were tested during the last 14 days by operating all reactors at low FM and CN (henceforth termed FM-CN). Stable nitrite accumulation (77%) was achieved through high FM-CN loading with a concurrent reduction in the abundance of Nitrospira. Subsequently, only two of the three reactors experiencing a switch back from high to low FM-CN recovered the nitrite oxidation function, with an increase in Nitrobacter as the predominant NOB, without a recovery of Nitrospira. The AOB community was more diverse, resistant and resilient than the NOB community. We showed that functional recovery and resilience can vary across replicate reactors, and that nitrification recovery need not coincide with a return to the initial nitrifying community structure.As a leading cause of death and morbidity, heart failure (HF) is responsible for a large portion of healthcare and disability costs worldwide. Current approaches to define specific HF subpopulations may fail to account for the diversity of etiologies, comorbidities, and factors driving disease progression, and therefore have limited value for clinical decision making and development of novel therapies. Here we present a novel and data-driven approach to understand and characterize the real-world manifestation of HF by clustering disease and symptom-related clinical concepts (complaints) captured from unstructured electronic health record clinical notes. We used natural language processing to construct vectorized representations of patient complaints followed by clustering to group HF patients by similarity of complaint vectors. We then identified complaints that were significantly enriched within each cluster using statistical testing. Breaking the HF population into groups of similar patients revealed a clinically interpretable hierarchy of subgroups characterized by similar HF manifestation. Importantly, our methodology revealed well-known etiologies, risk factors, and comorbid conditions of HF (including ischemic heart disease, aortic valve disease, atrial fibrillation, congenital heart disease, various cardiomyopathies, obesity, hypertension, diabetes, and chronic kidney disease) and yielded additional insights into the details of each HF subgroup's clinical manifestation of HF. Our approach is entirely hypothesis free and can therefore be readily applied for discovery of novel insights in alternative diseases or patient populations.Understanding the inner behaviour of multilayer perceptrons during and after training is a goal of paramount importance for many researchers worldwide. This article experimentally shows that relevant patterns emerge upon training, which are typically related to the underlying problem difficulty. The occurrence of these patterns is highlighted by means of [Formula see text] diagrams, a 2D graphical tool originally devised to support the work of researchers on classifier performance evaluation and on feature assessment. The underlying assumption being that multilayer perceptrons are powerful engines for feature encoding, hidden layers have been inspected as they were in fact hosting new input features. Interestingly, there are problems that appear difficult if dealt with using a single hidden layer, whereas they turn out to be easier upon the addition of further layers. The experimental findings reported in this article give further support to the standpoint according to which implementing neural architectures with multiple layers may help to boost their generalisation ability. A generic training strategy inspired by some relevant recommendations of deep learning has also been devised. A basic implementation of this strategy has been thoroughly used during the experiments aimed at identifying relevant patterns inside multilayer perceptrons. Further experiments performed in a comparative setting have shown that it could be adopted as viable alternative to the classical backpropagation algorithm.Stimulator of interferon genes (STING) controlled innate immune pathway is essential for host defense against pathogenic infection and effective anti-tumor adaptive immunity initiation. Although macrophages transformed across diverse phenotypes play crucial roles in anti-tumor immune response, events determining this transformation and the host-intrinsic role of STING in this process remain controversial. Here we report how STING signaling acts as a key switch to dominate the gene expression patterns of macrophage transformation for promoting priming and releasing immunosuppression. Furthermore, polyphyllin VII, a potential STING agonist, exerts anti-tumor efficacy upon macrophages priming and subsequent cytotoxic T lymphocytes intratumoral infiltration. Meanwhile, the simultaneous PD-L1 amplification on macrophages in response to PP VII is also ruled by STING, thus PP VII may benefit immune-checkpoint blockade therapy for combining. Moreover, PP VII suppresses carcinogenesis upon restraining the immunosuppressed macrophage transformation. This is due to the boosted STING that negatively regulates a STAT3 propagated crosstalk between immune cells and tumor cells. Overall, PP VII-stimulated STING in macrophages provides a paradigm for anti-tumor, and if possible, anti-infection immunotherapy.Specific intracellular manipulation of animal cells is a persistent goal in experimental cell biology. Such manipulations allow precise and targeted interference with signaling cascades, metabolic pathways, or bi-molecular interactions for subsequent tracking of functional consequences. However, most biomolecules capable of molecular recognition are membrane impermeable. The ability to introduce these molecules into the cytoplasm and then to apply appropriate readouts to monitor the corresponding cell response could prove to be an important research tool. This study describes such an experimental approach combining in situ electroporation (ISE) as a means to efficiently deliver biomolecules to the cytoplasm with an impedance-based, time-resolved analysis of cell status using electric cell-substrate impedance sensing (ECIS). In this approach, gold-film electrodes, deposited on the bottom of regular culture dishes, are used for both electroporation and monitoring. The design of the electrode layout and measurement chamber allows working with sample volumes as small as 10 µL. A miniaturized setup for combined electroporation and impedance sensing (µISE-ECIS) was applied to load different adherent cells with bioactive macromolecules including enzymes, antibodies, nucleic acids and quantum dot nanoparticles. The cell response after loading the cytoplasm with RNase A or cytochrome c (in the presence or absence of caspase inhibitors) was tracked by non-invasive impedance readings in real-time.
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