Effect of early exogenous supplementation of rhIGF-1 on oxygen-induced retinopathy in a mice model of prematurity, and on expressions of IGF-1 and VEGF

Purpose: To investigate the effect of early exogenous supplementation of recombinant human insulinlike growth factor (rhIGF-1) on oxygen-induced mouse model of retinopathy of prematurity (ROP). Methods: Three groups of healthy SPF grade C57BL/6 mice were used in this study, with 20 mice in each group. Hyperoxia saline (HS) and hyperoxia rhIGF-1 (HrGF) groups were placed in a closed oxygen chamber for one week and returned to the normal environment on the 15th day. The hyperoxia rhIGF-1 (HrGF) group was intraperitoneally injected with rhIGF-1 (1.5 mg/kg), while mice in high-oxygen saline (HS) group received normal saline. The air group (AG) was untreated. Changes in retinal blood vessel distributions, expression levels of serum IGF-1 and VEGF, and retinal IGF-1 and VEGF were determined. Results: On day 20, pronounced neo-vascularization was observed, but the distribution was disordered. Serum IGF-1 levels in AG and HrGF were significantly higher than that in HS group, but VEGF level was lower in HS mice (p < 0.05). VEGF level in hyperoxia rhIGF-1 group on days 11 and 15 decreased, relative to control value, while retinal IGF-1 and VEGF in AG and hyperoxia rhIGF-1 mice were elevated, relative to corresponding values in HS mice (p < 0.05). Conclusion: Early exogenous supplementation of rhIGF-1 exerts a therapeutic effect on ROP. Thus, rhIGF-1 may be a potential drug regimen for ROP in clinics

A New Viscoelastic Mechanics Model for the Creep Behaviour of Fibre Reinforced Asphalt Concrete

Based on the Burgers model, by adding a damper unit, this paper proposes a new viscoelastic model with five units and eight parameters to characterize the viscoelastic deformation of fibre reinforced asphalt concrete (FRAC). According to the creep tests of FRAC beams, this paper studies both the parameters in the model and the viscoelastic behaviour of FRAC with different fibre volume fraction and aspect ratio. In this model, this paper establishes the viscoelastic constitutive equation of asphalt concrete, which takes into account the impacts of fibre content characteristic parameter. Both the experimental study and theoretical analysis show that the new model has a high correlation with the results of creep experiment and plays a key role in describing the whole creep process of FRAC. The fibre content characteristic parameter can comprehensively reflect the effects of the fibre volume fraction and aspect ratio on the viscoelastic behaviour of FRAC. Within the range of this test, the optimum fibre volume fraction, fibre aspect ratio and fibre content characteristic parameter are 0.35%, 324 and 1.13

An Efficient Multi-solution Solver for the Inverse Kinematics of 3-Section Constant-Curvature Robots

Piecewise constant curvature is a popular kinematics framework for continuum robots. Computing the model parameters from the desired end pose, known as the inverse kinematics problem, is fundamental in manipulation, tracking and planning tasks. In this paper, we propose an efficient multi-solution solver to address the inverse kinematics problem of 3-section constant-curvature robots by bridging both the theoretical reduction and numerical correction. We derive analytical conditions to simplify the original problem into a one-dimensional problem. Further, the equivalence of the two problems is formalised. In addition, we introduce an approximation with bounded error so that the one dimension becomes traversable while the remaining parameters analytically solvable. With the theoretical results, the global search and numerical correction are employed to implement the solver. The experiments validate the better efficiency and higher success rate of our solver than the numerical methods when one solution is required, and demonstrate the ability of obtaining multiple solutions with optimal path planning in a space with obstacles.Comment: Robotics: Science and Systems 202

Altering stimulus timing via fast rhythmic sensory stimulation induces STDP-like recall performance in human episodic memory

Episodic memory provides humans with the ability to mentally travel back to the past,1 where experiences typically involve associations between multimodal information. Forming a memory of the association is thought to be dependent on modification of synaptic connectivity.2,3 Animal studies suggest that the strength of synaptic modification depends on spike timing between pre- and post-synaptic neurons on the order of tens of milliseconds, which is termed “spike-timing-dependent plasticity” (STDP).4 Evidence found in human in vitro studies suggests different temporal scales in long-term potentiation (LTP) and depression (LTD), compared with the critical time window of STDP in animals.5,6 In the healthy human brain, STDP-like effects have been shown in the motor cortex, visual perception, and face identity recognition.7,8,9,10,11,12,13 However, evidence in human episodic memory is lacking. We investigated this using rhythmic sensory stimulation to drive visual and auditory cortices at 37.5 Hz with four phase offsets. Visual relative to auditory cued recall accuracy was significantly enhanced in the 90° condition when the visual stimulus led at the shortest delay (6.67 ms). This pattern was reversed in the 270° condition when the auditory stimulus led at the shortest delay. Within cue modality, recall was enhanced when a stimulus of the corresponding modality led the shortest delay (6.67 ms) compared with the longest delay (20 ms). Our findings provide evidence for STDP in human episodic memory, which builds an important bridge from in vitro studies in animals to human memory behavior

A New Viscoelastic Mechanics Model for the Creep Behaviour of Fibre Reinforced Asphalt Concrete

Based on the Burgers model, by adding a damper unit, this paper proposes a new viscoelastic model with five units and eight parameters to characterize the viscoelastic deformation of fibre reinforced asphalt concrete (FRAC). According to the creep tests of FRAC beams, this paper studies both the parameters in the model and the viscoelastic behaviour of FRAC with different fibre volume fraction and aspect ratio. In this model, this paper establishes the viscoelastic constitutive equation of asphalt concrete, which takes into account the impacts of fibre content characteristic parameter. Both the experimental study and theoretical analysis show that the new model has a high correlation with the results of creep experiment and plays a key role in describing the whole creep process of FRAC. The fibre content characteristic parameter can comprehensively reflect the effects of the fibre volume fraction and aspect ratio on the viscoelastic behaviour of FRAC. Within the range of this test, the optimum fibre volume fraction, fibre aspect ratio and fibre content characteristic parameter are 0.35%, 324 and 1.13, respectively

Interaction between theta phase and spike timing-dependent plasticity simulates theta-induced memory effects

Rodent studies suggest that spike timing relative to hippocampal theta activity determines whether potentiation or depression of synapses arise. Such changes also depend on spike timing between presynaptic and postsynaptic neurons, known as spike timing-dependent plasticity (STDP). STDP, together with theta phase-dependent learning, has inspired several computational models of learning and memory. However, evidence to elucidate how these mechanisms directly link to human episodic memory is lacking. In a computational model, we modulate long-term potentiation (LTP) and long-term depression (LTD) of STDP, by opposing phases of a simulated theta rhythm. We fit parameters to a hippocampal cell culture study in which LTP and LTD were observed to occur in opposing phases of a theta rhythm. Further, we modulated two inputs by cosine waves with 0° and asynchronous phase offsets and replicate key findings in human episodic memory. Learning advantage was found for the in-phase condition, compared with the out-of-phase conditions, and was specific to theta-modulated inputs. Importantly, simulations with and without each mechanism suggest that both STDP and theta phase-dependent plasticity are necessary to replicate the findings. Together, the results indicate a role for circuit-level mechanisms, which bridge the gap between slice preparation studies and human memory

Auditory detection is modulated by theta phase of silent lip movements

Audiovisual speech perception relies, among other things, on our expertise to map a speaker's lip movements with speech sounds. This multimodal matching is facilitated by salient syllable features that align lip movements and acoustic envelope signals in the 4–8 Hz theta band. Although non-exclusive, the predominance of theta rhythms in speech processing has been firmly established by studies showing that neural oscillations track the acoustic envelope in the primary auditory cortex. Equivalently, theta oscillations in the visual cortex entrain to lip movements, and the auditory cortex is recruited during silent speech perception. These findings suggest that neuronal theta oscillations may play a functional role in organising information flow across visual and auditory sensory areas. We presented silent speech movies while participants performed a pure tone detection task to test whether entrainment to lip movements directs the auditory system and drives behavioural outcomes. We showed that auditory detection varied depending on the ongoing theta phase conveyed by lip movements in the movies. In a complementary experiment presenting the same movies while recording participants' electro-encephalogram (EEG), we found that silent lip movements entrained neural oscillations in the visual and auditory cortices with the visual phase leading the auditory phase. These results support the idea that the visual cortex entrained by lip movements filtered the sensitivity of the auditory cortex via theta phase synchronization

Single-trial phase entrainment of theta oscillations in sensory regions predicts human associative memory performance

Episodic memories are rich in sensory information and often contain integrated information from different sensory modalities. For instance, we can store memories of a recent concert with visual and auditory impressions being integrated in one episode. Theta oscillations have recently been implicated in playing a causal role synchronizing and effectively binding the different modalities together in memory. However, an open question is whether momentary fluctuations in theta synchronization predict the likelihood of associative memory formation for multisensory events. To address this question we entrained the visual and auditory cortex at theta frequency (4 Hz) and in a synchronous or asynchronous manner by modulating the luminance and volume of movies and sounds at 4 Hz, with a phase offset at 0° or 180°. EEG activity from human subjects (both sexes) was recorded while they memorized the association between a movie and a sound. Associative memory performance was significantly enhanced in the 0° compared with the 180° condition. Source-level analysis demonstrated that the physical stimuli effectively entrained their respective cortical areas with a corresponding phase offset. The findings suggested a successful replication of a previous study (Clouter et al., 2017). Importantly, the strength of entrainment during encoding correlated with the efficacy of associative memory such that small phase differences between visual and auditory cortex predicted a high likelihood of correct retrieval in a later recall test. These findings suggest that theta oscillations serve a specific function in the episodic memory system: binding the contents of different modalities into coherent memory episodes

Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection

Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it’s imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+ DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+ T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+ DNT cells was negatively correlated with CD4+ T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+ DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+ DNT cells in the HIV disease progression, and suggest that Foxp3+ DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection

Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.

Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSG mice. Treatment with pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition in both CDX and PDX tumors in HuNSG but not in NSG mice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearing HuNSG mice may represent an important, new model for preclinical immunotherapy research. FASEB J 2018 Mar; 32(3):1537-1549