The role of CD8+ regulatory T cells in anti-tumour immune responses in Hepatocellular Carcinoma

Tumour specific effector T-cells can be detected in the blood and tumours of patients with hepatocellular carcinoma (HCC) but fail to mount effective immune responses. Attempts to amplify anti-tumour immune responses using immunotherapy show promise, but are hampered by the presence of suppressive regulatory T-cells (Treg) that inhibit anti-tumour immune responses. Many different subsets of Treg have since been identified including regulatory T-cells expressing the surface marker CD8 (CD8$^+$Treg). A set of experiments was designed in an attempt to increase our understanding on how CD8$^+$Treg may disrupt anti-tumour response and by what mechanisms they are induced. CD8$^+$Treg was analysed by isolation of liver-derived T-cells from human HCC. Monocyte-derived dendritic cells (moDC) matured with tumour tissue conditioned medium were used to assess they potential to induce CD8$^+$Treg. CD8$^+$Treg infiltrating HCC demonstrated a suppressive phenotype. The co-culture of naïve CD8$^+$T-cells with tumour-conditioned moDC induces a population of CD8$^+$Treg through an IDO dependent mechanism. This population of induced T-cells was able to suppress via the CD39-adenosine pathway. The findings of the mechanisms involved in the induction of CD8$^+$Treg by DC and the involvement of CD39 in the suppressive capacity of these novel T-cells, may guide the development of future immunotherapeutic in HCC

A method for conducting suppression assays using small numbers of tissue-isolated regulatory T cells

The suppression assay is a commonly performed assay, measuring the ability of regulatory T cells (Treg) to suppress T cell proliferation. Most frequently, Treg are obtained from the peripheral blood or spleen. Lower yields are obtained by isolation from other tissues, rendering downstream suppression assays challenging to perform. Furthermore, the importance of suppressive subpopulations of Treg favours their isolation by fluorescent-activated cell sorting. Here we describe a method to isolate Treg from human tissues, using colorectal cancer tissue as an example. Treg suppressive capacity was further examined by expression of CCR5 to demonstrate the ability of our method to assess the suppressive capacity of regulatory T cell subsets. To optimise the standard suppression assay to achieve our research aims, the following modifications were made: • Treg, isolated from tissues, were sorted directly into a well-plate. • Responder T cells, which had been fluorescently-labelled prior to sorting, were added directly into the well-plate. • Human Treg Suppression Inspector beads (Miltenyi Biotec Ltd., UK) provided a polyclonal stimulus for proliferation and were added to each well at a bead:lymphocyte ratio of 1:2. This method quantified the suppression of responder T cell proliferation by small numbers of strictly-defined Treg populations isolated from tissues

General-relativistic simulations of the formation of a magnetized hybrid star

Strongly magnetized neutron stars are popular candidates for producing detectable electromagnetic and gravitational-wave signals. A rapid density increase in a neutron star core could also trigger the phase transition from hadrons to deconfined quarks and form a hybrid star. This formation process could release a considerable amount of energy in the form of gravitational waves and neutrinos. Hence, the formation of a magnetized hybrid star is an interesting scenario for detecting all these signals. These detections may provide essential probes for the magnetic field and composition of such stars. Thus far, a dynamical study of the formation of a magnetized hybrid star has yet to be realized. Here, we investigate the formation dynamics and the properties of a magnetized hybrid star through dynamical simulations. We find that the maximum values of rest-mass density and magnetic field strength increase slightly and these two quantities are coupled in phase during the formation. We then demonstrate that all microscopic and macroscopic quantities of the resulting hybrid star vary dramatically when the maximum magnetic field strength goes beyond a threshold of $\sim 5 \times 10^{17}$ G but they are insensitive to the magnetic field below this threshold. Specifically, the magnetic deformation makes the rest-mass density drop significantly, suppressing the matter fraction in the mixed phase. Therefore, this work provides a solid support for the magnetic effects on a hybrid star, so it is possible to link observational signals from the star to its magnetic field configuration.Comment: 8 pages, 3 figure

Gravitational wave signatures from the phase-transition-induced collapse of a magnetized neutron star

Strong magnetic fields make neutron stars potential sources of detectable electromagnetic and gravitational-wave signals. Hence, inferring these magnetic fields is critical to understand the emissions of neutron stars. However, due to the lack of direct observational evidence, the interior magnetic field configuration remains ambiguous. Here, for the first time, we show that the internal magnetic field strength along with the composition of a neutron star can be directly constrained by detecting the gravitational waves from the phase-transition-induced collapse of a magnetized neutron star. By dynamically simulating this collapsing event, we first find that the dominant peaks in the gravitational waveform are the fundamental $l=0$ quasi-radial $F$ mode and the fundamental $l=2$ quadrupolar $^2f$ mode. We next show that the maximum gravitational wave amplitude $|h|_\mathrm{max}$ increases with the maximum magnetic field strength of the interior toroidal field $\mathcal{B}_\mathrm{max}$ until the maximum rest-mass density at bounce $\rho_\mathrm{max,b}$ decreases due to the increasing $\mathcal{B}_\mathrm{max}$. We then demonstrated that the magnetic suppression of fundamental modes found in our previous work remains valid for the hybrid stars formed after the phase-transition-induced collapses. We finally show that measuring the frequency ratio between the two fundamental modes $f_{^2f}/f_{F}$ allows one to infer $\mathcal{B}_\mathrm{max}$ and the baryonic mass fraction of matter in the mixed phase $M_\mathrm{mp} / M_{0}$ of the resulting hybrid star. Consequently, taking $\mathcal{B}_\mathrm{max}$ and $M_\mathrm{mp} / M_{0}$ as examples, this work has demonstrated that much information inside neutron stars could be extracted similarly through measuring the oscillation modes of the stars.Comment: 12 pages, 4 figure

Transient Climate Response in Coupled Atmospheric–Ocean General Circulation Models

The equilibrium climate sensitivity (ECS) has a large uncertainty range among models participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) and has recently been presented as “inherently unpredictable.” One way to circumvent this problem is to consider the transient climate response (TCR). However, the TCR among AR4 models also differs by more than a factor of 2. The authors argue that the situation may not necessarily be so pessimistic, because much of the intermodel difference may be due to the fact that the models were run with their oceans at various stages of flux adjustment with their atmosphere. This is shown by comparing multimillennium-long runs of the Goddard Institute for Space Studies model, version E, coupled with the Hybrid Coordinate Ocean Model (GISS-EH) and the Community Climate System Model, version 4 (CCSM4) with what were reported to AR4. The long model runs here reveal the range of variability (~30%) in their TCR within the same model with the same ECS. The commonly adopted remedy of subtracting the “climate drift” is ineffective and adds to the variability. The culprit is the natural variability of the control runs, which exists even at quasi equilibration. Fortunately, for simulations with multidecadal time horizon, robust solutions can be obtained by branching off thousand-year-long control runs that reach “quasi equilibration” using a new protocol, which takes advantage of the fact that forced solutions to radiative forcing forget their initial condition after 30–40 yr and instead depend mostly on the trajectory of the radiative forcing

A Randomized Controlled Trial of Tai Chi for Tension Headaches

This study examined whether a traditional low-impact mind–body exercise, Tai Chi, affects health-related quality-of-life (HRQOL) and headache impact in an adult population suffering from tension-type headaches. Forty-seven participants were randomly assigned to either a 15 week intervention program of Tai Chi instruction or a wait-list control group. HRQOL (SF-36v2) and headache status (HIT-6™) were obtained at baseline and at 5, 10 and 15 weeks post-baseline during the intervention period. Statistically significant (P < 0.05) improvements in favor of the intervention were present for the HIT score and the SF-36 pain, energy/fatigue, social functioning, emotional well-being and mental health summary scores. A 15 week intervention of Tai Chi practice was effective in reducing headache impact and also effective in improving perceptions of some aspects of physical and mental health

Oscillations of Highly Magnetized Non-rotating Neutron Stars

Highly magnetized neutron stars are promising candidates to explain some of the most peculiar astronomical phenomena, for instance, fast radio bursts, gamma-ray bursts, and superluminous supernovae. Pulsations of these highly magnetized neutron stars are also speculated to produce detectable gravitational waves. In addition, pulsations are important probes of the structure and equation of state of the neutron stars. The major challenge in studying the pulsations of highly magnetized neutron stars is the demanding numerical cost of consistently solving the nonlinear Einstein and Maxwell equations under minimum assumptions. With the recent breakthroughs in numerical solvers, we investigate pulsation modes of non-rotating neutron stars which harbour strong purely toroidal magnetic fields of $10^{15-17}$ G through two-dimensional axisymmetric general-relativistic magnetohydrodynamics simulations. We show that stellar oscillations are insensitive to magnetization effects until the magnetic to binding energy ratio goes beyond 10%, where the pulsation mode frequencies are strongly suppressed. We further show that this is the direct consequence of the decrease in stellar compactness when the extreme magnetic fields introduce strong deformations of the neutron stars

Risk stratification of sudden cardiac death in asymptomatic female Brugada syndrome patients: A literature review

Background and Objectives Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome. Findings Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted. Conclusions Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients