Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages

Creatine is an indispensable organic compound utilized in physiological environments; however, its role in immunity is still poorly understood. Here, we show that creatine supplementation enhances anti-tumor immunity through the functional upregulation of macrophages by increasing adenosine triphosphate (ATP) production. Creatine supplementation significantly suppressed B16-F10-originated tumor growth in mice compared with the control treatment. Under these conditions, intratumor macrophages polarized towards the M1 phenotype rather than the M2 phenotype, and there was an increase in tumor antigen-specific CD8+ T cells in the mice. The cytokine production and antigen-presenting activity in the macrophages were enhanced by creatine supplementation, resulting in a substantial increase in tumor antigen-specific CD8+ T cells. ATP upregulation was achieved through the cytosolic phosphocreatine (PCr) system via extracellular creatine uptake, rather than through glycolysis and mitochondrial oxidative phosphorylation in the macrophages. Blockade of the creatine transporter (CrT) failed to upregulate ATP and enhance the immunological activity of macrophages in creatine supplementation, which also impaired CD8+ T cell activity. Consequently, CrT blockade failed to suppress tumor growth in the creatine-supplemented mice. Thus, creatine is an important nutrient that promotes macrophage function by increasing ATP levels, ultimately contributing to enhanced anti-tumor immunity orchestrated by CD8+ T cells

Effect of Dy substitution in the giant magnetocaloric properties of HoB2_{2}

Recently, a massive magnetocaloric effect near the liquefaction temperature of hydrogen has been reported in the ferromagnetic material HoB$_{2}$. Here we investigate the effects of Dy substitution in the magnetocaloric properties of Ho$_{1-x}$Dy$_{x}$B$_{2}$ alloys ($\textit{x}$ = 0, 0.3, 0.5, 0.7, 1.0). We find that the Curie temperature ($\textit{T}$$_{C}$) gradually increases upon Dy substitution, while the magnitude of the magnetic entropy change |$\Delta \textit{S}_{M}$| at $\textit{T}$ = $\textit{T}_{C}$ decreases from 0.35 to 0.15 J cm$^{-3}$ K$^{-1}$ for a field change of 5 T. Due to the presence of two magnetic transitions in these alloys, despite the change in the peak magnitude of |$\Delta \textit{S}_{M}$|, the refrigerant capacity ($\textit{RC}$) and refrigerant cooling power ($\textit{RCP}$) remains almost constant in all doping range, which as large as 5.5 J cm$^{-3}$ and 7.0 J cm$^{-3}$ for a field change of 5 T. These results imply that this series of alloys could be an exciting candidate for magnetic refrigeration in the temperature range between 10-50 K.Comment: 19 pages, 5 figures, 2 table

Spin Accumulation in Nondegenerate and Heavily Doped p-Type Germanium

Spin accumulation induced in p-type germanium from Fe/MgO tunnel contacts is studied as a function of hole concentration p (10^16 - 10^19 cm-3). For all p, the contacts are free of rectification and Schottky barrier, guaranteeing spin injection into the Ge and preventing spin accumulation enhancement by two-step tunneling via interface states. The observed spin accumulation is smallest for nondegenerate doping (p ~ 10^16 cm-3) and increases for heavily doped Ge. This trend is opposite to what is expected from spin injection and diffusion theory. For heavily doped Ge, the observed spin accumulation is orders of magnitude larger than predicted.Comment: To appear in Appl. Phys. Expres

Psychological factors that promote behavior modification by obese patients

<p>Abstract</p> <p>Background</p> <p>The weight-loss effect of team medical care in which counseling is provided by clinical psychologists was investigated in an university hospital obesity (OB) clinic. Nutritional and exercise therapy were also studied. In our previous study, we conducted a randomized, controlled trial with obese patients and confirmed that subjects who received counseling lost significantly more weight than those in a non-counseling group. The purpose of this study was to identify the psychological characteristics assessed by ego states that promote behavior modification by obese patients.</p> <p>Methods</p> <p>147 obese patients (116 females, 31 males; mean age: 45.9 ± 15.4 years) participated in a 6-month weight-loss program in our OB clinic. Their psychosocial characteristics were assessed using the Tokyo University Egogram (TEG) before and after intervention. The Wilcoxon signed rank test was used to compare weight and psychological factors before and after intervention. Multiple regression analysis was used to identify factors affecting weight loss.</p> <p>Results</p> <p>Overall, 101 subjects (68.7%) completed the program, and their data was analyzed. The subjects mean weight loss was 6.2 ± 7.3 kg (<it>Z </it>= 7.72, <it>p </it>< 0.01), and their mean BMI decreased by 2.4 ± 2.7 kg/m²(<it>Z </it>= 7.65, <it>p </it>< 0.01). Significant differences were observed for the Adult (A) ego state (0.68 ± 3.56, <it>Z </it>= 1.95, <it>p </it>< 0.05) and the Free Child (FC) ego state (0.59 ± 2.74, <it>Z </it>= 2.46, <it>p </it>< 0.01). The pre-FC ego state had a significant effect on weight loss (β = 0.33, <it>p </it>< 0.01), and a tendency for changes in the A ego state scores to affect weight loss (β = - 0.20, <it>p </it>= 0.06) was observed.</p> <p>Conclusion</p> <p>This study of a 6-month weight-loss program that included counseling by clinical psychologists confirmed that the A ego state of obese patients, which is related to their self-monitoring skill, and the FC ego state of them, which is related to their autonomy, were increased. Furthermore, the negative aspects of the FC ego state related to optimistic and instinctive characteristics inhibited the behavior modification, while the A ego state represented objective self-monitoring skills that may have contributed to weight loss.</p

Unbiased Recommender Learning from Missing-Not-At-Random Implicit Feedback

Recommender systems widely use implicit feedback such as click data because of its general availability. Although the presence of clicks signals the users' preference to some extent, the lack of such clicks does not necessarily indicate a negative response from the users, as it is possible that the users were not exposed to the items (positive-unlabeled problem). This leads to a difficulty in predicting the users' preferences from implicit feedback. Previous studies addressed the positive-unlabeled problem by uniformly upweighting the loss for the positive feedback data or estimating the confidence of each data having relevance information via the EM-algorithm. However, these methods failed to address the missing-not-at-random problem in which popular or frequently recommended items are more likely to be clicked than other items even if a user does not have a considerable interest in them. To overcome these limitations, we first define an ideal loss function to be optimized to realize recommendations that maximize the relevance and propose an unbiased estimator for the ideal loss. Subsequently, we analyze the variance of the proposed unbiased estimator and further propose a clipped estimator that includes the unbiased estimator as a special case. We demonstrate that the clipped estimator is expected to improve the performance of the recommender system, by considering the bias-variance trade-off. We conduct semi-synthetic and real-world experiments and demonstrate that the proposed method largely outperforms the baselines. In particular, the proposed method works better for rare items that are less frequently observed in the training data. The findings indicate that the proposed method can better achieve the objective of recommending items with the highest relevance.Comment: accepted at WSDM'2

Characterizing Reaction Route Map of Realistic Molecular Reactions based on Weight Rank Clique Filtration of Persistent Homology

A reaction route map (RRM) constructed using GRRM program is a collection of elementary reaction pathways, each of which consists of two equilibrium (EQ) geometries and one transition-state (TS) geometry, connected by the intrinsic reaction coordinate (IRC). An RRM can be mathematically represented by a graph with weights assigned to both vertices, corresponding to EQs, and edges, corresponding to TSs, representing the corresponding energies. In this study, we propose a method to extract topological descriptors of a weighted graph representing an RRM based on persistent homology (PH). The work of Mirth et al. [J. Chem. Phys. 2021, 154, 114114], in which PH analysis was applied to the (3N-6)-dimensional potential energy surface of an N atomic system, is related to the present method, but the latter is practically applicable to realistic molecular reactions. The results of this study suggest that the descriptors obtained using the proposed method reflect the characteristics of the chemical reactions and/or physicochemical properties of the system accurately.Comment: 38 pages, 19 figure