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The Rare Isotope Accelerator Complex for ON-line experiments (RAON) is an accelerator facility capable of generating and accelerating both stable and unstable heavy ions for various scientific research on rare isotopes. The facility can produce a variety of rare isotope beams using both the in-flight fragmentation and the isotope separation on-line methods. A unique feature of the RAON is its ability to produce very exotic rare isotope beams by combining the isotope separation on-line and the in-flight fragmentation methods. The in-flight fragmentation system is driven by a superconducting linear accelerator to accelerate heavy ions, while the isotope separation on-line system is driven by a 70-MeV proton cyclotron. The ultimate goal of the RAON is to accelerate various ion beams, ranging from protons to uranium, up to a beam power of 400 kW. After an 11-year construction project, which started in December 2011, the first beam extraction from the low-energy superconducting linear accelerator was achieved in May 2023. In this review, we describe the current status of the RAON heavy-ion accelerator, including the results of the initial beam commissioning of the low-energy linear accelerator.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

We surveyed randomized controlled trials (RCTs) examining the efficacy and safety of anifrolumab 300 mg in patients with active systemic lupus erythematosus (SLE) despite receiving standard therapy, using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis performed to determine treatment efficacy and safety outcomes of three RCTs (459 patients and 468 controls) revealed that the BICLA responses were significantly higher in the anifrolumab group than in the placebo group (OR = 2.071, 95%CI 1.575–2.725, p< 0.001). Steroid reduction and CLASI reduction were also significantly higher in the anifrolumab group than in the placebo group (OR = 1.811, 95%CI = 1.308–2.506, p< 0.001; OR = 2.245, 95%CI = 1.437–3.506, p< 0.001). Compared with placebo, anifrolumab significantly increased the SRI7 and SRI8 responses in SLE patients (OR = 1.866, 95%CI = 1.372–2.536, p< 0.001; OR = 1.925, 95%CI = 1.387–2.672, p< 0.001). The SRI4, 5, and 6 responses also tended to be higher in the anifrolumab group than in the placebo group. Adverse event incidence was significantly higher in the anifrolumab group than in the placebo group (OR = 1.815, 95%CI = 1.262–2.611, p= 0.001); serious adverse events were significantly lower in the anifrolumab group than in the placebo group (OR = 0.679, 95%CI = 0.468–0.986, p= 0.042). Herpes zoster infection was significantly higher in the anifrolumab group than in the placebo group (OR = 4.089, 95%CI = 1.750–9.522, p= 0.001). Anifrolumab is effective for treating active SLE. However, anifrolumab increased the incidence of herpes zoster infection compared with placebo.

An assessment of the relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to those of methotrexate (MTX) was performed in disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid arthritis (RA). We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) so as to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and MTX in DMARD-naïve RA patients. Four RCTs comprising 2185 patients met the inclusion criteria. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of achieving the American College of Rheumatology 20% (ACR20) response rate, followed by baricitinib 4 mg, tofacitinib 5 mg, filgotinib 200 mg, and MTX. Tofacitinib, baricitinib, upadacitinib, and filgotinib treatments achieved significantly higher ACR50 and ACR70 responses compared to MTX. Tofacitinib 5 mg had the highest probability of achieving the ACR50 and ACR70 response rates, followed by upadacitinib 15 mg, baricitinib 4 mg, filgotinib 200 mg, and MTX. The safety analysis based on serious adverse events, adverse events (AEs), and withdrawals due to AEs revealed no statistically significant differences between the respective intervention groups. In conclusion, tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for DMARD-naïve RA patients, suggesting a difference in efficacy and safety among the different JAK inhibitors.

Objective: Evaluation of the effectiveness and safety of secukinumab and ixekizumab in active ankylosing spondylitis (AS) patients. Methods: A Bayesian network meta-analysis was conducted using direct and indirect data from five randomized controlled trials that examined the efficacy and safety of secukinumab 150 mg every 4 weeks and ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) in active AS patients. Results: Data from 1433 patients were analyzed. The Assessment of Spondyloarthritis International Society evaluation 20% response rates (ASAS20) were significantly higher with secukinumab 150 mg, IXEQ2W, IXEQ2W, and adalimumab 40 mg (odds ratio [OR] 2.75, 95% Bayesian credible interval [CrI] 2.04–3.69; OR 2.59, 95% CrI 1.69–3.98; OR 2.45, 95% CrI 1.60–3.75; and OR 1.94, 95% CrI 1.13–3.37, respectively) compared to the placebo group. Efficacies of secukinumab and ixekizumab were numerically higher compared to adalimumab 40 mg, although there was no significant difference in the ASAS20 response rates. The ASAS40 response rate showed a pattern of distribution similar to the ASAS20 response rate, with the exception of the ixekizumab group, which was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ASAS40 response rate. Based on the SUCRA rating, secukinumab 150 mg had the highest probability of being the best ASAS20 response rate therapy, followed by IXEQ2W, IXEQ4W, adalimumab 40 mg, and placebo. There was no significant difference between the treatments regarding the number of serious adverse events (SAEs). Conclusion: Secukinumab and ixekizumab were effective in active AS treatment, without the risk of SAEs.

Objective: To systematically investigate the relationship between circulating interleukin-23 (IL‑23) levels and ankylosing spondylitis (AS) and establish a correlation between these hematological indices and AS activity/severity. Methods: We searched the Medline, Embase, and Cochrane databases; performed a meta-analysis comparing serum/plasma IL‑23 levels in patients with AS to those of controls; and examined the correlation coefficients between serum/plasma IL‑23 levels and AS activity. Results: Ten studies including 1724 patients with AS and 1589 controls were included in this meta-analysis. This meta-analysis showed that circulating IL‑23 levels were significantly higher in the AS than in the control group (standardized mean difference [SMD] 1.479; 95% confidence interval [CI] 0.308–2.650; p= 0.013). Stratification by ethnicity showed a significantly increased IL‑23 level in the AS group in an Asian population (SMD 1.551; 95% CI 0.543–2.558; p= 0.003). Stratification by adjustment for age and sex revealed significantly higher IL‑23 levels in the AS adjustment group. Subgroup analysis of sample size showed a significantly higher IL‑23 level for a small (n&lt; 150) sample number in the AS group. Meta-analysis of correlation coefficients revealed that the IL‑23 level was positively associated with the Bath Ankylosing Spondylitis Metrology Index (BASMI; correlation coefficient 0.464; 95% CI 0.027–0.752; p= 0.038), erythrocyte sedimentation rate (ESR; correlation coefficient 0.258; 95% CI 0.076–0.422;p= 0.006), and C‑reactive protein (CRP; correlation coefficient 0.291; 95% CI 0.053–0.498;p= 0.017). Conclusion: This meta-analysis demonstrated that the circulating IL‑23 level is significantly higher in patients with AS, and a significant positive correlation exists between the circulating IL‑23 level and BASMI, ESR, and CRP.

Objective: This study aimed to assess the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) in patients with active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: We performed a meta-analysis of four randomized clinical trials (RCTs; 300 patients) to examine the relative efficacy and safety of MMF compared to CYC in patients with active AAV. Results: There was no significant difference in remission at 6 months between MMF and CYC (odds ratio [OR] 1.311, 95% confidence interval [CI] 0.570–3.017, P= 0.524). Additionally, the relapse rate did not differ between the MMF and CYC groups (OR 1.331, 95% CI 0.497–3.568, P= 0.570). There was no significant difference in serious adverse event (SAE; OR 1.232, 95% CI 0.754–2.014, P= 0.404) and infection rates (OR 0.958, 95% CI 0.561–1.634, P= 0.873) between the MMF and CYC groups. Some heterogeneity was found in the meta-analysis of remission and relapse rates (I2= 57.4%, 63.4%), but no between-study heterogeneity was found during the meta-analysis of SAE and infection rate. Egger’s regression test showed no evidence of publication bias (Egger’s regression test P-values >0.1). Conclusion: MMF was an equally effective alternative treatment to CYC and MMF was comparable to CYC in patients with active AAV in terms of safety, suggesting that MMF can be used as an alternative to CYC for remission induction in AAV.

Objective: The relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib were assessed in patients with rheumatoid arthritis (RA) with inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARDs). Methods: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in RA patients with inadequate responses to bDMARDs. Results: Four RCTs comprising 1399 patients met the inclusion criteria. Tofacitinib, baricitinib, upadacitinib, and filgotinib achieved significant American College of Rheumatology 20% (ACR20) responses versus placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by filgotinib 200 mg, baricitinib 4 mg, filgotinib 100 mg, tofacitinib 5 mg, and placebo. The ranking in SUCRA based on the ACR50 response rate indicated that baricitinib 4 mg had the highest probability of achieving the ACR50 response rate, followed by filgotinib 200 mg, tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 100 mg, and placebo. Tofacitinib 5 mg showed a significantly higher ACR70 response rate than filgotinib 100 mg and upadacitinib 15 mg. Tofacitinib 5 mg, filgotinib 200 mg, and placebo showed a significantly lower serious adverse event rate than upadacitinib 15 mg. Conclusion: Tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for RA patients with an inadequate response to bDMARDs but with different efficacy and safety profiles.

Objective: To investigate whether periodontitis is causally associated with risk of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Methods: We performed two-sample Mendelian randomization (MR) analysis using the inverse variance-weighted (IVW), weighted median, and MR-Egger regression methods on publicly available summary statistics datasets using a periodontitis genome-wide association study (GWAS) as an exposure and RA and SLE GWASs on individuals of European descent as outcomes. Results: We selected 7 or 20 single-nucleotide polymorphisms from a periodontitis GWAS as instrumental variables for RA or SLE. The IVW method results support a causal association between periodontitis and RA (beta = 0.168, SE = 0.080, p= 0.035) and SLE (beta = 0.0001, SE = 0.0001, p= 0.046) risk; however, the weighted median approach did not indicate a significant causal association. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the RA (intercept = −0.115, p= 0.078) or SLE results (intercept = 4.68E-05, p= 0.394); no significant causal association was found between periodontitis and RA and SLE. The MR estimates from the IVW, weighted median, and MR-Egger regression analyses were not consistent. Conclusion: Only the results of MR analysis by the IVW method indicated that periodontitis is likely causally associated with an increased risk of RA and SLE incidence. Our MR showed weak causal association between periodontitis and RA or SLE. These findings may assist in elucidating the underlying mechanisms of the effects of periodontitis on RA and SLE incidence.

Objective: We compared the efficacy and safety of tofacitinib and filgotinib in patients with rheumatoid arthritis (RA) showing inadequate response to conventional synthetic (cs) or biologic (b) disease-modifying anti-rheumatic drugs (DMARDs). Methods: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and filgotinib in combination with methotrexate (MTX) in patients with RA exhibiting inadequate cs- or bDMARD response. Results: Nine RCTs consisting of 5466 patients met the inclusion criteria. We obtained 15 pairwise comparisons, including 11 direct comparisons from 6 interventions. Tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX were among the most effective treatments for active RA showing an inadequate cs- or bDMARD response, followed by tofacitinib 5 mg + MTX, filgotinib 100 mg + MTX, and adalimumab + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX showed the highest probability of being the best treatment options in terms of ACR20 response rate (SUCRA = 0.898, 0.782), followed by tofacitinib 5 mg + MTX (SUCRA = 0.602), filgotinib 100 mg + MTX (SUCRA = 0.359), adalimumab + MTX (SUCRA = 0.358), and placebo + MTX (SUCRA = 0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, filgotinib + MTX, adalimumab + MTX, or placebo + MTX. Conclusion: In patients with RA exhibiting an inadequate response to cs- or bDMARDs, tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX were the most efficacious interventions and risks of serious adverse events did not differ between tofacitinib and filgotinib groups.

Objective: This study systemically reviewed the evidence regarding associations between polymorphisms in interleukin-17 (IL-17) genes and osteoarthritis (OA) susceptibility, and the relationship between circulating IL-17 levels and OA. Methods: We performed a meta-analysis of the associations between the IL-17Ars2275913 and IL-17Frs763780 polymorphisms and risk for OA and serum/plasma IL-17 levels in OA patients and controls. Results: Eight studies including 2214 OA patients and 2474 controls were included. Our meta-analysis identified a significant association between OA and the AA genotype of the IL-17Ars2275913 polymorphism in a pooled cohort of affected individuals, compared to the case in a pooled cohort of control participants (OR = 1.516, 95% CI = 1.260–1.825, P&lt; 0.001), and a significant association between OA and the CC genotype of the IL-17Frs763780 polymorphism (OR = 2.257, 95% CI = 1.376–3.704, p= 0.001). OA site-based stratification identified an association between the AA genotype of the IL-17Ars2275913 polymorphism and the CC genotype of the IL-17Frs763780 polymorphism and knee OA, but not hip OA. Furthermore, the same patterns of significant associations between OA and the IL-17Ars2275913 andIL-17Frs763780 polymorphisms were identified based on homozygote contrasts. The OA patients showed significantly higher IL-17 levels than the control subjects (SMD = 1.830, 95% CI = 1.184–2.477, P&lt; 0.001). Conclusion: Our meta-analysis revealed associations between the IL-17Ars2275913 and IL-17Frs763780 polymorphisms and OA susceptibility, and the presence of significantly higher circulating IL-17 levels in OA patients.

Objective: This study systemically reviewed the evidence regarding the association between plasminogen activator inhibitor‑1 (PAI‑1) 4G/5Gpolymorphism and susceptibility to systemic lupus erythematous (SLE)/lupus nephritis (LN) and rheumatoid arthritis (RA) and the relationship between circulating PAI‑1 levels and SLE/LN and RA. Methods: We conducted a meta-analysis on the association between the PAI‑1 4G/5Gpolymorphism and SLE/LN or RA risk and serum/plasma PAI‑1 levels in patients with SLE/LN and RA and healthy controls. Results: Nine articles including 657 patients with SLE and 668 controls and 567 patients with RA and 772 controls were included. No association was revealed between SLE and PAI‑1 4Gallele in all study subjects (odds ratio [OR] = 0.944, 95% confidence interval [CI] = 0.808–1.102, p= 0.463). Ethnicity-based stratification showed no association between the PAI‑1 4Gallele and SLE among Europeans and Asians. No association was detected between LN and RA and the PAI‑1 4Gallele (OR = 0.886, 95% CI = 0.713–1.102, p= 0.278; OR = 0.8736, 95% CI = 0.747–1.020, p= 0.088, respectively) or between SLE/LN and RA and the PAI‑1 4G/5Gpolymorphism using the recessive and dominant models and homozygote contrast. The circulating PAI‑1 level was significantly higher in the SLE group than in the control group (standardized mean difference [SMD] = 0.337, 95% CI = 0.057–0.619, p= 0.019). However, serum/plasma PAI‑1 level showed no significant difference between RA and control group (SMD = 0.333, 95% CI = −0.6989–1.35, p= 0.527). Conclusions: There was no association between the PAI‑1 4G/5Gpolymorphism and SLE/LN and RA development and significantly higher levels of circulating PAI‑1 were observed in patients with SLE but not in those with RA.

Objectives: We assessed the relative efficacy and safety of once-daily administration of 15 and 30 mg upadacitinib (a JAK1-selective inhibitor) in patients with active rheumatoid arthritis (RA). Methods: We conducted a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) that examined the efficacy and safety of upadacitinib in patients with active RA. Results: Five RCTs involving 4381 patients met the inclusion criteria. There were 15 pairwise comparisons, including eight direct comparisons and six interventions. The ACR20 response rate was significantly higher in the upadacitinib 15 and 30 mg + MTX (methotrexate) groups than in the MTX group (OR: 4.98, 95% CrI: 2.66–10.10; OR: 4.73, 95% CrI: 2.25–10.98). Adalimumab 40 mg + MTX, upadacitinib 30 mg, and upadacitinib 15 mg groups showed a significantly higher ACR20 response rate than did the MTX group. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX was likely to achieve the best ACR20 response rate (SUCRA = 0.838), followed by upadacitinib 30 mg + MTX, adalimumab 40 mg + MTX, upadacitinib 30 mg, upadacitinib 15 mg, and MTX (SUCRA = 0.784, 0.495, 0.471, 0.404, and 0.008, respectively). The safety based on the number of serious adverse events (SAEs) did not differ significantly among the six interventions. Conclusions: Upadacitinib 15 and 30 mg administration once daily in combination with MTX was the most efficacious intervention for active RA, with no significant risk for SAEs.

Objective: To examine whether alcohol intake is causally associated with rheumatoid arthritis (RA). Methods: We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We used the publicly available summary statistics of alcohol intake frequency from the UK Biobank genome-wide association studies (GWASs; n?=?336,965) as the exposure and a GWAS meta-analysis of 5539 autoantibody-positive RA patients and 20,169 controls as the outcome. Results: We selected 24 single nucleotide polymorphisms (SNPs) associated with alcohol intake frequency at genome-wide significance as instrumental variables (IVs) to improve inference, 16 of which were inversely associated with RA. The IVW method showed no evidence of a causal association between alcohol intake and RA (beta?=?0.218, SE?=?0.213, p?=?0.306). The MR-Egger regression revealed that directional pleiotropy was unlikely to bias the result (intercept?=?0.027, p?=?0.292). The MR-Egger analysis and the weighted median approach showed no causal association between alcohol intake and RA (beta?=?-0.778, SE?=?0.947, p?=?0.420 and beta?=?-0.286, SE?=?0.302, p?=?0.344, respectively). Cochran’s Q test did not indicate heterogeneity between IV estimates based on the individual variants, and results from a “leave-one-out” analysis demonstrated that no single SNP was driving the IVW point estimate. Conclusion: The MR analysis does not support a causal inverse association between alcohol intake and RA occurrence.

Objectives: The relative efficacy and safety of tofacitinib and baricitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) or biologics. Methods: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and baricitinib in combination with DMARDs in RA patients with an inadequate DMARD or biologic response. Results: Twelve RCTs including 5883 patients met the inclusion criteria. There were 15 pairwise comparisons including 10 direct comparisons of 6 interventions. Tofacitinib 10 mg + methotrexate (MTX) and baricitinib 4 mg + MTX were among the most effective treatments for active RA with an inadequate DMARD or biologic response, followed by baricitinib 2 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest probability of being the best treatment to achieve the ACR20 response rate (SUCRA = 0.865), followed by baricitinib 4 mg + MTX (SUCRA = 0.774), baricitinib 2 mg + MTX (SUCRA = 0.552), tofacitinib 5 mg + MTX (SUCRA = 0.512), adalimumab + MTX (SUCRA = 0.297), and placebo + MTX (SUCRA &lt;0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, baricitinib + MTX, adalimumab + MTX, or placebo + MTX. Conclusions: In RA patients with an inadequate response to DMARDs or biologics, tofacitinib 10 mg + MTX and baricitinib 4 mg + MTX were the most efficacious interventions and were not associated with a significant risk of serious adverse events.

Purpose: PLC plays a critical role in many intracellular processes such as growth, differentiation and transformation. There are three major classes of PLCs, namely PLC-Β, [Gamma] and Δ. PLC-[Gamma]1 is [...]

Objective:Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain.Design:We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses.Results:In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-associated molecular patterns.Conclusions:Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.

Background/Objectives:We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice.Methods:Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1?mg?kg-1daily) was injected intraperitoneally for 20 weeks.Results:Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes.Conclusions:Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

We performed a retrospective study of 1868 consecutive unrelated donors to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs) and intention of a second donation in hematopoietic stem cell (HSC) donation. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0–10) and donor’s intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 h after HSC collection and at 1 week, 4 weeks, and 4 months thereafter. Predictors of general discomfort included female sex (P<0.0001), bone marrow (BM) collection (P<0.0001) or PBSC collection through a central line (CL; P=0.0349), 2-day collection (P=0.0150) and negative or undetermined intention of a second donation on day 1 (P<0.0001). Predictors of limitations in ADLs included age group of 30–39 years (P=0.0046), female sex (P<0.0001), BM collection (P<0.0001) or PBSC collection through a CL (P<0.0001) and negative or undetermined intention of a second donation on day 1 (P<0.0001). The only predictor of positive intention of a second donation was male sex (P=0.0007). Age, sex and collection method and period should be considered risk factors when unrelated HSC donation is performed.

Background/Objectives:: Activation of Notch signaling pathologically enhances lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that can modulate adipogenesis and muscle development in mice, was found as an inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic effect of exogenous DLK1 in vitroand in vivo. Subjects/Methods:: A soluble DLK1 peptide was generated with fusion between a human Fc fragment and extracellular domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle treated and DLK1-treated group (25?mg?kg-1, intraperitoneal injection, twice a week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in vitroexperiments. Results:: After 4 weeks of DLK1 administration, hepatic triglyceride content and lipid droplets in liver tissues, as well as serum levels of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower levels of fasting and random glucose, with improved glucose and insulin tolerance compared with the vehicle-treated group. Macrophage infiltration and proinflammatory cytokine levels in the epididymal fat were decreased in DLK1-treated db/db mice. Moreover, DLK1 suppressed glucose production from hepatocytes, which was blocked after co-administration of an AMPK inhibitor, compound C. DLK1-treated hepatocytes and mouse liver tissues showed lower PEPCK and G6Pase expression. DLK1 triggered AKT phosphorylation followed by cytosolic translocation of FOXO1 from the nucleus in hepatocytes. Conclusions:: The present study demonstrated that exogenous administration of DLK1 reduced hepatic steatosis and hyperglycemia via AMPK activation in the liver. This result suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and diabetes.

The breakup of East and West Gondwana occurred during the Jurassic, but the exact timing is uncertain due to the limited exposure of rocks suitable for radioisotopic dating. Trachytic rocks from Silhouette Island, Seychelles, yielded a range of zircon ages from Paleoproterozoic to Cenozoic. The 206Pb/238U age of the trachyte is 64.9 ± 1.6 Ma (Danian) but the majority of zircons yielded an age of 163.8 ± 1.8 Ma (Callovian) with a small subset yielding an age of 147.7 ± 4.5 Ma (Tithonian). The Hf isotopes of the Callovian (εHf(t) = +4.1 to +13.4) and Danian (εHf(t) = +1.9 to +7.1) zircons indicate that they were derived from moderately depleted mantle sources whereas the Tithonian zircons (εHf(t) = −7.0 to −7.3) were derived from an enriched source. The identification of middle Jurassic zircons indicates that rifting and magmatism were likely contemporaneous during the initial separation of East and West Gondwana. Callovian and Tithonian aged zircons are identified within the Seychelles microcontinentCallovian magmatism was derived from a moderately depleted mantle sourceMiddle Jurassic magmatism accompanied the break‐up between east and west Gondwana

Relaxation Oscillation SQUIDs (ROS) and Double Relaxation Oscillation SQUIDS (DROS) combine the sensitivity of dc-SQUIDS with a large transfer, thus enabling flux locked loop operation with direct voltage readout by a room-temperature dc-amplifier, without flux modulation techniques. We fabricated several ROSs and DROSs with relaxation frequencies from 5 to 180 MHz. The experimental flux-to-frequency curves of the ROSs can well be fitted with theory, and the transfer (up to 170MHz/Φo) is large enough for practical use in a FLL without flux modulation. The experimental flux-to-voltage characteristics of the DROSs show very large transfer values of typically 10 to 30 mV/Φo. A DROS operated in a simple FLL with direct voltage readout showed a white noise level of about 2 µΦo/√Hz. A three channel DROS magnetometer system for biomagnetic measurements is under construction. In the DROSs that are to be used in this system, the signal flux is coupled to the SQUID by a tightly coupled 50-turn input coil.

ABSTRACTThis paper investigates the lead-lag relationship and jump effect linkages between the Nikkei 225 returns and the changes in the Volatility Index Japan (hereafter VXJ). The empirical results show that the evidence regarding the market returns influences the feelings of the investors. It is found that both the jump components in investor sentiment and market returns are strong phenomena. Moreover, the results of this study also indicate that the time-varying arrival of correlated jumps is jointly determined by the volatility in the changes in the VXJ. Finally, the CBP-GARCH model can be used to examine the jump effect between Nikkei 225 returns and the changes in the VXJ.

The purpose of this study was to evaluate the risk of late displacement after the treatment of distal radial fractures with a locking volar plate, and to investigate the clinical and radiological factors that might correlate with re-displacement. From March 2007 to October 2009, 120 of an original cohort of 132 female patients with unstable fractures of the distal radius were treated with a volar locking plate, and were studied over a follow-up period of six months. In the immediate post-operative and final follow-up radiographs, late displacement was evaluated as judged by ulnar variance, radial inclination, and dorsal angulation. We also analysed the correlation of a variety of clinical and radiological factors with re-displacement. Ulnar variance was significantly overcorrected (p < 0.001) while radial inclination and dorsal angulation were undercorrected when compared statistically (p <  0.001) with the unaffected side in the immediate post-operative stage. During follow-up, radial shortening and dorsal angulation progressed statistically, but none had a value beyond the acceptable range. Bone mineral density measured at the proximal femur and the position of the screws in the subchondral region, correlated with slight progressive radial shortening, which was not clinically relevant.Volar locking plating of distal radial fractures is a reliable form of treatment without substantial late displacement.Cite this article: Bone Joint J2013;95-B:396–400.

An inkjet‐based ultrashort pulsed laser patterning on a polymer substrate is presented with high‐laser scanning speeds. The effects of the laser processing parameters on the ablation characteristics were studied to accomplish damage‐free laser ablation. Laser ablation characteristics depend on input energy, scanning speed, and number of scans. Final width of microelectrodes can be flexibly controlled by multiple selective ablations. Well‐defined, uniform microelectrodes without damaging their microstructure, and the underlying polymer substrate are demonstrated via a direct pattering process combining inkjet printing with ultrashort pulsed laser ablation. These microelectrodes exhibit little influence of thermal effect of laser ablation, resulting in little variation in their electrical performances.

This paper studies the thermal response on the mold surface of a circular cavity in the preheating process by high-temperature gas via a numerical approach, where the heat and mass transfer inside the cavity and mold are predicted by a two-fluid model. The dimensionless parameter group is identified from a dimensional analysis of the gas preheating problem. The correlations among dimensionless parameters are established by a least square method applied to the numerical predictions. The upper limit of the temperature rise on the cavity surface at a given gas flow rate is found approximately proportional to the square root of Q*and h*, respectively. The lower limit of gas flow rate to achieve a given temperature rise on the cavity surface is inversely proportional to h*but grows with (Q*)1.5. The first limiting line to describe the dependence of Q*on t*is independent of h*and T*, but the second one is governed by Q*c. For reaching a specified temperature rise on the cavity surface, the growth in the thickness of thermal resistive layer reduces the required preheating time but increases the corresponding gas flow rate. The dependence of (t*f, Q*f) on the parameter group (T*, h*) is given in this study to obtain the reasonable combinations of (t*f, Q*f) based on the balance between the allowable preheating time and heating capacity.

An investigation on the interface heat transfer coefficient during bulk forming of glass-coated Ti–6Al–4 V was carried out. Heat transfer experiments were conducted where two dies were heated to various temperatures and Ti–6Al–4 V cylindrical specimen heated to 970°C was upset tested. Temperature changes of the lower die consisting of AISI H13 were recorded in relation to the process variables such as reduction ratio, lubrication condition, and initial die temperature. The temperature change data were analysed to determine the interface heat transfer coefficients between lubricated die and glass-coated workpiece by using the plotting approach on calibration curves derived from analytical method and the inverse algorithm coupled to finite element (FE) analysis. The former was to determine the initial guessing values for applying the inverse algorithm. The validation of final coefficients determined by the inverse algorithm was made by comparison between the upsetting process and the FE analysis results.

The outcome of surgery in patients with medial epicondylitis of the elbow is less favourable in those with co-existent symptoms from the ulnar nerve. We wanted to know whether we could successfully treat such patients by using musculofascial lengthening of the flexor-pronator origin with simultaneous deep transposition of the ulnar nerve. We retrospectively reviewed 19 patients who were treated in this way. Seven had grade I and 12 had grade IIa ulnar neuropathy. At a mean follow-up of 38 months (24 to 48), the mean visual analogue scale pain scores improved from 3.7 to 0.3 at rest, from 6.6 to 2.1 with activities of daily living, and from 7.9 to 2.3 at work or sports, and the mean disabilities of the arm, shoulder and hand scores improved from 42.2 to 23.5.These results suggest that this technique can be effective in treating patients with medial epicondylitis and coexistent ulnar nerve symptoms.

We treated 32 displaced mallet finger fractures by a two extension block Kirschner-wire technique. The clinical and radiological outcomes were evaluated at a mean follow-up of 49 months (25 to 84). The mean joint surface involvement was 38.4% (33% to 50%) and 18 patients (56%) had accompanying joint subluxation. All 32 fractures united with a mean time to union of 6.2 weeks (5.1 to 8.2). Congruent joint surfaces and anatomical reduction were seen in all cases. The mean flexion of the distal interphalangeal joints was 83.1° (75° to 90°) and the mean extension loss was 0.9° (0° to 7°). No digit had a prominent dorsal bump or a recurrent mallet deformity. We believe that this technique, when properly applied, produces satisfactory results both clinically and radiologically.

Postweaning multisystemic wasting syndrome (PMWS) was reproduced in prenatally porcine circovirus 2 (PCV2)-infected pigs by either postnatal infection with porcine parvovirus (PPV) or by immunostimulation. Twenty-four randomly selected piglets from 3 sows, which had been experimentally infected during gestation with PCV2, were randomly divided into 3 groups; group 1 (prenatal PCV2 infection, with postnatal PPV infection), group 2 (prenatal PCV2 infection, with postnatal keyhole limpet hemocyanin, emulsified in incomplete Freund's adjuvant [KLH/ICFA] injection), and group 3 (prenatal PCV2 infection only). Twenty-four randomly selected piglets from 3 uninfected sows were randomly divided into 3 groups; group 4 (no prenatal infection, with postnatal PCV2 and PPV infection), group 5 (no prenatal infection, with postnatal PCV2 infection), and group 6 (negative control pigs). Body weight in negative control pigs (group 6) was increased significantly compared with pigs in groups 1, 2, and 4 at 49, 52, 56, 59, and 63 days of age. The granulomatous inflammatory reaction and lymphoid depletion that are typical lesions in pigs with PMWS were observed in the lymph node of piglets in groups 1, 2, and 4 at 63 days of age. Pigs in group 3 had significantly fewer PCV2-positive cells than those from groups 1,2,4, or 5. When the prenatally PCV2-infected pigs were infected with PPV or injected with immunostimulant in the postnatal period, they developed PMWS. Thus, factors that potentiate the progression of prenatal PCV2 infection to PMWS are postnatal infection with PPV or immune stimulation.

The automotive industry has shown a growing interest in tube hydroforming during recent years. The advantages of hydroforming (less thinning, a more efficient manufacturing process, etc.) can, for instance, be combined with the high strength of extra-high-strength steels, which are usually less formable, to produce structural automotive components which exhibit lower weight and improved service performance. Design and production of tubular components require knowledge about tube material and forming behaviour during hydroforming and how the hydroforming operation itself should be controlled. These issues are studied analytically in the present paper. In this study, the whole process of rear subframe parts development by tube hydroforming using steel material having a tensile strength of 440 MPa is presented. At the part design stage, it requires a feasibility study and process design assisted by computer aided engineering to confirm hydroformability in detail. The effects of parameters such as internal pressure, axial feeding, and geometry shape in the automotive rear subframe by the hydroforming process were carefully investigated. The overall possibility of hydroformable rear subframe parts could be examined by cross-sectional analyses. Moreover, it is essential to ensure the formability of tube material on every forming step such as pre-bending and hydroforming. In addition, all the components of a prototyping tool are designed and interference with a press is examined from the point of geometry and thinning.

For years, the quantum optics community has been testing the limits on laser size: How small can you go? Thanks to advances in semiconductor crystal growth and fabrication techniques, the answer is now wavelength-scale.

The synthesis of cation‐substituted 1D manganese oxide nanowires is achieved via a non‐hydrothermal oxidation reaction using a solid‐state precursor and conventional glassware. By changing the reaction conditions and precursor composition, it is possible to control the crystal structure and chemical composition of the resulting 1D nanostructured materials. The nanowires are found to exhibit promising electrochemical properties as cathode materials in lithium secondary batteries; moreover, the electrochemical properties of the nanowires can be improved by the partial replacement of Mn with Cr3+cations. The measurements strongly suggest that the cation composition of the nanostructured metal oxides is very important for optimizing their electrode performance. The non‐hydrothermal solution synthesis method presented here provides an effective composition‐tailored approach for the fabrication of large quantities of 1D manganese oxide nanowires.

The effect of dispersant structures for dispersing single‐walled carbon nanotubes (SWCNTs) is investigated. The monomer 3‐hexylthiophene is used as the starting material for the development of a series of oligomers that are used to disperse SWCNTs in an organic solvent. The series is obtained by varying the number of head groups, the regioregularity of head groups, and the head‐to‐tail ratios of the hexyl group in the oligomers. The SWCNT solutions are characterized with UV‐vis–near‐IR spectroscopy and transmission electron microscopy. An increase in the number of head groups improves the dispersity of SWCNTs, and a regioregular oligomer plays an important role in dispersing SWCNTs. Furthermore, Raman spectroscopy and X‐ray photoelectron spectroscopy shows that the sulfur atom head groups enhance interactions between the thiophenes and the SWCNT walls. The analysis demonstrated that a well‐designed thiophene oligomer could afford well‐dispersed SWCNT solutions with long‐term dispersion stability, even with an extremely low dispersant concentration (weight ratio of CNTs/dispersant is one and the dispersant concentration is 0.1 g L–1).

A simple and robust dip‐coating method for fabricating carbon nanotube (CNT) field emitters has been proposed. The thin multiwalled (tMW)CNTs synthesized by CVD were dispersed in various solutions such as N,N‐dimethylformamide (DMF), isopropyl alcohol (IPA), N‐methyl‐2‐pyrrolidinone (NMP), and dichloroethane (DCE). The weak adhesion between CNTs and substrate, a serious drawback of the dip‐coating approach, was resolved by anchoring CNTs to the substrate via the melting of an indium layer. We found that the uniformity and density of the CNTs could be optimized by controlling the degree of dispersion of CNTs in solvents. The field‐emission characteristics are also discussed.

We have performed a form of lunate replacement arthroplasty, which included excision of the lunate and insertion of a vascularised radial bone flap wrapped in pronator quadratus, for stage IIIB or stage IV Kienböck’s disease, in 41 patients who have been followed up for more than three years.All patients reported an improvement in their symptoms, and 20 of the 41 became free of pain after the operation. Extension and flexion of the wrist were increased by a mean of 9° and 6°, respectively (p < 0.05). The radioscaphoid angle and the carpal height ratio were not significantly changed and only minimal deterioration was observed due to degenerative change. The size, density or location of the inserted bone did not change with time.A vascularised radial bone flap wrapped in pronator quadratus can be a reliable treatment option for advanced Kienböck’s disease, when the pedicled bone and muscle envelope acts as a stable spacer for the excised lunate.

Densely packed assemblies of single-walled carbon nanotubes (SWCNTs) were characterized by N2 and CO2 adsorption techniques. We presented a convenient method for forming densely packed assembly structures of SWCNTs. The SWCNTs were treated with mixtures of HNO3/H2SO4 or H2O2/H2SO4 before and after purification, to control the packing density and porosity of the SWCNT samples. H2O2/H2SO4 treatment caused a dramatic increase in microporosity without significantly changing the mesoporosity, whereas HNO3/H2SO4 treatment decreased the mesoporosity and simultaneously increased the microporosity. This reduced mesoporosity originates from the contraction of the interbundle distance of SWCNTs. After HNO3/H2SO4 treatment of the purified SWCNTs, the micropore surface area increased about 8.6 times compared to the pristine sample, and the volume fraction of the micropores increased from 10% to 91%, indicating formation of densely packed assemblies of SWCNTs. Therefore, HNO3/H2SO4 treatment could control not only the SWCNT bundle size but also the interbundle distance of the SWCNTs. Moreover, the purification is of importance in promoting the formation of densely packed SWCNTs. We also demonstrated that acid treatments could develop narrow micropores, which was evidenced by CO2 adsorption at 273 K. We emphasize that this approach can simply control the packing density as well as the porosity of SWCNT assemblies.

Abstract The effects of the cytosolic expression of Escherichia coli pyrophosphatase (ppa) were investigated in the rosette leaves of transgenic Arabidopsis plants. During the daytime, glucose and fructose were found to accumulate at levels that were approximately two- to threefold higher in these plants than in the wild type. Interestingly, however, neither sucrose nor starch levels showed any distinctive build up in transgenic plants except under continuous white light growth conditions, during which they accumulated at high levels. Additionally, the leaves of transgenic Arabidopsis plants contain two- to threefold higher levels of inorganic phosphate (Pi) and two- to sixfold higher levels of uridine diphosphate-glucose than wild type plants during the diurnal cycle. In contrast, triose phosphate contents in the leaves of E. coli ppa transformants were either similar or slightly decreased when compared with wild type leaves. Furthermore, the photosynthetic activity of these transgenic plants was found to be reduced by 20–40% compared to normal levels. These results indicate that induction of ppa activity in the cytosol affects carbon partitioning between source and sink organs and also that the concomitant increase in Pi caused the accumulation of carbon metabolites and reduced photosynthetic activity.

Objectives. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a natural ligand that activates the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the nuclear receptor family implicated in the regulation of lipid metabolism and adipocyte differentiation. Recent data have shown that 15d-PGJ2 exerts anti-inflammatory action via inhibition of the interferon γ (IFN-γ)-induced Jak-STAT signalling pathway. The anti-inflammatory effect of IL-10 is mediated via activated STAT3 (signal transducer and activator of transcription 3). In this study, we investigated whether 15d-PGJ2 inhibit IL-10-induced STAT activation.Methods. We used western blotting, flow cytometric analysis and a real-time polymerase chain reaction.Results. 15d-PGJ2 blocked IL-10-induced STAT1 and STAT3 activation in primary human monocytes, macrophages and THP-1 cells. Inhibition was not specific for IL-10, as induction of STAT activation by IFN-γ and IL-6 was also inhibited by 15d-PGJ2. Inhibition of IL-10 signalling was induced within 1 h after pretreatment of 15d-PGJ2. Other PPARγ agonists, such as troglitazone, did not inhibit IL-10 signalling. Treatment with GW9662, a specific PPARγ antagonist, had no effect on 15d-PGJ2-mediated inhibition of IL-10 signalling even at higher concentrations (50 μM), indicating that 15d-PGJ2 affects the IL-10-induced Jak-STAT signalling pathway via an PPARγ-independent mechanism. Actinomycin D had no effect on 15d-PGJ2-mediated inhibition of IL-10 signalling, indicating that inhibition of IL-10 signalling occurs independently of de novo gene expression. Also, inhibitors of extracellular signal-regulated kinase (ERKs) (PD98059), p38 MAPK (mitogen-activated protein kinase) (SB203580) and protein kinase C (PKC) (GF109203X, calphostin C) had no effect on 15d-PGJ2-mediated inhibition of IL-10 signalling. These results show that MAPKs and PKC are not involved in the inhibition of IL-10 signalling.Conclusions. We showed that 15d-PGJ2 non-specifically inhibits STAT signalling of the anti-inflammatory cytokine IL-10 as well as the proinflammatory cytokine IFN-γ. These findings indicate the possibility that 15d-PGJ2 can have adverse effects in the management of diseases in which IL-10 plays a critical role in the suppression of inflammation.

Melt state properties of nylon-11 and its exfoliated silicate nanocomposite were monitored during extrusion compounding using an on-line dielectric slit die sensor, and solid-state properties were probed off-line below the melting temperature by a dielectric spectrometer. A comprehensive relaxation master map for nylon-11 and its exfoliated clay nanocomposite featuring six relaxation modes in both melt and semicrystalline states revealed changes in molecular dynamics upon the addition of nanofillers. α relaxation was observed in the neat resin as well as the composite, and a Maxwell−Wagner−Sillars (MWS) relaxation was detected in the composite melt yet absent from the neat molten nylon. The MWS relaxation mode, which exhibited a broader relaxation time distribution and a much greater dielectric intensity compared to the α relaxation, resulted from polarization at the filler/polymer interfaces. MWS can be used to distinguish the neat polymer from the composite during real-time processing. The presence of exfoliated clay particles accelerated the α relaxation dynamics in the semicrystalline state as delaminated silicate platelets diminished the intermolecular cooperativity of the amorphous chains. Randomization of molecular dipoles upon increasing temperature was only observed in the neat nylon. Hindered molecular dipole orientation due to the rigid silicate fillers in the nanocomposite was observed.

We have chemically created a superconducting-paramagnetic dual magnetic system by introducing molecular magnetic species into layered high-Tccuprate, where the weak ?-? interactions between planar ?-conjugated radicals appear to form a Pauli-type paramagnetic subsystem in the interlayer space of cuprate blocks. The intercalation-induced free radicals lead to a heterostructured spin-system, providing not only a probe for high-Tcsuperconductivity but also a new way of creating materials with spin- or magnetic field-dependent functionality unattainable from conventional solid-state materials.