Spin dynamics and spin freezing behavior in the two-dimensional antiferromagnet NiGa2_{2}S4_{4} revealed by Ga-NMR, NQR and μ\muSR measurements

We have performed $^{69,71}$Ga nuclear magnetic resonance (NMR) and nuclear quadrupole resonance (NQR) and muon spin rotation/resonance on the quasi two-dimensional antiferromagnet (AFM) NiGa$_2$S$_4$, in order to investigate its spin dynamics and magnetic state at low temperatures. Although there exists only one crystallographic site for Ga in NiGa$_2$S$_4$, we found two distinct Ga signals by NMR and NQR. The origin of the two Ga signals is not fully understood, but possibly due to stacking faults along the c axis which induce additional broad Ga NMR and NQR signals with different local symmetries. We found the novel spin freezing occurring at $T_{\rm f}$, at which the specific heat shows a maximum, from a clear divergent behavior of the nuclear spin-lattice relaxation rate $1/T_{1}$ and nuclear spin-spin relaxation rate $1/T_{2}$ measured by Ga-NQR as well as the muon spin relaxation rate $\lambda$. The main sharp NQR peaks exhibit a stronger tendency of divergence, compared with the weak broader spectral peaks, indicating that the spin freezing is intrinsic in NiGa$_2$S$_4$. The behavior of these relaxation rates strongly suggests that the Ni spin fluctuations slow down towards $T_{\rm f}$, and the temperature range of the divergence is anomalously wider than that in a conventional magnetic ordering. A broad structureless spectrum and multi-component $T_1$ were observed below 2 K, indicating that a static magnetic state with incommensurate magnetic correlations or inhomogeneously distributed moments is realized at low temperatures. However, the wide temperature region between 2 K and $T_{\rm f}$, where the NQR signal was not observed, suggests that the Ni spins do not freeze immediately below $T_{\rm f}$, but keep fluctuating down to 2 K with the MHz frequency range.Comment: 14 pages, 14 figures. To appear in Phys. Rev.

Denoising approach with deep learning-based reconstruction for neuromelanin-sensitive MRI: image quality and diagnostic performance

[Purpose]Neuromelanin-sensitive MRI (NM-MRI) has proven useful for diagnosing Parkinson’s disease (PD) by showing reduced signals in the substantia nigra (SN) and locus coeruleus (LC), but requires a long scan time. The aim of this study was to assess the image quality and diagnostic performance of NM-MRI with a shortened scan time using a denoising approach with deep learning-based reconstruction (dDLR).[Materials and methods]We enrolled 22 healthy volunteers, 22 non-PD patients and 22 patients with PD who underwentNM-MRI, and performed manual ROI-based analysis. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in ten healthy volunteers were compared among images with a number of excitations (NEX) of 1 (NEX1), NEX1 images with dDLR (NEX1+dDLR) and 5-NEX images (NEX5). Acquisition times for NEX1 and NEX5 were 3 min 12 s and 15 min 58 s, respectively. Diagnostic performances using the contrast ratio (CR) of the SN (CR_SN) and LC (CR_LC) and those by visual assessment for diferentiating PD from non-PD were also compared between NEX1 and NEX1+dDLR.[Results]Image quality analyses revealed that SNRs and CNRs of the SN and LC in NEX1+dDLR were signifcantly higherthan in NEX1, and comparable to those in NEX5. In diagnostic performance analysis, areas under the receiver operating characteristic curve (AUC) using CR_SN and CR_LC of NEX1+dDLR were 0.87 and 0.75, respectively, which had no signifcant diference with those of NEX1. Visual assessment showed improvement of diagnostic performance by applying dDLR.[Conclusion]Image quality for NEX1+dDLR was comparable to that of NEX5. dDLR has the potential to reduce scan time of NM-MRI without degrading image quality. Both 1-NEX NM-MRI with and without dDLR showed high AUCs for diagnosing PD by CR. The results of visual assessment suggest advantages of dDLR. Further tuning of dDLR would be expected to provide clinical merits in diagnosing PD

Genetic and physiological basis for antibody production by Kluyveromyces marxianus

Abstract Kluyveromyces marxianus is a thermotolerant, crabtree-negative yeast, which preferentially directs metabolism (e.g., from the tricarboxylic acid cycle) to aerobic alcoholic fermentation. Thus K. marxianus has great potential for engineering to produce various materials under aerobic cultivation conditions. In this study, we engineered K. marxianus to produce and secrete a single-chain antibody (scFv), a product that is highly valuable but has historically proven difficult to generate at large scale. scFv production was obtained with strains carrying either plasmid-borne or genomically integrated constructs using various combinations of promoters (P MDH1 or P ACO1 ) and secretion signal peptides (KmINUss or Scα-MFss). As the wild-type K. marxianus secretes endogenous inulinase predominantly, the corresponding INU1 gene was disrupted using a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)—associated protein (CRISPR–Cas9) system to re-direct resources to scFv production. Genomic integration was used to replace INU1 with sequences encoding a fusion of the INU1 signal peptide to scFv; the resulting construct yielded the highest scFv production among the strains tested. Optimization of growth conditions revealed that scFv production by this strain was enhanced by incubation at 30 °C in xylose medium containing 200 mM MgSO4. These results together demonstrate that K. marxianus has the potential to serve as a host strain for antibody production

MOESM1 of Genetic and physiological basis for antibody production by Kluyveromyces marxianus

Additional file 1: Table S1. Primers used in this study. Figure S1. Amino acid sequence of scFv. Figure S2. Sequence of codon optimized scFv fragment. Figure S3. Sequence of E02-014 plasmid. Figure S4. Sequence of KmPMDH1. Figure S5. Sequence of KmPACO1. Figure S6. Secreted scFv activity per cell amount

TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist–deficient mice

IL-1 receptor antagonist–deficient (IL-1Ra(–/–)) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell–deficient IL-1Ra(–/–) mice did not develop arthritis, and transfer of IL-1Ra(–/–) T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-α deficiency. We found that TNF-α induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-α plays an important role in activating T cells through induction of OX40