Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.

Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.

Longitudinal Spin Fluctuations Driving Field-Reinforced Superconductivity in UTe_{2}.

Our measurements of ^{125}Te NMR relaxations reveal an enhancement of electronic spin fluctuations above µ_{0}H^{*}∼15 T, leading to their divergence in the vicinity of the metamagnetic transition at µ_{0}H_{m}≈35 T, below which field-reinforced superconductivity appears when a magnetic field (H) is applied along the crystallographic b axis. The NMR data evidence that these fluctuations are dominantly longitudinal, providing a key to understanding the peculiar superconducting phase diagram in H∥b, where such fluctuations enhance the pairing interactions.

Liquid Structure of Tantalum under Internal Negative Pressure.

In situ femtosecond x-ray diffraction measurements and ab initio molecular dynamics simulations were performed to study the liquid structure of tantalum shock released from several hundred gigapascals (GPa) on the nanosecond timescale. The results show that the internal negative pressure applied to the liquid tantalum reached -5.6 (0.8) GPa, suggesting the existence of a liquid-gas mixing state due to cavitation. This is the first direct evidence to prove the classical nucleation theory which predicts that liquids with high surface tension can support GPa regime tensile stress.

Social distancing as a public good under the COVID-19 pandemic.

OBJECTIVES: The purpose of this study is to show that social distancing is a public good under the COVID-19 pandemic. STUDY DESIGN: We apply economic theory to analyse a cross-sectional survey. METHODS: Economic theory is complemented with empirical evidence. An online survey of those aged 30-49 years in Japan (n = 2177) was conducted between April 28 and May 7. Respondents were selected by quota sampling with regard to age group, gender and prefecture of residence. Our main figure shows the proportion of people who increased/did not change/decreased social distancing, relative to the level of altruism and sensitivity to public shaming. The results of OLS and logit models are shown in Supplementary Materials. RESULTS: Social distancing is a public good under the COVID-19 pandemic for which the free-rider problem is particularly severe. Altruism and social norms are crucial factors in overcoming this problem. Using an original survey, we show that people with higher altruistic concerns and sensitivity to shaming are more likely to follow social distancing measures. CONCLUSIONS: Altruism and social norms are important for reducing the economic cost of the pandemic.

Development and validation of the comprehensive assessment scale for chemotherapy-induced peripheral neuropathy in survivors of cancer.

BACKGROUND: Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity. METHODS: We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach's α. RESULTS: Factor analysis showed that the structure consisted of 15 items in four dimensions: "Threatened interference in daily life by negative feelings", "Impaired hand fine motor skills", "Confidence in choice of treatment/management," and "Dysesthesia of the palms and soles." The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula [q = 2r/(1 + r)] was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity. CONCLUSIONS: The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.

Muons at ISIS.

For the last 30 years, muon experiments at ISIS pulsed neutron and muon facility at the Rutherford Appleton Laboratory, Oxfordshire have been making a significant contribution to a number of scientific fields. The muon facilities at ISIS consist of eight experimental areas. The European Commission Muon facility consists of three experimental areas with a fixed momentum (28 MeV c-1). The RIKEN-RAL facility has a variable momentum (17-90 MeV c-1) and a choice of negative or positive muons delivering muons to four experimental areas. There is also an area recently used for a muon ionization cooling experiment. In this paper, the ISIS pulsed muon facilities are reviewed, including the beam characteristics that could be useful for muography experiments.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Candida albicans biofilms: comparative analysis of room-temperature and cryofixation for scanning electron microscopy.

Biofilms are frequently related to invasive fungal infections and are reported to be more resistant to antifungal drugs than planktonic cells. The structural complexity of the biofilm as well as the presence of a polymeric extracellular matrix (ECM) is thought to be associated with this resistant behavior. Scanning electron microscopy (SEM) after room temperature glutaraldehyde-based fixation, have been used to study fungal biofilm structure and drug susceptibility but they usually fail to preserve the ECM and, therefore, are not an optimised methodology to understand the complexity of the fungal biofilm. Thus, in this work, we propose a comparative analysis of room-temperature and cryofixation/freeze substitution of Candida albicans biofilms for SEM observation. Our experiments showed that room-temperature fixative protocols using glutaraldehyde and osmium tetroxide prior to alcohol dehydration led to a complete extraction of the polymeric ECM of biofilms. ECM from fixative and alcohol solutions were recovered after all processing steps and these structures were characterised by biochemistry assays, transmission electron microscopy and mass spectrometry. Cryofixation techniques followed by freeze-substitution lead to a great preservation of both ECM structure and C. albicans biofilm cells, allowing the visualisation of a more reliable biofilm structure. These findings reinforce that cryofixation should be the indicated method for SEM sample preparation to study fungal biofilms as it allows the visualisation of the EMC and the exploration of the biofilm structure to its fullest, as its structural/functional role in interaction with host cells, other pathogens and for drug resistance assays.

A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components.

Genotyping graft livers by short tandem repeats after human living-donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM-MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1-2% of BM-MSCs), called multilineage-differentiating stress-enduring (Muse) cells, for their ability to differentiate into liver-lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)-labeled human BM-MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species-specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP-positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM-MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM-MSCs that are capable of replacing major liver components during liver regeneration.

A radiographic analysis of alignment of the lower extremities--initiation and progression of varus-type knee osteoarthritis.

OBJECTIVE: This study aimed to investigate alignment based on age in normal knees and alignment based on deformity in osteoarthritis (OA) knees using detailed radiographic parameters. DESIGN: Various parameters were measured from weight-bearing long leg radiographs of 1251 legs (797 normal and 454 OA knees) as a cross-sectional study. Normal knees were classified by age (young, middle aged, aged, and elderly) and symptomatic OA knees on the basis of the alignment (femorotibial angle (FTA): mild, moderate, severe and profound). The mean measurements in each group were calculated and compared within each group. RESULTS: The femoral shaft showed medially bowed curvature (femoral bowing) of approximately 2° in the young normal group, which shifted to lateral bowing with age. However, OA knees showed larger lateral bowing with OA grade, which might reduce the condylar-shaft angle and subsequently shifted the mechanical axis medially. Progression of mild to moderate OA might be associated with a decreasing condylar-shaft angle (femoral condylar orientation) and widening condylar-plateau angle (joint space narrowing) rather than decreasing tibial plateau flattering. Steeping of the tibial plateau inclination due to increasing tibial plateau shift (tibial plateau compression) rather than medial tibial bowing might be the main contributor to worsening of varus deformity in knees with severe and profound OA. CONCLUSIONS: This cross-sectional study might provide the possibility of OA initiation and progression. The lateral curvature of the femoral shaft associated with aging may contribute to the initiation of varus-type OA of the knee. These changes in the femur may be followed by secondary signs of OA progression including varus femoral condylar orientation, medial joint space narrowing, and tibial plateau compression.

Origin of the tetragonal-to-orthorhombic phase transition in FeSe: a combined thermodynamic and NMR study of nematicity.

The nature of the tetragonal-to-orthorhombic structural transition at T_{s}≈90 K in single crystalline FeSe is studied using shear-modulus, heat-capacity, magnetization, and nuclear magnetic resonance measurements. The transition is shown to be accompanied by a large shear-modulus softening, which is practically identical to that of underdoped Ba(Fe,Co)_{2}As_{2}, suggesting a very similar strength of the electron-lattice coupling. On the other hand, a spin-fluctuation contribution to the spin-lattice relaxation rate is only observed below T_{s}. This indicates that the structural, or "nematic," phase transition in FeSe is not driven by magnetic fluctuations.

Magnetic skin effect in Pb(Fe _{1/2}$Nb _{1/2}$)O3.

Relaxor-ferroelectrics display exceptional dielectric properties resulting from the underlying random dipolar fields induced by strong chemical inhomogeneity. An unusual structural aspect of relaxors is a skin-effect where the near-surface region in single crystals exhibit structures and critical phenomena that differ from the bulk. Relaxors are unique in that this skin effect extends over a macroscopic lengthscale of ∼100 µmwhereas usual surface layers only extend over a few unit cells (or ∼nm). We present a muon spectroscopy study of Pb(Fe_{1/2}Nb_{1/2})O3(PFN) which displays ferroelectric order, including many relaxor-like dielectric properties such as a frequency broadened dielectric response, and antiferromagnetism with spatially short-range polar correlations and hence can be termed a multiferroic. In terms of the magnetic behavior determined by the Fe3+(S=5/2,L ≈ 0) ions, PFN has been characterized as a unique example of a 'cluster spin-glass'. We use variable momentum muon spectroscopy to study the depth dependence of the slow magnetic relaxations in a large 1 cm3crystal of PFN. Zero-fieldpositivemuon spin relaxation is parameterized using a stretched exponential, indicative of a distribution of relaxation rates of the Fe3+spins. This bandwidth of frequencies changes as a function of muon momentum, indicative of a change in the Fe3+relaxation rates as a function of muon implantation depth in our single crystal. Usingnegativemuon elemental analysis, we find small-to-no measurable change in the Fe3+/Nb5+concentration with depth implying that chemical concentration alone cannot account for the change in the relaxational dynamics. PFN displays an analogous magnetic skin effect reported to exist in the structural properties of relaxor-ferroelectrics.

Using strain to uncover the interplay between two- and three-dimensional charge density waves in high-temperature superconducting YBa2Cu3Oy.

Uniaxial pressure provides an efficient approach to control charge density waves in YBa2Cu3Oy. It can enhance the correlation volume of ubiquitous short-range two-dimensional charge-density-wave correlations, and induces a long-range three-dimensional charge density wave, otherwise only accessible at large magnetic fields. Here, we use x-ray diffraction to study the strain dependence of these charge density waves and uncover direct evidence for a form of competition between them. We show that this interplay is qualitatively described by including strain effects in a nonlinear sigma model of competing superconducting and charge-density-wave orders. Our analysis suggests that strain stabilizes the 3D charge density wave in the regions between disorder-pinned domains of 2D charge density waves, and that the two orders compete at the boundaries of these domains. No signatures of discommensurations nor of pair density waves are observed. From a broader perspective, our results underscore the potential of strain tuning as a powerful tool for probing competing orders in quantum materials.

Tunable terahertz emission from the intrinsic Josephson junctions in acute isosceles triangular Bi2Sr2CaCu2O8+δ mesas.

In order to determine if the mesa geometry might affect the properties of the coherent terahertz (THz) radiation emitted from the intrinsic Josephson junctions in mesas constructed from single crystals of the high-temperature superconductor, Bi2Sr2CaCu2O8+δ, we studied triangular mesas. For equilateral triangular mesas, the observed emission was found to be limited to the single mesa TM(1,0) mode. However, tunable radiation over the range from 0.495 to 0.934 THz was found to arise from an acute isosceles triangular mesa. This 47% tunability is the widest yet observed from the outer current-voltage characteristic branch of such mesas of any geometry. Although the radiation at a few of the frequencies in the tunable range appear to have been enhanced by cavity resonances, most frequencies are far from such resonance frequencies, and can only be attributed to the ac-Josephson effect.

Giant lattice softening at a Lifshitz transition in Sr2RuO4.

The interplay of electronic and structural degrees of freedom in solids is a topic of intense research. More than 60 years ago, Lifshitz discussed a counterintuitive possibility: lattice softening driven by conduction electrons at topological Fermi surface transitions. The effect that he predicted, however, was small and has not been convincingly observed. Using a piezo-based uniaxial pressure cell to tune the ultraclean metal strontium ruthenate while measuring the stress-strain relationship, we reveal a huge softening of the Young's modulus at a Lifshitz transition of a two-dimensional Fermi surface and show that it is indeed driven entirely by the conduction electrons of the relevant energy band.

Expanded quantum vortex liquid regimes in the electron nematic superconductors FeSe1-xSx and FeSe1-xTex.

The quantum vortex liquid (QVL) is an intriguing state of type-II superconductors in which intense quantum fluctuations of the superconducting (SC) order parameter destroy the Abrikosov lattice even at very low temperatures. Such a state has only rarely been observed, however, and remains poorly understood. One of the key questions is the precise origin of such intense quantum fluctuations and the role of nearby non-SC phases or quantum critical points in amplifying these effects. Here we report a high-field magnetotransport study of FeSe1-xSx and FeSe1-xTex which show a broad QVL regime both within and beyond their respective electron nematic phases. A clear correlation is found between the extent of the QVL and the strength of the superconductivity. This comparative study enables us to identify the essential elements that promote the QVL regime in unconventional superconductors and to demonstrate that the QVL regime itself is most extended wherever superconductivity is weakest.

Ferromagnetic quantum critical point in heavy-fermion iron oxypnictide Ce(Ru(1-x)Fe(x))PO.

We have performed (31)P-NMR measurements on Ce(Ru(1-x)Fe(x))PO in order to investigate ferromagnetic (FM) quantum criticality, since a heavy-fermion (HF) ferromagnet CeRuPO with a two-dimensional structure turns into a HF paramagnet by an isovalent Fe substitution for Ru. We found that Ce(Ru(0.15)Fe(0.85))PO shows critical fluctuations down to ~0.3 K, as well as the continuous suppression of Curie temperature and the ordered moments by the Fe substitution. These experimental results suggest the presence of a FM quantum critical point (QCP) at x~0.86, which is a rare example among itinerant ferromagnets. In addition, we point out that the critical behaviors in Ce(Ru(0.15)Fe(0.85))PO share a similarity with those in YbRh(2)Si(2), where the local criticality of f electrons has been discussed. We reveal that Ce(Ru(1-x)Fe(x))PO is a new system to study FM quantum criticality in HF compounds.

Superconductivity induced by longitudinal ferromagnetic fluctuations in UCoGe.

From detailed angle-resolved NMR and Meissner measurements on a ferromagnetic (FM) superconductor UCoGe (T(Curie)∼2.5 K and T(SC)∼0.6 K), we show that superconductivity in UCoGe is tightly coupled with longitudinal FM spin fluctuations along the c axis. We found that magnetic fields along the c axis (H∥c) strongly suppress the FM fluctuations and that the superconductivity is observed in the limited magnetic-field region where the longitudinal FM spin fluctuations are active. These results, combined with model calculations, strongly suggest that the longitudinal FM spin fluctuations tuned by H∥c induce the unique spin-triplet superconductivity in UCoGe. This is the first clear example that FM fluctuations are intimately related with superconductivity.

Magnetic-field-induced shape recovery by reverse phase transformation.

Large magnetic-field-induced strains have been observed in Heusler alloys with a body-centred cubic ordered structure and have been explained by the rearrangement of martensite structural variants due to an external magnetic field. These materials have attracted considerable attention as potential magnetic actuator materials. Here we report the magnetic-field-induced shape recovery of a compressively deformed NiCoMnIn alloy. Stresses of over 100 MPa are generated in the material on the application of a magnetic field of 70 kOe; such stress levels are approximately 50 times larger than that generated in a previous ferromagnetic shape-memory alloy. We observed 3 per cent deformation and almost full recovery of the original shape of the alloy. We attribute this deformation behaviour to a reverse transformation from the antiferromagnetic (or paramagnetic) martensitic to the ferromagnetic parent phase at 298 K in the Ni45Co5Mn36.7In13.3 single crystal.

Maximum voluntary ventilation as a sensitive measure to monitor the ventilatory function in cervical spondylotic myelopathy.

STUDY DESIGN: A prospective clinical cohort study. OBJECTIVES: To test if maximum voluntary ventilation (MVV), which is currently underutilized in diseases, serves for assessing subclinical ventilatory impairment in cervical spondylotic myelopathy (CSM). SETTING: Kochi Medical School, Japan. METHODS: We studied ventilatory function in 49 CSM patients and 20 age- and sex-matched control patients with either lumbar stenosis or lower limb osteoarthritis. All patients underwent ventilatory function studies consisting of flow volume curves, vital capacity (VC) and the MVV in 12 s before and after surgery. Tetraparesis was assessed by the functional scale of the Japanese Orthopaedic Association (JOA). RESULTS: The CSM group had significantly smaller %forced VC , %peak expiratory flow rate (%PEFR) and %MVV than the control group preoperatively. In contrast to the control group, the CSM group showed a significant increase in %MVV from 74.9±18.7% preoperatively to 80.3±19.0% postoperatively (P<0.005), but not in any other ventilatory measures. This postoperative increase in %MVV significantly correlated with the JOA score (r=0.493; P<0.001). As a possible effect of diaphragmatic recovery, the %PEFR significantly increased postoperatively only in patients with the primary site of involvement at or rostral to C3-4. CONCLUSION: Of the various ventilatory measurements, MVV was most sensitive to changes in tetraparesis in CSM, presumably because MVV, unlike the other ventilatory measures, reflects the coordination in addition to the strength of respiratory muscles.

Superconducting spin smecticity evidencing the Fulde-Ferrell-Larkin-Ovchinnikov state in Sr2RuO4.

Translational symmetry breaking is antagonistic to static fluidity but can be realized in superconductors, which host a quantum-mechanical coherent fluid formed by electron pairs. A peculiar example of such a state is the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state, induced by a time-reversal symmetry-breaking magnetic field applied to spin-singlet superconductors. This state is intrinsically accompanied by the superconducting spin smecticity, spin density-modulated fluidity with spontaneous translational-symmetry breaking. Detection of such spin smecticity provides unambiguous evidence for the FFLO state, but its observation has been challenging. Here, we report the characteristic "double-horn" nuclear magnetic resonance spectrum in the layered superconductor Sr2RuO4 near its upper critical field, indicating the spatial sinusoidal modulation of spin density that is consistent with superconducting spin smecticity. Our work reveals that Sr2RuO4 provides a versatile platform for studying FFLO physics.