Magnetic properties of the Ag-In-rare-earth 1/1 approximants

We have performed magnetic susceptibility and neutron scattering measurements on polycrystalline Ag-In-RE (RE: rare-earth) 1/1 approximants. In the magnetic susceptibility measurements, for most of the RE elements, inverse susceptibility shows linear behaviour in a wide temperature range, confirming well localized isotropic moments for the RE$^{3+}$ ions. Exceptionally for the light RE elements, such as Ce and Pr, non-linear behaviour was observed, possibly due to significant crystalline field splitting or valence fluctuation. For RE = Tb, the susceptibility measurement clearly shows a bifurcation of the field-cooled and zero-field-cooled susceptibility at $T_{\rm f} = 3.7$~K, suggesting a spin-glass-like freezing. On the other hand, neutron scattering measurements detect significant development of short-range antiferromagnetic spin correlations in elastic channel, which accompanied by a broad peak at $\hbar\omega = 4$~meV in inelastic scattering spectrum. These features have striking similarity to those in the Zn-Mg-Tb quasicrystals, suggesting that the short-range spin freezing behaviour is due to local high symmetry clusters commonly seen in both the systems.Comment: 14 pages, 12 figure

Wealth inequalities in physical and cognitive impairments across Japan and Europe: the role of health expenditure and infrastructure

Although prior research has provided insights into the association between country-level factors and health inequalities, key research gaps remain. First, most previous studies examine subjective rather than objective health measures. Second, the wealth dimension in health inequalities is understudied. Third, a handful of studies explicitly focus on older adults. To bridge these research gaps, this study measures wealth-related inequalities in physical and cognitive impairments and examines the extent to which welfare states moderate wealth inequalities in physical and cognitive impairments among older people across Japan and Europe. We utilized harmonized data on non-institutionalized individuals aged 50–75 from the Japanese Study of Aging and Retirement (JSTAR) and the Survey of Health, Ageing and Retirement in Europe (SHARE) (N = 31,969 for physical impairments and 31,348 for cognitive impairments). Our multilevel linear regression analyses examined whether national public health spending and healthcare access resources explained cross-country differences in wealth inequalities in physical and cognitive impairments. We applied a concentration index to quantify the degree of wealth inequalities in impairments. The findings indicate that inequalities in both impairment outcomes favored wealthier individuals in all countries, but the magnitude of inequality varied by country. Furthermore, a higher share of public health spending, lower out-of-pocket expenditure, and higher investment in healthcare resources were associated with lower wealth inequalities, especially for physical impairments. Our findings suggest that different health interventions and policies may be needed to mitigate specific impairment inequalities

Doping Dependence of Spin Dynamics in Electron-Doped Ba(Fe1-xCox)2As2

The spin dynamics in single crystal, electron-doped Ba(Fe1-xCox)2As2 has been investigated by inelastic neutron scattering over the full range from undoped to the overdoped regime. We observe damped magnetic fluctuations in the normal state of the optimally doped compound (x=0.06) that share a remarkable similarity with those in the paramagnetic state of the parent compound (x=0). In the overdoped superconducting compound (x=0.14), magnetic excitations show a gap-like behavior, possibly related to a topological change in the hole Fermi surface (Lifshitz transition), while the imaginary part of the spin susceptibility prominently resembles that of the overdoped cuprates. For the heavily overdoped, non-superconducting compound (x=0.24) the magnetic scattering disappears, which could be attributed to the absence of a hole Fermi-surface pocket observed by photoemission.Comment: 6 pages, 5 figures, published versio

Insights Into the Inhibition of MOX-1 \u3b2-Lactamase by S02030, a Boronic Acid Transition State Inhibitor

The rise of multidrug resistant (MDR) Gram-negative bacteria has accelerated the development of novel inhibitors of class A and C \u3b2-lactamases. Presently, the search for novel compounds with new mechanisms of action is a clinical and scientific priority. To this end, we determined the 2.13-\uc5 resolution crystal structure of S02030, a boronic acid transition state inhibitor (BATSI), bound to MOX-1 \u3b2-lactamase, a plasmid-borne, expanded-spectrum AmpC \u3b2-lactamase (ESAC) and compared this to the previously reported aztreonam (ATM)-bound MOX-1 structure. Superposition of these two complexes shows that S02030 binds in the active-site cavity more deeply than ATM. In contrast, the SO3 interactions and the positional change of the \u3b2-strand amino acids from Lys315 to Asn320 were more prominent in the ATM-bound structure. MICs were performed using a fixed concentration of S02030 (4 \u3bcg/ml) as a proof of principle. Microbiological evaluation against a laboratory strain of Escherichia coli expressing MOX-1 revealed that MICs against ceftazidime are reduced from 2.0 to 0.12 \u3bcg/ml when S02030 is added at a concentration of 4 \u3bcg/ml. The IC50 and Ki of S02030 vs. MOX-1 were 1.25 \ub1 0.34 and 0.56 \ub1 0.03 \u3bcM, respectively. Monobactams such as ATM can serve as informative templates for design of mechanism-based inhibitors such as S02030 against ESAC \u3b2-lactamases

AMPK Regulates Circadian Rhythms in a Tissue- and Isoform-Specific Manner

AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects the circadian rhythm by regulating at least two clock components, CKIα and CRY1, via direct phosphorylation. However, it is not known whether the catalytic activity of AMPK actually regulates circadian rhythm in vivo.THE CATALYTIC SUBUNIT OF AMPK HAS TWO ISOFORMS: α1 and α2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPKα1-/- and AMPKα2-/- mice. We found that both α1-/- and α2-/- mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but α1-/- mice have a shorter circadian period whereas α2-/- mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in α1-/- mice, but not in α2-/- mice. The circadian pattern of core clock gene expression was severely disrupted in fat in α1-/- mice, but it was severely disrupted in the heart and skeletal muscle of α2-/- mice. Interestingly, other genes that showed circadian pattern of expression were dysreguated in both α1-/- and α2-/- mice. The circadian rhythm of nicotinamide phosphoryl-transferase (NAMPT) activity, which converts nicotinamide (NAM) to NAD+, is an important regulator of the circadian clock. We found that the NAMPT rhythm was absent in AMPK-deficient tissues and cells.This study demonstrates that the catalytic activity of AMPK regulates circadian rhythm of behavior, energy metabolism and gene expression in isoform- and tissue-specific manners

Technologies of sleep research

Sleep is investigated in many different ways, many different species and under many different circumstances. Modern sleep research is a multidisciplinary venture. Therefore, this review cannot give a complete overview of all techniques used in sleep research and sleep medicine. What it will try to do is to give an overview of widely applied techniques and exciting new developments. Electroencephalography has been the backbone of sleep research and sleep medicine since its first application in the 1930s. The electroencephalogram is still used but now combined with many different techniques monitoring body and brain temperature, changes in brain and blood chemistry, or changes in brain functioning. Animal research has been very important for progress in sleep research and sleep medicine. It provides opportunities to investigate the sleeping brain in ways not possible in healthy volunteers. Progress in genomics has brought new insights in sleep regulation, the best example being the discovery of hypocretin/orexin deficiency as the cause of narcolepsy. Gene manipulation holds great promise for the future since it is possible not only to investigate the functions of different genes under normal conditions, but also to mimic human pathology in much greater detail

Plasticity of the Intrinsic Period of the Human Circadian Timing System

Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol), which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light (∼450 lux; ∼1.2 W/m2) for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration