Coulomb-Driven Cluster-Glass Behavior in Mn-Intercalated Ti1+yS2

We have investigated the low-temperature spin-glasslike phase in the intercalated transition-metal dichalcogenide Mn0.09Ti1.1S2. A departure from Curie–Weiss behavior in the paramagnetic regime indicated the formation of small ferromagnetically correlated clusters. The Vogel–Fulcher law provided an excellent description of relaxation times in the vicinity of the transition, showing that the glasslike phase occurs due to interaction between the clusters. Cole–Cole plots for data close to the transition were linear, which is consistent with a simple exponential distribution of cluster sizes. A Monte Carlo simulation of the dichalcogenide system, including excess self-intercalated Ti ions, gave an exponential cluster-size distribution for a relatively narrow range of concentration values of Mn and Ti ions, values that were consistent with those of the Mn0.09Ti1.1S2 sample. Strong commonality in the relaxation behavior with certain ferroelectric relaxor systems suggests underlying similarity in the microscopic structure of the clusters in both systems, which may be chainlike or quasi-one-dimensional

Xenopus fraseri: Mr. Fraser, where did your frog come from?

A comprehensive, accurate, and revisable alpha taxonomy is crucial for biodiversity studies, but is challenging when data from reference specimens are difficult to collect or observe. However, recent technological advances can overcome some of these challenges. To illustrate this, we used modern approaches to tackle a centuries-old taxonomic enigma presented by Fraser’s Clawed Frog, Xenopus fraseri, including whether X. fraseri is different from other species, and if so, where it is situated geographically and phylogenetically. To facilitate these inferences, we used high-resolution techniques to examine morphological variation, and we generated and analyzed complete mitochondrial genome sequences from all Xenopus species, including >150-year-old type specimens. Our results demonstrate that X. fraseri is indeed distinct from other species, firmly place this species within a phylogenetic context, and identify its minimal geographic distribution in northern Ghana and northern Cameroon. These data also permit novel phylogenetic resolution into this intensively studied and biomedically important group. Xenopus fraseri was formerly thought to be a rainforest endemic placed alongside species in the amieti species group; in fact this species occurs in arid habitat on the borderlands of the Sahel, and is the smallest member of the muelleri species group. This study illustrates that the taxonomic enigma of Fraser’s frog was a combined consequence of sparse collection records, interspecies conservation and intraspecific polymorphism in external anatomy, and type specimens with unusual morphology

Existential witness extraction in classical realizability and via a negative translation

We show how to extract existential witnesses from classical proofs using Krivine's classical realizability---where classical proofs are interpreted as lambda-terms with the call/cc control operator. We first recall the basic framework of classical realizability (in classical second-order arithmetic) and show how to extend it with primitive numerals for faster computations. Then we show how to perform witness extraction in this framework, by discussing several techniques depending on the shape of the existential formula. In particular, we show that in the Sigma01-case, Krivine's witness extraction method reduces to Friedman's through a well-suited negative translation to intuitionistic second-order arithmetic. Finally we discuss the advantages of using call/cc rather than a negative translation, especially from the point of view of an implementation.Comment: 52 pages. Accepted in Logical Methods for Computer Science (LMCS), 201

Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif

Optimization of the sulfonamide-based kappa opioid receptor (KOR) antagonist probe molecule ML140 through constraint of the sulfonamide nitrogen within a tetrahydroisoquinoline moiety afforded a marked increase in potency. This strategy, when combined with additional structure-activity relationship exploration, has led to a compound only six-fold less potent than norBNI, a widely utilized KOR antagonist tool compound, but significantly more synthetically accessible. The new optimized probe is suitably potent for use as an in vivo tool to investigate the therapeutic potential of KOR antagonists

Coercivity and Exchange Bias of Mn0.25Ti1.1S2 in the Cluster-Glass State

Magnetic measurements have been carried out on the Mn-intercalated transition-metal dichalcogenide Mn0.25Ti1+yS2. The material, which contained a concentration y≈0.1 of excess intercalated Ti, exhibited paramagnetic behavior at high temperatures with an effective moment per Mn ion of µeff=6.07 ± 0.23 µB, which shows that the system comprises localized Mn2+ moments. A Curie-Weiss temperature ΘCW=-26 ± 1 K indicated that antiferromagnetic interactions were dominant. Deviation from Curie-Weiss behavior below 100 K signaled the formation of antiferromagnetically correlated clusters. Bifurcation of the zero-fieldcooled and field-cooled magnetizations below 20 K indicated a transition to a cluster-glass state. The clusterglass state exhibited hysteresis and a loop shift indicating exchange bias. The behavior of the coercivity and exchange bias can be understood using a model in which frozen spins at the periphery of a cluster interact with the antiferromagnetically correlated interior

Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa

Rifampicin mono-resistant TB (RMR-TB, rifampicin resistance and isoniazid susceptibility) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting. Patient-level clinical data and stored RR-TB isolates from 2008-2017 with available whole genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare rifampicin-resistance (RR) conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semi-quantitative rifampicin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted Odds Ratio 1.4, 95% CI 1.1-1.9) and diagnosis between 2013-2017 versus 2008-2012 (aOR 1.3, 1.1-1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR-TB and MDR-TB isolates were observed. Mutations associated with high-level RR were more commonly found among MDR-TB isolates (811/889, 90.2% versus 162/230, 70.4% among RMR-TB, p<0.0001). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR-TB versus 10/889 (1.1%) in MDR-TB (p<0.0001). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 mug/ml (range 0.125-1 mug/ml). The majority (215/230, 93.5%) of RMR-TB isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection

Small Extracellular Vesicles from Peripheral Blood of Aged Mice Pass the Blood-Brain Barrier and Induce Glial Cell Activation

Extracellular vesicles (EVs), including small EVs (sEVs), are involved in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Yet, increased neuroinflammation can also be detected in the aging brain, and it is associated with increased glial activation. Changes in EV concentration are reported in aging tissues and senescence cells, suggesting a role of EVs in the process of aging. Here, we investigated the effect of peripheral sEVs from aged animals on neuroinflammation, specifically on glial activation. sEVs were isolated from the peripheral blood of young (3 months) and aged (24 months) C57BL/6J wildtype mice and injected into the peripheral blood from young animals via vein tail injections. The localization of EVs and the expression of selected genes involved in glial cell activation, including Gfap , Tgf- β , Cd68 , and Iba1 , were assessed in brain tissue 30 min, 4 h, and 24 h after injection. We found that sEVs from peripheral blood of aged mice but not from young mice altered gene expression in the brains of young animals. In particular, the expression of the specific astrocyte marker, Gfap , was significantly increased, indicating a strong response of this glial cell type. Our study shows that sEVs from aged mice can pass the blood-brain barrier (BBB) and induce glial cell activation