Discovery of Griffiths phase in itinerant magnetic semiconductor Fe_{1-x}Co_xS_2

Critical points that can be suppressed to zero temperature are interesting because quantum fluctuations have been shown to dramatically alter electron gas properties. Here, the metal formed by Co doping the paramagnetic insulator FeS$_2$, Fe$_{1-x}$Co$_x$S$_2$, is demonstrated to order ferromagnetically at $x>x_c=0.01\pm0.005$ where we observe unusual transport, magnetic, and thermodynamic properties. We show that this magnetic semiconductor undergoes a percolative magnetic transition with distinct similarities to the Griffiths phase, including singular behavior at $x_c$ and zero temperature.Comment: 10 pages, 4 figure

Magnetic and thermodynamic properties of cobalt doped iron pyrite: Griffiths Phase in a magnetic semiconductor

Doping of the band insulator FeS$_2$ with Co on the Fe site introduces a small density of itinerant carriers and magnetic moments. The lattice constant, AC and DC magnetic susceptibility, magnetization, and specific heat have been measured over the $0\le x\le 0.085$ range of Co concentration. The variation of the AC susceptibility with hydrostatic pressure has also been measured in a small number of our samples. All of these quantities show systematic variation with $x$ including a paramagnetic to disordered ferromagnetic transition at $x=0.007\pm 0.002$. A detailed analysis of the changes with temperature and magnetic field reveal small power law dependencies at low temperatures for samples near the critical concentration for magnetism, and just above the Curie temperature at higher $x$. In addition, the magnetic susceptibility and specific heat are non-analytic around H=0 displaying an extraordinarily sharp field dependence in this same temperature range. We interpret this behavior as due to the formation of Griffiths phases that result from the quenched disorder inherent in a doped semiconductor.Comment: 22 pages including 27 figure

Nicotinic Receptor Subtype-Selective Circuit Patterns in the Subthalamic Nucleus

The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about the mechanisms of cholinergic modulation in the STN, we studied cellular and circuit aspects of nicotinic acetylcholine receptors (nAChRs) in mouse STN. We discovered two largely divergent microcircuits in the STN; these are regulated in part by either α4β2 or α7 nAChRs. STN neurons containing α4β2 nAChRs (α4β2 neurons) received more glutamatergic inputs, and preferentially innervated GABAergic neurons in the substantia nigra pars reticulata. In contrast, STN neurons containing α7 nAChRs (α7 neurons) received more GABAergic inputs, and preferentially innervated dopaminergic neurons in the substantia nigra pars compacta. Interestingly, local electrical stimuli excited a majority (79%) of α4β2 neurons but exerted strong inhibition in 58% of α7 neurons, indicating an additional diversity of STN neurons: responses to electrical stimulation. Chronic exposure to nicotine selectively affects α4β2 nAChRs in STN: this treatment increased the number of α4β2 neurons, upregulated α4-containing nAChR number and sensitivity, and enhanced the basal firing rate of α4β2 neurons both ex vivo and in vivo. Thus, chronic nicotine enhances the function of the microcircuit involving α4β2 nAChRs. This indicates chronic exposure to nicotinic agonist as a potential pharmacological intervention to alter selectively the balance between these two microcircuits, and may provide a means to inhibit substantia nigra dopaminergic neurons

Multifaceted contributions : health workers and smallpox eradication in India

Smallpox eradication in South Asia was a result of the efforts of many grades of health-workers. Working from within the confines of international organisations and government structures, the role of the field officials, who were of various nationalities and also drawn from the cities and rural enclaves of the countries in these regions, was crucial to the development and deployment of policies. However, the role of these personnel is often downplayed in official histories and academic histories, which highlight instead the roles played by a handful of senior officials within the World Health Organization and the federal governments in the sub-continent. This article attempts to provide a more rounded assessment of the complex situation in the field. In this regard, an effort is made to underline the great usefulness of the operational flexibility displayed by field officers, wherein lessons learnt in the field were made an integral part of deploying local campaigns; careful engagement with the communities being targeted, as well as the employment of short term workers from amongst them, was an important feature of this work

Spectroscopy of 194^{194}Po

Prompt, in-beam $\gamma$ rays following the reaction $^{170}$Yb + 142 MeV $^{28}$Si were measured at the ATLAS facility using 10 Compton-suppressed Ge detectors and the Fragment Mass Analyzer. Transitions in $^{194}$Po were identified and placed using $\gamma$-ray singles and coincidence data gated on the mass of the evaporation residues. A level spectrum up to J$\approx$10$\hbar$ was established. The structure of $^{194}$Po is more collective than that observed in the heavier polonium isotopes and indicates that the structure has started to evolve towards the more collective nature expected for deformed nuclei.Comment: 8 pages, revtex 3.0, 4 figs. available upon reques

Urinary metabolomics identifies a molecular correlate of interstitial cystitis/bladder pain syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Cohort

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratory markers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3α-ol-17-one sulfate (Etio-S), a sulfoconjugated 5-β reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites) and could resolve high- from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3–6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS

Structure of the LDL receptor extracellular domain at endosomal pH

The low-density lipoprotein receptor mediates cholesterol homeostasis through endocytosis of lipoproteins. It discharges its ligand in the endosome at pH Ͻ 6. In the crystal structure at pH ϭ 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the epidermal growth factor precursor homology domain (the modules A, B, ␤ propeller, and C). The modules R4 and R5, which are critical for lipoprotein binding, associate with the ␤ propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in the endosome whereby the ␤ propeller functions as an alternate substrate for the ligand-binding domain, binding in a calcium-dependent way and promoting lipoprotein release. The low-density lipoprotein receptor (LDL-R) regulates cholesterol homeostasis in mammalian cells. LDL-R removes cholesterolcarrying lipoproteins from plasma circulation in a process known as receptor-mediated endocytosis (1). Ligands bound extracellularly by LDL-R at neutral pH are internalized and then released in the endosomes ( pH Ͻ 6), leading to their subsequent lysosomal degradation. The receptor then recycles to the cell surface. Mutations in the LDL-R gene cause familial hypercholesterolemia (FH), one of the most common simply inherited genetic diseases (2). FH heterozygotes exhibit a reduced rate of receptor-mediated removal of plasma LDL by the liver, ultimately leading to early onset coronary heart disease and atherosclerosis. More than 920 mutations in LDL-R are known, some of which have been functionally characterized (2, 3). The extracellular domain of LDL-R is composed of a "ligand-binding domain" (with cysteine-rich repeats R1 to R7) and an "epidermal growth factor (EGF) precursor homology domain" (with the EGF-like repeats A, B, and C, as well as a ␤ propeller between B and C) (4, 5). LDL-R binds LDL via the single protein in LDL, the 550-kD apolipoprotein B (apoB) (6); deleting R3, R4, R5, R6, or R7 reduces LDL binding to Ͻ20% of that of the wild-type LDL-R (7). LDL-R also binds to very low density lipoprotein (VLDL), ␤-VLDL, intermediate density lipoprotein (IDL), and chylomicron remnants via the 33-kD apolipoprotein E (apoE) (8, 9); disrupting R5 decreases ␤-VLDL binding to 30 to 50% of that of the wild-type receptor, whereas disrupting R4 or R6 reduces binding only slightly (7). At neutral pH, negative charges on repeats R1 to R7 are thought to interact with positive charges on apoB and apoE. Indeed, LDL binding to LDL-R can be disrupted competitively with polycations or permanently by selective chemical modification of positively charged residues on apoE or apoB Dissociation of ligands is crucial for receptor recycling and hence proper receptor function; mutations in LDL-R that impair ligand release produce FH (2). Deletion mutagenesis studies in LDL-R and the related VLDL-R have indicated that, although the ligand-binding domain is sufficient for binding lipoprotein particles, the receptor requires the EGF precursor homology domain for ligand release (16-18). The structural basis for LDL-R's ability to recognize a diverse group of lipoprotein particles, all varying in size, and release them at acidic pH is unknown. High-resolution crystal structures of modules R5 (12) and ␤ propeller-C (5) are known, and solution NMR structures are known for single and tandem repeats, including R1, R2, R5, R6, A, and B Structure determination. The extracellular domain of human LDL-R (residues 1 to 699) was crystallized at pH ϭ 5.3, with the symmetry of space group P3 1 21 (28). Soaking crystals in sodium 12-tungstophosphate (Na 3 PW 12 O 40 ) improved their diffractive quality and incorporated large anomalous scatterers. The asymmetric unit contains a single protein molecule and two tungsten clusters as well as half of a tungsten cluster on a crystallographic twofold axis. Data collection, structure determination, and model statistics are given in Monomer description. There is clear electron density in the crystal structure for the modules R2, R3, R4, R5, R6, R7, A, B, ␤ propeller, and C In the crystal, each monomer forms major contacts with five neighboring symmetry-related molecules. Although the relative orien