Magnetic-field effects on the fragile antiferromagnetism in YbBiPt.

We present neutron-diffraction data for the cubic-heavy-fermion YbBiPt that show broad magnetic diffraction peaks due to the fragile short-range antiferromagnetic (AFM) order persist under an applied magnetic-field H . Our results for H ⊥ [ 1 ¯ 1 0 ] and a temperature of T = 0.14 1 K show that 1 2 , 1 2 , 3 2 ) magnetic diffraction peak can be described by the same two-peak line shape found for µ 0 H = 0 T below the Néel temperature of T N = 0.4 K . Both components of the peak exist for µ 0 H ≲ 1.4 T , which is well past the AFM phase boundary determined from our new resistivity data. Using neutron-diffraction data taken at T = 0.13 ( 2 ) K for H ∥ 0 0 1 taken at or 1 1 0 , we show that domains of short-range AFM order change size throughout the previously determined AFM and non-Fermi liquid regions of the phase diagram, and that the appearance of a magnetic diffraction peak at 1 2 , 1 2 , 1 2 at µ 0 H ≈ 0.4 T signals canting of the ordered magnetic moment away from 1 1 1 . The continued broadness of the magnetic diffraction peaks under a magnetic field and their persistence across the AFM phase boundary established by detailed transport and thermodynamic experiments present an interesting quandary concerning the nature of YbBiPt's electronic ground state.

Pulsed field magnetization in rare-earth kagome systems.

The rare-earth kagome systems R 3Ga5SiO14 (R = Nd or Pr) exhibit cooperative paramagnetism at low temperatures. Evidence for correlated spin clusters in these weakly frustrated systems has previously been obtained from neutron scattering and from ESR and NMR results. The present pulsed field (0-60 T, 25 ms) magnetization measurements made on single crystals of Nd3Ga5SiO14 (NGS) and Pr3Ga5SiO14 (PGS) at temperatures down to 450 mK have revealed striking differences in the magnetic responses of the two materials. For NGS the magnetization shows a low field plateau, saturation in high transient fields, and significant hysteresis while the PGS magnetization does not saturate in transient fields up to 60 T and shows no hysteresis or plateaus. Nd(3+) is a Kramers ion while Pr(3+) is a non-Kramers ion and the crystal field effects are quite different in the two systems. For the conditions used in the experiments the magnetization behavior is not in agreement with Heisenberg model predictions for kagome systems in which easy-axis anisotropy is much larger than the exchange coupling. The extremely slow spin dynamics found below 4 K in NGS is, however, consistent with the model for Kramers ions and provides a basis for explaining the pulsed field magnetization features.

Successive Magnetic-Field-Induced Transitions and Colossal Magnetoelectric Effect in Ni_{3}TeO_{6}.

We report the discovery of a metamagnetic phase transition in a polar antiferromagnet Ni_{3}TeO_{6} that occurs at 52 T. The new phase transition accompanies a colossal magnetoelectric effect, with a magnetic-field-induced polarization change of 0.3 µC/cm^{2}, a value that is 4 times larger than for the spin-flop transition at 9 T in the same material, and also comparable to the largest magnetically induced polarization changes observed to date. Via density-functional calculations we construct a full microscopic model that describes the data. We model the spin structures in all fields and clarify the physics behind the 52 T transition. The high-field transition involves a competition between multiple different exchange interactions which drives the polarization change through the exchange-striction mechanism. The resultant spin structure is rather counterintuitive and complex, thus providing new insights on design principles for materials with strong magnetoelectric coupling.

Remarkably Robust and Correlated Coherence and Antiferromagnetism in (Ce(1-x)La(x))Cu2Ge2.

We present magnetic susceptibility, resistivity, specific heat, and thermoelectric power measurements on (Ce(1-x)La(x))Cu2Ge2 single crystals (0≤x≤1). With La substitution, the antiferromagnetic temperature TN is suppressed in an almost linear fashion and moves below 0.36 K, the base temperature of our measurements for x>0.8. Surprisingly, in addition to robust antiferromagnetism, the system also shows low temperature coherent scattering below Tcoh up to ∼0.9 of La, indicating a small percolation limit ∼9% of Ce. Tcoh as a function of magnetic field was found to have different behavior for x<0.9 and x>0.9. Remarkably, (Tcoh)(2) at H=0 was found to be linearly proportional to TN. The jump in the magnetic specific heat δCm at TN as a function of TK/TN for (Ce(1-x)La(x))Cu2Ge2 follows the theoretical prediction based on the molecular field calculation for the S=1/2 resonant level model.

Magnetic field induced transition in vanadium spinels.

We study vanadium spinels AV2O4 (A = Cd,Mg) in pulsed magnetic fields up to 65 T. A jump in magnetization at µ0H≈40 T is observed in the single-crystal MgV2O4, indicating a field induced quantum phase transition between two distinct magnetic orders. In the multiferroic CdV2O4, the field induced transition is accompanied by a suppression of the electric polarization. By modeling the magnetic properties in the presence of strong spin-orbit coupling characteristic of vanadium spinels, we show that both features of the field induced transition can be successfully explained by including the effects of the local trigonal crystal field.

Different associations of alcohol cue reactivity with negative alcohol expectancies in mandated and inpatient samples of young adults.

Alcohol cue reactivity, operationalized as a classically conditioned response to an alcohol related stimulus, can be assessed by changes in physiological functions such as heart rate variability (HRV), which reflect real time regulation of emotional and cognitive processes. Although ample evidence links drinking histories to cue reactivity, it is unclear whether in-the-moment cue reactivity becomes coupled to a set of consolidated beliefs about the effects of alcohol (i.e., expectancies) and whether treatment helps dissociate the relation of positive versus negative expectancies to cue reactivity. This study examined the relationship between reactivity to alcohol picture cues and alcohol expectancies in two groups of emerging adults: an inpatient sample with alcohol use disorders (n=28) and a college student sample who previously were mandated to a brief intervention for violating university policies about alcohol use in residence halls (n=43). Sequential regression analysis was conducted using several HRV indices and self-report arousal ratings as cue reactivity measures. Results indicated that the relationship between cue reactivity and negative alcohol outcome expectancies differed for the two groups. Greater cue reactivity, assessed using HRV indices, was associated with more negative expectancies in the inpatient sample but with less negative expectancies in the mandated student sample, while an opposite trend was found for subjective arousal. The present findings highlight the importance of characterizing cue reactivity through multi-dimensional assessment modalities that include physiological markers such as HRV.

Thermoelectric power of RAgSb(2) (R = Y, La, Ce, and Dy) in zero and applied magnetic fields.

We report the experimental results of measurements of the thermoelectric power on the ternary intermetallic compounds RAgSb(2) (R = Y, La, Ce, and Dy) over the temperature range from 2 to 300 K and in magnetic fields up to 140 kOe. In this work, we present the thermoelectric transport properties of four materials from the same family with different ground states: a non-moment bearing paramagnetic metallic system (YAgSb(2)), a non-moment bearing charge density wave system (LaAgSb(2)), a local moment bearing compound with XY-like antiferromagnetic order in the tetragonal basal plane as well as readily accessible metamagnetism (DyAgSb(2)), and a Kondo lattice system with ferromagnetic order below T(C) = 9.7 K (CeAgSb(2)). The thermoelectric power data from these materials exhibit complex temperature and magnetic field dependences, which are associated with modification of the electronic density of states and changes in magnetic scattering. At low temperatures, quantum oscillations in the thermoelectric power are also observed. These oscillations are associated with the Landau quantization of electronic energy in an applied magnetic field.

Phonon density of states of LaFeAsO(1-x)Fx.

We have studied the phonon density of states (PDOS) in LaFeAsO(1-x)Fx with inelastic neutron scattering methods. The PDOS of the parent compound (x=0) is very similar to the PDOS of samples optimally doped with fluorine to achieve the maximum Tc (x approximately 0.1). Good agreement is found between the experimental PDOS and first-principles calculations with the exception of a small difference in Fe mode frequencies. The PDOS reported here is not consistent with conventional electron-phonon mediated superconductivity.

Momentum dependence of the superconducting gap in NdFeAsO0.9F0.1 single crystals measured by angle resolved photoemission spectroscopy.

We use angle resolved photoemission spectroscopy to study the momentum dependence of the superconducting gap in NdFeAsO0.9F0.1 single crystals. We find that the Gamma hole pocket is fully gapped below the superconducting transition temperature. The value of the superconducting gap is 15+/-1.5 meV and its anisotropy around the hole pocket is smaller than 20% of this value-consistent with an isotropic or anisotropic s-wave symmetry of the order parameter. This is a significant departure from the situation in the cuprates, pointing to the possibility that the superconductivity in the iron arsenic based system arises from a different mechanism.

Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal.

CONTEXT AND OBJECTIVE: Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive beta-cell function and/or growth. PATIENTS AND METHODS: We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixed-meal challenge, in four subject groups: 1) with clinically significant hypoglycemia [neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts. RESULTS: Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients. CONCLUSION: A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response.

Six closely related YbT2Zn20 (T = Fe, Co, Ru, Rh, Os, Ir) heavy fermion compounds with large local moment degeneracy.

Heavy fermion compounds represent one of the most strongly correlated forms of electronic matter and give rise to low temperature states that range from small moment ordering to exotic superconductivity, both of which are often in close proximity to quantum critical points. These strong electronic correlations are associated with the transfer of entropy from the local moment degrees of freedom to the conduction electrons, and, as such, are intimately related to the low temperature degeneracy of the (originally) moment bearing ion. Here we report the discovery of six closely related Yb-based heavy fermion compounds, YbT(2)Zn(20), that are members of the larger family of dilute rare earth bearing compounds: RT(2)Zn(20) (T = Fe, Co, Ru, Rh, Os, Ir). This discovery doubles the total number of Yb-based heavy fermion materials. Given these compounds' dilute nature, systematic changes in T only weakly perturb the Yb site and allow for insight into the effects of degeneracy on the thermodynamic and transport properties of these model correlated electron systems.

Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia.

AIMS/HYPOTHESIS: Postprandial hypoglycaemia following gastric bypass for obesity is considered a late manifestation of the dumping syndrome and can usually be managed with dietary modification. We investigated three patients with severe postprandial hypoglycaemia and hyperinsulinaemia unresponsive to diet, octreotide and diazoxide with the aim of elucidating the pathological mechanisms involved. METHODS: Glucose, insulin, and C-peptide were measured in the fasting and postprandial state, and insulin secretion was assessed following selective intra-arterial calcium injection. Pancreas histopathology was assessed in all three patients. RESULTS: All three patients had evidence of severe postprandial hyperinsulinaemia and hypoglycaemia. In one patient, reversal of gastric bypass was ineffective in reversing hypoglycaemia. All three patients ultimately required partial pancreatectomy for control of neuroglycopenia; pancreas pathology of all patients revealed diffuse islet hyperplasia and expansion of beta cell mass. CONCLUSIONS/INTERPRETATION: These findings suggest that gastric bypass-induced weight loss may unmask an underlying beta cell defect or contribute to pathological islet hyperplasia, perhaps via glucagon-like peptide 1-mediated pathways.

Portal and peripheral cortisol levels in obese humans.

AIMS/HYPOTHESIS: Excess total body and visceral fat has been associated with insulin resistance, diabetes and the metabolic syndrome. Excess glucocorticoids produce both central obesity and diabetes. However, systemic glucocorticoid levels are normal in typical Type 2 diabetes and persons with idiopathic obesity. Glucocorticoids can be produced locally through the enzyme 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD-1). Transgenic mice with selective overexpression in adipose tissue of 11 beta HSD-1 to levels seen in humans develop visceral obesity, hyperlipidaemia and insulin-resistant diabetes associated with a 2.7-fold increase in corticosterone levels in portal compared to peripheral circulation. To examine whether the liver is exposed to higher levels of glucocorticoids, which may undergo metabolic degradation prior to measurement in the systemic circulation, we assessed concentrations of cortisol in the portal and peripheral circulation in morbidly obese humans. METHODS: Portal and peripheral blood samples were obtained simultaneously from six morbidly obese humans with and without diabetes during bariatric abdominal surgery. The samples were assessed for serum cortisol to determine whether an increase in the portal to peripheral circulation is found in obese humans. Insulin, which undergoes metabolic clearance in the liver, and thyroxin (free T(4)), which does not, were also assessed. RESULTS: Levels of serum cortisol (698.8+/-200.4 vs 696.3+/-232.4 nmol/l, portal vs peripheral, p=0.9) and free T(4) (22.0+/-7.8 vs 20.6+/-8.1 pmol/l, portal vs peripheral, p=0.3) were not significantly different in portal compared to peripheral circulation. Portal insulins were significantly higher than peripheral levels (466.7+/-302.9 vs 78.5+/-50.9 pmol/l, portal vs peripheral, p=0.03). CONCLUSIONS/INTERPRETATION: These observations suggest that in morbidly obese humans the liver is not exposed to excess glucocorticoids.

Protein kinase epsilon dampens the secretory response of model intestinal epithelia during ischemia.

BACKGROUND: Luminal fluid sequestration and diarrhea are early manifestations of mesenteric ischemia. This can be modeled in vitro with the use of T84 intestinal epithelia, where ischemia induces Cl(-) secretion with adenosine-mediated autocrine feedback. Protein kinase C (PKC) regulates epithelial transport and, in some organ systems, is involved in the response to ischemic stress. The purpose of this study was to define the role of PKC on epithelial transport during ischemia. METHODS: By voltage-current clamp, short-circuit current (Isc) equals Cl(-) secretion. Ischemic conditions were simulated with the use of a well-established chemical hypoxia protocol. RESULTS: Chemical hypoxia briskly activated Isc. Gö6850, an antagonist of novel and conventional PKC isoforms, markedly enhanced the ischemia-induced Isc response, although Gö6976 (which inhibits only conventional isoforms) had no effect. Rottlerin, a specific inhibitor of PKC delta, did not attenuate ischemic Isc. Both phorbol 12-myristate, 13-acetate and bryostatin-1, which selectively activate PKC epsilon in T84 cells, markedly attenuated the Isc response to ischemia. Both agents also inhibited the Isc response to exogenous adenosine. CONCLUSIONS: PKC (likely the novel epsilon isoform) in intestinal epithelia modulates ischemia-induced alterations in ion transport. Inhibition of PKC epsilon exaggerates the secretory response that is induced by ischemia and by authentic adenosine; conversely, augmented activation of PKC epsilon inhibits secretion. Manipulation of PKC epsilon could limit luminal fluid sequestration during mesenteric ischemia.

Current status of medical and surgical therapy for obesity.

The incidence of obesity (especially childhood obesity) and its associated health-related problems have reached epidemic proportions in the United States. Recent investigations suggest that the causes of obesity involve a complex interplay of genetic, environmental, psychobehavioral, endocrine, metabolic, cultural, and socioeconomic factors. Several genes and their protein products, such as leptin, may be particularly important in appetite and metabolic control, although the genetics of human obesity appear to involve multiple genes and metabolic pathways that require further elucidation. Severe obesity is frequently associated with significant comorbid medical conditions, including coronary artery disease, hypertension, type II diabetes mellitus, gallstones, nonalcoholic steatohepatitis, pulmonary hypertension, and sleep apnea. Long-term reduction of significant excess weight in these patients may improve or resolve many of these obesity-related health problems, although convincing evidence of long-term benefit is lacking. Available treatments of obesity range from diet, exercise, behavioral modification, and pharmacotherapy to surgery, with varying risks and efficacy. Nonsurgical modalities, although less invasive, achieve only relatively short-term and limited weight loss in most patients. Currently, surgical therapy is the most effective modality in terms of extent and duration of weight reduction in selected patients with acceptable operative risks. The most widely performed surgical procedure, Roux-en-Y gastric bypass, achieves permanent (followed up for more than 14 years) and significant weight loss (more than 50% of excess body weight) in more than 90% of patients.

Protein kinase C activation downregulates the expression and function of the basolateral Na+/K+/2Cl(-) cotransporter.

The basolateral Na+/K+/2Cl(-) cotransporter (NKCC1) has been shown to be an independent regulatory site for electrogenic Cl(-) secretion. The proinflammatory phorbol ester, phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), inhibits basal and cyclic adenosine monophosphate (cAMP)-stimulated NKCC1 activity in T84 intestinal epithelial cells and decreases the steady state levels of NKCC1 mRNA in a time- and dose-dependent manner. The levels of NKCC1 protein also fall in accordance with the NKCC1 mRNA transcript and these levels are unaffected by 4alpha-phorbol, which does not activate PKC. Inhibition of maximal (cAMP-stimulated) NKCC1 functional activity by PMA was first detected by 1 h, whereas decreases in the steady state levels of NKCC1 mRNA were not detectable until 4 h. NKCC1 mRNA expression recovers toward control levels with extended treatment of cells with PMA suggesting that the PMA effects on NKCC1 expression are mediated through activation of PKC. Although NKCC1 mRNA and protein levels return to control values after extended PMA exposure, NKCC1 functional activity does not recover. Immunofluorescence imaging suggest that the absence of functional recovery is due to failure of newly synthesized NKKC1 protein to reach the cell surface. We conclude that NKCC1 has the capacity to be regulated at the level of de novo expression by PKC, although decreased NKCC1 expression alone cannot account for either early or late loss of NKCC1 function.

Effects of bryostatin 1, a novel anticancer agent, on intestinal transport and barrier function: role of protein kinase C.

BACKGROUND: Bryostatin 1 is a novel chemotherapeutic agent that activates specific members of the protein kinase C (PKC) family in a complex pattern overlapping with, but distinct from, that of tumor-promoting phorbol esters. Phorbol esters profoundly altered epithelial phenotype, abolishing both barrier function and Cl secretion (the latter due to loss of a key transport site, the Na-K-Cl cotransporter). The effects of bryostatin 1 on these parameters are unknown. METHODS: Cl secretion and barrier function of T84 human intestinal epithelia were assessed as cyclic adenosine monophosphate-stimulated short-circuit current and transepithelial resistance, respectively. Na-K-Cl cotransporter function and mRNA expression were assayed by 86Rb uptake and Northern analysis. RESULTS: Bryostatin 1 reduced Cl secretion, Na-K-Cl cotransport, and cotransporter mRNA expression. Unlike phorbol esters, these effects were largely transient. In contrast to phorbol esters, bryostatin 1 did not decrease barrier function. CONCLUSIONS: Bryostatin 1 transiently inhibits Na-K-Cl cotransport and Cl secretion, possibly through a PKC isoform also targeted by phorbol esters. Unlike phorbol esters, bryostatin 1 does not impair barrier function. The data imply that bryostatin 1 and phorbol esters differentially affect a PKC isoform involved in junctional regulation, and that epithelial transport and barrier function may be regulated by distinct PKC isoforms.

Levamisole inhibits intestinal Cl- secretion via basolateral K+ channel blockade.

BACKGROUND & AIMS: Phenylimidazothiazoles have recently been shown to activate wild-type and mutant cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels in transfected cells and were proposed as therapy for cystic fibrosis. The aim of this study was to investigate the effects of phenylimidazothiazoles on regulated transepithelial Cl- transport in intact epithelia. METHODS: T84 intestinal epithelial cells grown on permeable supports and stripped human colonic mucosal sheets were studied by conventional current-voltage clamping. Selective permeabilization of apical or basolateral membranes with the monovalent ionophore nystatin was used to isolate basolateral K+ and apical Cl- channel activity, respectively. 86Rb+ uptake was assessed for Na/K/2Cl cotransporter and Na+,K(+)-adenosine triphosphatase activity. RESULTS: In T84 monolayers and human colon, levamisole and its brominated derivative bromotetramisole failed to activate transepithelial secretion. In fact, these compounds dose-dependently inhibited secretory responses to the cyclic adenosine monophosphate agonist forskolin and the Ca2+ agonist carbachol. In permeabilized T84 monolayers, phenylimidazothiazoles weakly activated apical Cl- currents (consistent with their reported action on CFTR) and did not affect bumetanide-sensitive or bumetanide-insensitive 86+Rb+ uptake. Instead, they profoundly inhibited the basolateral Ba(2+)-sensitive and Ba(2+)-insensitive K+ currents. CONCLUSIONS: Phenylimidazothiazoles block K+ channels required for Cl(-)-secretory responses elicited by diverse pathways in model epithelia and native colon, an effect that outweighs their ability to activate apical Cl- channels.

Osmotic regulation of intestinal epithelial Na(+)-K(+)-Cl- cotransport: role of Cl- and F-actin.

Previous data indicate that adenosine 3',5'-cyclic monophosphate activates the epithelial basolateral Na(+)-K(+)-Cl- cotransporter in microfilament-dependent fashion in part by direct action but also in response to apical Cl- loss (due to cell shrinkage or decreased intracellular Cl-). To further address the actin dependence of Na(+)-K(+)-Cl- cotransport, human epithelial T84 monolayers were exposed to anisotonicity, and isotopic flux analysis was performed. Na(+)-K(+)-Cl- cotransport was activated by hypertonicity induced by added mannitol but not added NaCl. Cotransport was also markedly activated by hypotonic stress, a response that appeared to be due in part to reduction of extracellular Cl- concentration and also to activation of K+ and Cl- efflux pathways. Stabilization of actin with phalloidin blunted cotransporter activation by hypotonicity and abolished hypotonic activation of K+ and Cl- efflux. However, phalloidin did not prevent activation of cotransport by hypertonicity or isosmotic reduction of extracellular Cl-. Conversely, hypertonic but not hypotonic activation was attenuated by the microfilament disassembler cytochalasin D. The results emphasize the complex interrelationship among intracellular Cl- activity, cell volume, and the actin cytoskeleton in the regulation of epithelial Cl- transport.

Characterization and regulation of adenosine transport in T84 intestinal epithelial cells.

Adenosine release from mucosal sources during inflammation and ischemia activates intestinal epithelial Cl- secretion. Previous data suggest that A2b receptor-mediated Cl- secretory responses may be dampened by epithelial cell nucleoside scavenging. The present study utilizes isotopic flux analysis and nucleoside analog binding assays to directly characterize the nucleoside transport system of cultured T84 human intestinal epithelial cells and to explore whether adenosine transport is regulated by secretory agonists, metabolic inhibition, or phorbol ester. Uptake of adenosine across the apical membrane displayed characteristics of simple diffusion. Kinetic analysis of basolateral uptake revealed a Na(+)-independent, nitrobenzylthioinosine (NBTI)-sensitive facilitated-diffusion system with low affinity but high capacity for adenosine. NBTI binding studies indicated a single population of high-affinity binding sites basolaterally. Neither forskolin, 5'-(N-ethylcarboxamido)-adenosine, nor metabolic inhibition significantly altered adenosine transport. However, phorbol 12-myristate 13-acetate significantly reduced both adenosine transport and the number of specific NBTI binding sites, suggesting that transporter number may be decreased through activation of protein kinase C. This basolateral facilitated adenosine transporter may serve a conventional function in nucleoside salvage and a novel function as a regulator of adenosine-dependent Cl- secretory responses and hence diarrheal disorders.