Two-dimensional electron gas with universal subbands at the surface of SrTiO(3).

As silicon is the basis of conventional electronics, so strontium titanate (SrTiO(3)) is the foundation of the emerging field of oxide electronics. SrTiO(3) is the preferred template for the creation of exotic, two-dimensional (2D) phases of electron matter at oxide interfaces that have metal-insulator transitions, superconductivity or large negative magnetoresistance. However, the physical nature of the electronic structure underlying these 2D electron gases (2DEGs), which is crucial to understanding their remarkable properties, remains elusive. Here we show, using angle-resolved photoemission spectroscopy, that there is a highly metallic universal 2DEG at the vacuum-cleaved surface of SrTiO(3) (including the non-doped insulating material) independently of bulk carrier densities over more than seven decades. This 2DEG is confined within a region of about five unit cells and has a sheet carrier density of ∼0.33 electrons per square lattice parameter. The electronic structure consists of multiple subbands of heavy and light electrons. The similarity of this 2DEG to those reported in SrTiO(3)-based heterostructures and field-effect transistors suggests that different forms of electron confinement at the surface of SrTiO(3) lead to essentially the same 2DEG. Our discovery provides a model system for the study of the electronic structure of 2DEGs in SrTiO(3)-based devices and a novel means of generating 2DEGs at the surfaces of transition-metal oxides.

Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases.

The naturally occurring mammalian endocannabinoids possess biological attributes that extend beyond interaction with cannabinoid receptors. These extended biological properties are the result of oxidative metabolism of the principal mammalian endocannabinoids arachidonoyl ethanolamide (anandamide; A-EA) and 2-arachidonoylglycerol (2-AG). Both endocannabinoids are oxidized by cyclo-oxygenase-2 (COX-2), but not by COX-1, to a series of prostaglandin derivatives (PGs) with quite different biological properties from those of the parent substrates. PG ethanolamides (prostamides, PG-EAs) and PG glyceryl esters (PG-Gs) are not only pharmacologically distinct from their parent endocannabinoids, they are distinct from the corresponding acidic PGs, and are differentiated from each other. Ethanolamides and glyceryl esters of the major prostanoids PGD2, PGE2, PGF2α, and PGI2 are formed by the various PG synthases, and thromboxane ethanolamides and glyceryl esters are not similarly produced. COX-2 is also of interest by virtue of its corollary central role in modulating endocannabinoid tone, providing a new therapeutic approach for treating pain and anxiety. Other major oxidative conversion pathways are provided for both A-EA and 2-AG by several lipoxygenases (LOXs), resulting in the formation of numerous hydroxyl metabolites. These do not necessarily represent inactivation pathways for endocannabinoids but may mimic or modulate the endocannabinoids or even display alternative pharmacology. Similarly, A-EA and 2-AG may be oxidized by P450 enzymes. Again a very diverse number of metabolites are formed, with either cannabinoid-like biological properties or an introduction of disparate pharmacology. The biological activity of epoxy and hydroxyl derivatives of the endocannabinoids remains to be fully elucidated. This review attempts to consolidate and compare the findings obtained to date in an increasingly important research area. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

N-Acyl ethanolamide and eicosanoid involvement in irritant dermatitis.

BACKGROUND: Sodium lauryl sulfate (SLS) and ultraviolet radiation (UVR) are two commonly encountered cutaneous inflammatory stimuli. Differing histopathological and clinical features implicate involvement of alternative inflammatory pathways; bioactive lipid mediators (eicosanoids, endocannabinoids and sphingolipids) are likely candidates for regulation of the divergent inflammatory responses. OBJECTIVES: To assess comprehensively bioactive lipid involvement in SLS- and UVR-induced inflammatory responses, to provide a better understanding of bioactive lipid mediator pathways in irritant inflammation. METHODS: Buttock skin from 10 healthy volunteers was treated with two minimal erythema doses of UVR (275-380 nm, peak 305 nm) or an SLS dose optimized for each individual, to produce a comparable, moderate erythema. Punch biopsies were taken 24 h postchallenge and from untreated skin, and separated into dermis and epidermis. Lipids [including 15 prostanoids, 15 hydroxy fatty acids (HFAs), nine endocannabinoids and related N-acyl ethanolamides (NAE), and 21 sphingolipids] were extracted and quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Increased epidermal NAE and HFA expression was observed in response to SLS but not UVR-induced low-level inflammation. Significant changes following SLS treatment included augmented levels of NAE, possessing proinflammatory and some reported anti-inflammatory properties, with 3·7-fold (P = 0·02) and threefold (P = 0·01) increased expression of palmitoyl and stearoyl ethanolamides, respectively, in addition to 1·9-fold (P = 0·02) increased expression of 12-hydroxyeicosatetraenoic acid. CONCLUSIONS: The differential bioactive lipid upregulation implicates their involvement in skin irritant responses, potentially reflecting roles in inflammatory cell recruitment and subsequent resolution of inflammation, giving scope for new treatment approaches to irritant dermatitis.

Spin-orbital entanglement and the breakdown of singlets and triplets in Sr2RuO4 revealed by spin- and angle-resolved photoemission spectroscopy.

Spin-orbit coupling has been conjectured to play a key role in the low-energy electronic structure of Sr2RuO4. By using circularly polarized light combined with spin- and angle-resolved photoemission spectroscopy, we directly measure the value of the effective spin-orbit coupling to be 130±30 meV. This is even larger than theoretically predicted and comparable to the energy splitting of the dxy and dxz,yz orbitals around the Fermi surface, resulting in a strongly momentum-dependent entanglement of spin and orbital character in the electronic wavefunction. As demonstrated by the spin expectation value ⟨sk⃗·s-k⃗⟩ calculated for a pair of electrons with zero total momentum, the classification of the Cooper pairs in terms of pure singlets or triplets fundamentally breaks down, necessitating a description of the unconventional superconducting state of Sr2RuO4 in terms of these newly found spin-orbital entangled eigenstates.

Polarity-driven surface metallicity in SmB6.

By a combined angle-resolved photoemission spectroscopy and density functional theory study, we discover that the surface metallicity is polarity driven in SmB6. Two surface states, not accounted for by the bulk band structure, are reproduced by slab calculations for coexisting B6 and Sm surface terminations. Our analysis reveals that a metallic surface state stems from an unusual property, generic to the (001) termination of all hexaborides: the presence of boron 2p dangling bonds, on a polar surface. The discovery of polarity-driven surface metallicity sheds new light on the 40-year old conundrum of the low-temperature residual conductivity of SmB6, and raises a fundamental question in the field of topological Kondo insulators regarding the interplay between polarity and nontrivial topological properties.

Determining the surface-to-bulk progression in the normal-state electronic structure of Sr(2)RuO(4) by angle-resolved photoemission and density functional theory.

We revisit the normal-state electronic structure of Sr(2)RuO(4) by angle-resolved photoemission spectroscopy with improved data quality, as well as ab initio band structure calculations in the local-density approximation with the inclusion of spin-orbit coupling. We find that the current model of a single surface layer (√2×√2)R45° reconstruction does not explain all detected features. The observed depth-dependent signal degradation, together with the close quantitative agreement with the slab calculations based on the surface crystal structure as determined by low-energy electron diffraction, reveal that-at a minimum-the subsurface layer also undergoes a similar although weaker reconstruction. This model accounts for all features-a key step in understanding the electronic structure-and indicates a surface-to-bulk progression of the electronic states driven by structural instabilities. Finally, we find no evidence for other phases stemming from either topological bulk properties or, alternatively, the interplay between spin-orbit coupling and the broken symmetry of the surface.

Hepatic arterial infusion with oxaliplatin and 5-FU/folinic acid for advanced biliary tract cancer: a phase II study.

BACKGROUND: Effective and tolerable chemotherapy with gemcitabine and cisplatin for advanced biliary tract cancer (BTC) has been established recently. However, overall prognosis is still poor, and additional therapeutic approaches are needed for patients with locally advanced, irresectable and/or pretreated tumors. Hepatic arterial infusion (HAI) of chemotherapy represents a safe and well-established treatment modality, but data on its use in patients with BTC are still sparse. METHODS: Patients with irresectable BTC predominant to the liver were included in a prospective, open phase II study investigating HAI provided through interventionally implanted port catheters. Intraarterial chemotherapy consisted of biweekly oxaliplatin (O) 85 mg/m(2) and folinic acid (F) 170 mg/m(2) with 5-FU (F) 600 mg/m(2). RESULTS: Between 2004 and 2010, 37 patients were enrolled. A total of 432 cycles of HAI were applied with a median of 9 (range 1-46) cycles. Objective response rate was 16 %, and tumor control was achieved in 24 of 37 (65 %) patients. Median progression-free survival was 6.5 months (range 0.5-26.0; 95 % CI 4.3-8.7), median overall survival was 13.5 (range 0.9-50.7; 95 % CI 11.1-15.9) months. The most frequent adverse event was sensory neuropathy grade 1/2 in 10/14 patients. CONCLUSIONS: Using a minimal invasive technique, repetitive HAI with OFF is feasible and results in clinically relevant tumor control with low toxicity in patients with liver predominant advanced BTC.

Resonant inelastic x-ray scattering data for Ruddlesden-Popper and reduced Ruddlesden-Popper nickelates.

Ruddlesden-Popper and reduced Ruddlesden-Popper nickelates are intriguing candidates for mimicking the properties of high-temperature superconducting cuprates. The degree of similarity between these nickelates and cuprates has been the subject of considerable debate. Resonant inelastic x-ray scattering (RIXS) has played an important role in exploring their electronic and magnetic excitations, but these efforts have been stymied by inconsistencies between different samples and the lack of publicly available data for detailed comparison. To address this issue, we present open RIXS data on La4Ni3O10 and La4Ni3O8.

Spin-polarized electron tunneling in bcc FeCo/MgO/FeCo(001) magnetic tunnel junctions.

In combining spin- and symmetry-resolved photoemission, magnetotransport measurements and ab initio calculations we detangled the electronic states involved in the electronic transport in Fe(1-x)Co(x)(001)/MgO/Fe(1-x)Co(x)(001) magnetic tunnel junctions. Contrary to previous theoretical predictions, we observe a large reduction in TMR (from 530 to 200% at 20 K) for Co content above 25 atomic% as well as anomalies in the conductance curves. We demonstrate that these unexpected behaviors originate from a minority spin state with Δ(1) symmetry that exists below the Fermi level for high Co concentration. Using angle-resolved photoemission, this state is shown to be a two-dimensional state that occurs at both Fe(1-x)Co(x)(001) free surface, and more importantly at the interface with MgO. The combination of this interface state with the peculiar density of empty states due to chemical disorder allows us to describe in details the complex conduction behavior in this system.

Experimental study of the incoherent spectral weight in the photoemission spectra of the misfit cobaltate [Bi_{2}Ba{2}O{4}][CoO{2}]{2}.

Previous angle-resolved photoemission spectroscopy experiments in NaxCoO2 reported both a strongly renormalized bandwidth near the Fermi level and moderately renormalized Fermi velocities, leaving it unclear whether the correlations are weak or strong and how they could be quantified. We explain why this situation occurs and solve the problem by extracting clearly the coherent and incoherent parts of the band crossing the Fermi level. We show that one can use their relative weight to estimate self-consistently a quasiparticle weight Z=0.15+/-0.05. We suggest this method could be a reliable way to study the evolution of correlations in cobaltates and for comparison with other strongly correlated systems.

Castleman's disease of the neck: report of a case and review of the literature.

OBJECTIVES: Castleman's disease is an uncommon disease of benign lymph node hyperplasia primarily affecting the mediastinum, with the head and neck region being the second most common site. CASE REPORT: A 27-year-old woman was admitted to our department due to a left lateral cervical mass. After a complete clinical and imaging examination, a neck dissection was performed, in which a mass, size 3.5 x 2.7 x 4.5 cm, was excised. The patient was diagnosed with Castleman's disease of the neck after histopathological examination. CONCLUSIONS: The diagnosis of Castleman's disease is always a clinical challenge, as the patient commonly presents with nonspecific signs and symptoms resembling other lymphatic diseases. Consequently, Castleman's disease should be in the differential diagnosis of congenital, inflammatory, or neoplastic cervical alterations. A review of literature, including histopathological characteristics, differential diagnosis, and treatment options is also presented.

Docosahexaenoic acid-induced changes in phospholipids in cortex of young and aged rats: a lipidomic analysis.

The age-related decline in cognitive function has been associated with biochemical changes that can be attenuated following n-3 polyunsaturated fatty acid treatment. Dietary supplementation with docosahexaenoic acid (DHA) has been shown to reverse age-related changes in synaptic function. Here, lipidomic analyses were undertaken to examine changes in lipid classes and phospholipid species in cortical tissue of young (2-4 months) and aged (20-22 months), control- and DHA-treated (10mg daily) rats following treatment for 8 weeks, aiming to explore the mechanism of DHA action. Dietary supplementation normalised the age-related decrease in unsaturation index, reduced the levels of arachidonic acid-containing phospholipids in both young and aged animals, and gave rise to production of new phosphatidylserine and phosphatidylinositol species. These findings suggest that DHA may mediate some of its effects through alterations in the membrane lipid composition that can consequently affect the production of pro-inflammatory mediators and signalling molecular species.

Evaluation of patients with liver metastases from colorectal cancer for locally ablative treatment with laser induced thermotherapy. Impact of PET with 18F-fluorodeoxyglucose on therapeutic decisions.

PURPOSE: Before locally ablative treatment of colorectal liver metastases, patients have to be carefully evaluated to decide whether this is the adequate therapy. In this study we determined the value of FDG-PET in comparison to conventional staging procedures. PATIENTS, METHODS: In 68 consecutive patients referred for laser induced thermotherapy (LITT) of liver metastases from colorectal cancer, pretherapeutic staging with conventional imaging (thoracic and abdominal CT, liver MRI, chest X-ray) and FDG-PET was performed. The examinations were analysed separately and blinded. Based on the staging information, therapeutic decisions were made by an interdisciplinary review board according to a standardized algorithm. The results were compared between conventional imaging and FDG-PET, and were validated by clinical follow up data and histopathology, respectively. RESULTS: On FDG-PET 210 lesions were interpreted as tumour manifestations. 48 of these were not seen on conventional imaging (true positive, n = 46). In contrast, 24 lesions were visualized by conventional imaging only (true positive, n = 12). Compared to conventional imaging, discrepant findings on FDG-PET led to treatment modifications in 25 patients (37%); these were correct in 20/25 patients. According to the actual treatment course, the inadequate treatment modifications in the remaining 5 patients were avoided by further diagnostic procedures (i.e. biopsies). CONCLUSION: In the evaluation of patients with known liver metastases from colorectal cancer before LITT, FDG-PET depicts relevant findings subsidiary to conventional imaging and thus is of high value for therapeutic decision making.

Tetrahymena thermophila: analysis of phospholipids and phosphonolipids by high-field 1H-NMR.

The phospholipids of control and lipid-modified Tetrahymena thermophila were identified and quantified, using 1-D and 2-D COSY proton NMR spectroscopy on intact lipids, before and after HPLC separation. The results are comparable to those obtained using classical lipid analytical techniques. The results indicate that the study of enzyme pathways and other metabolic processes involving phospholipids in Tetrahymena and related protozoa can be carried out using proton NMR spectroscopy as the investigating technique.

1H-NMR lipid profiles of human blood platelets; links with coronary artery disease.

Blood platelets are closely involved in the early development of atherosclerosis and in the events that lead to thrombosis, both of which are dominating factors in coronary artery disease (CAD). The aim of the present study was to evaluate the platelet lipid profiles of patients suffering from CAD and explore the possibility of a link between platelet lipids and CAD, using high-resolution high-field proton nuclear magnetic resonance spectroscopy as the analytical tool. The total platelet lipid profiles of healthy volunteers were compared with those of patients presenting with chest pain requiring coronary angiography. Two lipid groups changed significantly: cholesterol increased by 16.5% and total diacylglycerophospholipids decreased by 15.7%. There was also a significant decrease of the ethanolamine-containing phospholipids, by 4.7%; the extent of unsaturation of the fatty acid chains, by 0.2, and increase of the linoleate content of the fatty acid chains, by 1.9%. Our results suggest that platelet lipid abnormalities occur in patients with CAD and these changes may predate the development of overt atherosclerosis.

Abnormal noradrenergic function in posttraumatic stress disorder.

To evaluate possible abnormal noradrenergic neuronal regulation in patients with posttraumatic stress disorder (PTSD), the behavioral, biochemical, and cardiovascular effects of intravenous yohimbine hydrochloride (0.4 mg/kg) were determined in 18 healthy male subjects and 20 male patients with PTSD. A subgroup of patients with PTSD were observed to experience yohimbine-induced panic attacks (70% [14/20]) and flashbacks (40% [8/20]), and they had larger yohimbine-induced increases in plasma 3-methoxy-4-hydroxyphenylglycol levels, sitting systolic blood pressure, and heart rate than those in healthy subjects. In addition, in the patients with PTSD, yohimbine induced significant increases in core PTSD symptoms, such as intrusive traumatic thoughts, emotional numbing, and grief. These data were consistent with a large body of preclinical data that indicated that uncontrollable stress produces substantial increases in noradrenergic neuronal function. We discuss the implications of these abnormalities in noradrenergic functional regulation in relation to the long-term neurobiological sequelae of severe uncontrollable stress and the pathophysiological relationship between PTSD and other anxiety disorders, such as panic disorder.

Noradrenergic and serotonergic function in posttraumatic stress disorder.

BACKGROUND: Yohimbine hydrochloride produces marked behavioral and cardiovascular effects in combat veterans with posttraumatic stress disorder (PTSD). In the present study, yohimbine was used as a probe of noradrenergic activity, and meta-chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our knowledge, this is the first study to describe the behavioral and cardiovascular effects of meta-CPP in patients with PTSD, and to compare these effects with those of yohimbine. METHOD: Twenty-six patients with PTSD and 14 healthy subjects each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m-CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized balanced order and in double-blind fashion. Behavioral and cardiovascular measurements were determined at multiple times. RESULTS: Eleven (42%) of the patients with PTSD experienced yohimbine-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with PTSD experienced m-CPP-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, and in standing diastolic blood pressure. Yohimbine-induced panic attacks tended to occur in different patients from m-CPP-induced panic attacks. CONCLUSION: These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.

Probing single magnon excitations in Sr2IrO4 using O K-edge resonant inelastic x-ray scattering.

Resonant inelastic x-ray scattering (RIXS) at the L-edge of transition metal elements is now commonly used to probe single magnon excitations. Here we show that single magnon excitations can also be measured with RIXS at the K-edge of the surrounding ligand atoms when the center heavy metal elements have strong spin-orbit coupling. This is demonstrated with oxygen K-edge RIXS experiments on the perovskite Sr2IrO4, where low energy peaks from single magnon excitations were observed. This new application of RIXS has excellent potential to be applied to a wide range of magnetic systems based on heavy elements, for which the L-edge RIXS energy resolution in the hard x-ray region is usually poor.

Effects of the benzodiazepine antagonist flumazenil in PTSD.

OBJECTIVE: Evidence from preclinical and clinical studies suggests a role for alterations in the benzodiazepine/GABAA receptor complex in stress and anxiety. Flumazenil is a relatively pure benzodiazepine/GABAA antagonist with limited intrinsic activity. In panic disorder patients, but not healthy controls, flumazenil has been demonstrated to provoke panic attacks. METHOD: Vietnam combat veterans with PTSD (n = 14) received 90-second intravenous infusions of flumazenil 2 mg or placebo in a double-blind, crossover study design. PTSD symptomology was assessed using the PTSD Symptom Scale, and anxiety symptoms were measured with visual analogue rating scales. RESULTS: There was no significant difference in PTSD and anxiety symptoms between administration of flumazenil and placebo. CONCLUSION: Flumazenil administration does not produce an increase in anxiety and PTSD symptoms in patients with PTSD. This suggests that PTSD and panic disorder are dissimilar in terms of benzodiazepine/GABAA system function.