Monte Carlo methods in the manifold of Hartree-Fock-Bogoliubov wave functions.

We explore the possibility of implementing random walks in the manifold of Hartree-Fock-Bogoliubov wave functions. The goal is to extend state-of-the-art quantum Monte Carlo approaches, in particular the constrained-path auxiliary-field quantum Monte Carlo technique, to systems where finite pairing order parameters or complex pairing mechanisms, e.g., Fulde-Ferrell-Larkin-Ovchinnikov pairing or triplet pairing, may be expected. Leveraging the flexibility to define a vacuum state tailored to the physical problem, we discuss a method to use imaginary-time evolution of Hartree-Fock-Bogoliubov states to compute ground state correlations, extending beyond situations spanned by current formalisms. Illustrative examples are provided.

Exotic Superfluid Phases in Spin-Polarized Fermi Gases in Optical Lattices.

Leveraging cutting-edge numerical methodologies, we study the ground state of the two-dimensional spin-polarized Fermi gas in an optical lattice. We focus on systems at high density and small spin polarization, corresponding to the parameter regime believed to be most favorable to the formation of the elusive Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) superfluid phase. Our systematic study of large lattice sizes, hosting nearly 500 atoms, provides strong evidence of the stability of the FFLO state in this regime, as well as a high-accuracy characterization of its properties. Our results for the density correlation function reveal the existence of density order in the system, suggesting the possibility of an intricate coexistence of long-range orders in the ground state. The ground-state properties are seen to differ significantly from the standard mean-field description, providing a compelling avenue for future theoretical and experimental explorations of the interplay between spin imbalance, strong interactions, and superfluidity in an exotic phase of matter.

Ultracold Atoms in a Square Lattice with Spin-Orbit Coupling: Charge Order, Superfluidity, and Topological Signatures.

We present an ab initio, numerically exact study of attractive fermions in square lattices with Rashba spin-orbit coupling. The ground state of this system is a supersolid, with coexisting charge and superfluid order. The superfluid is composed of both singlet and triplet pairs induced by spin-orbit coupling. We perform large-scale calculations using the auxiliary-field quantum Monte Carlo method to provide the first full, quantitative description of the charge, spin, and pairing properties of the system. In addition to characterizing the exotic physics, our results will serve as essential high-accuracy benchmarks for the intense theoretical and especially experimental efforts in ultracold atoms to realize and understand an expanding variety of quantum Hall and topological superconductor systems.

Rashba Spin-Orbit Coupling, Strong Interactions, and the BCS-BEC Crossover in the Ground State of the Two-Dimensional Fermi Gas.

The recent experimental realization of spin-orbit coupled Fermi gases provides a unique opportunity to study the interplay between strong interaction and spin-orbit coupling (SOC) in a tunable, disorder-free system. We present here precision ab initio numerical results on the two-dimensional, unpolarized, uniform Fermi gas with attractive interactions and Rashba SOC. Using the auxiliary-field quantum Monte Carlo method and incorporating recent algorithmic advances, we carry out exact calculations on sufficiently large system sizes to provide accurate results systematically as a function of experimental parameters. We obtain the equation of state, the momentum distributions, the pseudospin correlations, and the pair wave functions. Our results help illuminate the rich pairing structure induced by SOC, and provide benchmarks for theory and guidance to future experimental efforts.

Attenuated liver fibrosis after bile duct ligation and defective hepatic stellate cell activation in neural cell adhesion molecule knockout mice.

AIM: Neural cell adhesion molecule (N-CAM) is expressed by activated hepatic stellate cells (HSC), portal fibroblasts, cholangiocytes and hepatic progenitor cells during liver injury. Its functional role in liver disease and fibrogenesis is unknown. The aim of this study was to investigate the role of N-CAM in liver fibrogenesis. METHODS: To induce fibrosis, N-CAM knockout mice and wild-type controls were subjected to bile duct ligation (BDL) or repeated carbon tetrachloride (CCl(4) ) injections. Fibrosis was quantified by hydroxyproline, immunhistochemistry staining and image analysis. Protein levels were determined with immunoblotting. HSCs were isolated by ultracentrifugation in a Larcoll gradient and thereafter in vitro stimulated with recombinant transforming growth factor (TGF)-ß1. RESULTS: Two weeks after BDL, wild-type mice had developed pronounced liver fibrosis while N-CAM-/- mice had less such alterations. N-CAM-/- mice had less deposition of collagen and fibronectin seen in immunhistochemistry. The protein levels of fibronectin were higher in the liver from the wild type, while laminin were unaltered. CCl(4) -treated N-CAM-/- and wild-type mice showed no significant difference in the extent of liver fibrosis or the expression levels of the above-mentioned genes. HSC isolated from N-CAM-/- mice showed declined levels of smooth muscle actin and desmin after stimulation in vitro with TGF-ß1. CONCLUSIONS: Loss of N-CAM results in decreased hepatic collagen and fibronectin deposition in mice subjected to BDL, but not in animals exposed to repeated CCl(4) injections. HSC isolated from N-CAM null mice show impaired activation in vitro. This indicates a role of N-CAM in cholestatic liver disease and HSC activation.

Ezrin-radixin-moesin-binding phosphoprotein (EBP50), an estrogen-inducible scaffold protein, contributes to biliary epithelial cell proliferation.

Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) anchors and regulates apical membrane proteins in epithelia. EBP50 is inducible by estrogen and may affect cell proliferation, although this latter function remains unclear. The goal of this study was to determine whether EBP50 was implicated in the ductular reaction that occurs in liver disease. EBP50 expression was examined in normal human liver, in human cholangiopathies (ie, cystic fibrosis, primary biliary cirrhosis, and primary sclerosing cholangitis), and in rats subjected to bile-duct ligation. The regulation of EBP50 by estrogens and its impact on proliferation were assessed in both bile duct-ligated rats and Mz-Cha-1 human biliary epithelial cells. Analyses of cell isolates and immunohistochemical studies showed that in normal human liver, EBP50 is expressed in the canalicular membranes of hepatocytes and, together with ezrin and cystic fibrosis transmembrane conductance regulator, in the apical domains of cholangiocytes. In both human cholangiopathies and bile duct-ligated rats, EBP50 was redistributed to the cytoplasmic and nuclear compartments. EBP50 underwent a transient increase in rat cholangiocytes after bile-duct ligation, whereas such expression was down-regulated in ovariectomized rats. In addition, in Mz-Cha-1 cells, EBP50 underwent up-regulation and intracellular redistribution in response to 17beta-estradiol, whereas its proliferation was inhibited by siRNA-mediated EBP50 knockdown. These results indicate that both the expression and distribution of EBP50 are regulated by estrogens and contribute to the proliferative response in biliary epithelial cells.

Radioactivity in trinitite six decades later.

The first nuclear explosion test, named the Trinity test, was conducted on July 16, 1945 near Alamogordo, New Mexico. In the tremendous heat of the explosion, the radioactive debris fused with the local soil into a glassy material named Trinitite. Selected Trinitite samples from ground zero (GZ) of the test site were investigated in detail for radioactivity. The techniques used included alpha spectrometry, high-efficiency gamma-ray spectrometry, and low-background beta counting, following the radiochemistry for selected radionuclides. Specific activities were determined for fission products (90Sr, 137Cs), activation products (60Co, 133Ba, 152Eu, 154Eu, 238Pu, 241Pu), and the remnants of the nuclear fuel (239Pu, 240Pu). Additionally, specific activities of three natural radionuclides (40K, 232Th, 238U) and their progeny were measured. The determined specific activities of radionuclides and their relationships are interpreted in the context of the fission process, chemical behavior of the elements, as well as the nuclear explosion phenomenology.

FFLO order in ultra-cold atoms in three-dimensional optical lattices.

We investigate different ground-state phases of attractive spin-imbalanced populations of fermions in three-dimensional optical lattices. Detailed numerical calculations are performed using Hartree-Fock-Bogoliubov theory to determine the ground-state properties systematically for different values of density, spin polarization and interaction strength. We first consider the high density and low polarization regime, in which the effect of the optical lattice is most evident. We then proceed to the low density and high polarization regime where the effects of the underlying lattice are less significant and the system begins to resemble a continuum Fermi gas. We explore the effects of density, polarization and interaction on the character of the phases in each regime and highlight the qualitative differences between the two regimes. In the high-density regime, the order is found to be of Larkin-Ovchinnikov type, linearly oriented with one characteristic wave vector but varying in its direction with the parameters. At lower densities the order parameter develops more structures involving multiple wave vectors.

The liver in heart failure.

Severe congestive heart failure is associated with two distinct forms of liver dysfunction: jaundice that is related to passive congestion and acute hepatocellular necrosis that is caused by impaired perfusion. Cardiac cirrhosis (fibrosis) may result from prolonged recurrent congestive heart failure. Ischemic hepatitis (shock liver) usually manifests as asymptomatic elevation of the serum aminotransferase levels after an episode of hypotension, although the clinical presentation may mimic that of acute viral hepatitis. In most cases, ischemic hepatitis is of little clinical consequence and is self-limited. Acute liver failure may occur in patients with preexisting cirrhosis, severe chronic heart failure, or sustained hepatic ischemia.

Microvesicular fat, inter cellular adhesion molecule-1 and regulatory T-lymphocytes are of importance for the inflammatory process in livers with non-alcoholic steatohepatitis.

Great progress has been made in understanding the development of non-alcoholic fatty liver disease (NAFLD) but less is known about the mechanisms underlying the progress from steatosis to steatohepatitis (NASH). Our aim was to evaluate if the amount and type of storage of fat in hepatocytes is of importance for hepatocyte injury. We also wanted to show if not only the innate immunity but also the adaptive immunity is involved in NASH. Thirty-one patients with NASH or borderline NASH and 18 non-NASH patients were investigated. Liver biopsies were scored for NASH according to Kleiner et al. Paraffin-embedded liver biopsies were stained with antibodies against CD3, TLR4, CD68, Cleaved Caspase-3, ICAM1, Foxp3 and ApopTag by immunohistochemistry. Serum soluble ICAM-1 (sICAM-1) were analysed by ELISA. The volume density of fat was 59% in the NASH patients and microvesicular fat, increased in high NAS score patients. ICAM-1 positive hepatocytes were seen in NASH patients and were localized in areas with microvesicular fat. Non-NASH biopsies were negative for ICAM-1 positive hepatocytes. The sICAM-1 were significantly higher in NASH-patients (339.8 ± 34.07) than in non-NASH patients (229.5 ± 12.14), p = 0.0015. Patients with NAS score over four had higher area of CD68 positive cells p = 0.0011 and Foxp3 positive cells (p = 0.024) than non-NASH patients. In liver tissue with NASH, hepatocytes with microvesicular steatosis seem to be expressing more inflammatory markers, and in this liver tissue an increased number of CD68 cells and regulatory T-cells (Tregs, e.g. Foxp3+ cells) were seen, indicating an involvement of, both the innate and the adaptive immunity.

Psoriasis patients with diabetes type 2 are at high risk of developing liver fibrosis during methotrexate treatment.

BACKGROUND/AIMS: We investigated the impact of diabetes mellitus type 2, overweight, alcohol over-consumption, and chronic hepatitis B or C as risk factors, for liver fibrosis in psoriasis patients treated with methotrexate. METHODS: One hundred and sixty-nine liver biopsies from 71 patients who underwent liver biopsies as part of the monitoring of methotrexate treatment for psoriasis were reviewed. Fibrosis, steatosis and inflammation were staged according to the NAFLD activity score. RESULTS: Twenty-six patients had one or more of the risk factors and 25 (96%) of these (median cumulative dose methotrexate 1500 mg) developed liver fibrosis. Of those without risk factor, 26 (58%) (p=0.012) developed fibrosis (median cumulative dose methotrexate 2100 mg). Ten (38%) of the patients with risk factor(s) had severe fibrosis (stage 3-4) (mean cumulative dose methotrexate 1600 mg), while four (9%) (p=0.0012) of those without risk factors had severe fibrosis (median cumulative dose methotrexate 1900 mg). CONCLUSIONS: Patients with methotrexate treated psoriasis and risk factors for liver disease, especially diabetes type 2 or overweight, are at higher risk of developing severe liver fibrosis compared to those without such risk factors, even when lower cumulative methotrexate doses are given.

Advanced glycation end products (AGE) and the receptor for AGE are present in gastrointestinal tract of familial amyloidotic polyneuropathy patients but do not induce NF-kappaB activation.

Familial amyloidotic polyneuropathy (FAP), Portuguese type, is a hereditary amyloidosis caused by mutated transthyretin (ATTR) in which an exchange of valine for methionine at position 30 has taken place (ATTR Val30Met). Gastrointestinal complications, such as nausea, diarrhoea and malabsorption, have a significant impact on survival since the cause of death in the majority of cases is a consequence of extreme malnutrition due to dysmotility of the gastrointestinal tract. Recently, a role of the receptor for advanced glycation end products (RAGE) has been implicated in amyloid toxicity. Transthyretin (TTR) amyloid fibrils have been shown to have affinity for RAGE and subsequently induce NF-kappaB activation and apoptosis. Since gastrointestinal dysfunction plays an important role in FAP, we wanted to investigate if amyloid toxicity in the gastrointestinal tract is related to RAGE, NF-kappaB activation and apoptosis. Gastrointestinal tract autopsy samples were studied for the distribution of amyloid, RAGE, advanced glycation end products (AGE) and NF-kappaB. Furthermore, we examined the immunoreactivity of an apoptotic marker to investigate if an apoptotic pathway contributes to amyloid toxicity. The distribution of RAGE and AGE strongly correlated to that of amyloid deposits. Sequential immunofluorescence staining revealed a clear relationship between TTR, AGE and RAGE. No correlation between NF-kappaB, apoptotic marker and amyloid deposits was found. We conclude that RAGE-AGE or RAGE-TTR interaction might play important roles for gastrointestinal dysfunction and amyloid toxicity, although not through NF-kappaB activation and apoptosis.

Rapidly progressive fibrosing cholestatic hepatitis--hepatitis C virus in HIV coinfection.

Fibrosing cholestatic hepatitis (FCH) is a severe and progressive form of liver dysfunction seen in organ transplant recipients infected with hepatitis B virus or hepatitis C virus (HCV) and has been attributed to cytopathic liver injury. To date, no case of FCH due to HCV has been reported in HIV-positive individuals. We describe two cases of HCV-induced FCH in two patients coinfected with HIV, culminating in rapidly progressive liver failure and death. Histological features and progression in both cases were not consistent with drug effect or obstruction. Late institution of interferon-based therapy was ultimately unsuccessful. The HCV RNA was not markedly elevated in these cases, suggesting that the cytopathic effect of HCV in these patients was not simply a consequence of viral load. FCH may in part explain the accelerated development of cirrhosis previously observed among coinfected patients. Clinicians should remain vigilant for FCH in the HIV/HCV population and consider antiviral treatment in this setting.