Fermionic-propagator and alternating-basis quantum Monte Carlo methods for correlated electrons on a lattice.

Ultracold-atom simulations of the Hubbard model provide insights into the character of charge and spin correlations in and out of equilibrium. The corresponding numerical simulations, on the other hand, remain a significant challenge. We build on recent progress in the quantum Monte Carlo (QMC) simulation of electrons in continuous space and apply similar ideas to the square-lattice Hubbard model.

Universal Magnetic Oscillations of dc Conductivity in the Incoherent Regime of Correlated Systems.

Using the dynamical mean field theory we investigate the magnetic field dependence of dc conductivity in the Hubbard model on the square lattice, fully taking into account the orbital effects of the field introduced via the Peierls substitution. In addition to the conventional Shubnikov-de Haas quantum oscillations, associated with the coherent cyclotron motion of quasiparticles and the presence of a well-defined Fermi surface, we find an additional oscillatory component with a higher frequency that corresponds to the total area of the Brillouin zone. These paradigm-breaking oscillations appear at elevated temperature.

Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field.

Based on the finding that a central antihypertensive agent with high affinity for I1-type imidazoline receptors - rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α-adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α-adrenoceptors belong to the rhodopsin-like class A of G-protein-coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class.

Conductivity in the Square Lattice Hubbard Model at High Temperatures: Importance of Vertex Corrections.

Recent experiments on cold atoms in optical lattices allow for a quantitative comparison of the measurements to the conductivity calculations in the square lattice Hubbard model. However, the available calculations do not give consistent results, and the question of the exact solution for the conductivity in the Hubbard model remained open. In this Letter, we employ several complementary state-of-the-art numerical methods to disentangle various contributions to conductivity and identify the best available result to be compared to experiment.

The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot .

The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5-8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, "Drug Synthesis and Analysis," meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams.

Fierz Convergence Criterion: A Controlled Approach to Strongly Interacting Systems with Small Embedded Clusters.

We present an embedded-cluster method, based on the triply irreducible local expansion formalism. It turns the Fierz ambiguity, inherent to approaches based on a bosonic decoupling of local fermionic interactions, into a convergence criterion. It is based on the approximation of the three-leg vertex by a coarse-grained vertex computed from a self-consistently determined cluster impurity model.

Rational Drug Design of Antineoplastic Agents Using 3D-QSAR, Cheminformatic, and Virtual Screening Approaches.

Background: Computer-Aided Drug Design has strongly accelerated the development of novel antineoplastic agents by helping in the hit identification, optimization, and evaluation.

Results: Computational approaches such as cheminformatic search, virtual screening, pharmacophore modeling, molecular docking and dynamics have been developed and applied to explain the activity of bioactive molecules, design novel agents, increase the success rate of drug research, and decrease the total costs of drug discovery. Similarity, searches and virtual screening are used to identify molecules with an increased probability to interact with drug targets of interest, while the other computational approaches are applied for the design and evaluation of molecules with enhanced activity and improved safety profile.

3D-QSAR, Virtual Screening, Docking and Design of Dual PI3K/mTOR Inhibitors with Enhanced Antiproliferative Activity.

Aim And Objective: Altered activity of PI3K/mTOR signaling pathway is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably attractive concept in potential cancer treatment. The main aim of this work was to design novel PI3K/mTOR inhibitors with enhanced antiproliferative activity.

Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids.

Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17β-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test.

Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of α-adrenergic/imidazoline receptor ligands, and QSPR analysis.

For this study, 31 compounds, including 16 imidazoline/α-adrenergic receptor (IRs/α-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k and log k, respectively). Based on the retention factor (log k) and slope of the linear curve (S) the isocratic parameter (φ) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds.

Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies.

HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction.

A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin.

The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I1-type imidazoline receptors (I1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from α2-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine-derived compounds with anticancer potential and devoid of α2-adrenoceptor effects by means of ligand- and structure-based drug design approaches.

Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs.

Tocopherols and tocotrienols belong to the family of vitamin E (VE) with the well-known antioxidant properties. For certain α-tocopherol and γ-tocotrienol derivatives used as the lead compounds in this study, antitumor activities against various cancer cell types have been reported. In the course of the last decade, structural analogs of VE (esters, ethers and amides) with an enhanced antiproliferative and proapoptotic activity against various cancer cells were synthesized.

Quantitative structure-retention relationship of selected imidazoline derivatives on α1-acid glycoprotein column.

The retention behaviour of 22 selected imidazoline drugs and derivatives was investigated on α1-acid glycoprotein (AGP) column using Sørensen phosphate buffer (pH 7.0) and 2-propanol as organic modifier. Quantitative Structure-Retention Relationships (QSRR) models were built using extrapolated logkw values as well as isocratic retention factors (logk5, logk8, logk10, logk12, logk15 obtained for 5%, 8%, 10%, 12%, and 15%, of 2-propanol in mobile phase, respectively) as dependant variables and calculated physicochemical parameters as independant variables.

Bad-Metal Behavior Reveals Mott Quantum Criticality in Doped Hubbard Models.

Bad-metal (BM) behavior featuring linear temperature dependence of the resistivity extending to well above the Mott-Ioffe-Regel (MIR) limit is often viewed as one of the key unresolved signatures of strong correlation. Here we associate the BM behavior with the Mott quantum criticality by examining a fully frustrated Hubbard model where all long-range magnetic orders are suppressed, and the Mott problem can be rigorously solved through dynamical mean-field theory. We show that for the doped Mott insulator regime, the coexistence dome and the associated first-order Mott metal-insulator transition are confined to extremely low temperatures, while clear signatures of Mott quantum criticality emerge across much of the phase diagram.

Preclinical discovery and development of maraviroc for the treatment of HIV.

Introduction: Maraviroc is a first-in-class antiretroviral (ARV) drug acting on a host cell target (CCR5), which blocks the entry of the HIV virus into the cell. Maraviroc is currently indicated for combination ARV treatment in adults infected only with CCR5-tropic HIV-1.

Areas Covered: This drug discovery case history focuses on the key studies that led to the discovery and approval of maraviroc, as well as on post-launch clinical reports.

Prediction of blood-brain barrier permeation of α-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis.

Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both α2-adrenoreceptors (α2-AR) and imidazoline receptors (IRs). Recent hypotheses connect those ligands with several neurological disorders. Therefore some IRs ligands are examined as novel centrally acting antihypertensives and drug candidates for treatment of various neurological diseases.

Occupational exposure to blood and body fluids among health-care workers in Serbia.

Objectives: The aim of this study was to examine the epidemiology of occupational accidents and self-reported attitude of health-care workers (HCWs) in Serbia.

Subjects And Methods: A cross-sectional study was conducted among HCWs in selected departments of five tertiary care hospitals and in one secondary care hospital in February 2012. A previously developed self-administered questionnaire was provided to HCWs who had direct daily contact with patients.

Quantum critical transport near the Mott transition.

We perform a systematic study of incoherent transport in the high temperature crossover region of the half filled one-band Hubbard model. We demonstrate that the family of resistivity curves displays characteristic quantum critical scaling of the form ρ(T, δU) = ρ(c)(T)f(T/T₀(δU)), with T₀(δU) ~ |δU|(zν), and ρ(c)(T) ~ T. The corresponding β function displays a "strong coupling" form β ~ ln(ρ(c)/ρ), reflecting the peculiar mirror symmetry of the scaling curves.

[Diagnosis of breast cancer in women age 40 and younger: mammography and breast ultrasound].

Breast cancer is the leading cause of mortality among women aged 25 to 44 years in Serbia. The purpose of this study was to determine basic clinical and radiological features of breast cancer in young women. 93 women aged 31.