Electrostatic considerations affecting the calculated HOMO-LUMO gap in protein molecules.

A detailed study of energy differences between the highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO gaps) in protein systems and water clusters is presented. Recent work questioning the applicability of Kohn-Sham density-functional theory to proteins and large water clusters (E. Rudberg, J. Phys.: Condens. Mat. 2012, 24, 072202) has demonstrated vanishing HOMO-LUMO gaps for these systems, which is generally attributed to the treatment of exchange in the functional used. The present work shows that the vanishing gap is, in fact, an electrostatic artefact of the method used to prepare the system. Practical solutions for ensuring the gap is maintained when the system size is increased are demonstrated. This work has important implications for the use of large-scale density-functional theory in biomolecular systems, particularly in the simulation of photoemission, optical absorption and electronic transport, all of which depend critically on differences between energies of molecular orbitals.Comment: 13 pages, 4 figure

O(N) methods in electronic structure calculations

Linear scaling methods, or O(N) methods, have computational and memory requirements which scale linearly with the number of atoms in the system, N, in contrast to standard approaches which scale with the cube of the number of atoms. These methods, which rely on the short-ranged nature of electronic structure, will allow accurate, ab initio simulations of systems of unprecedented size. The theory behind the locality of electronic structure is described and related to physical properties of systems to be modelled, along with a survey of recent developments in real-space methods which are important for efficient use of high performance computers. The linear scaling methods proposed to date can be divided into seven different areas, and the applicability, efficiency and advantages of the methods proposed in these areas is then discussed. The applications of linear scaling methods, as well as the implementations available as computer programs, are considered. Finally, the prospects for and the challenges facing linear scaling methods are discussed.Comment: 85 pages, 15 figures, 488 references. Resubmitted to Rep. Prog. Phys (small changes

Idiopathic osteonecrosis of the medial tibial plateau

Osteonecrosis of the medial tibial plateau is characterized by acute pain on the medial aspect of the knee. Progression can lead to articular collapse and requires early diagnosis and treatment. We studied seven patients affected of idiopathic osteonecrosis of the tibial plateau. The mean age was 62 years and the mean follow-up 42 months. We performed roentgenograms in all patients, bone scans in three patients and magnetic resonance image (MRI) in five. MRI shows T1-weighted low-intensity signal and T2-weighted high-intensity signal with a surrounding area of intermediate low-intensity signal. An increased focal uptake was seen at bone scan. Histological findings showed necrotic bone with empty lacunae. Surgical treatment consisted of tibial subchondral drilling in four patients-two of them by failure of conservative treatment, and a total knee arthroplasty in other two. One patient had a satisfactory evolution with conservative treatment. Idiopathic osteonecrosis of the tibial plateau must be considered in elderly patients with knee pain over the medial tibial plateau. At early stages, decompression with tibial drilling must be considered. This procedure allows a prompt and effective relief of symptom

Towards Graphene Nanoribbon-based Electronics

The successful fabrication of single layer graphene has greatly stimulated the progress of the research on graphene. In this article, focusing on the basic electronic and transport properties of graphene nanoribbons (GNRs), we review the recent progress of experimental fabrication of GNRs, and the theoretical and experimental investigations of physical properties and device applications of GNRs. We also briefly discuss the research efforts on the spin polarization of GNRs in relation to the edge states.Comment: 9pages,10figure

Maternal but Not Paternal Association of Ambulatory Blood Pressure With Albumin Excretion in Young Offspring With Type 1 Diabetes

OBJECTIVE: Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes. RESEARCH DESIGN AND METHODS: Twenty-four-hour ABP monitoring was performed in 509 young offspring (mean +/- SD age 15.8 +/- 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-to-creatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring. RESULTS: All paternal ABP parameters, except for nighttime SBP, were independently related to the offspring's ABP (24-h SBP beta = 0.18, 24-h DBP beta = 0.22, daytime SBP beta = 0.25, daytime DBP beta = 0.23, and nighttime DBP beta = 0.18; all P < 0.01). Maternal 24-h DBP (beta = 0.19, P = 0.004), daytime DBP (beta = 0.09, P = 0.04), and nighttime SBP (beta = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offspring's logACR and maternal ABP. The association with 24-h DBP (beta = 0.16, P = 0.02), daytime DBP (beta = 0.16 P = 0.02), and nighttime DBP (beta = 0.15 P = 0.03) persisted even after adjustment for the offspring's ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05). CONCLUSIONS: In this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk

Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H Inhibitor Design

Human leukotriene A4 hydrolase (hLTA4H) is a bi-functional enzyme catalyzes the hydrolase and aminopeptidase functions upon the fatty acid and peptide substrates, respectively, utilizing the same but overlapping binding site. Particularly the hydrolase function of this enzyme catalyzes the rate-limiting step of the leukotriene (LT) cascade that converts the LTA4 to LTB4. This product is a potent pro-inflammatory activator of inflammatory responses and thus blocking this conversion provides a valuable means to design anti-inflammatory agents. Four structurally very similar chemical compounds with highly different inhibitory profile towards the hydrolase function of hLTA4H were selected from the literature. Molecular dynamics (MD) simulations of the complexes of hLTA4H with these inhibitors were performed and the results have provided valuable information explaining the reasons for the differences in their biological activities. Binding mode analysis revealed that the additional thiophene moiety of most active inhibitor helps the pyrrolidine moiety to interact the most important R563 and K565 residues. The hLTA4H complexes with the most active compound and substrate were utilized in the development of hybrid pharmacophore models. These developed pharmacophore models were used in screening chemical databases in order to identify lead candidates to design potent hLTA4H inhibitors. Final evaluation based on molecular docking and electronic parameters has identified three compounds of diverse chemical scaffolds as potential leads to be used in novel and potent hLTA4H inhibitor design

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic