A generalization of Alternating Sign Matrices

In alternating sign matrices the first and last nonzero entry in each row and column is specified to be +1. Such matrices always exist. We investigate a generalization by specifying independently the sign of the first and last nonzero entry in each row and column to be either a +1 or a -1. We determine necessary and sufficient conditions for such matrices to exist.Comment: 14 page

Sustainable Producing Process using 3D Printing

This study is Sustainable producing process using the 3D Printing based on sustainable design. Generally, an approach of sustainability is strong to environmental aspects. 3D Printing technology has been in the spotlight of fabrication field as the new sustainable producing system. Additional, the progress of 3d printing will bring results to the personalizing producing system. It means that it can be produced from necessity. Also, it enables to producing part of discontinued models. The power of these advancements prevents over producing and reduces the lifecycle of product. Namely it reduces the term of works and saves the cost curtails the product lunching period. Therefore, it is the solution to the energy problem and resource saving. The guides line for sustainable producing is required to be controlled the problem of environment and social constraints. This research walks you through a few guidelines. And it offers the practical ways of doing sustainable system centered at the 3Dprinting producing system

The atomistic level structure for the activated human κ-opioid receptor bound to the full Gi protein and the MP1104 agonist

The kappa opioid receptor (κOR) is an important target for pain therapeutics to reduce depression and other harmful side effects of existing medications. The analgesic activity is mediated by κOR signaling through the adenylyl cyclase-inhibitory family of Gi protein. Here, we report the three-dimensional (3D) structure for the active state of human κOR complexed with both heterotrimeric Gi protein and MP1104 agonist. This structure resulted from long molecular dynamics (MD) and metadynamics (metaMD) simulations starting from the 3.1-Å X-ray structure of κOR–MP1104 after replacing the nanobody with the activated Gi protein and from the 3.5-Å cryo-EM structure of μOR–Gi complex after replacing the 168 missing residues. Using MD and metaMD we discovered interactions to the Gi protein with strong anchors to two intracellular loops and transmembrane helix 6 of the κOR. These anchors strengthen the binding, contributing to a contraction in the binding pocket but an expansion in the cytoplasmic region of κOR to accommodate G protein. These remarkable changes in κOR structure reveal that the anchors are essential for activation

Predicted structures of agonist and antagonist bound complexes of adenosine A_3 receptor

We used the GEnSeMBLE Monte Carlo method to predict ensemble of the 20 best packings (helix rotations and tilts) based on the neutral total energy (E) from a vast number (10 trillion) of potential packings for each of the four subtypes of the adenosine G protein-coupled receptors (GPCRs), which are involved in many cytoprotective functions. We then used the DarwinDock Monte Carlo methods to predict the binding pose for the human A_3 adenosine receptor (hAA_3R) for subtype selective agonists and antagonists. We found that all four A_3 agonists stabilize the 15th lowest conformation of apo-hAA_3R while also binding strongly to the 1st and 3rd. In contrast the four A_3 antagonists stabilize the 2nd or 3rd lowest conformation. These results show that different ligands can stabilize different GPCR conformations, which will likely affect function, complicating the design of functionally unique ligands. Interestingly all agonists lead to a trans χ1 angle for W6.48 that experiments on other GPCRs associate with G-protein activation while all 20 apo-AA_3R conformations have a W6.48 gauche+ χ1 angle associated experimentally with inactive GPCRs for other systems. Thus docking calculations have identified critical ligand-GPCR structures involved with activation. We found that the predicted binding site for selective agonist Cl-IB-MECA to the predicted structure of hAA_3R shows favorable interactions to three subtype variable residues, I253^(6.58), V169^(EL2), and Q167^(EL2), while the predicted structure for hAA_(2A)R shows weakened to the corresponding amino acids: T256^(6.58), E169^(EL2), and L167^(EL2), explaining the observed subtype selectivity

Predicted Structures and Dynamics for Agonists and Antagonists Bound to Serotonin 5-HT2B and 5-HT2C Receptors

Subtype 2 serotonin (5-hydroxytryptamine, 5-HT) receptors are major drug targets for schizophrenia, feeding disorders, perception, depression, migraines, hypertension, anxiety, hallucinogens, and gastrointestinal dysfunctions.' We report here the predicted structure of 5-HT2B and 5-HT2C receptors bound to highly potent and selective 5-HT2B antagonist PRX-08066 3, (pKi: 30 nM), including the key binding residues [V103 (2.53), L132 (3.29), V190 (4.60), and L347 (6.58)] determining the selectivity of binding to 5-HT2B over 5-HT2A. We also report structures of the endogenous agonist (5 HT) and a HT2B selective antagonist 2 (1-methyl-1-1,6,7,8-tetrahydro-pyrrolo [2,3-g]quinoline-5-carboxylic acid pyridine-3-ylamide). We examine the dynamics for the agonist-and antagonist-bound HT2B receptors in explicit membrane and water finding dramatically different patterns of water migration into the NPxxY motif and the binding site that correlates with the stability of ionic locks in the D(E)RY region

Symmetry Breaking Phase Transitions in ABJM Theory with a Finite U(1) Chemical Potential

We consider the U(1) charged sector of ABJM theory at finite temperature, which corresponds to the Reissner-Nordstrom AdS black hole in the dual type IIA supergravity description. Including back-reaction to the bulk geometry, we show that phase transitions occur to a broken phase where SU(4) R-symmetry of the field theory is broken spontaneously by the condensation of dimension one or two operators. We show both numerically and analytically that the relevant critical exponents for the dimension one operator agree precisely with those of mean field theory in the strongly coupled regime of the large N planar limit.Comment: 22 pages, 6 figures, typos corrected, references added, improved figures, minor changes, accepted for publication in Phys. Rev.

Relativistic calculation of non-dipole effects in high harmonic generation

We present results of relativistic calculations of even order harmonic generation from various atomic targets. The even order harmonics appear due to the relativistic non-dipole effects. We take these relativistic effects into account by using an approach based on the solution of the time-dependent Dirac equation. The spectra of the non-dipole even harmonics look qualitatively similar to the spectra of the dipole harmonics obeying the same classical cutoff rule. The temporal dynamics of the formation of the non-dipole harmonics is, however, distinctly different from the process of dipole harmonics formation. Even order harmonics emission is strongly suppressed at the beginning of the laser pulse, and the emission times of the non-dipole harmonics are shifted with respect to the bursts of the dipole emission. These features are partly explained by a simple modification of the classical three-step model which takes into account selection rules governing the emission of harmonic photons