Expanding the solvent chemical space for self-assembly of dipeptide nanostructures.

Nanostructures composed of short, noncyclic peptides represent a growing field of research in nanotechnology due to their ease of production, often remarkable material properties, and biocompatibility. Such structures have so far been almost exclusively obtained through self-assembly from aqueous solution, and their morphologies are determined by the interactions between building blocks as well as interactions between building blocks and water. Using the diphenylalanine system, we demonstrate here that, in order to achieve structural and morphological control, a change in the solvent environment represents a simple and convenient alternative strategy to the chemical modification of the building blocks. Diphenylalanine (FF) is a dipeptide capable of self-assembly in aqueous solution into needle-like hollow micro- and nanocrystals with continuous nanoscale channels that possess advantageous properties such as high stiffness and piezoelectricity and have so emerged as attractive candidates for functional nanomaterials. We investigate systematically the solubility of diphenylalanine in a range of organic solvents and probe the role of the solvent in the kinetics of self-assembly and the structures of the final materials. Finally, we report the crystal structure of the FF peptide in microcrystalline form grown from MeOH solution at 1 Å resolution and discuss the structural changes relative to the conventional materials self-assembled in aqueous solution. These findings provide a significant expansion of the structures and morphologies that are accessible through FF self-assembly for existing and future nanotechnological applications of this peptide. Solvent mediation of molecular recognition and self-association processes represents an important route to the design of new supramolecular architectures deriving their functionality from the nanoscale ordering of their components.We thank the Newman Foundation (T.O.M., T.P.J.K.), the FEBS and the Tel Aviv University Center for Nanoscience and Nanotechnology (A.L.), the BBSRC (T.P.J.K.), and the Leverhulme Trust and Magdalene College (A.K.B.) for financial support. A.L. thanks Or Berger for his assistance with the HR-SEM imaging. The X-ray diffraction data collection experiments were performed in the crystallographic X-ray facility at the Department of Biochemistry, University of Cambridge. The authors thank Pavel Afonin for help with PHENIX software suite in the refinement of the structures.This is the accepted manuscript for a paper published in ACS Nano, 2014, 8 (2), pp 1243–1253 DOI: 10.1021/nn404237f , Publication Date (Web): January 14, 201

N-Methylimidazole Promotes The Reaction Of Homophthalic Anhydride With Imines

The addition of N-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-N-trifluoroethylimine (9) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate 10. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of 10 is also described

Metaphoric coherence: Distinguishing verbal metaphor from `anomaly\u27

Theories and computational models of metaphor comprehension generally circumvent the question of metaphor versus “anomaly” in favor of a treatment of metaphor versus literal language. Making the distinction between metaphoric and “anomalous” expressions is subject to wide variation in judgment, yet humans agree that some potentially metaphoric expressions are much more comprehensible than others. In the context of a program which interprets simple isolated sentences that are potential instances of cross‐modal and other verbal metaphor, I consider some possible coherence criteria which must be satisfied for an expression to be “conceivable” metaphorically. Metaphoric constraints on object nominals are represented as abstracted or extended along with the invariant structural components of the verb meaning in a metaphor. This approach distinguishes what is preserved in metaphoric extension from that which is “violated”, thus referring to both “similarity” and “dissimilarity” views of metaphor. The role and potential limits of represented abstracted properties and constraints is discussed as they relate to the recognition of incoherent semantic combinations and the rejection or adjustment of metaphoric interpretations

Quarkonium and hydrogen spectra with spin dependent relativistic wave equation

A non-linear non-perturbative relativistic atomic theory introduces spin in the dynamics of particle motion. The resulting energy levels of Hydrogen atom are exactly same as the Dirac theory. The theory accounts for the energy due to spin-orbit interaction and for the additional potential energy due to spin and spin-orbit coupling. Spin angular momentum operator is integrated into the equation of motion. This requires modification to classical Laplacian operator. Consequently the Dirac matrices and the k operator of Dirac's theory are dispensed with. The theory points out that the curvature of the orbit draws on certain amount of kinetic and potential energies affecting the momentum of electron and the spin-orbit interaction energy constitutes a part of this energy. The theory is developed for spin 1/2 bound state single electron in Coulomb potential and then further extended to quarkonium physics by introducing the linear confining potential. The unique feature of this quarkonium model is that the radial distance can be exactly determined and does not have a statistical interpretation. The established radial distance is then used to determine the wave function. The observed energy levels are used as the input parameters and the radial distance and the string tension are predicted. This ensures 100% conformance to all observed energy levels for the heavy quarkonium.Comment: 14 pages, v7: Journal reference adde

Nasty Viruses, Costly Plasmids, Population Dynamics, and the Conditions for Establishing and Maintaining CRISPR-Mediated Adaptive Immunity in Bacteria

Clustered, Regularly Interspaced Short Palindromic Repeats (CRISPR) abound in the genomes of almost all archaebacteria and nearly half the eubacteria sequenced. Through a genetic interference mechanism, bacteria with CRISPR regions carrying copies of the DNA of previously encountered phage and plasmids abort the replication of phage and plasmids with these sequences. Thus it would seem that protection against infecting phage and plasmids is the selection pressure responsible for establishing and maintaining CRISPR in bacterial populations. But is it? To address this question and provide a framework and hypotheses for the experimental study of the ecology and evolution of CRISPR, I use mathematical models of the population dynamics of CRISPR-encoding bacteria with lytic phage and conjugative plasmids. The results of the numerical (computer simulation) analysis of the properties of these models with parameters in the ranges estimated for Escherichia coli and its phage and conjugative plasmids indicate: (1) In the presence of lytic phage there are broad conditions where bacteria with CRISPR-mediated immunity will have an advantage in competition with non-CRISPR bacteria with otherwise higher Malthusian fitness. (2) These conditions for the existence of CRISPR are narrower when there is envelope resistance to the phage. (3) While there are situations where CRISPR-mediated immunity can provide bacteria an advantage in competition with higher Malthusian fitness bacteria bearing deleterious conjugative plasmids, the conditions for this to obtain are relatively narrow and the intensity of selection favoring CRISPR weak. The parameters of these models can be independently estimated, the assumption behind their construction validated, and the hypotheses generated from the analysis of their properties tested in experimental populations of bacteria with lytic phage and conjugative plasmids. I suggest protocols for estimating these parameters and outline the design of experiments to evaluate the validity of these models and test these hypotheses

Modes of Foreign Entry under Asymmetric Information about Potential Technology Spillovers

This paper studies the effect of technology spillovers on the entry decision of a multinational enterprise into a foreign market. Two alternative entry modes for a foreign direct investment are considered: Greenfield investment versus acquisition. We find that with quantity competition a spillover makes acquisitions less attractive, while with price competition acquisitions become more attractive. Asymmetric information about potential spillovers always reduces the number of acquisitions independently of whether the host country or the entrant has private information. Interestingly, we find that asymmetric information always hurts the entrant, while it sometimes is in favor of the host country

Glauber Dynamics for the mean-field Potts Model

We study Glauber dynamics for the mean-field (Curie-Weiss) Potts model with $q\geq 3$ states and show that it undergoes a critical slowdown at an inverse-temperature $\beta_s(q)$ strictly lower than the critical $\beta_c(q)$ for uniqueness of the thermodynamic limit. The dynamical critical $\beta_s(q)$ is the spinodal point marking the onset of metastability. We prove that when $\beta<\beta_s(q)$ the mixing time is asymptotically $C(\beta, q) n \log n$ and the dynamics exhibits the cutoff phenomena, a sharp transition in mixing, with a window of order $n$. At $\beta=\beta_s(q)$ the dynamics no longer exhibits cutoff and its mixing obeys a power-law of order $n^{4/3}$. For $\beta>\beta_s(q)$ the mixing time is exponentially large in $n$. Furthermore, as $\beta \uparrow \beta_s$ with $n$, the mixing time interpolates smoothly from subcritical to critical behavior, with the latter reached at a scaling window of $O(n^{-2/3})$ around $\beta_s$. These results form the first complete analysis of mixing around the critical dynamical temperature --- including the critical power law --- for a model with a first order phase transition.Comment: 45 pages, 5 figure

Detection of Heteroplasmic Mitochondrial DNA in Single Mitochondria

BACKGROUND: Mitochondrial DNA (mtDNA) genome mutations can lead to energy and respiratory-related disorders like myoclonic epilepsy with ragged red fiber disease (MERRF), mitochondrial myopathy, encephalopathy, lactic acidosis and stroke (MELAS) syndrome, and Leber's hereditary optic neuropathy (LHON). It is not well understood what effect the distribution of mutated mtDNA throughout the mitochondrial matrix has on the development of mitochondrial-based disorders. Insight into this complex sub-cellular heterogeneity may further our understanding of the development of mitochondria-related diseases. METHODOLOGY: This work describes a method for isolating individual mitochondria from single cells and performing molecular analysis on that single mitochondrion's DNA. An optical tweezer extracts a single mitochondrion from a lysed human HL-60 cell. Then a micron-sized femtopipette tip captures the mitochondrion for subsequent analysis. Multiple rounds of conventional DNA amplification and standard sequencing methods enable the detection of a heteroplasmic mixture in the mtDNA from a single mitochondrion. SIGNIFICANCE: Molecular analysis of mtDNA from the individually extracted mitochondrion demonstrates that a heteroplasmy is present in single mitochondria at various ratios consistent with the 50/50 heteroplasmy ratio found in single cells that contain multiple mitochondria

A Newcomer's Guide to the Challenges of a Complex Space-to-Ground Experiment, With Lessons from Analog-1

An astronaut controlling a complex robot on the surface of earth from the ISS. This is exactly what we have done in ANALOG-1. Luca Parmitano teleoperated a rover in a moon-analogue geological mission scenario. On first sight the primary technical challenges seem to be the design of the robotic systems for space and ground. On a second look - with the perspective of using the system with an astronaut on the ISS in loop with an operations team in different ground centers - the scope and challenges drastically increase. In this paper we take a look behind the scenes, and gives insights which could guide future payload developers going on a similar endeavour. This paper outlines the Analog-1 experiment, itself, what it aimed to achieve, and how it was done, and uses it as a case study to outline the challenges and solutions a project team and particularly the payload developer - will have to overcome when designing an ISS experiment. This article may be especially insightful and a good starting point for those from a small research team at a university or other research institution with budget and time pressure. We will present it from the payload developers perspective and on concrete examples of the payloads we flown