Study of Virus-Like Particles in Male Mice Carrying Mammary Tumour Agent

SEVERAL investigations had been conducted in order to study the origin and distribution of mammary tumour agent (MTA) in various organs of high cancer strain mice. It (MTA) is known to be harboured also by the males of the same strains in their reproductive organs and accessory glands (Andervont and Dunn, 1948a) from which it can be transmitted to virus susceptible females in the course of repeated mating to these same females and eventually to their young ones (Andervont and Dunn, 1948b) through the milk (Bittner, 1952). Muhlbock (1950) established the presence of this agent in the sperms passed from the end of the epididymis. He (Muhlbock, 1952) had experimentally shown that agent free females develop mammary tumours after mating with the males of high-cancer strain. He had also shown that the seminal vesicle of such males shows biological activity for these agents and can produce mammary tumours in the females. Recently Feldman (1963) has shown virus-like particles within the endoplasmic reticulum of the epididymis of both high-cancer strain, and agent free males. Further investigations in this line of work were thought to be quite pertinent

First-Principle Description of Correlation Effects in Layered Materials

We present a first-principles description of anisotropic materials characterized by having both weak (dispersion-like) and strong covalent bonds, based on the Adiabatic--Connection Fluctuation--Dissipation Theorem within Density Functional Theory. For hexagonal boron nitride the in-plane and out of plane bonding as well as vibrational dynamics are well described both at equilibrium and when the layers are pulled apart. Also bonding in covalent and ionic solids is described. The formalism allows to ping-down the deficiencies of common exchange-correlation functionals and provides insight towards the inclusion of dispersion interactions into the correlation functional.Comment: Accepted for publication in Physical Review Letter

Excitons in boron nitride nanotubes: dimensionality effects

We show that the optical absorption spectra of boron nitride (BN) nanotubes are dominated by strongly bound excitons. Our first-principles calculations indicate that the binding energy for the first and dominant excitonic peak depends sensitively on the dimensionality of the system, varying from 0.7 eV in bulk hexagonal BN via 2.1 eV in the single sheet of BN to more than 3 eV in the hypothetical (2,2) tube. The strongly localized nature of this exciton dictates the fast convergence of its binding energy with increasing tube diameter towards the sheet value. The absolute position of the first excitonic peak is almost independent of the tube radius and system dimensionality. This provides an explanation for the observed "optical gap" constancy for different tubes and bulk hBN [R. Arenal et al., to appear in Phys. Rev. Lett. (2005)].Comment: 5 pages, 2 figure

Noninvasive Embedding of Single Co Atoms in Ge(111)2x1 Surfaces

We report on a combined scanning tunneling microscopy (STM) and density functional theory (DFT) based investigation of Co atoms on Ge(111)2x1 surfaces. When deposited on cold surfaces, individual Co atoms have a limited diffusivity on the atomically flat areas and apparently reside on top of the upper pi-bonded chain rows exclusively. Voltage-dependent STM imaging reveals a highly anisotropic electronic perturbation of the Ge surface surrounding these Co atoms and pronounced one-dimensional confinement along the pi-bonded chains. DFT calculations reveal that the individual Co atoms are in fact embedded in the Ge surface, where they occupy a quasi-stationary position within the big 7-member Ge ring in between the 3rd and 4th atomic Ge layer. The energy needed for the Co atoms to overcome the potential barrier for penetration in the Ge surface is provided by the kinetic energy resulting from the deposition process. DFT calculations further demonstrate that the embedded Co atoms form four covalent Co-Ge bonds, resulting in a Co4+ valence state and a 3d5 electronic configuration. Calculated STM images are in perfect agreement with the experimental atomic resolution STM images for the broad range of applied tunneling voltages.Comment: 19 pages, 15 figures, 3 table

Interaction of Oscillatory Flow with a Non Uniformly Rotating Lamina

The problem of the boundary layer flow near the stagnation point of a lamina rotating unsteadily in the presence of a fluctuating free stream directed normally towards it, has been studies in this paper. The velocity distribution has been obtained for the two limiting cases of large and small values of the frequency of oscillation. The transitional frequencies for which the two approximate solutions overlap have been obtained and presented in a tabulated form

Targeting Pro-Inflammatory Function of Microglia Using Small Molecules to Combat Neurodegeneration

Microglia are the brain’s resident immune cells that are responsible for maintaining homeostasis in healthy conditions. During injury or infection, resting microglia get activated and produce pro-inflammatory cytokines such as IL-1b, IL-1a, IL-6, etc. along with reactive oxygen species like nitric oxide (NO) to combat neuroinflammatory diseases such as Alzheimer’s disease (AD). Inflammation is characterized by the activation of resident-immune cells in the brain called microglia that respond to the eat-me signals released by the toxic amyloid beta peptides as well as the dying neurons in the microenvironment. Recent studies have shown that activated microglia induce neuronal death by secreting IL-1a, TNF-a, and C1q. However, the cellular and molecular mechanisms in this process are not well understood. Furthermore, it has been previously shown that IL-1a and TNF-a promote neuronal death via the activation of astrocytes during inflammation. We used BV2 mouse microglia to investigate the IL-1a and TNF-a cytokine production in response to LPS activation using enzyme-linked immunosorbent assay (ELISA). In addition, the viability of the cells along with their NO production was evaluated using cell titer blue assay (CTB) and Griess assay. In this study, we show that small molecules can be used in single treatment and in combination to combat the inflammatory functions of microglia. These small molecules that modulate microglial functions may play an important role in developing new therapeutics for neuroinflammation

From social machines to social protocols:Software engineering foundations for sociotechnical systems

The overarching vision of social machines is to facilitate social processes by having computers provide administrative support. We conceive of a social machine as a sociotechnical system (STS): a software-supported system in which autonomous principals such as humans and organizations interact to exchange information and services. Existing approaches for social machines emphasize the technical aspects and inadequately support the meanings of social processes, leaving them informally realized in human interactions. We posit that a fundamental rethinking is needed to incorporate accountability, essential for addressing the openness of the Web and the autonomy of its principals. We introduce Interaction-Oriented Software Engineering (IOSE) as a paradigm expressly suited to capturing the social basis of STSs. Motivated by promoting openness and autonomy, IOSE focuses not on implementation but on social protocols, specifying how social relationships, characterizing the accountability of the concerned parties, progress as they interact. Motivated by providing computational support, IOSE adopts the accountability representation to capture the meaning of a social machine’s states and transitions. We demonstrate IOSE via examples drawn from healthcare. We reinterpret the classical software engineering (SE) principles for the STS setting and show how IOSE is better suited than traditional software engineering for supporting social processes. The contribution of this paper is a new paradigm for STSs, evaluated via conceptual analysis

Computational Drug Design: A Multitargeted Approach in Bladder Cancer

Cancer is a complex, robust disease with multiple redundant disease pathways which lead to tumor development, growth, and eventually even death. Despite known redundancies, cancer therapeutics continue to be developed against a single protein target. Initial disease regression occurs followed by relapse in a drug resistant disease state. In response, combinational drug clinical trial targeting multiple pathways began, and have failed due to increased toxicity caused by adverse drug interactions. Development of a single drug that differentially targets multiple disease pathways will result in a more potent therapeutic while inducing minimal toxicity. This was done computationally through in-lab software packages, like CANDOCK, designed to build novel therapeutics that selectively target user defined protein targets. Four protein targets (androgen receptor, estrogen receptor, glucocorticoid receptor, and peroxisome proliferator-activated receptor gamma) were chosen for their known involvement in bladder cancer proliferation and metastasis. Computationally designed compounds were then synthesized and screened for high potency in bladder cancer cell lines using the CellTiter-Blue cell viability assay. Several compounds decreased the cell viability and hindered growth in both mouse and two human bladder cancer cell lines (MB49, T24, and 5637 cell lines, respectively). In addition, some potent compounds displayed decreased nitrous oxide production in RAW 264.7 cells, a mouse macrophage model, using a Griess assay. Thus showing that these compounds could decrease immunosuppression in the tumor microenvironment and slow cancer cell proliferation in vivo

P09-15. Selection of higher avidity HLA-restricted T cell responses as a viral adaptation strategy

Loss of immune reactivity due to HIV mutational escape is well described. Data generated from a large population-based study (n>800) suggested that certain CD8 T cell epitopes are created as a result of HIV adaptation and are associated with enhanced viral replication. Here we sought to investigate the HLA-restricted T-cell responses associated with seven such adaptations