The design and fabrication of supramolecular semiconductor nanowires formed by benzothienobenzothiophene (BTBT)-conjugated peptides

π-Conjugated small molecules based on a [1]benzothieno[3,2-b]benzothiophene (BTBT) unit are of great research interest in the development of solution-processable semiconducting materials owing to their excellent charge-transport characteristics. However, the BTBT π-core has yet to be demonstrated in the form of electro-active one-dimensional (1D) nanowires that are self-assembled in aqueous media for potential use in bioelectronics and tissue engineering. Here we report the design, synthesis, and self-assembly of benzothienobenzothiophene (BTBT)–peptide conjugates, the BTBT–peptide (BTBT-C3–COHN-Ahx-VVAGKK-Am) and the C8-BTBT–peptide (C8-BTBT-C3–COHN-Ahx-VVAGKK-Am), as β-sheet forming amphiphilic molecules, which self-assemble into highly uniform nanofibers in water with diameters of 11–13(±1) nm and micron-size lengths. Spectroscopic characterization studies demonstrate the J-type π–π interactions among the BTBT molecules within the hydrophobic core of the self-assembled nanofibers yielding an electrical conductivity as high as 6.0 × 10−6 S cm−1. The BTBT π-core is demonstrated, for the first time, in the formation of self-assembled peptide 1D nanostructures in aqueous media for potential use in tissue engineering, bioelectronics and (opto)electronics. The conductivity achieved here is one of the highest reported to date in a non-doped state

Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans

Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models. New initiatives sponsored by several US federal agencies seek to address this problem by funding the development of physiologically relevant human organ models on microscopic chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the organ models, thereby replacing animal testing in drug discovery and development. As part of this initiative, we aim to build a three-dimensional human liver chip that mimics the acinus, the smallest functional unit of the liver, including its oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three-dimensional co-culture environment with stable synthetic and enzymatic function for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be integrated into the chip to provide multiplexed, real-time readouts of key liver functions and pathology. We are also developing a database to manage experimental data and harness external information to interpret the multimodal data and create a predictive platform

Shopping with violence: Black Friday sales in the British context

This article argues that the 2014 adoption of the US shopping tradition of Black Friday sales to stores and supermarkets in the United Kingdom and beyond represents an important point of enquiry for the social sciences. We claim that the importation of the consumer event, along with the disorder and episodes of violence that accompany it, are indicative of the triumph of liberal capitalist consumer ideology while reflecting an embedded and cultivated form of insecurity and anxiety concomitant with the barbaric individualism, social envy and symbolic competition of consumer culture. Through observation and qualitative interviews, this article presents some initial analyses of the motivations and meanings attached to the conduct of those we begin to understand as ‘extreme shoppers’ and seeks to understand these behaviours against the context of the social harms associated with consumer culture

Falsification Of The Atmospheric CO2 Greenhouse Effects Within The Frame Of Physics

The atmospheric greenhouse effect, an idea that many authors trace back to the traditional works of Fourier (1824), Tyndall (1861), and Arrhenius (1896), and which is still supported in global climatology, essentially describes a fictitious mechanism, in which a planetary atmosphere acts as a heat pump driven by an environment that is radiatively interacting with but radiatively equilibrated to the atmospheric system. According to the second law of thermodynamics such a planetary machine can never exist. Nevertheless, in almost all texts of global climatology and in a widespread secondary literature it is taken for granted that such mechanism is real and stands on a firm scientific foundation. In this paper the popular conjecture is analyzed and the underlying physical principles are clarified. By showing that (a) there are no common physical laws between the warming phenomenon in glass houses and the fictitious atmospheric greenhouse effects, (b) there are no calculations to determine an average surface temperature of a planet, (c) the frequently mentioned difference of 33 degrees Celsius is a meaningless number calculated wrongly, (d) the formulas of cavity radiation are used inappropriately, (e) the assumption of a radiative balance is unphysical, (f) thermal conductivity and friction must not be set to zero, the atmospheric greenhouse conjecture is falsified.Comment: 115 pages, 32 figures, 13 tables (some typos corrected

Musical organics: a heterarchical approach to digital organology

Gaining a comprehensive understanding of new musical technologies is fraught with difficulties. The digital materials from which they are formed are of such diverse origins and nature, that they do not match traditional organological classifications. This article traces the history of musical instrument classifications relevant to the understanding of new instruments, and proposes an alternative approach to the centuries-old tree-structure of downwards divisions. The proposed musical organics is a multi-dimensional, heterarchical, and organic approach to the analysis and classification of both traditional and new musical instruments that suits the rhizomatic nature of their material design and technical origins. Outlines of a hypothetical organological informatics retrieval system are also presented

Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans

Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models. New initiatives sponsored by several US federal agencies seek to address this problem by funding the development of physiologically relevant human organ models on microscopic chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the organ models, thereby replacing animal testing in drug discovery and development. As part of this initiative, we aim to build a three-dimensional human liver chip that mimics the acinus, the smallest functional unit of the liver, including its oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three-dimensional co-culture environment with stable synthetic and enzymatic function for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be integrated into the chip to provide multiplexed, real-time readouts of key liver functions and pathology. We are also developing a database to manage experimental data and harness external information to interpret the multimodal data and create a predictive platform. © 2013 BioMed Central Ltd

Characterizing early drug resistance-related events using geometric ensembles from HIV protease dynamics:

The use of antiretrovirals (ARVs) has drastically improved the life quality and expectancy of HIV patients since their introduction in health care. Several millions are still afflicted worldwide by HIV and ARV resistance is a constant concern for both healthcare practitioners and patients, as while treatment options are finite, the virus constantly adapts via complex mutation patterns to select for resistant strains under the pressure of drug treatment. The HIV protease is a crucial enzyme for viral maturation and has been a game changing drug target since the first application. Due to similarities in protease inhibitor designs, drug cross-resistance is not uncommon across ARVs of the same class

Role of Hsp70 ATPase Domain Intrinsic Dynamics and Sequence Evolution in Enabling its Functional Interactions with NEFs

Catalysis of ADP-ATP exchange by nucleotide exchange factors (NEFs) is central to the activity of Hsp70 molecular chaperones. Yet, the mechanism of interaction of this family of chaperones with NEFs is not well understood in the context of the sequence evolution and structural dynamics of Hsp70 ATPase domains. We studied the interactions of Hsp70 ATPase domains with four different NEFs on the basis of the evolutionary trace and co-evolution of the ATPase domain sequence, combined with elastic network modeling of the collective dynamics of the complexes. Our study reveals a subtle balance between the intrinsic (to the ATPase domain) and specific (to interactions with NEFs) mechanisms shared by the four complexes. Two classes of key residues are distinguished in the Hsp70 ATPase domain: (i) highly conserved residues, involved in nucleotide binding, which mediate, via a global hinge-bending, the ATPase domain opening irrespective of NEF binding, and (ii) not-conserved but co-evolved and highly mobile residues, engaged in specific interactions with NEFs (e.g., N57, R258, R262, E283, D285). The observed interplay between these respective intrinsic (pre-existing, structure-encoded) and specific (co-evolved, sequence-dependent) interactions provides us with insights into the allosteric dynamics and functional evolution of the modular Hsp70 ATPase domain