23 research outputs found
Oxidation resistance of graphene-coated Cu and Cu/Ni alloy
The ability to protect refined metals from reactive environments is vital to
many industrial and academic applications. Current solutions, however,
typically introduce several negative effects, including increased thickness and
changes in the metal physical properties. In this paper, we demonstrate for the
first time the ability of graphene films grown by chemical vapor deposition to
protect the surface of the metallic growth substrates of Cu and Cu/Ni alloy
from air oxidation. SEM, Raman spectroscopy, and XPS studies show that the
metal surface is well protected from oxidation even after heating at 200
\degree C in air for up to 4 hours. Our work further shows that graphene
provides effective resistance against hydrogen peroxide. This protection method
offers significant advantages and can be used on any metal that catalyzes
graphene growth
Chemical structure-guided design of dynapyrazoles, potent cell-permeable dynein inhibitors with a unique mode of action
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has in part been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally constrained isosteres. These studies identified dynapyrazoles, inhibitors more potent than ciliobrevins. At single-digit micromolar concentrations dynapyrazoles block intraflagellar transport in the cilium and lysosome motility in the cytoplasm, processes that depend on cytoplasmic dyneins. Further, we find that while ciliobrevins inhibit both dynein's microtubule-stimulated and basal ATPase activity, dynapyrazoles strongly block only microtubule-stimulated activity. Together, our studies suggest that chemical-structure-based analyses can lead to inhibitors with improved properties and distinct modes of inhibition
Physics of leptoquarks in precision experiments and at particle colliders
We present a comprehensive review of physics effects generated by leptoquarks
(LQs), i.e., hypothetical particles that can turn quarks into leptons and vice
versa, of either scalar or vector nature. These considerations include
discussion of possible completions of the Standard Model that contain LQ
fields. The main focus of the review is on those LQ scenarios that are not
problematic with regard to proton stability. We accordingly concentrate on the
phenomenology of light leptoquarks that is relevant for precision experiments
and particle colliders. Important constraints on LQ interactions with matter
are derived from precision low-energy observables such as electric dipole
moments, (g-2) of charged leptons, atomic parity violation, neutral meson
mixing, Kaon, B, and D meson decays, etc. We provide a general analysis of
indirect constraints on the strength of LQ interactions with the quarks and
leptons to make statements that are as model independent as possible. We
address complementary constraints that originate from electroweak precision
measurements, top, and Higgs physics. The Higgs physics analysis we present
covers not only the most recent but also expected results from the Large Hadron
Collider (LHC). We finally discuss direct LQ searches. Current experimental
situation is summarized and self-consistency of assumptions that go into
existing accelerator-based searches is discussed. A progress in making
next-to-leading order predictions for both pair and single LQ productions at
colliders is also outlined.Comment: 136 pages, 22 figures, typographical errors fixed, the Physics
Reports versio
Structure and immune recognition of trimeric pre-fusion HIV-1 Env.
CAPRISA, 2014.The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 Å resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation
REGULARITIES AND PROSPECTS OF TRANSFORMATION OF RURAL SETTLEMENTS IN THE NONCHERNOZEM ZONE OF THE RSFSR
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Chemical structure-guided design of dynapyrazoles, cell-permeable dynein inhibitors with a unique mode of action.
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has in part been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally constrained isosteres. These studies identified dynapyrazoles, inhibitors more potent than ciliobrevins. At single-digit micromolar concentrations dynapyrazoles block intraflagellar transport in the cilium and lysosome motility in the cytoplasm, processes that depend on cytoplasmic dyneins. Further, we find that while ciliobrevins inhibit both dynein's microtubule-stimulated and basal ATPase activity, dynapyrazoles strongly block only microtubule-stimulated activity. Together, our studies suggest that chemical-structure-based analyses can lead to inhibitors with improved properties and distinct modes of inhibition
Recommended from our members
Chemical structure-guided design of dynapyrazoles, cell-permeable dynein inhibitors with a unique mode of action.
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has in part been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally constrained isosteres. These studies identified dynapyrazoles, inhibitors more potent than ciliobrevins. At single-digit micromolar concentrations dynapyrazoles block intraflagellar transport in the cilium and lysosome motility in the cytoplasm, processes that depend on cytoplasmic dyneins. Further, we find that while ciliobrevins inhibit both dynein's microtubule-stimulated and basal ATPase activity, dynapyrazoles strongly block only microtubule-stimulated activity. Together, our studies suggest that chemical-structure-based analyses can lead to inhibitors with improved properties and distinct modes of inhibition
Physics at a future neutrino factory and super-beam facility
The conclusions of the Physics Working Group of the International Scoping Study of a future Neutrino Factory and super-beam facility (the ISS) are presented. The ISS was carried out by the international community between NuFact05, (the 7th International Workshop on Neutrino Factories and Super-beams, Laboratori Nazionali di Frascati, Rome, 21-26 June 2005) and NuFact06 (Ivine, CA, 24-30 August 2006). The physics case for an extensive experimental programme to understand the properties of the neutrino is presented and the role of high-precision measurements of neutrino oscillations within this programme is discussed in detail. The performance of second-generation super-beam experiments, beta-beam facilities and the Neutrino Factory are evaluated and a quantitative comparison of the discovery potential of the three classes of facility is presented. High-precision studies of the properties of the muon are complementary to the study of neutrino oscillations. The Neutrino Factory has the potential to provide extremely intense muon beams and the physics potential of such beams is discussed in the final section of the report