94 research outputs found
Synthesis of kinase inhibitors containing a pentafluorosulfanyl moiety
A series of 3-methylidene-1H-indol-2(3H)-ones substituted with a 5- or 6- pentafluorosulfanyl group has been synthesized by a Knoevenagel condensation reaction of SF5-substituted oxindoles with a range of aldehydes. The resulting products were characterized by x-ray crystallography studies and were tested for biological activity versus a panel of cell lines and protein kinases. Some exhibited single digit nM activity
Fully gapped topological surface states in BiSe films induced by a d-wave high-temperature superconductor
Topological insulators are a new class of materials, that exhibit robust
gapless surface states protected by time-reversal symmetry. The interplay
between such symmetry-protected topological surface states and symmetry-broken
states (e.g. superconductivity) provides a platform for exploring novel quantum
phenomena and new functionalities, such as 1D chiral or helical gapless
Majorana fermions, and Majorana zero modes which may find application in
fault-tolerant quantum computation. Inducing superconductivity on topological
surface states is a prerequisite for their experimental realization. Here by
growing high quality topological insulator BiSe films on a d-wave
superconductor BiSrCaCuO using molecular beam epitaxy,
we are able to induce high temperature superconductivity on the surface states
of BiSe films with a large pairing gap up to 15 meV. Interestingly,
distinct from the d-wave pairing of BiSrCaCuO, the
proximity-induced gap on the surface states is nearly isotropic and consistent
with predominant s-wave pairing as revealed by angle-resolved photoemission
spectroscopy. Our work could provide a critical step toward the realization of
the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274
Experimental observation of topological Fermi arcs in type-II Weyl semimetal MoTe2
Weyl semimetal is a new quantum state of matter [1-12] hosting the condensed
matter physics counterpart of relativisticWeyl fermion [13] originally
introduced in high energy physics. The Weyl semimetal realized in the TaAs
class features multiple Fermi arcs arising from topological surface states [10,
11, 14-16] and exhibits novel quantum phenomena, e.g., chiral anomaly induced
negative mag-netoresistance [17-19] and possibly emergent supersymmetry [20].
Recently it was proposed theoretically that a new type (type-II) of Weyl
fermion [21], which does not have counterpart in high energy physics due to the
breaking of Lorentz invariance, can emerge as topologically-protected touching
between electron and hole pockets. Here, we report direct spectroscopic
evidence of topological Fermi arcs in the predicted type-II Weyl semimetal
MoTe2 [22-24]. The topological surface states are confirmed by directly
observing the surface states using bulk-and surface-sensitive angle-resolved
photoemission spectroscopy (ARPES), and the quasi-particle interference (QPI)
pattern between the two putative Fermi arcs in scanning tunneling microscopy
(STM). Our work establishes MoTe2 as the first experimental realization of
type-II Weyl semimetal, and opens up new opportunities for probing novel
phenomena such as exotic magneto-transport [21] in type-II Weyl semimetals.Comment: submitted on 01/29/2016. Nature Physics, in press. Spectroscopic
evidence of the Fermi arcs from two complementary surface sensitive probes -
ARPES and STS. A comparison of the calculated band structure for T_d and 1T'
phase to identify the topological Fermi arcs in the T_d phase is also
included in the supplementary informatio
Mice expressing a human KATP channel mutation have altered channel ATP sensitivity but no cardiac abnormalities
AIMS/HYPOTHESIS: Patients with severe gain-of-function mutations in the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, have neonatal diabetes, muscle hypotonia and mental and motor developmental delay-a condition known as iDEND syndrome. However, despite the fact that Kir6.2 forms the pore of the cardiac K(ATP) channel, patients show no obvious cardiac symptoms. The aim of this project was to use a mouse model of iDEND syndrome to determine whether iDEND mutations affect cardiac function and cardiac K(ATP) channel ATP sensitivity. METHODS: We performed patch-clamp and in vivo cine-MRI studies on mice in which the most common iDEND mutation (Kir6.2-V59M) was targeted to cardiac muscle using Cre-lox technology (m-V59M mice). RESULTS: Patch-clamp studies of isolated cardiac myocytes revealed a markedly reduced K(ATP) channel sensitivity to MgATP inhibition in m-V59M mice (IC(50) 62 μmol/l compared with 13 μmol/l for littermate controls). In vivo cine-MRI revealed there were no gross morphological differences and no differences in heart rate, end diastolic volume, end systolic volume, stroke volume, ejection fraction, cardiac output or wall thickening between m-V59M and control hearts, either under resting conditions or under dobutamine stress. CONCLUSIONS/INTERPRETATION: The common iDEND mutation Kir6.2-V59M decreases ATP block of cardiac K(ATP) channels but was without obvious effect on heart function, suggesting that metabolic changes fail to open the mutated channel to an extent that affects function (at least in the absence of ischaemia). This may have implications for the choice of sulfonylurea used to treat neonatal diabetes
Quasistationary Stabilization of the Decay of a Weakly-Bound Level and Its Breakdown in a Strong Laser Field
Although it was pointed out about 10 years ago that an atomic decay rate might decrease as the intensity of a high-frequency laser field increases, there still does not exist any complete understanding of either the physical origin of this interesting nonlinear phenomenon or its dependence on the atomic and field parameters. Essentially, the problem consists in that the phenomenon requires a major modification of the standard picture of photoeffect in a strong laser field. In Reference #1 the origin of this stabilization is related to a particular distortion of an atomic potential by an intense monochromatic high-frequency field. This phenomenon is called adiabatic or quasistationary stabilization (QS). For the case of Rydberg levels, another (interference) mechanism of QS was suggested. Both theories predict an unlimited decrease of the decay rate (or of the width Γ of an atomic level, i.e., of the imaginary part of the complex quasienergy, ε = Re ε – iΓ/2 ) as the laser field amplitude increases. In recent years the idea of “dynamic stabilization” (DS) has become popular. It originates from the pulse form of a laser field rather than from any intrinsic property of the atom in a strong monochromatic field. Within this model the numerous simulations point also to the possibility of a breakdown of stabilization for the case of superintense short laser pulses. However, a recent paper, using the quasistationary quasienergy states (QQES) as an adiabatic basis for the laser pulse has shown that DS has the same (quasistationary) origin as QS. Finally, a number of authors deny the existence of stabilization, in particular, of QS for ionization from a short-range potential and of DS in pulsed fields. Obviously, these controversies and ambiguities are caused by the complexity of the numerical solution of the Cauchy problem for the time-dependent Schrödinger equation in a strong field and by the absence of analyses for exactly solvable analytical models. We analyze the exactly solvable problem of an electron in a three-dimensional, short-range potential and consider the two questions: does a QS-like behavior of the decay rate exist for this model, and, if so, is there an upper intensity limit of the QS regime
Proteins with Complex Architecture as Potential Targets for Drug Design: A Case Study of Mycobacterium tuberculosis
Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only
Semiconductor Spintronics
Spintronics refers commonly to phenomena in which the spin of electrons in a
solid state environment plays the determining role. In a more narrow sense
spintronics is an emerging research field of electronics: spintronics devices
are based on a spin control of electronics, or on an electrical and optical
control of spin or magnetism. This review presents selected themes of
semiconductor spintronics, introducing important concepts in spin transport,
spin injection, Silsbee-Johnson spin-charge coupling, and spindependent
tunneling, as well as spin relaxation and spin dynamics. The most fundamental
spin-dependent nteraction in nonmagnetic semiconductors is spin-orbit coupling.
Depending on the crystal symmetries of the material, as well as on the
structural properties of semiconductor based heterostructures, the spin-orbit
coupling takes on different functional forms, giving a nice playground of
effective spin-orbit Hamiltonians. The effective Hamiltonians for the most
relevant classes of materials and heterostructures are derived here from
realistic electronic band structure descriptions. Most semiconductor device
systems are still theoretical concepts, waiting for experimental
demonstrations. A review of selected proposed, and a few demonstrated devices
is presented, with detailed description of two important classes: magnetic
resonant tunnel structures and bipolar magnetic diodes and transistors. In most
cases the presentation is of tutorial style, introducing the essential
theoretical formalism at an accessible level, with case-study-like
illustrations of actual experimental results, as well as with brief reviews of
relevant recent achievements in the field.Comment: tutorial review; 342 pages, 132 figure
- …