739 research outputs found
Implementation of a Toffoli Gate with Superconducting Circuits
The quantum Toffoli gate allows universal reversible classical computation.
It is also an important primitive in many quantum circuits and quantum error
correction schemes. Here we demonstrate the realization of a Toffoli gate with
three superconducting transmon qubits coupled to a microwave resonator. By
exploiting the third energy level of the transmon qubit, the number of
elementary gates needed for the implementation of the Toffoli gate, as well as
the total gate time can be reduced significantly in comparison to theoretical
proposals using two-level systems only. We characterize the performance of the
gate by full process tomography and Monte Carlo process certification. The gate
fidelity is found to be %.Comment: 4 pages, 5figure
An equal right to inherit? Women's land rights, customary law and constitutional reform in Tanzania
This article explores contemporary contestations surrounding women’s inheritance of land in Africa. Legal activism has gained momentum, both in agendas for law reform and in test case litigation, which reached United Nations Committee on the Elimination of Discrimination against Women in ES and SC v. United Republic of Tanzania. Comparing the approach of Tanzania to that of its neighbours, Uganda, Kenya and Rwanda, this article explores patterns of resistance and omission towards enshrining an equal right to inherit in land and succession laws. It identifies two main reasons: neoliberal drivers for land law reform of the 1990s and sociopolitical sensitivity surrounding inheritance of land. It argues that a progressive approach to constitutional and law reform on women’s land rights requires understanding of the realities of claims to family land based on kinship relations. It calls for a holistic approach to land, marriage and inheritance law reform underpinned with constitutional rights to equality and progressive interpretations of living customary law
Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice
Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals,
there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death
receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival
and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic
proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To
investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1
transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional
Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the
macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was
striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells
(TCRβ+
CD4–
CD8–
B220+
) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr
mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating
autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene
by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell
population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the
development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other
haemopoietic cell types
Random walk with barriers: Diffusion restricted by permeable membranes
Restrictions to molecular motion by barriers (membranes) are ubiquitous in
biological tissues, porous media and composite materials. A major challenge is
to characterize the microstructure of a material or an organism
nondestructively using a bulk transport measurement. Here we demonstrate how
the long-range structural correlations introduced by permeable membranes give
rise to distinct features of transport. We consider Brownian motion restricted
by randomly placed and oriented permeable membranes and focus on the
disorder-averaged diffusion propagator using a scattering approach. The
renormalization group solution reveals a scaling behavior of the diffusion
coefficient for large times, with a characteristically slow inverse square root
time dependence. The predicted time dependence of the diffusion coefficient
agrees well with Monte Carlo simulations in two dimensions. Our results can be
used to identify permeable membranes as restrictions to transport in disordered
materials and in biological tissues, and to quantify their permeability and
surface area.Comment: 8 pages, 3 figures; origin of dispersion clarified, refs adde
Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay
Assessment of the chemosensitivity of dendritic cells (DC) may allow more rational development of combined chemotherapy and immunotherapy protocols. Human monocyte-derived DC generated reproducible results in the MTS (Owen’s reagent) assay, which was then used to study DC survival after treatment with four different chemotherapy agents. DC preparations from three different donors were used per drug. DC were sensitive to doxorubicin (concentration range 0.1–50 μM) with variation in sensitivity between donors (IC50 244–1100 nM). The most extreme variation was seen for vinblastine (concentration range 250–0.025 μM with IC50 0.15–17.25 μM). In contrast, there was relative resistance to etoposide (concentration range 0.2–200 μM) and 5-fluorouracil (concentration range 0.7–7700 μM) with no toxicity seen until 50 μM and 770 μM respectively. The function of DC in allogeneic mixed leucocyte reactions closely paralleled results from the MTS assays. The differential sensitivity to chemotherapy agents did not appear to be due to expression of P-glycoprotein. These results suggest that etoposide or 5-fluorouracil is less likely to reduce the immunotherapeutic potential of DC and may be valuable in the design of prodrug activation therapy. © 1999 Cancer Research Campaig
Critical Roles of the WASP N-Terminal Domain and Btk in LPS-Induced Inflammatory Response in Macrophages
While Wiskott-Aldrich syndrome protein (WASP) plays critical roles in TCR signaling as an adaptor molecule, how it transduces innate immune signals remains to be elucidated. To investigate the roles of WASP in innate immune cells, we established bone marrow-derived macrophage (BMDM) cell lines from WASP15 transgenic (Tg) mice overexpressing the WASP N-terminal region (exons 1–5). Upon LPS stimulation, WASP15 Tg BMDM cell lines produce lower levels of inflammatory cytokines, such as TNF-α, IL-6, and IL-12p40 than the wild-type BMDM cell line. In addition, the production of nitric oxide by WASP15 Tg BMDM cells in response to LPS and IFN-γ was significantly impaired. Furthermore, we uncovered that the WASP N-terminal domain associates with the Src homology (SH) 3 domain of Bruton's tyrosine kinase (Btk). Overexpression of the WASP N-terminal domain diminishes the extent of tyrosine phosphorylation of endogenous WASP in WASP15 Tg BMDM cells, possibly by interfering with the specific binding between endogenous WASP and Btk during LPS signaling. These observations strongly suggest that the interaction between WASP N-terminal domain and Btk plays important roles in the LPS signaling cascade in innate immunity
The Anti-Apoptotic Bcl-xL Protein, a New Piece in the Puzzle of Cytochrome C Interactome
A structural model of the adduct between human cytochrome c and the human
anti-apoptotic protein Bcl-xL, which defines the protein-protein
interaction surface, was obtained from solution NMR chemical shift perturbation
data. The atomic level information reveals key intermolecular contacts
identifying new potentially druggable areas on cytochrome c and
Bcl-xL. Involvement of residues on cytochrome c other than those
in its complexes with electron transfer partners is apparent. Key differences in
the contact area also exist between the Bcl-xL adduct with the Bak
peptide and that with cytochrome c. The present model provides insights to the
mechanism by which cytochrome c translocated to cytosol can be intercepted, so
that the apoptosome is not assembled
Quantum Computing
Quantum mechanics---the theory describing the fundamental workings of
nature---is famously counterintuitive: it predicts that a particle can be in
two places at the same time, and that two remote particles can be inextricably
and instantaneously linked. These predictions have been the topic of intense
metaphysical debate ever since the theory's inception early last century.
However, supreme predictive power combined with direct experimental observation
of some of these unusual phenomena leave little doubt as to its fundamental
correctness. In fact, without quantum mechanics we could not explain the
workings of a laser, nor indeed how a fridge magnet operates. Over the last
several decades quantum information science has emerged to seek answers to the
question: can we gain some advantage by storing, transmitting and processing
information encoded in systems that exhibit these unique quantum properties?
Today it is understood that the answer is yes. Many research groups around the
world are working towards one of the most ambitious goals humankind has ever
embarked upon: a quantum computer that promises to exponentially improve
computational power for particular tasks. A number of physical systems,
spanning much of modern physics, are being developed for this task---ranging
from single particles of light to superconducting circuits---and it is not yet
clear which, if any, will ultimately prove successful. Here we describe the
latest developments for each of the leading approaches and explain what the
major challenges are for the future.Comment: 26 pages, 7 figures, 291 references. Early draft of Nature 464, 45-53
(4 March 2010). Published version is more up-to-date and has several
corrections, but is half the length with far fewer reference
Inhibition of HIF-1α by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo
In a previous study, we showed that a novel anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd) increased the antitumour efficacy of X-irradiation. However, its effects on hypoxic cells in tumours remain unclarified. Here, we show that TAS106 enhances the induction of apoptosis in X-irradiated human gastric adenocarcinoma MKN45 and MKN28 cells under hypoxia in vitro. At the same time, the accumulation of HIF-1α observed under hypoxia was shown to be decreased to the level of normoxia in the presence of 0.1 μM TAS106. To study the function of HIF-1α protein in apoptosis of hypoxic cells, we employed an HIF-1α reductive approach using its specific antisense oligodeoxynucleotide. The reduction of HIF-1α gene expression dramatically enhanced X-ray-induced apoptosis in hypoxic cells. In in vivo experiments in which MKN45 cells were transplanted into severe combined immunodeficient (SCID) mice, TAS106 (0.5 mg kg−1) suppressed HIF-1α expression and subsequently reduced the area of the hypoxic region in the tumour and enhanced the induction of apoptosis in the hypoxic region when combined with 2 Gy of X-irradiation. These results suggest the possibility that TAS106 acts as a potent radiosensitiser through the inhibition of HIF-1α expression and can be a useful agent against radiotherapy-resistant hypoxic cells in solid tumours
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