56 research outputs found
Signaling Network Assessment of Mutations and Copy Number Variations Predicts Breast Cancer Subtype-specific Drug Targets
Individual cancer cells carry a bewildering number of distinct genomic
alterations i.e., copy number variations and mutations, making it a challenge
to uncover genomic-driven mechanisms governing tumorigenesis. Here we performed
exome-sequencing on several breast cancer cell lines which represent two
subtypes, luminal and basal. We integrated this sequencing data, and functional
RNAi screening data (i.e., for identifying genes which are essential for cell
proliferation and survival), onto a human signaling network. Two
subtype-specific networks were identified, which potentially represent
core-signaling mechanisms underlying tumorigenesis. Within both networks, we
found that genes were differentially affected in different cell lines; i.e., in
some cell lines a gene was identified through RNAi screening whereas in others
it was genomically altered. Interestingly, we found that highly connected
network genes could be used to correctly classify breast tumors into subtypes
based on genomic alterations. Further, the networks effectively predicted
subtype-specific drug targets, which were experimentally validated.Comment: 4 figs, more related papers at http://www.cancer-systemsbiology.org,
appears in Cell Reports, 201
Identification of high-quality cancer prognostic markers and metastasis network modules
There has been great interest in attempting to
identify gene expression signatures that predict cancer survival. In this study a new
algorithm is developed to analyse gene expression datasets that accurately classify both ER+
and ER− breast cancers into low- and high-risk groups
Regional disparities in infant mortality in Canada: a reversal of egalitarian trends
<p>Abstract</p> <p>Background</p> <p>Although national health insurance plans and social programs introduced in the 1960s led to reductions in regional disparities in infant mortality in Canada, it is unclear if such patterns prevailed in the 1990s when the health care and related systems were under fiscal duress. This study examined regional patterns of change in infant mortality in Canada in recent decades.</p> <p>Methods</p> <p>We analysed regional changes in crude infant mortality rates and in infant mortality rates among live births with a birth weight ≥ 500 g and ≥ 1,000 g in Canada from 1945 to 2002. Associations between baseline infant mortality rates in the provinces and territories (e.g., in 1985–89) and the change observed in infant mortality rates over the subsequent period (e.g., between 1985–89 and 1995–99) were assessed using Spearman's rank correlation coefficient. Trends in regional disparities were also assessed by calculating period-specific rate ratios between provinces/territories with the highest versus the lowest infant mortality.</p> <p>Results</p> <p>Provincial/territorial infant mortality rates in 1945–49 were not correlated with changes in infant mortality over the next 10 years (rho = 0.01, P = 0.99). However, there was a strong negative correlation between infant mortality rates in 1965–69 and the subsequent decline in infant mortality (rho = - 0.85, P = 0.002). Provinces/territories with higher infant mortality rates in 1965–69 (Northwest Territories 64.7 vs British Columbia 20.7 per 1,000 live births) experienced relatively larger reductions in infant mortality between 1965–69 and 1975–79 (53.7% decline in the Northwest Territories vs a 36.6% decline in British Columbia). This pattern was reversed in the more recent decades. Provinces/territories with higher infant mortality rates ≥ 500 g in 1985–89 experience relatively smaller reductions in infant mortality between 1985–89 and 2000–02 (rho = 0.82, P = 0.004). The infant mortality ≥ 500 g rate ratio (contrasting the province/territory with the highest versus lowest infant mortality) was 3.2 in 1965–69, 2.4 in 1975–79, 2.2 in 1985–89, 3.1 in 1995–99 and 4.1 in 2000–02.</p> <p>Conclusion</p> <p>Fiscal constraints in the 1990s led to a reversal of provincial/territorial patterns of change in infant mortality in Canada and to an increase in regional health disparities.</p
A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects
BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. METHODS: This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS: The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34). The rates of NTDs fell by 78% (95% CI 65%–86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B(12 )deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B(12 )deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue
Readout of a quantum processor with high dynamic range Josephson parametric amplifiers
We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in
which the active nonlinear element is implemented using an array of rf-SQUIDs.
The device is matched to the 50 environment with a Klopfenstein-taper
impedance transformer and achieves a bandwidth of 250-300 MHz, with input
saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor
was used to benchmark these devices, providing a calibration for readout power,
an estimate of amplifier added noise, and a platform for comparison against
standard impedance matched parametric amplifiers with a single dc-SQUID. We
find that the high power rf-SQUID array design has no adverse effect on system
noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on
amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with
this design show no degradation in readout fidelity due to gain compression,
which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure
Suppressing quantum errors by scaling a surface code logical qubit
Practical quantum computing will require error rates that are well below what
is achievable with physical qubits. Quantum error correction offers a path to
algorithmically-relevant error rates by encoding logical qubits within many
physical qubits, where increasing the number of physical qubits enhances
protection against physical errors. However, introducing more qubits also
increases the number of error sources, so the density of errors must be
sufficiently low in order for logical performance to improve with increasing
code size. Here, we report the measurement of logical qubit performance scaling
across multiple code sizes, and demonstrate that our system of superconducting
qubits has sufficient performance to overcome the additional errors from
increasing qubit number. We find our distance-5 surface code logical qubit
modestly outperforms an ensemble of distance-3 logical qubits on average, both
in terms of logical error probability over 25 cycles and logical error per
cycle ( compared to ). To investigate
damaging, low-probability error sources, we run a distance-25 repetition code
and observe a logical error per round floor set by a single
high-energy event ( when excluding this event). We are able
to accurately model our experiment, and from this model we can extract error
budgets that highlight the biggest challenges for future systems. These results
mark the first experimental demonstration where quantum error correction begins
to improve performance with increasing qubit number, illuminating the path to
reaching the logical error rates required for computation.Comment: Main text: 6 pages, 4 figures. v2: Update author list, references,
Fig. S12, Table I
Non-Abelian braiding of graph vertices in a superconducting processor
Indistinguishability of particles is a fundamental principle of quantum
mechanics. For all elementary and quasiparticles observed to date - including
fermions, bosons, and Abelian anyons - this principle guarantees that the
braiding of identical particles leaves the system unchanged. However, in two
spatial dimensions, an intriguing possibility exists: braiding of non-Abelian
anyons causes rotations in a space of topologically degenerate wavefunctions.
Hence, it can change the observables of the system without violating the
principle of indistinguishability. Despite the well developed mathematical
description of non-Abelian anyons and numerous theoretical proposals, the
experimental observation of their exchange statistics has remained elusive for
decades. Controllable many-body quantum states generated on quantum processors
offer another path for exploring these fundamental phenomena. While efforts on
conventional solid-state platforms typically involve Hamiltonian dynamics of
quasi-particles, superconducting quantum processors allow for directly
manipulating the many-body wavefunction via unitary gates. Building on
predictions that stabilizer codes can host projective non-Abelian Ising anyons,
we implement a generalized stabilizer code and unitary protocol to create and
braid them. This allows us to experimentally verify the fusion rules of the
anyons and braid them to realize their statistics. We then study the prospect
of employing the anyons for quantum computation and utilize braiding to create
an entangled state of anyons encoding three logical qubits. Our work provides
new insights about non-Abelian braiding and - through the future inclusion of
error correction to achieve topological protection - could open a path toward
fault-tolerant quantum computing
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Social Movements and International Relations: A Relational Framework
Social movements are increasingly recognized as significant features of contemporary world politics, yet to date their treatment in international relations theory has tended to obfuscate the considerable diversity of these social formations, and the variegated interactions they may establish with state actors and different structures of world order. Highlighting the difficulties conventional liberal and critical approaches have in transcending conceptions of movements as moral entities, the article draws from two under-exploited literatures in the study of social movements in international relations, the English School and Social Systems Theory, to specify a wider range of analytical interactions between different categories of social movements and of world political structures. Moreover, by casting social movement phenomena as communications, the article opens international relations to consideration of the increasingly diverse trajectories and second-order effects produced by social movements as they interact with states, intergovernmental institutions, and transnational actors
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