200 research outputs found
Transition states and greedy exploration of the QAOA optimization landscape
The QAOA is a variational quantum algorithm, where a quantum computer
implements a variational ansatz consisting of p layers of alternating unitary
operators and a classical computer is used to optimize the variational
parameters. For a random initialization the optimization typically leads to
local minima with poor performance, motivating the search for initialization
strategies of QAOA variational parameters. Although numerous heuristic
intializations were shown to have a good numerical performance, an analytical
understanding remains evasive. Inspired by the study of energy landscapes, in
this work we focus on so-called transition states (TS) that are saddle points
with a unique negative curvature direction that connects to local minima.
Starting from a local minimum of QAOA with p layers, we analytically construct
2p + 1 TS for QAOA with p + 1 layers. These TS connect to new local minima, all
of which are guaranteed to lower the energy compared to the minimum found for p
layers. We introduce a Greedy procedure to effectively maneuver the
exponentially increasing number of TS and corresponding local minima. The
performance of our procedure matches the best available initialization
strategy, and in addition provides a guarantee for the minimal energy to
decrease with an increasing number of layers p. Generalization of analytic TS
and the Greedy approach to other ans\"atze may provide a universal framework
for initialization of variational quantum algorithms.Comment: 5 pages, 4 figures, comments are welcom
Fabrication and characterization of dual function nanoscale pH-scanning ion conductance microscopy (SICM) probes for high resolution pH mapping
The easy fabrication and use of nanoscale dual function pH-scanning ion conductance microscopy (SICM) probes is reported. These probes incorporate an iridium oxide coated carbon electrode for pH measurement and an SICM barrel for distance control, enabling simultaneous pH and topography mapping. These pH-SICM probes were fabricated rapidly from laser pulled theta quartz pipets, with the pH electrode prepared by in situ carbon filling of one of the barrels by the pyrolytic decomposition of butane, followed by electrodeposition of a thin layer of hydrous iridium oxide. The other barrel was filled with an electrolyte solution and Ag/AgCl electrode as part of a conductance cell for SICM. The fabricated probes, with pH and SICM sensing elements typically on the 100 nm scale, were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and various electrochemical measurements. They showed a linear super-Nernstian pH response over a range of pH (pH 2–10). The capability of the pH-SICM probe was demonstrated by detecting both pH and topographical changes during the dissolution of a calcite microcrystal in aqueous solution. This system illustrates the quantitative nature of pH-SICM imaging, because the dissolution process changes the crystal height and interfacial pH (compared to bulk), and each is sensitive to the rate. Both measurements reveal similar dissolution rates, which are in agreement with previously reported literature values measured by classical bulk methods
What Shall I Do Next? Intention Mining for Flexible Process Enactment
International audienceBesides the benefits of flexible processes, practical implementations of process aware information systems have also revealed difficulties encountered by process participants during enactment. Several support and guidance solutions based on process mining have been proposed, but they lack a suitable semantics for human reasoning and decisions making as they mainly rely on low level activities. Applying design science, we created FlexPAISSeer, an intention mining oriented approach, with its component artifacts: 1) IntentMiner which discovers the intentional model of the executable process in an unsupervised manner; 2) In-tentRecommender which generates recommendations as intentions and confidence factors, based on the mined intentional process model and probabilistic calculus. The artifacts were evaluated in a case study with a Netherlands software company, using a Childcare system that allows flexible data-driven process enactment
Candida albicans repetitive elements display epigenetic diversity and plasticity
Transcriptionally silent heterochromatin is associated with repetitive DNA. It is poorly understood whether and how heterochromatin differs between different organisms and whether its structure can be remodelled in response to environmental signals. Here, we address this question by analysing the chromatin state associated with DNA repeats in the human fungal pathogen Candida albicans. Our analyses indicate that, contrary to model systems, each type of repetitive element is assembled into a distinct chromatin state. Classical Sir2-dependent hypoacetylated and hypomethylated chromatin is associated with the rDNA locus while telomeric regions are assembled into a weak heterochromatin that is only mildly hypoacetylated and hypomethylated. Major Repeat Sequences, a class of tandem repeats, are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Marker gene silencing assays and genome-wide RNA sequencing reveals that C. albicans heterochromatin represses expression of repeat-associated coding and non-coding RNAs. We find that telomeric heterochromatin is dynamic and remodelled upon an environmental change. Weak heterochromatin is associated with telomeres at 30?°C, while robust heterochromatin is assembled over these regions at 39?°C, a temperature mimicking moderate fever in the host. Thus in C. albicans, differential chromatin states controls gene expression and epigenetic plasticity is linked to adaptation
PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis
PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in
mitosis. Numerous roles for PICH have been proposed from protein depletion experiments,
but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells
causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of
Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH-/- cells undergo sister
chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localises
with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both
structures depends on the ATPase activity of PICH. Purified PICH protein strongly
stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH-/- cell
line exhibits chromosome instability and chromosome condensation and decatenation
defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II
cooperate to prevent chromosome missegregation events in mitosis
Gingival Fibroblasts Display Reduced Adhesion and Spreading on Extracellular Matrix: A Possible Basis for Scarless Tissue Repair?
Unlike skin, oral gingiva do not scar in response to injury. The basis of this difference is likely to be revealed by comparing the responses of dermal and gingival fibroblasts to fibrogenic stimuli. Previously, we showed that, compared to dermal fibroblasts, gingival fibroblasts are less responsive to the potent pro-fibrotic cytokine TGFβ, due to a reduced production of endothelin-1 (ET-1). In this report, we show that, compared to dermal fibroblasts, human gingival fibroblasts show reduced expression of pro-adhesive mRNAs and proteins including integrins α2 and α4 and focal adhesion kinase (FAK). Consistent with these observations, gingival fibroblasts are less able to adhere to and spread on both fibronectin and type I collagen. Moreover, the enhanced production of ET-1 mRNA and protein in dermal fibroblasts is reduced by the FAK/src inhibitor PP2. Given our previous observations suggesting that fibrotic fibroblasts display elevated adhesive properties, our data suggest that scarring potential may be based, at least in part, on differences in adhesive properties among fibroblasts resident in connective tissue. Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury
Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients
BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor
(PAI-1) play essential roles in tumor invasion and metastasis. High levels
of both uPA and PAI-1 are associated with poor prognosis in breast cancer
patients. To confirm the prognostic value of uPA and PAI-1 in primary
breast cancer, we reanalyzed individual patient data provided by members
of the European Organization for Research and Treatment of Cancer-Receptor
and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets
involving 8377 breast cancer patients. During follow-up (median 79
months), 35% of the patients relapsed and 27% died. Levels of uPA and
PAI-1 in tumor tissue extracts were determined by different immunoassays;
values were ranked within each dataset and divided by the number of
patients in that dataset to produce fractional ranks that could be
compared directly across datasets. Associations of ranks of uPA and PAI-1
levels with relapse-free survival (RFS) and overall survival (OS) were
analyzed by Cox multivariable regression analysis stratified by dataset,
including the following traditional prognostic variables: age, menopausal
status, lymph node status, tumor size, histologic grade, and steroid
hormone-receptor status. All P values were two-sided. RESULTS: Apart from
lymph node status, high levels of uPA and PAI-1 were the strongest
predictors of both poor RFS and poor OS in the analyses of all patients.
Moreover, in both lymph node-positive and lymph node-negative patients,
higher uPA and PAI-1 values were independently associated with poor RFS
and poor OS. For (untreated) lymph node-negative patients in particular,
uPA and PAI-1 included together showed strong prognostic ability (all
P<.001). CONCLUSIONS: This pooled analysis of the EORTC-RBG datasets
confirmed the strong and independent prognostic value of uPA and PAI-1 in
primary breast cancer. For patients with lymph node-negative breast
cancer, uPA and PAI-1 measurements in primary tumors may be especially
useful for designing individualized treatment strategies
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