Efficient First-Order Algorithms for Large-Scale, Non-Smooth Maximum Entropy Models with Application to Wildfire Science.

Maximum entropy (MaxEnt) models are a class of statistical models that use the maximum entropy principle to estimate probability distributions from data. Due to the size of modern data sets, MaxEnt models need efficient optimization algorithms to scale well for big data applications. State-of-the-art algorithms for MaxEnt models, however, were not originally designed to handle big data sets; these algorithms either rely on technical devices that may yield unreliable numerical results, scale poorly, or require smoothness assumptions that many practical MaxEnt models lack.

Accelerating gradient descent and Adam via fractional gradients.

We propose a class of novel fractional-order optimization algorithms. We define a fractional-order gradient via the Caputo fractional derivatives that generalizes integer-order gradient. We refer it to as the Caputo fractional-based gradient, and develop an efficient implementation to compute it.

Periodic Artifact Removal With Applications to Deep Brain Stimulation.

Deep brain stimulation (DBS) therapies have shown clinical success in the treatment of a number of neurological illnesses, including obsessive-compulsive disorder, epilepsy, and Parkinson's disease. An emerging strategy for increasing the efficacy of DBS therapies is to develop closed-loop, adaptive DBS systems that can sense biomarkers associated with particular symptoms and in response, adjust DBS parameters in real-time. The development of such systems requires extensive analysis of the underlying neural signals while DBS is on, so that candidate biomarkers can be identified and the effects of varying the DBS parameters can be better understood.

The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes.

Purpose: Receptor-interacting protein of 140 kDa (RIP140) is a transcriptional cofactor for nuclear receptors involved in reproduction and energy homeostasis. Our aim was to investigate its role in the regulation of E2F1 activity and target genes both in breast cancer cell lines and in tumor biopsies.

Experimental Design: Glutathione S-transferase pull-down assays, coimmunoprecipitation experiments, and chromatin immunoprecipitation analysis were used to evidence interaction between RIP140 and E2F1.

CIP2A is associated with human breast cancer aggressivity.

Purpose: To investigate the clinical relevance of the recently characterized human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) in human breast cancer.

Experimental Design: CIP2A expression (mRNA and protein) was measured in three different sets of human mammary tumors and compared with clinicopathologic variables. The functional role of CIP2A in breast cancer cells was evaluated by small interfering RNA-mediated depletion of the protein followed by an analysis of cell proliferation, migration, anchorage-independent growth, and xenograft growth.

SAR image regularization with fast approximate discrete minimization.

Synthetic aperture radar (SAR) images, like other coherent imaging modalities, suffer from speckle noise. The presence of this noise makes the automatic interpretation of images a challenging task and noise reduction is often a prerequisite for successful use of classical image processing algorithms. Numerous approaches have been proposed to filter speckle noise.

[Gene expression profiling of ER+ breast cancers: to discriminate the poor prognosis tumors or to define the most suitable treatment?].

The cDNA microarray technology allows the simultaneous analysis of all genes expressed in a tumor. This approach has already permitted to propose a molecular classification of breast cancers. Gene expression profiling is now expected to define prognosis signatures claiming the disease outcome as well as signatures predicting response to therapy.

A gene expression signature that can predict the recurrence of tamoxifen-treated primary breast cancer.

Purpose: The identification of a molecular signature predicting the relapse of tamoxifen-treated primary breast cancers should help the therapeutic management of estrogen receptor-positive cancers.

Experimental Design: A series of 132 primary tumors from patients who received adjuvant tamoxifen were analyzed for expression profiles at the whole-genome level by 70-mer oligonucleotide microarrays. A supervised analysis was done to identify an expression signature.

A new molecular breast cancer subclass defined from a large scale real-time quantitative RT-PCR study.

Background: Current histo-pathological prognostic factors are not very helpful in predicting the clinical outcome of breast cancer due to the disease's heterogeneity. Molecular profiling using a large panel of genes could help to classify breast tumours and to define signatures which are predictive of their clinical behaviour.

Methods: To this aim, quantitative RT-PCR amplification was used to study the RNA expression levels of 47 genes in 199 primary breast tumours and 6 normal breast tissues.

Shape-based hand recognition.

The problem of person recognition and verification based on their hand images has been addressed. The system is based on the images of the right hands of the subjects, captured by a flatbed scanner in an unconstrained pose at 45 dpi. In a pre-processing stage of the algorithm, the silhouettes of hand images are registered to a fixed pose, which involves both rotation and translation of the hand and, separately, of the individual fingers.

Regulation of Chk2 phosphorylation by interaction with protein phosphatase 2A via its B' regulatory subunit.

Chk2 is a key player of the DNA damage signalling pathway. To identify new regulators of this kinase, we performed a yeast two-hybrid screen and found that Chk2 associated with the B' regulatory subunit of protein phosphatase PP2A. In vitro GST-Chk2 pulldowns demonstrated that B'gamma isoforms bound to Chk2 with the strongest apparent affinity.

MAP kinase-dependent degradation of p27Kip1 by calpains in choroidal melanoma cells. Requirement of p27Kip1 nuclear export.

We investigated the status and the regulation of the cyclin-dependent kinases (CDK) inhibitor p27(Kip1) in a choroidal melanoma tumor-derived cell line (OCM-1). By contrast to normal choroidal melanocytes, the expression level of p27(Kip1) was low in these cells and the mitogen-activated protein (MAP) kinase pathway was constitutively activated. Genetic or chemical inhibition of this pathway induced p27(Kip1) accumulation, whereas MAP kinase reactivation triggered a down-regulation of p27(Kip1) that could be partially reversed by calpain inhibitors.

Cell adhesion protects c-Raf-1 against ubiquitin-dependent degradation by the proteasome.

MAP kinase activation by growth factors depends on cell adhesion to the extracellular matrix. Disrupting the cell adhesion process in NIH 3T3 fibroblasts induced an almost complete inhibition of MAP kinase, which was impaired by proteasome inhibitors. In the absence of cell anchorage, c-Raf-1 expression was dramatically decreased after 24 h.

Etoposide and adriamycin but not genistein can activate the checkpoint kinase Chk2 independently of ATM/ATR.

We have investigated the effects of three unrelated topoisomerase 2 inhibitors, genistein, adriamycin, and etoposide, on phosphorylation/activation of the checkpoint kinase Chk2 in normal or ATM-deficient (ATM-) human fibroblasts and in cells overexpressing a catalytically inactive ATR kinase. We demonstrate that genistein activates Chk2 in a strictly ATM-dependent manner, whereas etoposide and adriamycin can trigger Chk2 activation in long-term cultures of ATM- cells. Moreover, these two latter genotoxic compounds were found to activate Chk2 in fibroblasts expressing the dominant negative form of ATR.

The p42/p44 mitogen-activated protein kinase activation triggers p27Kip1 degradation independently of CDK2/cyclin E in NIH 3T3 cells.

The p42/p44 mitogen-activated protein (MAP) kinase is stimulated by various mitogenic stimuli, and its sustained activation is necessary for cell cycle G(1) progression and G(1)/S transition. G(1) progression and G(1)/S transition also depend on sequential cyclin-dependent kinase (CDK) activation. Here, we demonstrate that MAP kinase inhibition leads to accumulation of the CDK inhibitor p27(Kip1) in NIH 3T3 cells.

Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1.

We have investigated the effects of a series of flavonoids on cell proliferation and cell cycle distribution in human melanoma cells OCM-1. Among the compounds that potently inhibited OCM-1 cell proliferation, we show that the presence of a hydroxyl group at the 3'-position of the ring B in quercetin and luteolin, correlated to a G1 cell cycle arrest while its absence in kaempferol and apigenin correlated to a G2 block. Genistein with a hydroxyl at 5-position of the ring A arrested cells in G2 while daidzein which lacks it, induced an accumulation of cells in G1.

Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase.

The bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation. We report that upon CDT treatment CDC25C is fully sequestered in the cytoplasmic compartment, an effect that is reminiscent of DNA damage-dependent checkpoint activation. We show that the checkpoint kinase CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT treatment.

Cisplatin and UV radiation induce activation of the stress-activated protein kinase p38gamma in human melanoma cells.

The p38 alpha mitogen-activated protein kinase has been implicated in the cellular response to genotoxic agents. Here we show that another p38 family member is also activated in response to cisplatin exposure in human melanoma cells. We identified this isoform as p38gamma based on its recognition by specific antibodies and because, in contrast to p38alpha, its activity was not affected by SB203580.

Cyclin-dependent kinase inhibitory protein expression in human choroidal melanoma tumors.

Purpose: Recent studies have demonstrated the close link between oncogenesis and cell cycle machinery. Cyclin-dependent kinase inhibitory proteins (CKIs) have been shown to play a critical role in the regulation of cell cycle progression. Alteration of CKI levels and/or functions could be implicated in cell transformation.

p21CIP1 is dispensable for the G2 arrest caused by genistein in human melanoma cells.

We have investigated the effect of genistein on cell cycle distribution of the human choroidal melanoma cell line OCM-1. We report that this isoflavonoid arrested cells in G2. This effect was correlated with the induction of the CDK inhibitor p21CIP1.

Distinct Chk2 activation pathways are triggered by genistein and DNA-damaging agents in human melanoma cells.

Genistein, a natural isoflavone found in soybeans, exerts a number of biological actions suggesting that it may have a role in cancer prevention. We have previously shown that it potently inhibits OCM-1 melanoma cell proliferation by inducing a G(2) cell cycle arrest. Here we show that genistein exerts this effect by impairing the Cdc25C-dependent Tyr-15 dephosphorylation of Cdk1, as the overexpression of this phosphatase allows the cells to escape G(2) arrest and enter an abnormal chromatin condensation stage.