1,706 research outputs found

    Association rule mining for customer segmentation in the SMEs sector using the apriori algorithm

    Get PDF
    Customer´s segmentation is used as a marketing differentiation tool which allows organizations to understand their customers and build differentiated strategies. This research focuses on a database from the SMEs sector in Colombia, the CRISP-DM methodology was applied for the Data Mining process. The analysis was made based on the PFM model (Presence, Frequency, Monetary Value), and the following grouping algorithms were applied on this model: k -means, k-medoids, and Self-Organizing Maps (SOM). For validating the result of the grouping algorithms and selecting the one that provides the best quality groups, the cascade evaluation technique has been used applying a classification algorithm. Finally, the Apriori algorithm was used to find associations between products for each group of customers, so determining association according to loyalty

    Why are the K dwarfs in the Pleiades so Blue?

    Full text link
    The K dwarfs in the Pleiades fall nearly one half magnitude below a main sequence isochrone when plotted in a color-magnitude diagram utilizing V magnitude as the luminosity index and B-V as the color index. This peculiarity has been known for forty years but has gone unexplained and mostly ignored. When compared to Praesepe members, the Pleiades K dwarfs again are subluminous (or blue) in a color-magnitude diagram using B-V as the color index. However, using V-I as the color index, stars in the two clusters are coincident to M_V ~ 10; using V-K as the color index, Pleiades late K and M stars fall above the main sequence locus defined by Praesepe members. We believe that the anomalous spectral energy distributions for the Pleiades K dwarfs, as compared to older clusters, are a consequence of rapid stellar rotation and may be primarily due to spottedness. If so, the required areal filling factor for the cool component has to be very large (=> 50%). Weak-lined T Tauri stars have similar color anomalies, and we suspect this is a common feature of all very young K dwarfs (sp. type > K3). The peculiar spectral energy distribution needs to be considered in deriving accurate pre-main sequence isochrone-fitting ages for clusters like the Pleiades since the age derived will depend on the temperature index used.Comment: 41 pages, 15 figures, AASTeX5.0. Accepted 05 May 2003; Scheduled for publication in the Astronomical Journal (August 2003

    Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study

    Get PDF
    Background & Aims Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims: evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. Methods Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n=48) or placebo (n=46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n=47/48; placebo crossover, n=46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. Results Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. Conclusions Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life

    A critical review of the formation of mono- and dicarboxylated metabolic intermediates of alkylphenol polyethoxylates during wastewater treatment and their environmental significance

    Get PDF
    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.Alkylphenoxyacetic acids, the metabolic biodegradation products of alkylphenol ethoxylates, are commonly found in wastewaters and sewage effluents. These persistent hydrophilic derivatives possess intrinsic estrogenic activity, which can mimic natural hormones. Their concentrations increase through the sewage treatment works as a result of biodegradation and biotransformation, and when discharged can disrupt endocrine function in fish. These acidic metabolites represent the dominant alkylphenolic compounds found in wastewater effluent and their presence is cause for concern as, potentially, through further biotransformation and biodegradation, they can act as sources of nonylphenol, which is toxic and estrogenic. The authors aim to assess the mechanisms of formation as well as elimination of alkylphenoxyacetic acids within conventional sewage treatment works with the emphasis on the activated sludge process. In addition, they evaluate the various factors influencing their degradation and formation in laboratory scale and full-scale systems. The environmental implications of these compounds are considered, as is the need for tertiary treatment processes for their removal

    Spitzer Observations of G Dwarfs in the Pleiades: Circumstellar Debris Disks at 100 Myr Age

    Full text link
    Fluxes and upper limits in the wavelength range from 3.6 to 70 microns from the Spitzer Space Telescope are provided for twenty solar-mass Pleiades members. One of these stars shows a probable mid-IR excess and two others have possible excesses, presumably due to circumstellar debris disks. For the star with the largest, most secure excess flux at MIPS wavelengths, HII1101, we derive Log(L[dust]/L[Sun]) ~ -3.8 and an estimated debris disk mass of 4.2 x 10^-5 M(Earth) for an assumed uniform dust grain size of 10 microns If the stars with detected excesses are interpreted as stars with relatively recent, large collision events producing a transient excess of small dust particles, the frequency of such disk transients is about ~ 10 % for our ~ 100 Myr, Pleiades G dwarf sample. For the stars without detected 24-70 micron excesses, the upper limits to their fluxes correspond to approximate 3 sigma upper limits to their disk masses of 6 x 10^-6 M(Earth) using the MIPS 24 micron upper limit, or 2 x 10^-4 M(Earth) using the MIPS 70 micron limit. These upper limit disk masses (for "warm" and "cold" dust, respectively) are roughly consistent, but somewhat lower than, predictions of a heuristic model for the evolution of an "average" solar-mass star's debris disk based on extrapolation backwards in time from current properties of the Sun's Kuiper belt.Comment: 32 postscript pages including 8 figues and 3 tables. To appear in the Astronomical Journa

    A Proposal for a Three Detector Short-Baseline Neutrino Oscillation Program in the Fermilab Booster Neutrino Beam

    Get PDF
    A Short-Baseline Neutrino (SBN) physics program of three LAr-TPC detectors located along the Booster Neutrino Beam (BNB) at Fermilab is presented. This new SBN Program will deliver a rich and compelling physics opportunity, including the ability to resolve a class of experimental anomalies in neutrino physics and to perform the most sensitive search to date for sterile neutrinos at the eV mass-scale through both appearance and disappearance oscillation channels. Using data sets of 6.6e20 protons on target (P.O.T.) in the LAr1-ND and ICARUS T600 detectors plus 13.2e20 P.O.T. in the MicroBooNE detector, we estimate that a search for muon neutrino to electron neutrino appearance can be performed with ~5 sigma sensitivity for the LSND allowed (99% C.L.) parameter region. In this proposal for the SBN Program, we describe the physics analysis, the conceptual design of the LAr1-ND detector, the design and refurbishment of the T600 detector, the necessary infrastructure required to execute the program, and a possible reconfiguration of the BNB target and horn system to improve its performance for oscillation searches.Comment: 209 pages, 129 figure

    Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

    Get PDF
    The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells

    A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus

    Get PDF
    Lymph- and blood-borne retroviruses exploit CD169/Siglec-1-mediated capture by subcapsular sinus and marginal zone metallophilic macrophages for trans-infection of permissive lymphocytes. However, the impact of CD169-mediated virus capture on retrovirus dissemination and pathogenesis in vivo is unknown. In a murine model of the splenomegaly-inducing retrovirus Friend virus complex (FVC) infection, we find that while CD169 promoted draining lymph node infection, it limited systemic spread to the spleen. At the spleen, CD169-expressing macrophages captured incoming blood-borne retroviruses and limited their spread to the erythroblasts in the red pulp where FVC manifests its pathogenesis. CD169-mediated retroviral capture activated conventional dendritic cells 1 (cDC1s) and promoted cytotoxic CD8+ T cell responses, resulting in efficient clearing of FVC-infected cells. Accordingly, CD169 blockade led to higher viral loads and accelerated death in susceptible mouse strains. Thus, CD169 plays a protective role during FVC pathogenesis by reducing viral dissemination to erythroblasts and eliciting an effective cytotoxic T lymphocyte response via cDC1s

    EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks

    Get PDF
    Abstract Acute hepatic porphyria comprises a group of rare, genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months prior to the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a healthcare facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased healthcare utilization. Conclusions: Patients experienced attacks often requiring treatment in a healthcare facility and/or with hemin, as well as chronic symptoms that adversely influence day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. This article is protected by copyright. All rights reserved.Peer reviewe
    • …
    corecore