58 research outputs found
Towards an exact adaptive algorithm for the determinant of a rational matrix
In this paper we propose several strategies for the exact computation of the
determinant of a rational matrix. First, we use the Chinese Remaindering
Theorem and the rational reconstruction to recover the rational determinant
from its modular images. Then we show a preconditioning for the determinant
which allows us to skip the rational reconstruction process and reconstruct an
integer result. We compare those approaches with matrix preconditioning which
allow us to treat integer instead of rational matrices. This allows us to
introduce integer determinant algorithms to the rational determinant problem.
In particular, we discuss the applicability of the adaptive determinant
algorithm of [9] and compare it with the integer Chinese Remaindering scheme.
We present an analysis of the complexity of the strategies and evaluate their
experimental performance on numerous examples. This experience allows us to
develop an adaptive strategy which would choose the best solution at the run
time, depending on matrix properties. All strategies have been implemented in
LinBox linear algebra library
An introspective algorithm for the integer determinant
We present an algorithm computing the determinant of an integer matrix A. The
algorithm is introspective in the sense that it uses several distinct
algorithms that run in a concurrent manner. During the course of the algorithm
partial results coming from distinct methods can be combined. Then, depending
on the current running time of each method, the algorithm can emphasize a
particular variant. With the use of very fast modular routines for linear
algebra, our implementation is an order of magnitude faster than other existing
implementations. Moreover, we prove that the expected complexity of our
algorithm is only O(n^3 log^{2.5}(n ||A||)) bit operations in the dense case
and O(Omega n^{1.5} log^2(n ||A||) + n^{2.5}log^3(n||A||)) in the sparse case,
where ||A|| is the largest entry in absolute value of the matrix and Omega is
the cost of matrix-vector multiplication in the case of a sparse matrix.Comment: Published in Transgressive Computing 2006, Grenade : Espagne (2006
HIV-1 Subtype D Infections among Caucasians from Northwestern Poland—Phylogenetic and Clinical Analysis
Background: HIV-1 subtype D infections, which are associated with a faster rate of progression and lymphocyte CD4 decline, cognitive deficit and higher mortality, have rarely been found in native Europeans. In Northwestern Poland, however, infections with this subtype had been identified. This study aimed to analyze the sequence and clinical data for patients with subtype D using molecular phylogeography and identify transmission clusters and ancestry, as well as drug resistance, baseline HIV tropism and antiretroviral treatment efficacy. Methods: Phylogenetic analyses of local HIV-1 subtype D sequences were performed, with time to the most recent common ancestor inferred using Bayesian modeling. Sequence and drug resistance data were linked with the clinical and epidemiological information. Results: Subtype D was found in 24 non-immigrant Caucasian, heterosexually infected patients (75 % of females, median age at diagnosis of 49.5 years; IQR: 29–56 years). Partial pol sequences clustered monophyletically with the clades of Ugandan origin and no evidence of transmission from other European countries was found. Time to the most common recent ancestor was 1989.24 (95 % HPD: 1968.83–1994.46). Baseline drug resistance to nucleoside reverse transcriptase inhibitors was observed in 54.5 % of cases (mutations: M41L, K103N, T215S/D) with evidence of clustering, no baseline integrase or protease resistance and infrequent non-R5 tropism (13.6%). Virologic failure was observed in 60 % of cases an
Risk of All-Cause Mortality in HIV Infected Patients Is Associated with Clinical, Immunologic Predictors and the CCR5 Δ32 Deletion
OBJECTIVE: Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era. DESIGN: Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed. METHODS: Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed. RESULTS: A mortality rate of 2.66 (CI 2.57-3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16-5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1-3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0-7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95-8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39-8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03-2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23). CONCLUSIONS: The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender
Diamond nanoparticles modity curcumin activity:<i>in vitro</i> studies on cancer and normal cells and <i>in ovo</i> studies on chicken embryo model
Curcumin has been studied broadly for its wide range of biological activities, including anticancer properties. The major problem with curcumin is its poor bioavailability, which can be improved by the addition of carriers, such as diamond nanoparticles (DN). They are carbon allotropes, and are therefore biocompatible and easily taken up by cells. DN are non-toxic and have antiangiogenic properties with potential applications in cancer therapy. Their large surface makes them promising compounds in a drug delivery system for bioactive agents, as DN create bio-complexes in a fast and simple process of self-organisation. We investigated the cytotoxicity of such bio-complexes against liver cancer cells and normal fibroblasts, revealing that conjugation of curcumin with DN significantly improves its activity. The experiment performed in a chicken embryo model demonstrated that neither curcumin nor DN nor bio-complexes affect embryo development, even though DN can form deposits in tissues. Preliminary results confirmed the applicability of DN as an efficient carrier of curcumin, which improves its performance against cancer cells in vitro, yet is not toxic to an organism, which makes the bio-complex a promising anticancer agent
Children and adolescents with pulmonary arterial hypertension : baseline and follow-up data from the polish registry of pulmonary hypertension (BNP-PL)
We present the results from the pediatric arm of the Polish Registry of Pulmonary
Hypertension. We prospectively enrolled all pulmonary arterial hypertension (PAH) patients,
between the ages of 3 months and 18 years, who had been under the care of each PAH center
in Poland between 1 March 2018 and 30 September 2018. The mean prevalence of PAH was
11.6 per million, and the estimated incidence rate was 2.4 per million/year, but it was geographically
heterogeneous. Among 80 enrolled children (females, n = 40; 50%), 54 (67.5%) had PAH associated
with congenital heart disease (CHD-PAH), 25 (31.25%) had idiopathic PAH (IPAH), and 1 (1.25%)
had portopulmonary PAH. At the time of enrolment, 31% of the patients had significant impairment
of physical capacity (WHO-FC III). The most frequent comorbidities included shortage of growth
(n = 20; 25%), mental retardation (n = 32; 40%), hypothyroidism (n = 19; 23.8%) and Down syndrome
(n = 24; 30%). The majority of children were treated with PAH-specific medications, but only half of
them with double combination therapy, which improved after changing the reimbursement policy.
The underrepresentation of PAH classes other than IPAH and CHD-PAH, and the geographically
heterogeneous distribution of PAH prevalence, indicate the need for building awareness of PAH
among pediatricians, while a frequent coexistence of PAH with other comorbidities calls for a
multidisciplinary approach to the management of PAH children
Inhibition of ERβ Induces Resistance to Cisplatin by Enhancing Rad51–Mediated DNA Repair in Human Medulloblastoma Cell Lines
Cisplatin is one of the most widely used and effective anticancer drugs against solid tumors including cerebellar tumor of the childhood, Medulloblastoma. However, cancer cells often develop resistance to cisplatin, which limits therapeutic effectiveness of this otherwise effective genotoxic drug. In this study, we demonstrate that human medulloblastoma cell lines develop acute resistance to cisplatin in the presence of estrogen receptor (ER) antagonist, ICI182,780. This unexpected finding involves a switch from the G2/M to G1 checkpoint accompanied by decrease in ATM/Chk2 and increase in ATR/Chk1 phosphorylation. We have previously reported that ERβ, which is highly expressed in medulloblastomas, translocates insulin receptor substrate 1 (IRS-1) to the nucleus, and that nuclear IRS-1 binds to Rad51 and attenuates homologous recombination directed DNA repair (HRR). Here, we demonstrate that in the presence of ICI182,780, cisplatin-treated medulloblastoma cells show recruitment of Rad51 to the sites of damaged DNA and increase in HRR activity. This enhanced DNA repair during the S phase preserved also clonogenic potential of medulloblastoma cells treated with cisplatin. In conclusion, inhibition of ERβ considered as a supplemental anticancer therapy, has been found to interfere with cisplatin–induced cytotoxicity in human medulloblastoma cell lines
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Tuberous sclerosis complex neuropathology requires glutamate-cysteine ligase
Introduction: Tuberous sclerosis complex (TSC) is a genetic disease resulting from mutation in TSC1 or TSC2 and subsequent hyperactivation of mammalian Target of Rapamycin (mTOR). Common TSC features include brain lesions, such as cortical tubers and subependymal giant cell astrocytomas (SEGAs). However, the current treatment with mTOR inhibitors has critical limitations. We aimed to identify new targets for TSC pharmacotherapy. Results: The results of our shRNA screen point to glutamate-cysteine ligase catalytic subunit (GCLC), a key enzyme in glutathione synthesis, as a contributor to TSC-related phenotype. GCLC inhibition increased cellular stress and reduced mTOR hyperactivity in TSC2-depleted neurons and SEGA-derived cells. Moreover, patients’ brain tubers showed elevated GCLC and stress markers expression. Finally, GCLC inhibition led to growth arrest and death of SEGA-derived cells. Conclusions: We describe GCLC as a part of redox adaptation in TSC, needed for overgrowth and survival of mutant cells, and provide a potential novel target for SEGA treatment. Electronic supplementary material The online version of this article (doi:10.1186/s40478-015-0225-z) contains supplementary material, which is available to authorized users
We Do Not Like It: A Likert-Type Scale Survey on the Attitudes of a Young Population towards the Transhumanistic Theory of Education
Transhumanists assume that future education may be purely based on technological stimulation. The question is: Do potential clients of education “like” such vision? In order to check this, we asked over one thousand two hundred young Poles to evaluate their identification with the transhumanistic theory of education. The results are quite surprising: its show that they disagree with the assumptions of this theory, while they rather agree with the postulates of more traditional (and no technology-based) concepts of education
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