67 research outputs found
Finding the Minimum-Weight k-Path
Given a weighted -vertex graph with integer edge-weights taken from a
range , we show that the minimum-weight simple path visiting
vertices can be found in time \tilde{O}(2^k \poly(k) M n^\omega) = O^*(2^k
M). If the weights are reals in , we provide a
-approximation which has a running time of \tilde{O}(2^k
\poly(k) n^\omega(\log\log M + 1/\varepsilon)). For the more general problem
of -tree, in which we wish to find a minimum-weight copy of a -node tree
in a given weighted graph , under the same restrictions on edge weights
respectively, we give an exact solution of running time \tilde{O}(2^k \poly(k)
M n^3) and a -approximate solution of running time
\tilde{O}(2^k \poly(k) n^3(\log\log M + 1/\varepsilon)). All of the above
algorithms are randomized with a polynomially-small error probability.Comment: To appear at WADS 201
Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation
Here, we identify CD44(+)CD90(+)CD73(+)CD34(â)CD45(â) cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs). VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFĂ1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes
An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis
Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is
a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a
complex disease caused by metastasis of tumor cells from their primary site and
is characterized by intricate interplay of molecular interactions.
Identification of targets for multifactorial diseases such as SBC, the most
frequent complication of breast and prostate cancers, is a challenge. Towards
achieving our aim of identification of targets specific to SBC, we constructed
a 'Cancer Genes Network', a representative protein interactome of cancer genes.
Using graph theoretical methods, we obtained a set of key genes that are
relevant for generic mechanisms of cancers and have a role in biological
essentiality. We also compiled a curated dataset of 391 SBC genes from
published literature which serves as a basis of ontological correlates of
secondary bone cancer. Building on these results, we implement a strategy based
on generic cancer genes, SBC genes and gene ontology enrichment method, to
obtain a set of targets that are specific to bone metastasis. Through this
study, we present an approach for probing one of the major complications in
cancers, namely, metastasis. The results on genes that play generic roles in
cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have
broader implications in understanding the role of molecular regulators in
mechanisms of cancers. Specifically, our study provides a set of potential
targets that are of ontological and regulatory relevance to secondary bone
cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary
information). Revised after critical reviews. Accepted for Publication in
PLoS ON
Contrast medium-induced nephropathy. Aspects on incidence, consequences, risk factors and prevention
Contrast media-induced nephropathy (CIN) is a well-known complication of radiological examinations employing iodine contrast media (I-CM). The rapid development and frequent use of coronary interventions and multi-channel detector computed tomography with concomitant administration of relatively large doses of I-CM has contributed to an increasing number of CIN cases during the last few years. Reduced renal function, especially when caused by diabetic nephropathy or renal arteriosclerosis, in combination with dehydration, congestive heart failure, hypotension, and administration of nephrotoxic drugs are risk factors for the development of CIN. When CM-based examinations cannot be replaced by other techniques in patients at risk of CIN, focus should be directed towards analysis of number and type of risk factors, adequate estimation of GFR, institution of proper preventive measures including hydration and post-procedural observation combined with surveillance of serum creatinine for 1-3 days. For the radiologist, there are several steps to consider in order to minimise the risk for CIN: use of âlow-â or âiso-osmolarâ I-CM and dosing the I-CM in relation to GFR and body weight being the most important as well as utilizing radiographic techniques to keep the I-CM dose in gram iodine as low as possible below the numerical value of estimated GFR. There is as yet no pharmacological prevention that has been proven to be effective
Training Signaling Pathway Maps to Biochemical Data with Constrained Fuzzy Logic: Quantitative Analysis of Liver Cell Responses to Inflammatory Stimuli
Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL), converts a prior knowledge network (obtained from literature or interactome databases) into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a) generating experimentally testable biological hypotheses concerning pathway crosstalk, (b) establishing capability for quantitative prediction of protein activity, and (c) prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone.National Institutes of Health (U.S.) (NIH grant P50-GM68762)National Institutes of Health (U.S.) (Grant U54-CA112967)United States. Dept. of Defense (Institute for Collaborative Biotechnologies
The impact of transposable element activity on therapeutically relevant human stem cells
Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative
medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing
worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a
wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use,
including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and
molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic
potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell
genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human
stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and
pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We
describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome,
and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only
represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell
genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the
most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the
assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for
the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016-
21395 and SAF2015â71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015â71589-
P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the
Federal Republic of Germany (FKZ2518FSB403)
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic
COVID-19 perception and self reported impact of pandemic on Parkinsonâs disease symptoms of patients with physically independent Parkinsonâs disease
Objective: The novel coronavirus disease 2019 (Covid-19) pandemic has affected many people with chronic diseases, including Parkinsonâs disease (PD). We aimed to investigate the perception of Covid-19 and the self-reported impact of the pandemic on PD symptoms of a group of patients with physically independent PD from Turkey. Methods: We applied a questionnaire to idiopathic PD patients aged ?65 years, who did not have known dementia, who were physically independent and who had at least one visit in the year before the telephone interview. The study patients were selected from the medical records of two different centers in Kirikkale, Turkey. Two neurologists conducted a semi-structured telephone interview to evaluate the perception of Covid-19 and new or worsening PD symptoms after the home quarantine. Results: In total, 86 patients were included in the study. Although most of the patients (97.7%) knew of Covid-19, knowledge of the Covid-19 symptoms was moderate (54.7%). Most patients reported that they washed their hands often (100%) and wore a mask (98.8%); 76 (88.4%) of them stayed at home. Compliance with other preventive measures was above 80%. In total, 40 (46.5%) patients (28 male, 12 female) reported worsening bradykinesia. Fatigue (24.4%), daytime sleepiness (20.9%), pain (20.9%) and anxiety (15.2%) were the most common new or worsening non-motor symptoms. Conclusions: The Covid-19 knowledge in a group of patients with PD from Turkey can be considered adequate. They have a high compliance with preventive measures. However, reduced non-exercise physical activity due to the pandemic affected both their motor symptoms and non-motor symptoms. © 2020, ASEAN Neurological Association. All rights reserved
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