193 research outputs found
Kinetic Roughening in Slow Combustion of Paper
We present results from an experimental study on the kinetic roughening of slow combustion fronts in paper sheets. The sheets were positioned inside a combustion chamber and ignited from the top to minimize convection effects. The emerging fronts were videotaped and digitized to obtain their time-dependent heights. The data were analyzed by calculating two-point correlation functions in the saturated regime. Both the growth and roughening exponents were determined and found consistent with the Kardar-Parisi-Zhang equation, in agreement with recent theoretical work.Peer reviewe
Symbolic Partial-Order Execution for Testing Multi-Threaded Programs
We describe a technique for systematic testing of multi-threaded programs. We
combine Quasi-Optimal Partial-Order Reduction, a state-of-the-art technique
that tackles path explosion due to interleaving non-determinism, with symbolic
execution to handle data non-determinism. Our technique iteratively and
exhaustively finds all executions of the program. It represents program
executions using partial orders and finds the next execution using an
underlying unfolding semantics. We avoid the exploration of redundant program
traces using cutoff events. We implemented our technique as an extension of
KLEE and evaluated it on a set of large multi-threaded C programs. Our
experiments found several previously undiscovered bugs and undefined behaviors
in memcached and GNU sort, showing that the new method is capable of finding
bugs in industrial-size benchmarks.Comment: Extended version of a paper presented at CAV'2
Role of fibroblast growth factor receptors (FGFR) and FGFR like-1 (FGFRL1) in mesenchymal stromal cell differentiation to osteoblasts and adipocytes
Fibroblast growth factors (FGF) and their receptors (FGFRs) regulate many developmental processes including differentiation of mesenchymal stromal cells (MSC). We developed two MSC lines capable of differentiating to osteoblasts and adipocytes and studied the role of FGFRs in this process. We identified FGFR2 and fibroblast growth factor receptor like-1 (FGFRL1) as possible actors in MSC differentiation with gene microarray and qRT-PCR. FGFR2 and FGFRL1 mRNA expression strongly increased during MSC differentiation to osteoblasts. FGF2 treatment, resulting in downregulation
of FGFR2, or silencing FGFR2 expression with siRNAs inhibited
osteoblast differentiation. During adipocyte differentiation expression
of FGFR1
and FGFRL1 increased and was down-regulated by FGF2. FGFR1 knockdown
inhibited adipocyte differentiation. Silencing FGFR2 and FGFR1 in MSCs
was associated with decreased FGFRL1 expression in osteoblasts and
adipocytes, respectively. Our results suggest that FGFR1 and FGFR2
regulate FGFRL1 expression. FGFRL1 may mediate or modulate FGFR
regulation of MSC differentiation together with FGFR2 in osteoblastic
and FGFR1 in adipocytic lineage.</div
Health promoting potential of herbal teas and tinctures from Artemisia campestris subsp maritima: from traditional remedies to prospective products
This work explored the biotechnological potential of the medicinal halophyte Artemisia campestris subsp. maritima (dune wormwood) as a source of health promoting commodities. For that purpose, infusions, decoctions and tinctures were prepared from roots and aerial-organs and evaluated for in vitro antioxidant, anti-diabetic and tyrosinase-inhibitory potential, and also for polyphenolic and mineral contents and toxicity. The dune wormwood extracts had high polyphenolic content and several phenolics were identified by ultra-high performance liquid chromatography-photodiode array-mass-spectrometry (UHPLC-PDA-MS). The main compounds were quinic, chlorogenic and caffeic acids, coumarin sulfates and dicaffeoylquinic acids; several of the identified phytoconstituents are here firstly reported in this A. campestris subspecies. Results obtained with this plant's extracts point to nutritional applications as mineral supplementary source, safe for human consumption, as suggested by the moderate to low toxicity of the extracts towards mammalian cell lines. The dune wormwood extracts had in general high antioxidant activity and also the capacity to inhibit a-glucosidase and tyrosinase. In summary, dune wormwood extracts are a significant source of polyphenolic and mineral constituents, antioxidants and a-glucosidase and tyrosinase inhibitors, and thus, relevant for different commercial segments like the pharmaceutical, cosmetic and/or food industries.FCT - Foundation for Science and Technology [CCMAR/Multi/04326/2013]; Portuguese National Budget; FCT [IF/00049/2012, SFRH/BD/94407/2013]; Research Foundation - Flanders (FWO) [12M8315N]info:eu-repo/semantics/publishedVersio
Effects of FGFR inhibitors TKI258, BGJ398 and AZD4547 on breast cancer cells in 2D, 3D and tissue explant cultures
Purpose Fibroblast growth factor receptors (FGFR) and pathways are important players in breast cancer (BC) development. They are commonly altered, and BCs exhibiting FGFR gene amplification are currently being studied for drug development. Here, we aimed to compare the effects of three FGFR inhibitors (FGFRis), i.e., non-selective TKI258 and selective BGJ398 and AZD4547, on different BC-derived cell lines (BCCs) and primary tissues. Methods The human BCCs MCF-7 and MDA-MB-231(SA) (wild-type FGFR) and MFM223 (amplified FGFR1 and FGFR2) were analyzed for FGFR expression using qRT-PCR, and the effects of FGFRis on FGFR signaling by Western blotting. The effects of FGFRis on proliferation, viability, migration and invasion of BCCs were assessed in 2D cultures using live-cell imaging, and in 3D cultures using phenotypic analysis of organoids. To study radio-sensitization, FGFRi treatment was combined with irradiation. Patient-derived BC samples were treated with FGFRis in explant cultures and immunostained for Ki67 and cleaved caspase 3. Results We found that all FGFRis tested decreased the growth and viability of BC cells in 2D and 3D cultures. BGJ398 and AZD4547 were found to be potent at low concentrations in FGFR-amplified MFM233 cells, whereas higher concentrations were required in non-amplified MCF7 and MDA-MB-231(SA) cells. TKI258 inhibited the migration and invasion, whereas BGJ398 and AZD4547 only inhibited the invasion of MDA-MB-231(SA) cells. FGFRi treatment of MCF7 and MFM223 cells enhanced the inhibitory effect of radiotherapy, but this effect was not observed in MDA-MB-231(SA) cells. FGFRi-treated primary BC explants with moderate FGFR levels showed a tendency towards decreased proliferation and increased apoptosis. Conclusions Our results indicate that, besides targeting FGFR-amplified BCs with selective FGFRis, also BCs without FGFR amplification/activation may benefit from FGFRi-treatment. Combination with other treatment modalities, such as radiotherapy, may allow the use of FGFRis at relatively low concentrations and, thereby, contribute to better BC treatment outcomes.</p
Critical evaluation of the subcutaneous engraftments of hormone naïve primary prostate cancer
Background: Patient-derived xenografts (PDXs) are considered to better recapitulate the histopathological and molecular heterogeneity of human cancer than other preclinical models. Despite technological advances, PDX models from hormone naïve primary prostate cancer are scarce. We performed a detailed analysis of PDX methodology using a robust subcutaneous model and fresh tissues from patients with primary hormone naïve prostate cancer.Methods: Clinical prostate tumor specimens (n=26, Gleason score 6–10) were collected from robotic-assisted laparoscopic radical prostatectomies at Turku University Hospital (Turku, Finland), cut into pieces, and implanted subcutaneously into 84 immunodeficient mice. Engraftments and the adjacent material from prostatic surgical specimens were compared using histology, immunohistochemistry and DNA sequencing.Results: The probability of a successful engraftment correlated with the presence of carcinoma in the implanted tissue. Tumor take rate was 41%. Surprisingly, mouse hormone supplementation inhibited tumor take rate, whereas the degree of mouse immunodeficiency did not have an effect. Histologically, the engrafted tumors closely mimicked their parental tumors, and the Gleason grades and copy number variants of the engraftments were similar to those of their primary tumors. Expression levels of androgen receptor, prostate-specific antigen, and keratins were retained in engraftments, and a detailed genomic analysis revealed high fidelity of the engraftments with their corresponding primary tumors. However, in the second or third passage of tumors, the carcinoma areas were almost completely replaced by benign tissue with frequent degenerative or metaplastic changes.Conclusions: Subcutaneous primary prostate engraftments preserve the phenotypic and genotypic landscape. Thus, they serve a potential model for personalized medicine and preclinical research but their use may be limited to the first passage.</p
Antimicrobial activity and bioactive compounds of portuguese wild edible mushrooms methanolic extracts
The antimicrobial properties of phenolic extracts of Portuguese wild edible mushroom species (Lactarius deliciosus,
Sarcodon imbricatus and Tricholoma portentosum)
against pathogens were investigated. The minimal inhibitory
concentrations (MICs) were evaluated for the entire mushroom,
the cap and the stipe, separately; the portion of the
mushroom used proved to be influenced in the results obtained,
which are directly correlated with the content of total
phenols and flavonoids in the extracts. The growth of Grampositive
bacteria (Bacillus cereus, B. subtilis,) was well inhibited
by these mushrooms, while Escherichia coli (Gramnegative
bacteria) was resistant. The study on the antifungal
effect of these mushrooms revealed that Candida albicans
and Cryptococcus neoformans were differently inhibited for
the mushrooms used
The neurochemical basis of human cortical auditory processing: combining proton magnetic resonance spectroscopy and magnetoencephalography
BACKGROUND: A combination of magnetoencephalography and proton magnetic resonance spectroscopy was used to correlate the electrophysiology of rapid auditory processing and the neurochemistry of the auditory cortex in 15 healthy adults. To assess rapid auditory processing in the left auditory cortex, the amplitude and decrement of the N1m peak, the major component of the late auditory evoked response, were measured during rapidly successive presentation of acoustic stimuli. We tested the hypothesis that: (i) the amplitude of the N1m response and (ii) its decrement during rapid stimulation are associated with the cortical neurochemistry as determined by proton magnetic resonance spectroscopy. RESULTS: Our results demonstrated a significant association between the concentrations of N-acetylaspartate, a marker of neuronal integrity, and the amplitudes of individual N1m responses. In addition, the concentrations of choline-containing compounds, representing the functional integrity of membranes, were significantly associated with N1m amplitudes. No significant association was found between the concentrations of the glutamate/glutamine pool and the amplitudes of the first N1m. No significant associations were seen between the decrement of the N1m (the relative amplitude of the second N1m peak) and the concentrations of N-acetylaspartate, choline-containing compounds, or the glutamate/glutamine pool. However, there was a trend for higher glutamate/glutamine concentrations in individuals with higher relative N1m amplitude. CONCLUSION: These results suggest that neuronal and membrane functions are important for rapid auditory processing. This investigation provides a first link between the electrophysiology, as recorded by magnetoencephalography, and the neurochemistry, as assessed by proton magnetic resonance spectroscopy, of the auditory cortex
Alcohol breaks down interhemispheric inhibition in females but not in males: Alcohol and frontal connectivity
Prediction of prostate cancer aggressiveness using 18 F-Fluciclovine (FACBC) PET and multisequence multiparametric MRI
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