66 research outputs found
3D-printed PMMA preform for hollow-core POF drawing
In this paper we report the first, to our knowledge, 3D-printed hollow-core poly(methyl methacrylate) (PMMA) preform for polymer optical fibre drawing. It was printed of commercial PMMA by means of fused deposition modelling technique. The preform was drawn to cane, proving good enough quality of drawing process and the PMMA molecular weight to be appropriate for drawing. This ascertains that the manufacturing process provides preforms suitable for hollow-core fibre drawing. The paper focuses on maximisation of transparency of PMMA 3D printouts by optimising printing process parameters: nozzle temperature, printing speed and infill
Embedding low loss polymer optical fibre Bragg gratings:two different approaches
In this paper, we present two different ways to embed polymer fibre Bragg gratings (FBGs) into polymer matrices. In the first experiment, we embedded the FBG into a 3D printed polymer structure, whereas in the second experiment, the coating was polymerized around the fibre. In both cases, the response of the grating was unchanged, without any loss or distortion of the FBG signal compared with the bare fibre response. The design of the polymer coating was optimised for the measurement of a single measurand. We highlighted two possible applications: surface bend deformation monitoring and improved-sensitivity temperature sensing
PARP1 catalytic variants reveal branching and chain length-specific functions of poly(ADP-ribose) in cellular physiology and stress response
Poly(ADP-ribosyl)ation regulates numerous cellular processes like genome maintenance and cell death, thus providing protective functions but also contributing to several pathological conditions. Poly(ADP-ribose) (PAR) molecules exhibit a remarkable heterogeneity in chain lengths and branching frequencies, but the biological significance of this is basically unknown. To unravel structure-specific functions of PAR, we used PARP1 mutants producing PAR of different qualities, i.e. short and hypobranched (PARP1\G972R), short and moderately hyperbranched (PARP1\Y986S), or strongly hyperbranched PAR (PARP1\Y986H). By reconstituting HeLa PARP1 knockout cells, we demonstrate that PARP1\G972R negatively affects cellular endpoints, such as viability, cell cycle progression and genotoxic stress resistance. In contrast, PARP1\Y986S elicits only mild effects, suggesting that PAR branching compensates for short polymer length. Interestingly, PARP1\Y986H exhibits moderate beneficial effects on cell physiology. Furthermore, different PARP1 mutants have distinct effects on molecular processes, such as gene expression and protein localization dynamics of PARP1 itself, and of its downstream factor XRCC1. Finally, the biological relevance of PAR branching is emphasized by the fact that branching frequencies vary considerably during different phases of the DNA damage-induced PARylation reaction and between different mouse tissues. Taken together, this study reveals that PAR branching and chain length essentially affect cellular functions, which further supports the notion of a ‘PAR code’
Fluorouracil leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer
Purpose
This randomized study assessed whether the best overall response rate (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The influence of KRAS mutation status was investigated.
Patients and Methods
Patients received cetuximab (400 mg/m(2) initial dose followed by 250 mg/m(2)/wk thereafter) plus FOLFOX-4 (oxaliplatin 85 mg/m(2) on day 1, plus leucovorin 200 mg/m(2) and fluorouracil as a 400 mg/m(2) bolus followed by a 600 mg/m(2) infusion during 22 hours on days 1 and 2; n = 169) or FOLFOX-4 alone (n = 168). Treatment was continued until disease progression or unacceptable toxicity. KRAS mutation status was assessed in the subset of patients with assessable tumor samples (n = 233).
Results
The confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone (46% v 36%). A statistically significant increase in the odds for a response with the addition of cetuximab to FOLFOX-4 could not be established (odds ratio = 1.52; P = .064). In patients with KRAS wild-type tumors, the addition of cetuximab to FOLFOX-4 was associated with a clinically significant increased chance of response (ORR = 61% v 37%; odds ratio = 2.54; P = .011) and a lower risk of disease progression (hazard ratio = 0.57; P = .0163) compared with FOLFOX-4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated.
Conclusion
KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer
Mszaki jako element krajobrazu kulturowego: biologia, miejsce, rola
Bryophytes are small spore plants which occurs in all climates zones and plant formations. They form zonal (tundra) and azonal (bogs) environments or are integral part of other communities. They are very well adapted to the colonization of extreme and initial habitats. Civilization development has created for them adequate ecological niches like walls, roofs, sidewalks, lawns, parks or cemeteries. The bryophytes spontaneously colonize them, becoming an integral part of the small-town and metropolitan landscape. This paper presents the biology of bryophytes, pays attention to the key features enabling them to inhabit architectural elements. The role and place of these plants in the urbanized space were characterized, the urbanophile bryophyte species were pointed, and places in the cultural landscape where they abundantly grow were indicated. Also the potential exploiting of bryophytes in the urban conditions in utilitarian, functional and decorative form were highlighted.Mszaki to niewielkie rośliny zarodnikowe obecne we wszystkich strefach klimatycznych i ekosystemach. Tworzą zonalne (tundra) i ekstrazonale (torfowiska) formacje roślinne lub są integralnym elementem innych zbiorowisk. Są bardzo dobrze przystosowane do kolonizacji ekstremalnych i inicjalnych siedlisk, a rozwój cywilizacyjny wykreował dla nich także nisze ekologiczne w postaci murów, dachów, chodników, trawników, parków czy cmentarzy. Mszaki spontanicznie je zasiedliły, stając się integralną częścią krajobrazów małomiasteczkowych i wielkomiejskich. W niniejszym opracowaniu przybliżono biologię mszaków, zwracając uwagę na cechy kluczowe przy zasiedlaniu elementów architektonicznych. Określono rolę i miejsce tych roślin w przestrzeni zurbanizowanej, wskazano gatunki urbanofilne oraz miejsca w krajobrazie kulturowym, gdzie obficie występują. Zwrócono także uwagę na potencjał wykorzystania mszaków w warunkach miejskich w utylitarnej, funkcjonalnej i dekora- cyjnej formie
The natural values of selected dry grasslands under sheep grazing in the Kozki Nature Reserve
The studies of vegetation were carried out in the years 2010–2013. One of the study objectives was to update the assessment of the natural value of psammophilous grasslands 20 years after the establishment of Kózki nature reserve (mazowieckie voivodship). The phytosociological survey results were compared with the archive survey results available in the nature reserve’s documentation. There were noted some significant changes in the species composition of plant communities. The assessment of natural values of psammophilous grasslands confirmed the occurrence a simplified form of the Corynephoro-Silenetum tataricae association – priority habitats for protection, the presence of 6 dry grassland indicator species, one endangered species (Carex praecox) and one plant species (Helichrysum arenarium) under legal protection was determined
A contribution to the moss and liverwort flora of the Reberce Nature Reserve at the Przemyśl Foothills (Western Carpathians, Poland)
The paper presents the results of studies on bryophyte flora of the Reberce forest reserve located
in the Przemyśl foothills. Thirty-three species of liverworts, 70 species and two varieties of mosses
were found. Terrestrial (66 species) and epixylic (58) bryophytes formed the largest ecological groups in
the reserve. Twenty-four protected species were also recorded, eight endangered bryophytes and six taxa
considered as primeval forest species. The most interesting finds are: Bazzania trilobata, Buxbaumia viridis,
Calypogeia suecica, Cephalozia catenulata, Frullania dilatata, Metzgeria conjugata, Nowellia curvifolia, Orthotrichum
lyellii, O. stramineum, Trichocolea tomentella and Ulota crispa
A contribution to the moss and liverwort flora of the Reberce Nature Reserve at the Przemysl Foothills (Western Carpathians, Poland)
The paper presents the results of studies on bryophyte flora of the Reberce forest reserve located
in the Przemyśl foothills. Thirty-three species of liverworts, 70 species and two varieties of mosses
were found. Terrestrial (66 species) and epixylic (58) bryophytes formed the largest ecological groups in
the reserve. Twenty-four protected species were also recorded, eight endangered bryophytes and six taxa
considered as primeval forest species. The most interesting finds are: Bazzania trilobata, Buxbaumia viridis,
Calypogeia suecica, Cephalozia catenulata, Frullania dilatata, Metzgeria conjugata, Nowellia curvifolia, Orthotrichum
lyellii, O. stramineum, Trichocolea tomentella and Ulota crispa
Analyzing structure-function relationships of artificial and cancer-associated PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells
Contains fulltext :
171327.pdf (publisher's version ) (Open Access)Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure-function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1-PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\L713F expression triggered apoptosis, whereas PARP1\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure-function relationships of natural and artificial PARP1 variants
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