Experimental and theoretical studies of fluctuations in nucleus-nucleus interactions at high energies have started to play a major role in understanding of the concept of strong interactions. The ...elaborated procedures have been developed to disentangle different processes happening during nucleus-nucleus collisions. The fluctuations caused by a variation of the number of nucleons which participated in a collision are frequently considered the unwanted one. The methods to reduce the impact of these fluctuations in fixed-target experiments are reviewed and tested. They can be of key importance in the following ongoing fixed-target heavy-ion experiments: NA61/SHINE at the CERN SPS, STAR-FXT at the BNL RHIC, BMN at JINR Nuclotron, HADES at the GSI SIS18 and in future experiments such as NA60+ at the CERN SPS, CBM at the FAIR SIS100, JHITS at J-PARC-HI MR.
The essential idea of regenerative medicine is to fix or replace tissues or organs with alive and patient-specific implants. Pluripotent stem cells are able to indefinitely self-renew and ...differentiate into all cell types of the body which makes them a potent substantial player in regenerative medicine. The easily accessible source of induced pluripotent stem cells may allow obtaining and cultivating tissues
in vitro
. Reprogramming refers to regression of mature cells to its initial pluripotent state. One of the approaches affecting pluripotency is the usage of low molecular mass compounds that can modulate enzymes and receptors leading to the formation of pluripotent stem cells (iPSCs). It would be great to assess the general character of such compounds and reveal their new derivatives or modifications to increase the cell reprogramming efficiency. Many improvements in the methods of pluripotency induction have been made by various groups in order to limit the immunogenicity and tumorigenesis, increase the efficiency and accelerate the kinetics. Understanding the epigenetic changes during the cellular reprogramming process will extend the comprehension of stem cell biology and lead to potential therapeutic approaches. There are compounds which have been already proven to be or for now only putative inducers of the pluripotent state that may substitute for the classic reprogramming factors (Oct3/4, Sox2, Klf4, c-Myc) in order to improve the time and efficiency of pluripotency induction. The effect of small molecules on gene expression is dosage-dependent and their application concentration needs to be strictly determined. In this review we analysed the role of small molecules in modulations leading to pluripotency induction, thereby contributing to our understanding of stem cell biology and uncovering the major mechanisms involved in that process.
Small molecules cause pluripotency induction through epigenetic changes such as DNA methylation, histone modifications, RNA noncoding and chromatin remodeling.
One of the physics goals of the NA61/SHINE collaboration at the CERN Super Proton Synchrotron is to study the phase diagram of hadronic matter. To this end, a series of heavy ion collision ...measurements are performed. It is believed that above a certain collision energy and system size a phase transition between the hadronic matter and quark–gluon plasma occurs. A number of observables have been developed to determine which of the phases was created at the early stage of the collision. This report discusses the dependence of the ratio of the mean number of produced pions to the mean number of wounded nucleons on the Fermi energy measure. For comparison with other measurements this is often presented in the form of the “kink” plot. This plot is presented enriched with preliminary results for
40
Ar+
45
Sc central collisions at 13
A
, 19
A
, 30
A
, 40
A
, 75
A
and 150
A
GeV/
c
beam momenta. The results are finally compared to data from other experiments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We discuss the
-dependence of the
K
+
/π
+
ratio in heavy-ion collisions (the “horn” effect) within a Mott-Anderson localization model for chemical freeze-out. The different response of pion and kaon ...radii to the hot and dense hadronic medium results in different freeze-out conditions. We demonstrate within a simple model that this circumstance enhances the “horn” effect relative to statistical models with universal chemical freeze-out.
Abstract
Background
Valproic acid (VPA) is a first-line antiepileptic drug for glioblastoma (GBM) patients. There is also some evidence it improves the clinical outcome in those patients. However, ...the exact mechanism of VPA action is vague. Temozolomide (TMZ) is a first-line chemotherapeutic in GBM. Epigenetics offers a connection between genetic and environmental factors that influence the development of the disease. The best-characterized epigenetic mark is 5-methylcytosine (m5C) in DNA. The aim of that project is to show the effects of VPA administration on the total DNA methylation level.
Material and Methods
Using the nucleotide post-labeling method, we analyzed the total amount of m5C in DNA of GBM (T98G, U118, U138), cancer (HeLa) and normal (HaCaT) cell lines treated with VPA, and a combination of VPA and with TMZ.
Results
We adjusted the VPA doses to the ones achieved in the central nervous system during treatment. We observed dose-dependent changes in the total DNA methylation in neoplastic cell lines and the lack of such effect in a normal cell line. VPA alone produced a clear dose-dependent increase in total DNA methylation in GBM cell lines and scarce in the non-neoplastic cell line. In GBM cell lines, TMZ decreased the level of m5C. However, the exposition of GBM cells to the combination of VPA and TMZ caused an adverse synergistic effect resulting in DNA demethylation. The highest loss of m5C was observed at the highest concentration of TMZ (100 μM) and VPA (350 μM), after 3 h of incubation in the T98G cell line.
Conclusion
Total DNA methylation changes in glioma cell lines under VPA treatment suggest the new mechanism of that drug action and promote clinical implications for adjusting VPA and TMZ therapy in GBM patients. Our results show the potential and possible obstacles of the combined therapy of TMZ with VPA. Our experiments show that combined therapy with both drugs leads to total DNA hypomethylation. Therefore the conclusion would be to stop VPA administration during TMZ chemotherapy temporarily.
Abstract
Background
The role of epigenetic events in gliomagenesis is undoubtful. However, the role of specific pathological events is not so clear. It was shown that loss in total DNA methylation ...correlates with higher tumor malignancy and oxidative DNA damage. But promoter methylation of many genes was reported to be significant for gliomas’ malignancy and predictive for the treatment outcome. In carcinogenesis in general global DNA hypomethylation and focal hypermethylation coexist. The aim of our project was to evaluate the correlation between total DNA methylation and promoter methylation of selected genes.
Material and Methods
We analysed glioma tissues from 60 patients. For total DNA methylation analysis we used the radiolabelling method with TLC separation of nucleotides and content estimation with phosphoimager. For promoter methylation analysis we have chosen: MGMT (O-6-Methylguanine-DNA Methyltransferase), MPG (DNA-3-methyladenine glycosylase), GJA1 (Gap junction alpha-1 protein / connexin 43). The promoter methylation level was evaluated with the methylation-sensitive high-resolution melting (MS-HRM) method.
Results
Total DNA methylation was reversely correlated with brain tumor grade, confirming that 5-methylcytosine loss is important step in gliomagenesis. From 3 genes only MPG promoter methylation showed clear low reverse correlation with tumor grade. Promoter methylation in GJA1 show low correlation with both, MGMT and MPG, but there was no link between MGMT and MPG. IDHwt presence was significantly correlated with higher tumor grade. Promoter methylations in MPG and GJA1 were better correlated with IDH status than in MGMT.
Conclusion
There is a clear correlation between total DNA methylation and tumor malignancy. Gene promoter methylation is not highly correlated with total DNA methylation and shows low significance in selected cases. Promoter methylation showed clear correlation with tumor grade only in MPG case. That suggests diverse mechanisms steering DNA methylation in general and local changes. It also shows that total DNA methylation is best predictor of tumor grade.
Measurements of hadron production in p + C interactions at 31 GeV/c are performed using the NA61/SHINE spectrometer at the CERN SPS. The analysis is based on the full set of data collected in 2009 ...using a graphite target with a thickness of 4 % of a nuclear interaction length. Inelastic and production cross sections as well as spectra of $\pi ^{\pm }$ , $K^{\pm }$ , p, $K^0_S$ and $\varLambda $ are measured with high precision. These measurements are essential for improved calculations of the initial neutrino fluxes in the T2K long-baseline neutrino oscillation experiment in Japan. A comparison of the NA61/SHINE measurements with predictions of several hadroproduction models is presented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper reports measurements of two-pion femtoscopic correlations in Be+Be collisions at a beam momentum of 150
A
GeV
/
c
(energy available in the center-of-mass system for nucleon pair
s
NN
=
...16.84
GeV) by the NA61/SHINE experiment at the CERN SPS accelerator. The obtained momentum space correlation functions can be well described by a Lévy distributed source model. The transverse mass dependence of the Lévy source parameters is presented, and their possible theoretical interpretations are discussed. The results show that the Lévy exponent
α
is approximately constant as a function of
m
T
, and far from both the Gaussian case of
α
=
2
or the conjectured value at the critical endpoint,
α
=
0.5
. The radius scale parameter
R
shows a slight decrease in
m
T
, which can be explained as a signature of transverse flow. Finally, an approximately constant trend of the intercept parameter
λ
as a function of
m
T
was observed, similar to previous NA44 S + Pb results (obtained with a Gaussian approximation, but unlike RHIC results).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a measurement of the momentum spectra of π±, K±, p±, Λ, ¯Λ, and K0S produced in interactions of negatively charged pions with carbon nuclei at beam momenta of 158 and 350 GeV/c. The total ...production cross sections are measured as well. The data were collected with the large-acceptance spectrometer of the fixed target experiment NA61/SHINE at the CERN SPS. The obtained double-differential p−pT spectra provide a unique reference dataset with unprecedented precision and large phase-space coverage to tune models used for the simulation of particle production in extensive air showers in which pions are the most numerous projectiles.
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