Gain of Function (GOF) Mutant p53 in Cancer-Current Therapeutic Approaches.

Continuous development of personalized treatments is undoubtedly beneficial for oncogenic patients' comfort and survival rate. Mutant is associated with a worse prognosis due to the occurrence of metastases, increased chemoresistance, and tumor growth. Currently, numerous compounds capable of p53 reactivation or the destabilization of mutant p53 are being investigated.

Content of Health-Promoting Fatty Acids in Commercial Sheep, Cow and Goat Cheeses.

The study aimed to examine samples of different market original sheep cow and goat cheeses, in respect of the content and profile of FA with special emphasis on health-promoting FA. The content of fatty acids in the examined cheeses was highly differentiated and depended on the sort and type of cheese. The content of fatty acid groups in milk fat varied within the limits: SFA, 55.

Ester derivatives of salinomycin efficiently eliminate breast cancer cells via ER-stress-induced apoptosis.

The polyether ionophore salinomycin (SAL) has been found to selectively target breast cancer cells, including those with stem-like phenotype. On the other hand, SAL amides and esters obtained through derivatisation of the C1 carboxyl of the ionophore were found to exhibit anticancer properties, whilst reducing potential toxicity issues which often occur during standard chemotherapy. However, the studies on the activity and especially on the mechanisms of action of this class of semi-synthetic products against breast cancer cells are very limited.

Simultaneous Inhibition of BCR-ABL1 Tyrosine Kinase and PAK1/2 Serine/Threonine Kinase Exerts Synergistic Effect against Chronic Myeloid Leukemia Cells.

Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia in the chronic phase (CML-CP). However, it is unlikely that they can completely "cure" the disease. This might be because some subpopulations of CML-CP cells such as stem and progenitor cells are resistant to chemotherapy, even to the new generation of TKIs.

Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. At the molecular level, the disorder results from t(9;22)(q34;q11) reciprocal translocation between chromosomes, which leads to the formation of an oncogenic gene fusion. Instead of progress in the understanding of the molecular etiology of CML and the development of novel therapeutic strategies, clinicians still face many challenges in the effective treatment of patients.

In Vitro and In Vivo (Rabbit, Guinea Pig, Mouse) Properties of a Novel Resorbable Polymer and Allogenic Bone Composite for Guided Bone Regeneration and Orthopedic Implants.

Introduction: Currently, there is no bone fixation material that could be fully replaced by the competent recipient bone. The creeping substitution of the bone graft by the recipient bone is the result of its unique potential related to the presence of bone morphogenetic proteins (BMPs). However, the size of the human bone limits the use of allogenic implants for surgical (orthopedic) fixation.

Biological characterization of the modified poly(dimethylsiloxane) surfaces based on cell attachment and toxicity assays.

Poly(dimethylsiloxane) (PDMS) is a material applicable for tissue and biomedical engineering, especially based on microfluidic devices. PDMS is a material used in studies aimed at understanding cell behavior and analyzing the cell adhesion mechanism. In this work, biological characterization of the modified PDMS surfaces based on cell attachment and toxicity assays was performed.

Measurement of Atmospheric Neutrino Oscillations at 6-56 GeV with IceCube DeepCore.

We present a measurement of the atmospheric neutrino oscillation parameters using three years of data from the IceCube Neutrino Observatory. The DeepCore infill array in the center of IceCube enables the detection and reconstruction of neutrinos produced by the interaction of cosmic rays in Earth's atmosphere at energies as low as ∼5  GeV. That energy threshold permits measurements of muon neutrino disappearance, over a range of baselines up to the diameter of the Earth, probing the same range of L/E_{ν} as long-baseline experiments but with substantially higher-energy neutrinos.

Search for neutrinos from decaying dark matter with IceCube: IceCube Collaboration.

With the observation of high-energy astrophysical neutrinos by the IceCube Neutrino Observatory, interest has risen in models of PeV-mass decaying dark matter particles to explain the observed flux. We present two dedicated experimental analyses to test this hypothesis. One analysis uses 6 years of IceCube data focusing on muon neutrino 'track' events from the Northern Hemisphere, while the second analysis uses 2 years of 'cascade' events from the full sky.

Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are not curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L), or CALR(del52) accumulated reactive oxygen species-induced DNA double-strand breaks (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP) inhibitors olaparib and BMN673.

Measurement of the energy spectrum with IceCube-79: IceCube Collaboration.

IceCube is a neutrino observatory deployed in the glacial ice at the geographic South Pole. The energy unfolding described in this paper is based on data taken with IceCube in its 79-string configuration. A sample of muon neutrino charged-current interactions with a purity of 99.

Constraints on Ultrahigh-Energy Cosmic-Ray Sources from a Search for Neutrinos above 10 PeV with IceCube.

We report constraints on the sources of ultrahigh-energy cosmic rays (UHECRs) above 10^{9}  GeV, based on an analysis of seven years of IceCube data. This analysis efficiently selects very high- energy neutrino-induced events which have deposited energies from 5×10^{5}  GeV to above 10^{11}  GeV. Two neutrino-induced events with an estimated deposited energy of (2.

Searches for Sterile Neutrinos with the IceCube Detector.

The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous ν_{μ} or ν[over ¯]_{μ} disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3+1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation.

Evidence for Astrophysical Muon Neutrinos from the Northern Sky with IceCube.

Results from the IceCube Neutrino Observatory have recently provided compelling evidence for the existence of a high energy astrophysical neutrino flux utilizing a dominantly Southern Hemisphere data set consisting primarily of ν(e) and ν(τ) charged-current and neutral-current (cascade) neutrino interactions. In the analysis presented here, a data sample of approximately 35,000 muon neutrinos from the Northern sky is extracted from data taken during 659.5 days of live time recorded between May 2010 and May 2012.

Development of a general analysis and unfolding scheme and its application to measure the energy spectrum of atmospheric neutrinos with IceCube: IceCube Collaboration.

We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector.

Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube.

A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the IceCube Neutrino Observatory. Here we extend this analysis to probe the astrophysical flux down to 35 TeV and analyze its flavor composition by classifying events as showers or tracks. Taking advantage of lower atmospheric backgrounds for showerlike events, we obtain a shower-biased sample containing 129 showers and 8 tracks collected in three years from 2010 to 2013.

Observation of high-energy astrophysical neutrinos in three years of IceCube data.

A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8)  GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ.

DNA methyltransferase inhibitors improve the effect of chemotherapeutic agents in SW48 and HT-29 colorectal cancer cells.

DNA methylation is an epigenetic phenomenon known to play an important role in the development and progression of human cancer. Enzyme responsible for this process is DNA methyltransferase 1 (DNMT1) that maintains an altered methylation pattern by copying it from parent to daughter DNA strands after replication. Aberrant methylation of the promoter regions of genes critical for normal cellular functions is potentially reversible.

Evidence for high-energy extraterrestrial neutrinos at the IceCube detector.

We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds.

Measurement of atmospheric neutrino oscillations with IceCube.

We present the first statistically significant detection of neutrino oscillations in the high-energy regime (>20 GeV) from an analysis of IceCube Neutrino Observatory data collected in 2010 and 2011. This measurement is made possible by the low-energy threshold of the DeepCore detector (~20 GeV) and benefits from the use of the IceCube detector as a veto against cosmic-ray-induced muon background. The oscillation signal was detected within a low-energy muon neutrino sample (20-100 GeV) extracted from data collected by DeepCore.

DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer.

The DNA methyltransferase (DNMT) inhibitors azacytidine and decitabine are the most successful epigenetic drugs to date and are still the most widely used as epigenetic modulators, even though their application for oncological diseases is restricted by their relative toxicity and poor chemical stability. Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one), a more stable and less toxic cytidine analog, is another inhibitor of DNMT with concomitant inhibitory activity towards cytidine deaminase. Unfortunately, there is no new information related to the possible clinical applications of zebularine.

First observation of PeV-energy neutrinos with IceCube.

We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04±0.16 and 1.

A microfluidic system to study the cytotoxic effect of drugs: the combined effect of celecoxib and 5-fluorouracil on normal and cancer cells.

We have investigated the response of normal and cancer cells to exposure a combination of celecoxib (Celbx) and 5-fluorouracil (5-FU) using a lab-on-a-chip microfluidic device. Specifically, we have tested the cytotoxic effect of Celbx on normal mouse embryo cells (Balb/c 3T3) and human lung carcinoma cells (A549). The single drugs or their combinations were adjusted to five different concentrations using a concentration gradient generator (CGG) in a single step.

Sensitivity of Mycobacterium avium subsp paratuberculosis, Escherichia coli and Salmonella enterica serotype Typhimurium to low pH, high organic acids and ensiling.

Aims: To evaluate the persistence of Mycobacterium avium subsp paratuberculosis (Myco. paratuberculosis), Salmonella enterica serotype Typhimurium (Salm.Typhimurium) and a commensal Escherichia coli (E.