279 research outputs found
Recommended from our members
Mitochondrial recoupling: a novel therapeutic strategy for cancer?
Recent findings link metabolic transformation of cancer cells to aberrant functions of mitochondrial uncoupling proteins (UCPs). By inducing proton leak, UCPs interfere with mitochondrial synthesis of adenosine 5′-triphosphate, which is also a key determinant of glycolytic pathways. In addition, UCP suppress the generation of superoxide, a byproduct of mitochondrial electron transport and a major source of oxidative stress. The near ubiquitous UCP2 becomes highly abundant in some cancers and may advance metabolic reprogramming, further disrupt tumour suppression, and promote chemoresistance. Here we review current evidence to suggest that inhibition of mitochondrial uncoupling may eliminate these responses and reveal novel anti-cancer strategies
Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds
Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chemical synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacological properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and Se-77-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge
Cancer epidemiology in Central and South Eastern European countries
Aim To collect cancer epidemiology data in South Eastern
European countries as a basis for potential comparison of
their performance in cancer care.
Methods The South Eastern European Research Oncology
Group (SEEROG) collected and analyzed epidemiological
data on incidence and mortality that reflect cancer management
in 8 countries – Croatia, Czech Republic, Hungary,
Romania, Poland, Slovakia, and Serbia and Montenegro
in the last 20-40 years.
Results The most common cancer type in men in all countries
was lung cancer, followed by colorectal and prostate
cancer, with the exception of the Czech Republic, where
prostate cancer and colorectal cancer were more common.
The most frequent cancer in women was breast cancer
followed by colorectal cancer, with the exceptions of
Romania and Central Serbia where cervical cancer was the
second most common. Cancer mortality data from the last
20-40 years revealed two different patterns in men. In Romania
and in Serbia and Montenegro, there was a trend
toward an increase, while in the other countries mortality
was declining, after increasing for a number of years. In
women, a steady decline was observed over many years
in the Czech Republic, Hungary, and Slovakia, while in the
other countries it remained unchanged.
Conclusions There are striking variations in the risk of different
cancers by geographic area. Most of the international
variation is due to exposure to known or suspected
risk factors which provides a clear challenge to prevention.
There are some differences in incidence and mortality that
cannot be explained by exposure to known risk factors or
treatment availabilities
Bond of NSM FRP strengthened concrete: round robin test initiative
Despite the extensive research that has been conducted on the debonding behaviour of FRP
strengthening systems, no standard methodology has been yet established on its experimental
characterization. In this context, to assess the performance and reliability of small scale testing
on NSM (near surface mounted) FRP strengthening systems, an experimental program was
carried out on a series of nine NSM FRP strengthening systems, in the framework of an
international Round Robin Testing (RRT). Eleven laboratories and seven manufacturers and
suppliers participated in this extensive international exercise, which regarded both NSM and
EBR FRP strengthening systems. Test results obtained for the NSM systems by the
participating laboratories are discussed and compared in this paper to investigate the feasibility
of the adopted single/double pulling shear test method, to investigate the mechanism of bond
between NSM FRP reinforcement and concrete, and to investigate the level of variability
obtained between the participating laboratories testing the same material batches.
It is concluded that the tested variants in the adopted single/double shear pulling test have a
significant influence, stressing the importance of the level of detail of standardized test
protocols for bond verification. On overall, given the variants included in this study, the
obtained variation in bond stress-slip behaviour between the laboratories remained fairly
limited.The authors wish to acknowledge the financial assistance of the European Union for the Marie Curie Research Training Network En-Core, and the support of TG 9.3 of the International Federation for Structural Concrete (fib). Hughes Brothers and Fortius, Magmatech, Schock, S&P, Sika, ATP, and Sto Scandinavia AB are acknowledged for their participation in the RRT and for supplying the test materials
Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds
Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, N17A/F32T-AnTx{,} which showed comparable Kv1.3 affinity to the wild-type peptide{,} but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace{,} by chemical synthesis{,} all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly{,} the key pharmacological properties of the Sec-N17A/F32T-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-N17A/F32T-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge
RESEARCH ON THE REALIZATION OF BIOCOMPOSITE ECOFERTILIZING GRANULAR MATERIALS BASED ON PEAT
Lately, fertilizer researches focuses on reducing the negative impact of using it on the environment and consumers, and finding new, less costly fertilizer sources.The application of organo-mineral fertilizers is a better approach to sustaining soil fertility and crop yield than applying only chemical or organic fertilizers.The paper presents the results of the researches regarding the realization and characterization of granular biocomposite biofertilizers based on peat.In order to improve the fertilizer role of the peat, the used recipe contains urea as a source of nitrogen monoammonium phosphate (MAP) as a source of phosphorus and nitrogen, sugar beet molasses as a source of organic nitrogen, potassium and vitamins, protein hydrolyzate, as the source of protein and other microelements
Development of an international standard set of outcome measures for patients with atrial fibrillation: a report of the International Consortium for Health Outcomes Measurement (ICHOM) atrial fibrillation working group.
AIMS: As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings. METHODS AND RESULTS: Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set. CONCLUSION: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF
High magnetic field scales and critical currents in SmFeAs(O,F) crystals: promising for applications
Superconducting technology provides most sensitive field detectors, promising
implementations of qubits and high field magnets for medical imaging and for
most powerful particle accelerators. Thus, with the discovery of new
superconducting materials, such as the iron pnictides, exploring their
potential for applications is one of the foremost tasks. Even if the critical
temperature Tc is high, intrinsic electronic properties might render
applications rather difficult, particularly if extreme electronic anisotropy
prevents effective pinning of vortices and thus severely limits the critical
current density, a problem well known for cuprates. While many questions
concerning microscopic electronic properties of the iron pnictides have been
successfully addressed and estimates point to a very high upper critical field,
their application potential is less clarified. Thus we focus here on the
critical currents, their anisotropy and the onset of electrical dissipation in
high magnetic fields up to 65 T. Our detailed study of the transport properties
of optimally doped SmFeAs(O,F) single crystals reveals a promising combination
of high (>2 x 10^6 A/cm^2) and nearly isotropic critical current densities
along all crystal directions. This favorable intragrain current transport in
SmFeAs(O,F), which shows the highest Tc of 54 K at ambient pressure, is a
crucial requirement for possible applications. Essential in these experiments
are 4-probe measurements on Focused Ion Beam (FIB) cut single crystals with
sub-\mu\m^2 cross-section, with current along and perpendicular to the
crystallographic c-axis and very good signal-to-noise ratio (SNR) in pulsed
magnetic fields. The pinning forces have been characterized by scaling the
magnetically measured "peak effect"
Round robin testing initiative for fiber reinforced polymer (FRP) reinforcement
An international Round Robin Testing (RRT) programme on FRP reinforcement was
conducted within the framework of the Marie Curie Research Training Network, ENCORE,
and with the support of Task Group 9.3 of the International Federation for
Structural Concrete (fib). Eleven laboratories and six manufacturers and suppliers
participated in this exercise. As part of this extensive experimental endeavour, one or more
of the following tests were performed by the participating laboratories: 1) tensile tests on
FRP bars and strips; 2) tensile tests on FRP laminates; 3) double bond shear tests on FRP
laminates (Externally Bonded Reinforcement, EBR) and FRP bars/strip (Near Surface
Mounted reinforcement, NSM). This paper will discusses the results of the RRT initiative,
among which the experimental results of bond tests on concrete specimens strengthened
with EBR and NSM FRP
- …