601 research outputs found
The singlet scalar as FIMP dark matter
The singlet scalar model is a minimal extension of the Standard Model that
can explain the dark matter. We point out that in this model the dark matter
constraint can be satisfied not only in the already considered WIMP regime but
also, for much smaller couplings, in the Feebly Interacting Massive Particle
(FIMP) regime. In it, dark matter particles are slowly produced in the early
Universe but are never abundant enough to reach thermal equilibrium or
annihilate among themselves. This alternative framework is as simple and
predictive as the WIMP scenario but it gives rise to a completely different
dark matter phenomenology. After reviewing the calculation of the dark matter
relic density in the FIMP regime, we study in detail the evolution of the dark
matter abundance in the early Universe and the predicted relic density as a
function of the parameters of the model. A new dark matter compatible region of
the singlet model is identified, featuring couplings of order 10^-11 to 10^-12
for singlet masses in the GeV to TeV range. As a consequence, no signals at
direct or indirect detection experiments are expected. The relevance of this
new viable region for the correct interpretation of recent experimental bounds
is emphasized.Comment: 12 pages, 6 figure
The Emergence of Precision Urologic Oncology: A Collaborative Review on Biomarker-driven Therapeutics
CONTEXT:
Biomarker-driven cancer therapy, also referred to as precision oncology, has received increasing attention for its promise of improving patient outcomes by defining subsets of patients more likely to respond to various therapies.
OBJECTIVES:
In this collaborative review article, we examine recent literature regarding biomarker-driven therapeutics in urologic oncology, to better define the state of the field, explore the current evidence supporting utility of this approach, and gauge potential for the future.
EVIDENCE ACQUISITION:
We reviewed relevant literature, with a particular focus on recent studies about targeted therapy, predictors of response, and biomarker development.
EVIDENCE SYNTHESIS:
The recent advances in molecular profiling have led to a rapid expansion of potential biomarkers and predictive information for patients with urologic malignancies. Across disease states, distinct molecular subtypes of cancers have been identified, with the potential to inform choices of management strategy. Biomarkers predicting response to standard therapies (such as platinum-based chemotherapy) are emerging. In several malignancies (particularly renal cell carcinoma and castration-resistant prostate cancer), targeted therapy against commonly altered signaling pathways has emerged as standard of care. Finally, targeted therapy against alterations present in rare patients (less than 2%) across diseases has the potential to drastically alter patterns of care and choices of therapeutic options.
CONCLUSIONS:
Precision medicine has the highest potential to impact the care of patients. Prospective studies in the setting of clinical trials and standard of care therapy will help define reliable predictive biomarkers and new therapeutic targets leading to real improvement in patient outcomes.
PATIENT SUMMARY:
Precision oncology uses molecular information (DNA and RNA) from the individual and the tumor to match the right patient with the right treatment. Tremendous strides have been made in defining the molecular underpinnings of urologic malignancies and understanding how these predict response to treatmentâthis represents the future of urologic oncology
Modelling the nucleon wave function from soft and hard processes
Current light-cone wave functions for the nucleon are unsatisfactory since
they are in conflict with the data of the nucleon's Dirac form factor at large
momentum transfer. Therefore, we attempt a determination of a new wave function
respecting theoretical ideas on its parameterization and satisfying the
following constraints: It should provide a soft Feynman contribution to the
proton's form factor in agreement with data; it should be consistent with
current parameterizations of the valence quark distribution functions and
lastly it should provide an acceptable value for the \jp \to N \bar N decay
width. The latter process is calculated within the modified perturbative
approach to hard exclusive reactions. A simultaneous fit to the three sets of
data leads to a wave function whose -dependent part, the distribution
amplitude, shows the same type of asymmetry as those distribution amplitudes
constrained by QCD sum rules. The asymmetry is however much more moderate as in
those amplitudes. Our distribution amplitude resembles the asymptotic one in
shape but the position of the maximum is somewhat shifted.Comment: 32 pages RevTex + PS-file with 5 figures in uu-encoded, compressed
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Stress related epigenetic changes may explain opportunistic success in biological invasions in Antipode mussels
Different environmental factors could induce epigenetic changes, which are likely involved in the biological invasion process. Some of these factors are driven by humans as, for example, the pollution and deliberate or accidental introductions and others are due to natural conditions such as salinity. In this study, we have analysed the relationship between different stress factors: time in the new location, pollution and salinity with the methylation changes that could be involved in the invasive species tolerance to new environments. For this purpose, we have analysed two different musselsâ species, reciprocally introduced in antipode areas: the Mediterranean blue mussel Mytilus galloprovincialis and the New Zealand pygmy mussel Xenostrobus securis, widely recognized invaders outside their native distribution ranges. The demetylathion was higher in more stressed population, supporting the idea of epigenetic is involved in plasticity process. These results can open a new management protocols, using the epigenetic signals as potential pollution monitoring tool. We could use these epigenetic marks to recognise the invasive status in a population and determine potential biopollutants
IGF1 activates cell cycle arrest following irradiation by reducing binding of ÎNp63 to the p21 promoter
Radiotherapy for head and neck tumors often results in persistent loss of function in salivary glands. Patients suffering from impaired salivary function frequently terminate treatment prematurely because of reduced quality of life caused by malnutrition and other debilitating side-effects. It has been previously shown in mice expressing a constitutively active form of Akt (myr-Akt1), or in mice pretreated with IGF1, apoptosis is suppressed, which correlates with maintained salivary gland function measured by stimulated salivary flow. Induction of cell cycle arrest may be important for this protection by allowing cells time for DNA repair. We have observed increased accumulation of cells in G2/M at acute time-points after irradiation in parotid glands of mice receiving pretreatment with IGF1. As p21, a transcriptional target of the p53 family, is necessary for maintaining G2/M arrest, we analyzed the roles of p53 and p63 in modulating IGF1-stimulated p21 expression. Pretreatment with IGF1 reduces binding of ÎNp63 to the p21 promoter after irradiation, which coincides with increased p53 binding and sustained p21 transcription. Our data indicate a role for ÎNp63 in modulating p53-dependent gene expression and influencing whether a cell death or cell cycle arrest program is initiated
Preserving ovarian function in patients receiving cyclophosphamide
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68327/2/10.1191_096120399678847335.pd
The genomic evolution of human prostate cancer.
Prostate cancers are highly prevalent in the developed world, with inheritable risk contributing appreciably to tumour development. Genomic heterogeneity within individual prostate glands and between patients derives predominantly from structural variants and copy-number aberrations. Subtypes of prostate cancers are being delineated through the increasing use of next-generation sequencing, but these subtypes are yet to be used to guide the prognosis or therapeutic strategy. Herein, we review our current knowledge of the mutational landscape of human prostate cancer, describing what is known of the common mutations underpinning its development. We evaluate recurrent prostate-specific mutations prior to discussing the mutational events that are shared both in prostate cancer and across multiple cancer types. From these data, we construct a putative overview of the genomic evolution of human prostate cancer
Interplay of LFV and slepton mass splittings at the LHC as a probe of the SUSY seesaw
We study the impact of a type-I SUSY seesaw concerning lepton flavour
violation (LFV) both at low-energies and at the LHC. The study of the di-lepton
invariant mass distribution at the LHC allows to reconstruct some of the masses
of the different sparticles involved in a decay chain. In particular, the
combination with other observables renders feasible the reconstruction of the
masses of the intermediate sleptons involved in decays. Slepton mass splittings can be either
interpreted as a signal of non-universality in the SUSY soft breaking-terms
(signalling a deviation from constrained scenarios as the cMSSM) or as being
due to the violation of lepton flavour. In the latter case, in addition to
these high-energy processes, one expects further low-energy manifestations of
LFV such as radiative and three-body lepton decays. Under the assumption of a
type-I seesaw as the source of neutrino masses and mixings, all these LFV
observables are related. Working in the framework of the cMSSM extended by
three right-handed neutrino superfields, we conduct a systematic analysis
addressing the simultaneous implications of the SUSY seesaw for both high- and
low-energy lepton flavour violation. We discuss how the confrontation of
slepton mass splittings as observed at the LHC and low-energy LFV observables
may provide important information about the underlying mechanism of LFV.Comment: 50 pages, 42 eps Figures, typos correcte
In-cell NMR in E. coli to Monitor Maturation Steps of hSOD1
In-cell NMR allows characterizing the folding state of a protein as well as posttranslational events at molecular level, in the cellular context. Here, the initial maturation steps of human copper, zinc superoxide dismutase 1 are characterized in the E. coli cytoplasm by in-cell NMR: from the apo protein, which is partially unfolded, to the zinc binding which causes its final quaternary structure. The protein selectively binds only one zinc ion, whereas in vitro also the copper site binds a non-physiological zinc ion. However, no intramolecular disulfide bridge formation occurs, nor copper uptake, suggesting the need of a specific chaperone for those purposes
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