236 research outputs found
One-Loop Calculation of the Oblique S Parameter in Higgsless Electroweak Models
We present a one-loop calculation of the oblique S parameter within Higgsless
models of electroweak symmetry breaking and analyze the phenomenological
implications of the available electroweak precision data. We use the most
general effective Lagrangian with at most two derivatives, implementing the
chiral symmetry breaking SU(2)_L x SU(2)_R -> SU(2)_{L+R} with Goldstones,
gauge bosons and one multiplet of vector and axial-vector massive resonance
states. Using the dispersive representation of Peskin and Takeuchi and imposing
the short-distance constraints dictated by the operator product expansion, we
obtain S at the NLO in terms of a few resonance parameters. In
asymptotically-free gauge theories, the final result only depends on the
vector-resonance mass and requires M_V > 1.8 TeV (3.8 TeV) to satisfy the
experimental limits at the 3 \sigma (1\sigma) level; the axial state is always
heavier, we obtain M_A > 2.5 TeV (6.6 TeV) at 3\sigma (1\sigma). In
strongly-coupled models, such as walking or conformal technicolour, where the
second Weinberg sum rule does not apply, the vector and axial couplings are not
determined by the short-distance constraints; but one can still derive a lower
bound on S, provided the hierarchy M_V < M_A remains valid. Even in this less
constrained situation, we find that in order to satisfy the experimental limits
at 3\sigma one needs M_{V,A} > 1.8 TeV.Comment: 34 pages, 9 figures. Version published in JHEP. Some references and
sentences have been added to facilitate the discussio
Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.
Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015
Oblique S and T Constraints on Electroweak Strongly-Coupled Models with a Light Higgs
Using a general effective Lagrangian implementing the chiral symmetry breaking SU(2)L x SU(2)R -> SU(2){L+R}, we present a one-loop calculation of the oblique S and T parameters within electroweak strongly-coupled models with a light scalar. Imposing a proper ultraviolet behaviour, we determine S and T at next-to-leading order in terms of a few resonance parameters. The constraints from the global fit to electroweak precision data force the massive vector and axial-vector states to be heavy, with masses above the TeV scale, and suggest that the W+W- and ZZ couplings of the Higgs-like scalar should be close to the Standard Model value. Our findings are generic, since they only rely on soft requirements on the short-distance properties of the underlying strongly-coupled theory, which are widely satisfied in more specific scenarios
Thermorheological and textural behaviour of gluten-free gels obtained from chestnut and rice flours
Nowadays, as celiac disease is becoming more
common the consumers’ demand for gluten-free products
with high nutritional and taste quality is increasing. This
work deals with the study of the impact of four novelty
gluten-free sources: chestnut flour (Cf), whole rice flour
(Rw), Carolino rice flour (Rc) and Agulha rice flour (Ra).
Textural, thermorheological and stability performance of
gluten-free gels using different experimental techniques
were evaluated. Mixed gels were also produced for comparison.
Texture parameters were determined from the texture
profile analysis using a texturometer. Thermorheological
oscillatory measurements were conducted in a stresscontrolled
rheometer in order to clarify the kinetics of gel
formation and to characterise the structure of the matured
gels. The stability of the gels was evaluated using transmittance
profiling of the gels under gravitational fields
(LUMiSizer®). Texture studies suggested that gels from mixtures of chestnut flour at 30 % and rice flour at 20 %
showed the right texture to develop gel-based new desserts.
Rheological results showed that the thermal profiles on
heating of Cf gels were similar to those obtained for Rw
and Ra, whereas Rc gels exhibited a particular pattern. Once
the final gelatinisation temperature was achieved, no significant
differences on the viscoelastic properties were noticed
for all the tested gels. Stability tests showed that gels with
Rc should present an industrial advantage over the other
assayed formulations, since the stability of these gels is of
the order of four times larger
The management of cancer in the elderly: targeted therapies in oncology
Cancer is universally considered a disease of ageing. Today the management of elderly cancer patients poses many specific problems and it should be revisited in the light of the most recent advances in both diagnosis and treatment of human malignancies. In particular, the potential use of novel therapeutic options, based on therapeutic agents raised against molecular targets (the so called targeted therapy), appears to be promising in this clinical settings especially in view of the limited side-effects. The mainstays of cancer treatment during the twentieth century were surgery, radiation and chemotherapy. However, surgery is not curative in metastatic disease, radiation and chemotherapy are limited by side effects because they can't discriminate between healthy and cancerous cells. When key molecular changes responsible for malignant transformation were identified (e.g. growth factors and their receptors), it was hoped that new targeted agents, by inhibiting cancer-specific pathways, would spare normal cells and thereby offer improved safety benefits and a higher therapeutic index over standard chemotherapeutics. The most common targeted therapies used in clinical practice, i.e. monoclonal antibodies and small molecules, are described
The Smc5–Smc6 Complex Is Required to Remove Chromosome Junctions in Meiosis
Meiosis, a specialized cell division with a single cycle of DNA replication round and two consecutive rounds of nuclear segregation, allows for the exchange of genetic material between parental chromosomes and the formation of haploid gametes. The structural maintenance of chromosome (SMC) proteins aid manipulation of chromosome structures inside cells. Eukaryotic SMC complexes include cohesin, condensin and the Smc5–Smc6 complex. Meiotic roles have been discovered for cohesin and condensin. However, although Smc5–Smc6 is known to be required for successful meiotic divisions, the meiotic functions of the complex are not well understood. Here we show that the Smc5–Smc6 complex localizes to specific chromosome regions during meiotic prophase I. We report that meiotic cells lacking Smc5–Smc6 undergo catastrophic meiotic divisions as a consequence of unresolved linkages between chromosomes. Surprisingly, meiotic segregation defects are not rescued by abrogation of Spo11-induced meiotic recombination, indicating that at least some chromosome linkages in smc5–smc6 mutants originate from other cellular processes. These results demonstrate that, as in mitosis, Smc5-Smc6 is required to ensure proper chromosome segregation during meiosis by preventing aberrant recombination intermediates between homologous chromosomes
Mre11-Rad50 Promotes Rapid Repair of DNA Damage in the Polyploid Archaeon Haloferax volcanii by Restraining Homologous Recombination
Polyploidy is frequent in nature and is a hallmark of cancer cells, but little is known about the strategy of DNA repair in polyploid organisms. We have studied DNA repair in the polyploid archaeon Haloferax volcanii, which contains up to 20 genome copies. We have focused on the role of Mre11 and Rad50 proteins, which are found in all domains of life and which form a complex that binds to and coordinates the repair of DNA double-strand breaks (DSBs). Surprisingly, mre11 rad50 mutants are more resistant to DNA damage than the wild-type. However, wild-type cells recover faster from DNA damage, and pulsed-field gel electrophoresis shows that DNA double-strand breaks are repaired more slowly in mre11 rad50 mutants. Using a plasmid repair assay, we show that wild-type and mre11 rad50 cells use different strategies of DSB repair. In the wild-type, Mre11-Rad50 appears to prevent the repair of DSBs by homologous recombination (HR), allowing microhomology-mediated end-joining to act as the primary repair pathway. However, genetic analysis of recombination-defective radA mutants suggests that DNA repair in wild-type cells ultimately requires HR, therefore Mre11-Rad50 merely delays this mode of repair. In polyploid organisms, DSB repair by HR is potentially hazardous, since each DNA end will have multiple partners. We show that in the polyploid archaeon H. volcanii the repair of DSBs by HR is restrained by Mre11-Rad50. The unrestrained use of HR in mre11 rad50 mutants enhances cell survival but leads to slow recovery from DNA damage, presumably due to difficulties in the resolution of DNA repair intermediates. Our results suggest that recombination might be similarly repressed in other polyploid organisms and at repetitive sequences in haploid and diploid species
Cytochrome 450 1B1 (CYP1B1) polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC) patients
BACKGROUND:
The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC) patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1) gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen.
METHODS:
CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition), 4326C>G (432LeuVal), and 4390A>G (453AsnSer) polymorphisms and treatment response, progression-free-survival (PFS) and overall-survival (OS) was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test.
RESULTS:
Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014), shorter progression-free-survival (P = 0.032) and overall-survival (P < 0.001). Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS. No significant associations were found among other polymorphisms and both response and clinical outcome.
CONCLUSIONS:
CYP1B1-4326C>G (432LeuVal) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment
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