Kaon decays and the flavour problem

After a brief introduction to the so-called flavour problem, we discuss the role of rare K decays in probing the mechanism of quark-flavour mixing. Particular attention is devoted to the formulation of the Minimal Flavour Violation hypothesis, as a general and natural solution to the flavour problem, and to the fundamental role of K -> pi nu nu-bar decays in testing this scenario.Comment: 10 pages, 6 figures, contribution to TH 2002 (Paris, July 2002

Mass-Matching in Higgsless

Modern extra-dimensional Higgsless scenarios rely on a mass-matching between fermionic and bosonic KK resonances to evade constraints from precision electroweak measurements. After analyzing all of the Tevatron and LEP bounds on these so-called Cured Higgsless scenarios, we study their LHC signatures and explore how to identify the mass-matching mechanism, the key to their viability. We find singly and pair produced fermionic resonances show up as clean signals with 2 or 4 leptons and 2 hard jets, while neutral and charged bosonic resonances are visible in the dilepton and leptonic WZ channels, respectively. A measurement of the resonance masses from these channels shows the matching necessary to achieve $S\simeq 0$. Moreover, a large single production of KK-fermion resonances is a clear indication of compositeness of SM quarks. Discovery reach is below 10 fb$^{-1}$ of luminosity for resonances in the 700 GeV range.Comment: 28 pages, 18 figure

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

The existence of global weak solutions for a weakly dissipative Camassa-Holm equation in H1(R)

The existence of global weak solutions to the Cauchy problem for a weakly dissipative Camassa-Holm equation is established in the space C([0,∞)×R)nL∞([0,∞);H1(R)) under the assumption that the initial value u 0 (x) only belongs to the space H 1 (R) . The limit of viscous approximations, a one-sided super bound estimate and a space-time higher-norm estimate for the equation are established to prove the existence of the global weak solution

Visual tests predict dementia risk in Parkinson's disease

OBJECTIVE To assess the role of visual measures and retinal volume to predict the risk of Parkinson disease (PD) dementia. METHODS In this cohort study, we collected visual, cognitive, and motor data in people with PD. Participants underwent ophthalmic examination, retinal imaging using optical coherence tomography, and visual assessment including acuity and contrast sensitivity and high-level visuoperception measures of skew tolerance and biological motion. We assessed the risk of PD dementia using a recently described algorithm that combines age at onset, sex, depression, motor scores, and baseline cognition. RESULTS One hundred forty-six people were included in the study (112 with PD and 34 age-matched controls). The mean disease duration was 4.1 (±2·5) years. None of these participants had dementia. Higher risk of dementia was associated with poorer performance in visual measures (acuity: ρ = 0.29, p = 0.0024; contrast sensitivity: ρ = −0.37, p < 0.0001; skew tolerance: ρ = −0.25, p = 0.0073; and biological motion: ρ = −0.26, p = 0.0054). In addition, higher risk of PD dementia was associated with thinner retinal structure in layers containing dopaminergic cells, measured as ganglion cell layer (GCL) and inner plexiform layer (IPL) thinning (ρ = −0.29, p = 0.0021; ρ = −0.33, p = 0.00044). These relationships were not seen for the retinal nerve fiber layer that does not contain dopaminergic cells and were not seen in unaffected controls. CONCLUSION Visual measures and retinal structure in dopaminergic layers were related to risk of PD dementia. Our findings suggest that visual measures and retinal GCL and IPL volumes may be useful to predict the risk of dementia in PD

Comparing self-reported reactogenicity between adolescents and adults following the use of BNT162b2 (Pfizer-BioNTech) messenger RNA Covid-19 vaccine: a prospective cohort study

Objectives: Although clinical data have shown that the BNT162b2 vaccine, which is widely used in many countries, is safe and effective as a protection against the Covid-19 infection, extant research in adverse reactions using real-world data of various socio-demographic characteristics is scant. Methods: We conducted a prospective cohort study to compare age differences in self-reported reactogenicity of BNT162b2 in Hong Kong. A total of 1,516 participants were intensively followed up for two weeks following both doses of BNT162b2 vaccination, during which their basic demographic, health conditions, and medication information were collected. Results: Results from generalized mixed model showed that compared with adults aged 18 – 59, older adults aged 60 or above had a lower risk of adverse reactions, and adolescents aged 12 – 17 had a moderately higher risk. Conclusions: Results of this study should be informative to parents considering BNT162b2 vaccination for their children in that moderately increased reactogenicity compared with adults is anticipated

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Topical microbicides to prevent the transmission of HIV: formulation gaps and challenges

The efforts of the topical microbicide field to identify a safe and effective topical microbicide were realized in July of 2010 with the reporting of the results of the Centre for the AIDS Programme of Research in South Africa 004 trial. In this trial, a 1% tenofovir gel was found to reduce women’s risk for HIV acquisition by 39% compared to placebo. To understand the impact of this trial on future microbicide development, we must view it from the historical perspective of previous phases 2 and 3 clinical trials with detergents and sulfated polyanions. This knowledge and emerging information must then be parlayed into the next steps needed to create a safe, effective, and acceptable topical microbicide. This review will look at the lessons learned from preclinical and clinical development of topical microbicides, focusing on two significant future challenges: (1) topical microbicide formulation safety and (2) the critical role that adherence to product use has in determining safety and efficacy in clinical trials and ultimately commercial viability of the licensed product. In addition to framing these issues within our current understanding of formulation and prevention of HIV acquisition, recent advances in our understanding of the mechanism of HIV transmission and how it informs on future formulation strategies will be briefly discussed

Adaptive Response in Mice Exposed to 900 MHz Radiofrequency Fields: Primary DNA Damage

The phenomenon of adaptive response (AR) in animal and human cells exposed to ionizing radiation is well documented in scientific literature. We have examined whether such AR could be induced in mice exposed to non-ionizing radiofrequency fields (RF) used for wireless communications. Mice were pre-exposed to 900 MHz RF at 120 µW/cm2 power density for 4 hours/day for 1, 3, 5, 7 and 14 days and then subjected to an acute dose of 3 Gy γ-radiation. The primary DNA damage in the form of alkali labile base damage and single strand breaks in the DNA of peripheral blood leukocytes was determined using the alkaline comet assay. The results indicated that the extent of damage in mice which were pre-exposed to RF for 1 day and then subjected to γ-radiation was similar and not significantly different from those exposed to γ-radiation alone. However, mice which were pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage and was significantly different from those exposed to γ-radiation alone. Thus, the data indicated that RF pre-exposure is capable of inducing AR and suggested that the pre-exposure for more than 4 hours for 1 day is necessary to elicit such AR

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others