Discriminating Electroweak-ino Parameter Ordering at the LHC and Its Impact on LFV Studies

Current limit on the dark matter relic abundance may suggest that $|\mu|$ should be smaller than prediction in the minimal supergravity scenario (mSUGRA) for moderate $m_0$ and $m_{1/2}$. The electroweak-ino parameter $M_1, M_2$ and $|\mu|$ are then much closer to each other. This can be realized naturally in the non-universal Higgs mass model (NUHM). Since the heaviest neutralino ($\tilde\chi^0_4$) and chargino ($\tilde\chi^\pm_2$) have significant gaugino components, they may appear frequently in the left-handed squark decay and then be detectable at the LHC. In such a case, we showed that the hierarchy of $M_1, M_2$ and $|\mu|$ can be determined. In the light slepton mass scenario with non-vanishing lepton-flavor violation (LFV) in the right-handed sector, NUHM with small $|\mu|$ corresponds to region of parameter space where strong cancellation among leading contributions to $Br(\mu\to e\gamma)$ can occur. We showed that determination of electroweak-ino hierarchy plays a crucial role in resolving cancellation point of $Br(\mu\to e\gamma)$ and determination of LFV parameters. We also discussed test of the universality of the slepton masses at the LHC and the implications to SUSY flavor models.Comment: 34 pages, 16 figure

(No) Eternal Inflation and Precision Higgs Physics

Even if nothing but a light Higgs is observed at the LHC, suggesting that the Standard Model is unmodified up to scales far above the weak scale, Higgs physics can yield surprises of fundamental significance for cosmology. As has long been known, the Standard Model vacuum may be metastable for low enough Higgs mass, but a specific value of the decay rate holds special significance: for a very narrow window of parameters, our Universe has not yet decayed but the current inflationary period can not be future eternal. Determining whether we are in this window requires exquisite but achievable experimental precision, with a measurement of the Higgs mass to 0.1 GeV at the LHC, the top mass to 60 MeV at a linear collider, as well as an improved determination of alpha_s by an order of magnitude on the lattice. If the parameters are observed to lie in this special range, particle physics will establish that the future of our Universe is a global big crunch, without harboring pockets of eternal inflation, strongly suggesting that eternal inflation is censored by the fundamental theory. This conclusion could be drawn even more sharply if metastability with the appropriate decay rate is found in the MSSM, where the physics governing the instability can be directly probed at the TeV scale.Comment: 25 pages, 3 figures. v2: updated value of top mass, added references, JHEP published versio

Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma

© 2015, Grosso et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer.This work was supported by Fundação para a Ciência e Tecnologia (FCT), Portugal (PTDC/BIM-ONC/0384-2012 to SFdA). MRM is a FCT PhD fellow (SFRH/BD/92208/2013). ACV is a Lisbon BioMed PhD fellow funded by FCT (SFRH/BD/52232/2013). ARG is the recipient of a FCT Investigator award (IF/00510/2014).info:eu-repo/semantics/publishedVersio

Can HIV self-testing reach first-time testers? A telephone survey among self-test end users in Côte d'Ivoire, Mali, and Senegal

BACKGROUND: Coverage of HIV testing remains sub-optimal in West Africa. Between 2019 and 2022, the ATLAS program distributed ~400 000 oral HIV self-tests (HIVST) in Côte d'Ivoire, Mali, and Senegal, prioritising female sex workers (FSW) and men having sex with men (MSM), and relying on secondary redistribution of HIVST to partners, peers and clients to reach individuals not tested through conventional testing. This study assesses the proportion of first-time testers among HIVST users and the associated factors. METHODS: A phone-based survey was implemented among HIVST users recruited using dedicated leaflets inviting them to anonymously call a free phone number. We collected socio-demographics, sexual behaviours, HIV testing history, HIVST use, and satisfaction with HIVST. We reported the proportion of first-time testers and computed associated factors using logistic regression. RESULTS: Between March and June 2021, 2 615 participants were recruited for 50 940 distributed HIVST (participation rate: 5.1%). Among participants, 30% received their HIVST kit through secondary distribution (from a friend, sexual partner, family member, or colleague). The proportion who had never tested for HIV before HIVST (first-time testers) was 41%. The main factors associated with being a first-time tester were sex, age group, education level, condom use, and secondary distribution. A higher proportion was observed among those aged 24 years or less (55% vs 32% for 25-34, aOR: 0.37 [95%CI: 0.30-0.44], and 26% for 35 years or more, aOR: 0.28 [0.21-0.37]); those less educated (48% for none/primary education vs 45% for secondary education, aOR: 0.60 [0.47-0.77], and 29% for higher education, aOR: 0.33 [0.25-0.44]). A lower proportion was observed among women (37% vs 43%, aOR: 0.49 [0.40-0.60]); those reporting always using a condom over the last year (36% vs 51% for those reporting never using them, aOR: 2.02 [1.59-2.56]); and those who received their HISVST kit through primary distribution (39% vs 46% for secondary distribution, aOR: 1.32 [1.08-1.60]). CONCLUSION: ATLAS HIVST strategy, including secondary distribution, successfully reached a significant proportion of first-time testers. HIVST has the potential to reach underserved populations and contribute to the expansion of HIV testing services in West Africa

Decoy receptor 1 (DCR1) promoter hypermethylation and response to irinotecan in metastatic colorectal cancer

Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI)). In the discovery (n=185) and initial validation set (n=166), patients with methylated Decoy Receptor 1 (DCR1) did not benefit from CAPIRI over Capecitabine treatment (discovery set: HR=1.2 (95%CI 0.7-1.9, p=0.6), validation set: HR=0.9 (95%CI 0.6-1.4, p=0.5)), whereas patients with unmethylated DCR1 did (discovery set: HR=0.4 (95%CI 0.3-0.6, p=0.00001), validation set: HR=0.5 (95%CI 0.3-0.7, p=0.0008)). These results could not be replicated in the external data set (n=467), where a similar effect size was found in patients with methylated and unmethylated DCR1 for FOLFIRI over 5FU treatment (methylated DCR1: HR=0.7 (95%CI 0.5-0.9, p=0.01), unmethylated DCR1: HR=0.8 (95%CI 0.6-1.2, p=0.4)). In conclusion, DCR1 promoter hypermethylation status is a potential predictive biomarker for response to treatment with irinotecan, when combined with capecitabine. This finding could not be replicated in an external validation set, in which irinotecan was combined with 5FU. These results underline the challenge and importance of extensive clinical evaluation of candidate biomarkers in multiple trials

Constraining Supersymmetry

We review constraints on the minimal supersymmetric extension of the Standard Model (MSSM) coming from direct searches at accelerators such as LEP, indirect measurements such as b -> s gamma decay and the anomalous magnetic moment of the muon. The recently corrected sign of pole light-by-light scattering contributions to the latter is taken into account. We combine these constraints with those due to the cosmological density of stable supersymmetric relic particles. The possible indications on the supersymmetric mass scale provided by fine-tuning arguments are reviewed critically. We discuss briefly the prospects for future accelerator searches for supersymmetry.Comment: 21 LaTeX pages, 9 eps figures, Invited Contribution to the New Journal of Physics Focus Issue on Supersymmetr

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of $\sim$1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg$^2$ at a luminosity distance of $40^{+8}_{-8}$ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Msun. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at $\sim$40 Mpc) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over $\sim$10 days. Following early non-detections, X-ray and radio emission were discovered at the transient's position $\sim$9 and $\sim$16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. (Abridged

Global meta‐analysis of over 50 years of multidisciplinary and international collaborations on transmissible cancers

International audienceAlthough transmissible cancers have, so far, only been documented in three independent animal groups, they not only impact animals that have high economic, environmental and social significance, but they are also one of the most virulent parasitic life forms. Currently known transmissible cancers traverse terrestrial and marine environments, and are predicted to be more widely distributed across animal groups; thus, the implementation of effective collaborative scientific networks is important for combating existing and emerging forms. Here, we quantify how collaborative effort on the three known transmissible cancers has advanced through the formation of collaborative networks among institutions and disciplines. These three cancers occur in bivalves (invertebrates—disseminated neoplasia; DN), Tasmanian devils (vertebrate—marsupial; devil facial tumour disease; DFTD) and dogs (vertebrate—eutherian mammal; canine transmissible venereal tumour; CTVT). Research on CTVT and DN has been conducted since 1876 and 1969, respectively, whereas systematic research on DFTD only started in 2006. Yet, collaborative effort on all three diseases is global, encompassing six major Scopus subject areas. Collaborations steadily increased between 1963 and 2006 for CTVT and DN, with similar acceleration for all three cancers since 2006. Network analyses demonstrated that scientists are organizing themselves into efficient collaborative networks; however, these networks appear to be far stronger for DFTD and DN, possibly due to the recent detection of new strains adding impetus to research and associated publications (enhancing citation trajectories). In particular, global and multidisciplinary collaborations formed almost immediately after DFTD research was initiated, leading to similar research effort and relatively greater research outputs compared to the other two diseases. Therefore, in the event of outbreaks of new lineages of existing transmissible cancers, or the discovery of new transmissible cancers in the future, the rapid formation of international collaborations spanning relevant disciplines is vital for the efficient management of these diseases