Falsifying High-Scale Leptogenesis at the LHC

Measuring a nonzero value for the cross section of any lepton number violating (LNV) process would put a strong lower limit on the washout factor for the effective lepton number density in the early Universe at times close to the electroweak phase transition and thus would lead to important constraints on any high-scale model for the generation of the observed baryon asymmetry based on LNV. In particular, for leptogenesis (LG) models with masses of the right-handed neutrinos heavier than the mass scale observed at the LHC, the implied large washout factors would lead to a violation of the out-of-equilibrium condition and exponentially suppress the net lepton number produced in such LG models. We thus demonstrate that the observation of LNV processes at the LHC results in the falsification of high-scale LG models. However, no conclusions about the viability of LG models can be drawn from the nonobservation of LNV processes

Falsifying high-scale baryogenesis with neutrinoless double beta decay and lepton flavor violation

Interactions that manifest themselves as lepton number violating processes at low energies in combination with sphaleron transitions typically erase any preexisting baryon asymmetry of the Universe. In this article, we discuss the constraints obtained from an observation of neutrinoless double beta decay in this context. If a new physics mechanism of neutrinoless double beta decay other than the standard light neutrino exchange is observed, typical scenarios of high-scale baryogenesis will be excluded unless the baryon asymmetry is stabilized via some new mechanism. We also sketch how this conclusion can be extended beyond the first lepton generation by incorporating lepton flavor violating processes

Combined collider constraints on neutralinos and charginos

Searches for supersymmetric electroweakinos have entered a crucial phase, as the integrated luminosity of the Large Hadron Collider is now high enough to compensate for their weak production cross-sections. Working in a framework where the neutralinos and charginos are the only light sparticles in the Minimal Supersymmetric Standard Model, we use gambit to perform a detailed likelihood analysis of the electroweakino sector. We focus on the impacts of recent ATLAS and CMS searches with 36 fb$^{-1}$ of 13 TeV proton-proton collision data. We also include constraints from LEP and invisible decays of the $Z$ and Higgs bosons. Under the background-only hypothesis, we show that current LHC searches do not robustly exclude any range of neutralino or chargino masses. However, a pattern of excesses in several LHC analyses points towards a possible signal, with neutralino masses of $(m_{\tilde{\chi}_1^0}, m_{\tilde{\chi}_2^0}, m_{\tilde{\chi}_3^0}, m_{\tilde{\chi}_4^0})$ = (8-155, 103-260, 130-473, 219-502) GeV and chargino masses of $(m_{\tilde{\chi}_1^{\pm}}, m_{\tilde{\chi}_2^{\pm}})$ = (104-259, 224-507) GeV at the 95% confidence level. The lightest neutralino is mostly bino, with a possible modest Higgsino or wino component. We find that this excess has a combined local significance of $3.3\sigma$, subject to a number of cautions. If one includes LHC searches for charginos and neutralinos conducted with 8 TeV proton-proton collision data, the local significance is lowered to 2.9$\sigma$. We briefly consider the implications for dark matter, finding that the correct relic density can be obtained through the Higgs-funnel and $Z$-funnel mechanisms, even assuming that all other sparticles are decoupled. All samples, gambit input files and best-fit models from this study are available on Zenodo.Comment: 38 pages, 16 figures, v3 is the version accepted by EPJ

Combined collider constraints on neutralinos and charginos

This work is licensed under a Creative Commons Attribution 4.0 International License.Searches for supersymmetric electroweakinos have entered a crucial phase, as the integrated luminosity of the Large Hadron Collider is now high enough to compensate for their weak production cross-sections. Working in a framework where the neutralinos and charginos are the only light sparticles in the Minimal Supersymmetric Standard Model, we use GAMBIT to perform a detailed likelihood analysis of the electroweakino sector. We focus on the impacts of recent ATLAS and CMS searches with of 13 TeV proton-proton collision data. We also include constraints from LEP and invisible decays of the Z and Higgs bosons. Under the background-only hypothesis, we show that current LHC searches do not robustly exclude any range of neutralino or chargino masses. However, a pattern of excesses in several LHC analyses points towards a possible signal, with neutralino masses of = (8–155, 103–260, 130–473, 219–502) GeV and chargino masses of = (104–259, 224–507) GeV at the 95% confidence level. The lightest neutralino is mostly bino, with a possible modest Higgsino or wino component. We find that this excess has a combined local significance of 3.3, subject to a number of cautions. If one includes LHC searches for charginos and neutralinos conducted with 8 TeV proton-proton collision data, the local significance is lowered to 2.9. We briefly consider the implications for dark matter, finding that the correct relic density can be obtained through the Higgs-funnel and Z-funnel mechanisms, even assuming that all other sparticles are decoupled. All samples, GAMBIT input files and best-fit models from this study are available on Zenodo

The two-pore channel TPCN2 mediates NAADP-dependent Ca2+-release from lysosomal stores

Second messenger-induced Ca2+-release from intracellular stores plays a key role in a multitude of physiological processes. In addition to 1,4,5-inositol trisphosphate (IP3), Ca2+, and cyclic ADP ribose (cADPR) that trigger Ca2+-release from the endoplasmatic reticulum (ER), nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as a cellular metabolite that mediates Ca2+-release from lysosomal stores. While NAADP-induced Ca2+-release has been found in many tissues and cell types, the molecular identity of the channel(s) conferring this release remained elusive so far. Here, we show that TPCN2, a novel member of the two-pore cation channel family, displays the basic properties of native NAADP-dependent Ca2+-release channels. TPCN2 transcripts are widely expressed in the body and encode a lysosomal protein forming homomers. TPCN2 mediates intracellular Ca2+-release after activation with low-nanomolar concentrations of NAADP while it is desensitized by micromolar concentrations of this second messenger and is insensitive to the NAADP analog nicotinamide adenine dinucleotide phosphate (NADP). Furthermore, TPCN2-mediated Ca2+-release is almost completely abolished when the capacity of lysosomes for storing Ca2+ is pharmacologically blocked. By contrast, TPCN2-specific Ca2+-release is unaffected by emptying ER-based Ca2+ stores. In conclusion, these findings indicate that TPCN2 is a major component of the long-sought lysosomal NAADP-dependent Ca2+-release channel

Raman spectroscopy in head and neck cancer

In recent years there has been much interest in the use of optical diagnostics in cancer detection. Early diagnosis of cancer affords early intervention and greatest chance of cure. Raman spectroscopy is based on the interaction of photons with the target material producing a highly detailed biochemical 'fingerprint' of the sample. It can be appreciated that such a sensitive biochemical detection system could confer diagnostic benefit in a clinical setting. Raman has been used successfully in key health areas such as cardiovascular diseases, and dental care but there is a paucity of literature on Raman spectroscopy in Head and Neck cancer. Following the introduction of health care targets for cancer, and with an ever-aging population the need for rapid cancer detection has never been greater. Raman spectroscopy could confer great patient benefit with early, rapid and accurate diagnosis. This technique is almost labour free without the need for sample preparation. It could reduce the need for whole pathological specimen examination, in theatre it could help to determine margin status, and finally peripheral blood diagnosis may be an achievable target

Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease