Spinless photon dark matter from two universal extra dimensions

We explore the properties of dark matter in theories with two universal extra dimensions, where the lightest Kaluza-Klein state is a spin-0 neutral particle, representing a six-dimensional photon polarized along the extra dimensions. Annihilation of this 'spinless photon' proceeds predominantly through Higgs boson exchange, and is largely independent of other Kaluza-Klein particles. The measured relic abundance sets an upper limit on the spinless photon mass of 500 GeV, which decreases to almost 200 GeV if the Higgs boson is light. The phenomenology of this dark matter candidate is strikingly different from Kaluza-Klein dark matter in theories with one universal extra dimension. Elastic scattering of the spinless photon with quarks is helicity suppressed, making its direct detection challenging, although possible at upcoming experiments. The prospects for indirect detection with gamma rays and antimatter are similar to those of neutralinos. The rates predicted at neutrino telescopes are below the sensitivity of next-generation experiments.Comment: 22 pages. Figure 7 corrected, leading to improved prospects for direct detection. Some clarifying remarks include

The New Fat Higgs: Slimmer and More Attractive

In this paper we increase the MSSM tree level higgs mass bound to a value that is naturally larger than the LEP-II search constraint by adding to the superpotential a $\lambda S H_{u}H_{d}$ term, as in the NMSSM, and UV completing with new strong dynamics {\it before} $\lambda$ becomes non-perturbative. Unlike other models of this type the higgs fields remain elementary, alleviating the supersymmetric fine-tuning problem while maintaining unification in a natural way.Comment: 14 pages and 2 figures. Added references and updated argument about constraints from reheating temperatur

Precision Electroweak Observables in the Minimal Moose Little Higgs Model

Little Higgs theories, in which the Higgs particle is realized as the pseudo-Goldstone boson of an approximate global chiral symmetry have generated much interest as possible alternatives to weak scale supersymmetry. In this paper we analyze precision electroweak observables in the Minimal Moose model and find that in order to be consistent with current experimental bounds, the gauge structure of this theory needs to be modified. We then look for viable regions of parameter space in the modified theory by calculating the various contributions to the S and T parameters.Comment: v2: 17 pages, 9 figures. Typeset in JHEP style. Added a references and two figures showing parameter space for each of two reference points. Corrected typo

Isolation and propagation of primary human cholangiocyte organoids for the generation of bioengineered biliary tissue.

Pediatric liver transplantation is often required as a consequence of biliary disorders because of the lack of alternative treatments for repairing or replacing damaged bile ducts. To address the lack of availability of pediatric livers suitable for transplantation, we developed a protocol for generating bioengineered biliary tissue suitable for biliary reconstruction. Our platform allows the derivation of cholangiocyte organoids (COs) expressing key biliary markers and retaining functions of primary extra- or intrahepatic duct cholangiocytes within 2 weeks of isolation. COs are subsequently seeded on polyglycolic acid (PGA) scaffolds or densified collagen constructs for 4 weeks to generate bioengineered tissue retaining biliary characteristics. Expertise in organoid culture and tissue engineering is desirable for optimal results. COs correspond to mature functional cholangiocytes, differentiating our method from alternative organoid systems currently available that propagate adult stem cells. Consequently, COs provide a unique platform for studies in biliary physiology and pathophysiology, and the resulting bioengineered tissue has broad applications for regenerative medicine and cholangiopathies

Diagonalization of the neutralino mass matrix and boson-neutralino interaction

We analyze a connection between neutralino mass sign, parity and structure of the neutralino-boson interaction. Correct calculation of spin-dependent and spin-independent contributions to neutralino-nuclear scattering should consider this connection. A convenient diagonalization procedure, based on the exponetial parametrization of unitary matrix, is suggested.Comment: 21 pages, RevTex

Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture in humans

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. Here, we surveyed the immune compartment of 15 tissues of six deceased adult donors by single-cell RNA sequencing and paired VDJ sequencing. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of 45 finely phenotyped immune cell types and states, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. In summary, our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing. One Sentence Summary We provide an immune cell atlas, including antigen receptor repertoire profiling, across lymphoid and non-lymphoid human tissues

DNA replication timing is deterministic at the level of chromosomal domains but stochastic at the level of replicons in Xenopus egg extracts

Replication origins in Xenopus egg extracts are located at apparently random sequences but are activated in clusters that fire at different times during S phase under the control of ATR/ATM kinases. We investigated whether chromosomal domains and single sequences replicate at distinct times during S phase in egg extracts. Replication foci were found to progressively appear during early S phase and foci labelled early in one S phase colocalized with those labelled early in the next S phase. However, the distribution of these two early labels did not coincide between single origins or origin clusters on single DNA fibres. The 4 Mb Xenopus rDNA repeat domain was found to replicate later than the rest of the genome and to have a more nuclease-resistant chromatin structure. Replication initiated more frequently in the transcription unit than in the intergenic spacer. These results suggest for the first time that in this embryonic system, where transcription does not occur, replication timing is deterministic at the scale of large chromatin domains (1–5 Mb) but stochastic at the scale of replicons (10 kb) and replicon clusters (50–100 kb)

Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73.

The adoptive transfer of regulatory T-cells (Tregs) is a promising therapeutic approach in transplantation and autoimmunity. However, because large cell numbers are needed to achieve a therapeutic effect, in vitro expansion is required. By comparing their function, phenotype and transcriptomic profile against ex vivo Tregs, we demonstrate that expanded human Tregs switch their metabolism to aerobic glycolysis and show enhanced suppressive function through hypoxia-inducible factor 1-alpha (HIF1A) driven acquisition of CD73 expression. In conjunction with CD39, CD73 expression enables expanded Tregs to convert ATP to immunosuppressive adenosine. We conclude that for maximum therapeutic benefit, Treg expansion protocols should be optimised for CD39/CD73 co-expression

Can we distinguish between h^{SM} and h^0 in split supersymmetry?

We investigate the possibility to distinguish between the Standard Model Higgs boson and the lightest Higgs boson in Split Supersymmetry. We point out that the best way to distinguish between these two Higgs bosons is through the decay into two photons. It is shown that there are large differences of several percent between the predictions for \Gamma(h\to\gamma\gamma) in the two models, making possible the discrimination at future photon-photon colliders. Once the charginos are discovered at the next generation of collider experiments, the well defined predictions for the Higgs decay into two photons will become a cross check to identify the light Higgs boson in Split Supersymmetry.Comment: 8 pages, 3 Figures, typos fixed, version published in J.Phys. G31 (2005) 563-56

Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans

Rare hematopoietic stem and progenitor cell (HSPC) pools outside the bone marrow (BM) contribute to blood production in stress and disease but remain ill-defined. Although non-mobilized peripheral blood (PB) is routinely sampled for clinical management, the diagnosis and monitoring potential of PB HSPCs remains untapped, as no healthy PB HSPC baseline has been reported. Here we comprehensively delineate human extramedullary HSPC compartments comparing spleen, PB and mobilized PB (mPB) to BM using single-cell RNA-seq and/or functional assays. We uncover HSPC features shared by extramedullary tissues and others unique to PB. First, in contrast to actively dividing BM HSPCs, we find no evidence of substantial ongoing hematopoiesis in extramedullary tissues at steady state, but report increased splenic HSPC proliferative output during stress erythropoiesis. Second, extramedullary stem cells/multipotent progenitors (HSC/MPPs) from spleen, PB and mPB share a common transcriptional signature and increased abundance of lineage-primed subsets compared to BM. Third, healthy PB HSPCs display a unique bias towards erythroid-megakaryocytic differentiation. At HSC/MPP level, this is functionally imparted by a subset of phenotypic CD71+ HSC/MPPs, exclusively producing erythrocytes and megakaryocytes, highly abundant in PB but rare in other adult tissues. Finally, the unique erythroid-megakaryocytic-skewing of PB is perturbed with age, in essential thrombocythemia and in beta-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are non-proliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction