Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Hypercharge and baryon minus lepton number in E6

We study assignments of the hypercharge and baryon minus lepton number for particles in the $E_6$ grand unification model. It is shown that there are three assignments of hypercharge and three assignments of baryon minus lepton number which are consistent with the Standard Model. Their explicit expressions and detailed properties are given. In particular, we show that the $U(1)_{B-L}$ symmetry in $E_6$ cannot be orthogonal to the $SU(3)_R$ symmetry. Based on these investigations, we propose an alternative SU(5) grand unification model.Comment: 16 pages, JHEP3.cls, To appear in JHE

Mixing state of atmospheric particles over the North China Plain

In this unique processing study, the mixing state of ambient submicron aerosol particles in terms of hygroscopicity and volatility was investigated with a Hygroscopicity Tandem Differential Mobility Analyzer and a Volatility Tandem Differential Mobility Analyzer. The measurements were conducted at a regional atmospheric observational site in the North China Plain (NCP) from 8 July to 9 August, 2013. Multimodal patterns were observed in the probability density functions of the hygroscopicity parameter κ and the shrink factor, indicating that ambient particles are mostly an external mixture of particles with different hygroscopicity and volatility. Linear relationships were found between the number fraction of hydrophobic and non-volatile populations, reflecting the dominance of soot in hydrophobic and non-volatile particles. The number fraction of non-volatile particles is lower than that of hydrophobic particles in most cases, indicating that a certain fraction of hydrophobic particles is volatile. Distinct diurnal patterns were found for the number fraction of the hydrophobic and non-volatile particles, with a higher level at nighttime and a lower level during the daytime. The result of air mass classification shows that aerosol particles in air masses coming from north with high moving speed have a high number fraction of hydrophobic/non-volatile population, and are more externally mixed. Only minor differences can be found between the measured aerosol properties for the rest of the air masses. With abundant precursor in the NCP, no matter where the air mass originates, as far as it stays in the NCP for a certain time, aerosol particles may get aged and mixed with newly emitted particles in a short time

Leptogenesis Bound on Spontaneous Symmetry Breaking of Global Lepton Number

We propose a new class of leptogenesis bounds on the spontaneous symmetry breaking of global lepton number. These models have a generic feature of inducing new lepton number violating interactions, due to the presence of the Majorons. We analyzed the singlet Majoron model with right-handed neutrinos and find that the lepton number should be broken above 10^5 GeV to realize a successful leptogenesis because the annihilations of the right-handed neutrinos into the massless Majorons and into the standard model Higgs should go out of equilibrium before the sphaleron process is over. We then argue that this type of leptogenesis constraint should exist in the singlet-triplet Majoron models as well as in a class of R-parity violating supersymmetric Majoron models.Comment: 4 pages, 2 figure

Four Light Neutrinos in Singular Seesaw Mechanism with Abelian Flavor Symmetry

The four light neutrino scenario, which explains the atmosphere, solar and LSND neutrino experiments, is studied in the framework of the seesaw mechanism. By taking both the Dirac and Majorana mass matrix of neutrinos to be singular, the four neutrino mass spectrum consisting of two almost degenerate pairs separated by a mass gap $\sim 1$ eV is naturally generated. Moreover the right-handed neutrino Majorana mass can be at $\sim 10^{14}$ GeV scale unlike in the usual singular seesaw mechanism. Abelian flavor symmetry is used to produce the required neutrino mass pattern. A specific example of the flavor charge assignment is provided to show that maximal mixings between the $\nu_\mu-\nu_\tau$ and $\nu_e-\nu_s$ are respectively attributed to the atmosphere and solar neutrino anomalies while small mixing between two pairs to the LSND results. The implication in the other fermion masses is also discussed.Comment: Firnal version to appear in PR

Pair production of neutralinos via gluon-gluon collisions

The production of a neutralino pair via gluon-gluon fusion is studied in the minimal supersymmetric model(MSSM) at proton-proton colliders. The numerical analysis of their production rates are carried out in the mSUGRA scenario. The results show that this cross section may reach about 80 femto barn for $\tilde{\chi}^{0}_{1}\tilde{\chi}^{0}_{2}$ pair production and 23 femto barn for $\tilde{\chi}^{0}_{2}\tilde{\chi}^{0}_{2}$ pair production with suitable input parameters at the future LHC collider. It shows that this loop mediated process can be competitive with the quark-antiquark annihilation process at the LHC.Comment: LaTex file, l4 pages, 5 EPS figure

Low scale gravity as the source of neutrino masses?

We address the question whether low-scale gravity alone can generate the neutrino mass matrix needed to accommodate the observed phenomenology. In low-scale gravity the neutrino mass matrix in the flavor basis is characterized by one parameter (the gravity scale M_X) and by an exact or approximate flavor blindness (namely, all elements of the mass matrix are of comparable size). Neutrino masses and mixings are consistent with the observational data for certain values of the matrix elements, but only when the spectrum of mass is inverted or degenerate. For the latter type of spectra the parameter M_{ee} probed in double beta experiments and the mass parameter probed by cosmology are close to existing upper limits.Comment: 10 pages, 1 figur

Origin of Life

The evolution of life has been a big enigma despite rapid advancements in the fields of biochemistry, astrobiology, and astrophysics in recent years. The answer to this puzzle has been as mind-boggling as the riddle relating to evolution of Universe itself. Despite the fact that panspermia has gained considerable support as a viable explanation for origin of life on the Earth and elsewhere in the Universe, the issue remains far from a tangible solution. This paper examines the various prevailing hypotheses regarding origin of life like abiogenesis, RNA World, Iron-sulphur World, and panspermia; and concludes that delivery of life-bearing organic molecules by the comets in the early epoch of the Earth alone possibly was not responsible for kick-starting the process of evolution of life on our planet.Comment: 32 pages, 8 figures,invited review article, minor additio