An SO(10) Grand Unified Theory of Flavor

We present a supersymmetric SO(10) grand unified theory (GUT) of flavor based on an $S_4$ family symmetry. It makes use of our recent proposal to use SO(10) with type II seesaw mechanism for neutrino masses combined with a simple ansatz that the dominant Yukawa matrix (the {\bf 10}-Higgs coupling to matter) has rank one. In this paper, we show how the rank one model can arise within some plausible assumptions as an effective field theory from vectorlike {\bf 16} dimensional matter fields with masses above the GUT scale. In order to obtain the desired fermion flavor texture we use $S_4$ flavon multiplets which acquire vevs in the ground state of the theory. By supplementing the $S_4$ theory with an additional discrete symmetry, we find that the flavon vacuum field alignments take a discrete set of values provided some of the higher dimensional couplings are small. Choosing a particular set of these vacuum alignments appears to lead to an unified understanding of observed quark-lepton flavor: (i) the lepton mixing matrix that is dominantly tri-bi-maximal with small corrections related to quark mixings; (ii) quark lepton mass relations at GUT scale: $m_b\simeq m_{\tau}$ and $m_\mu\simeq 3 m_s$ and (iii) the solar to atmospheric neutrino mass ratio $m_\odot/m_{\rm atm}\simeq \theta_{\rm Cabibbo}$ in agreement with observations. The model predicts the neutrino mixing parameter, $U_{e3} \simeq \theta_{\rm Cabibbo}/(3\sqrt2) \sim 0.05$, which should be observable in planned long baseline experiments.Comment: Final version of the paper as it will appear in JHEP

Rν\nuMDM and Lepton Flavor Violation

A model relating radiative seesaw and minimal dark matter mass scales without beyond the standard model (SM) gauge symmetry (R$\nu$MDM) is constructed. In addition to the SM particles, the R$\nu$MDM contains, a Majorana fermion multiplet $N_R$ and scalar multiplet $\chi$ that transform respectively as $(1,5,0)$ and $(1,6,-1/2)$ under the SM gauge group $SU(3)_C\times SU(2)_L\times U(1)_Y$. The neutral component $N_R^0$ plays the role of dark matter with a mass in the range of 9 to 10 TeV. This scale also sets the lower limit for the scale for the heavy degrees of freedom in $N_R$ and $\chi$ which generate light neutrino masses through the radiative seesaw mechanism. The model predicts an $N_R^0$-nucleus scattering cross section that would be accessible with future dark matter direct detection searches as well as observable effects in present and searches for charged lepton flavor violating processes, such as $l_i\to l_j \gamma$ and $\mu - e$ conversion.Comment: Latex 18 pages with 7 figures. Discussions added in dark matter section and a few references adde

Predictive Value of POSSUM and ACPGBI Scoring in Mortality and Morbidity of Colorectal Resection: A Case–Control Study

Contains fulltext : 97239.pdf (publisher's version ) (Open Access)BACKGROUND: Preoperative risk prediction to assess mortality and morbidity may be helpful to surgical decision making. The aim of this study was to compare mortality and morbidity of colorectal resections performed in a tertiary referral center with mortality and morbidity as predicted with physiological and operative score for enumeration of mortality and morbidity (POSSUM), Portsmouth POSSUM (P-POSSUM), and colorectal POSSUM (CR-POSSUM). The second aim of this study was to analyze the accuracy of different POSSUM scores in surgery performed for malignancy, inflammatory bowel diseases, and diverticulitis. POSSUM scoring was also evaluated in colorectal resection in acute vs. elective setting. In procedures performed for malignancy, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) score was assessed in the same way for comparison. METHODS: POSSUM, P-POSSUM, and CR-POSSUM predictor equations for mortality were applied in a retrospective case-control study to 734 patients who had undergone colorectal resection. The total group was assessed first. Second, the predictive value of outcome after surgery was assessed for malignancy (n = 386), inflammatory bowel diseases (n = 113), diverticulitis (n = 91), and other indications, e.g., trauma, endometriosis, volvulus, or ischemia (n = 144). Third, all subgroups were assessed in relation to the setting in which surgery was performed: acute or elective. In patients with malignancy, the ACPGBI score was calculated as well. In all groups, receiver operating characteristic (ROC) curves were constructed. RESULTS: POSSUM, P-POSSUM, and CR-POSSUM have a significant predictive value for outcome after colorectal surgery. Within the total population as well as in all four subgroups, there is no difference in the area under the curve between the POSSUM, P-POSSUM, and CR-POSSUM scores. In the subgroup analysis, smallest areas under the ROC curve are seen in operations performed for malignancy, which is significantly worse than for diverticulitis and in operations performed for other indications. For elective procedures, P-POSSUM and CR-POSSUM predict outcome significantly worse in patients operated for carcinoma than in patients with diverticulitis. In acute surgical interventions, CR-POSSUM predicts mortality better in diverticulitis than in patients operated for other indications. The ACPGBI score has a larger area under the curve than any of the POSSUM scores. Morbidity as predicted by POSSUM is most accurate in procedures for diverticulitis and worst when the indication is malignancy. CONCLUSION: The POSSUM scores predict outcome significantly better than can be expected by chance alone. Regarding the indication for surgery, each POSSUM score predicts outcome in patients operated for diverticulitis or other indications more accurately than for malignancy. The ACPGBI score is found to be superior to the various POSSUM scores in patients who have (elective) resection of colorectal malignancy

Hydrogen Sulfide Protects against Chemical Hypoxia-Induced Cytotoxicity and Inflammation in HaCaT Cells through Inhibition of ROS/NF-κB/COX-2 Pathway

Hydrogen sulfide (H2S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H2S protects human skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl2), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H2S) for 30 min before exposure to CoCl2 for 24 h significantly attenuated CoCl2-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl2-induced COX-2 overexpression and PGE2 secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H2S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl2-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl2. Notably, NAC, a ROS scavenger, conferred a similar protective effect of H2S against CoCl2-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H2S protects HaCaT cells against CoCl2-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway

Controlled intermittent shortening contractions of a muscle-tendon complex: muscle fibre damage and effects on force transmission from a single head of rat EDL

This study was performed to examine effects of prolonged (3 h) intermittent shortening (amplitude 2 mm) contractions (muscles were excited maximally) of head III of rat extensor digitorum longus muscle (EDL III) on indices of muscle damage and on force transmission within the intact anterior crural compartment. Three hours after the EDL III exercise, muscle fibre damage, as assessed by immunohistochemical staining of structural proteins (i.e. dystrophin, desmin, titin, laminin-2), was found in EDL, tibialis anterior (TA) and extensor hallucis longus (EHL) muscles. The damaged muscle fibres were not uniformly distributed throughout the muscle cross-sections, but were located predominantly near the interface of TA and EDL muscles as well as near intra- and extramuscular neurovascular tracts. In addition, changes were observed in desmin, muscle ankyrin repeat protein 1, and muscle LIM protein gene expression: significantly (P < 0.01) higher (1.3, 45.5 and 2.3-fold, respectively) transcript levels compared to the contralateral muscles. Post-EDL III exercise, length-distal force characteristics of EDL III were altered significantly (P < 0.05): at high EDL III lengths, active forces decreased and the length range between active slack length and optimum length increased. For all EDL III lengths tested, proximal passive and active force of EDL decreased. The slope of the EDL III length-TA + EHL force curve decreased, which indicates a decrease of the degree of intermuscular interaction between EDL III and TA + EHL. It is concluded that prolonged intermittent shortening contractions of a single head of multi-tendoned EDL muscle results in structural damage to muscle fibres as well as altered force transmission within the compartment. A possible role of myofascial force transmission is discussed. © Springer 2005