2,295 research outputs found
Flavor in Minimal Conformal Technicolor
We construct a complete, realistic, and natural UV completion of minimal
conformal technicolor that explains the origin of quark and lepton masses and
mixing angles. As in "bosonic technicolor", we embed conformal technicolor in a
supersymmetric theory, with supersymmetry broken at a high scale. The exchange
of heavy scalar doublets generates higher-dimension interactions between
technifermions and quarks and leptons that give rise to quark and lepton masses
at the TeV scale. Obtaining a sufficiently large top quark mass requires strong
dynamics at the supersymmetry breaking scale in both the top and technicolor
sectors. This is natural if the theory above the supersymmetry breaking also
has strong conformal dynamics. We present two models in which the strong top
dynamics is realized in different ways. In both models, constraints from
flavor-changing effects can be easily satisfied. The effective theory below the
supersymmetry breaking scale is minimal conformal technicolor with an
additional light technicolor gaugino. We argue that this light gaugino is a
general consequence of conformal technicolor embedded into a supersymmetric
theory. If the gaugino has mass below the TeV scale it will give rise to an
additional pseudo Nambu-Goldstone boson that is observable at the LHC.Comment: 37 pages; references adde
The Maximal Inverse Seesaw from Operator and Oscillating Asymmetric Sneutrino Dark Matter
The maximal supersymmetric inverse seesaw mechanism (MSIS)
provides a natural way to relate asymmetric dark matter (ADM) with neutrino
physics. In this paper we point out that, MSIS is a natural outcome if one
dynamically realizes the inverse seesaw mechanism in the next-to minimal
supersymmetric standard model (NMSSM) via the dimension-five operator
, with the NMSSM singlet developing TeV scale VEV; it
slightly violates lepton number due to the suppression by the fundamental scale
, thus preserving maximally. The resulting sneutrino is a
distinguishable ADM candidate, oscillating and favored to have weak scale mass.
A fairly large annihilating cross section of such a heavy ADM is available due
to the presence of singlet.Comment: journal versio
Asymmetric Origin for Gravitino Relic Density in the Hybrid Gravity-Gauge Mediated Supersymmetry Breaking
We propose the hybrid gravity-gauge mediated supersymmetry breaking where the
gravitino mass is about several GeV. The strong constraints on supersymmetry
viable parameter space from the CMS and ATLAS experiments at the LHC can be
relaxed due to the heavy colored supersymmetric particles, and it is consistent
with null results in the dark matter (DM) direct search experiments such as
XENON100. In particular, the possible maximal flavor and CP violations from the
relatively small gravity mediation may naturally account for the recent LHCb
anomaly. In addition, because the gravitino mass is around the asymmetric DM
mass, we propose the asymmetric origin of the gravitino relic density and solve
the cosmological coincident problem on the DM and baryon densities \Omega_{\rm
DM}:\Omega_{B}\approx 5:1. The gravitino relic density arises from asymmetric
metastable particle (AMP) late decay. However, we show that there is no AMP
candidate in the minimal supersymmetric Standard Model (SM) due to the robust
gaugino/Higgsino mediated wash-out effects. Interestingly, AMP can be realized
in the well motivated supersymmetric SMs with vector-like particles or
continuous U(1)_R symmetry. Especially, the lightest CP-even Higgs boson mass
can be lifted in the supersymmetric SMs with vector-like particles.Comment: RevTex4, 21 pages, 1 figure, minor corrections, JHEP versio
Asymmetric Dark Matter from Leptogenesis
We present a new realization of asymmetric dark matter in which the dark
matter and lepton asymmetries are generated simultaneously through two-sector
leptogenesis. The right-handed neutrinos couple both to the Standard Model and
to a hidden sector where the dark matter resides. This framework explains the
lepton asymmetry, dark matter abundance and neutrino masses all at once. In
contrast to previous realizations of asymmetric dark matter, the model allows
for a wide range of dark matter masses, from keV to 10 TeV. In particular, very
light dark matter can be accommodated without violating experimental
constraints. We discuss several variants of our model that highlight
interesting phenomenological possibilities. In one, late decays repopulate the
symmetric dark matter component, providing a new mechanism for generating a
large annihilation rate at the present epoch and allowing for mixed warm/cold
dark matter. In a second scenario, dark matter mixes with the active neutrinos,
thus presenting a distinct method to populate sterile neutrino dark matter
through leptogenesis. At late times, oscillations and dark matter decays lead
to interesting indirect detection signals.Comment: 32 pages + appendix, references added, minor change
Targeted inhibition of mitochondrial Hsp90 suppresses localised and metastatic prostate cancer growth in a genetic mouse model of disease
BACKGROUND: The molecular chaperone heat shock protein-90 (Hsp90) is a promising cancer drug target, but current Hsp90-based therapy has so far shown limited activity in the clinic.
METHODS: We tested the efficacy of a novel mitochondrial-targeted, small-molecule Hsp90 inhibitor, Gamitrinib (GA mitochondrial matrix inhibitor), in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The TRAMP mice receiving 3-week or 5-week systemic treatment with Gamitrinib were evaluated for localised or metastatic prostate cancer, prostatic intraepithelial neoplasia (PIN) or localised inflammation using magnetic resonance imaging, histology and immunohistochemistry. Treatment safety was assessed histologically in organs collected at the end of treatment. The effect of Gamitrinib on mitochondrial dysfunction was studied in RM1 cells isolated from TRAMP tumours.
RESULTS: Systemic administration of Gamitrinib to TRAMP mice inhibited the formation of localised prostate tumours of neuroendocrine or adenocarcinoma origin, as well as metastatic prostate cancer to abdominal lymph nodes and liver. The Gamitrinib treatment had no effect on PIN or prostatic inflammation, and caused no significant animal weight loss or organ toxicity. Mechanistically, Gamitrinib triggered acute mitochondrial dysfunction in RM1 cells, with loss of organelle inner membrane potential and release of cytochrome-c in the cytosol.
CONCLUSIONS: The Gamitrinib has pre-clinical activity and favourable tolerability in a genetic model of localised and metastatic prostate cancer in immunocompetent mice. Selective targeting of mitochondrial Hsp90 could provide novel molecular therapy for patients with advanced prostate cancer
Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry
It is well known that R-symmetric models dramatically alleviate the SUSY
flavor and CP problems. We study particular modifications of existing
R-symmetric models which share the solution to the above problems, and have
interesting consequences for electroweak baryogenesis and the Dark Matter (DM)
content of the universe. In particular, we find that it is naturally possible
to have a strongly first-order electroweak phase transition while
simultaneously relaxing the tension with EDM experiments. The R-symmetry (and
its small breaking) implies that the gauginos (and the neutralino LSP) are
pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The
singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role
in making the electroweak phase transition strongly first-order. The
pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac
particle during freeze-out, but like a Majorana particle for annihilation today
and in scattering against nuclei, thus being consistent with current
constraints. Assuming a standard cosmology, it is possible to simultaneously
have a strongly first-order phase transition conducive to baryogenesis and have
the LSP provide the full DM relic abundance, in part of the allowed parameter
space. However, other possibilities for DM also exist, which are discussed. It
is expected that upcoming direct DM searches as well as neutrino signals from
DM annihilation in the Sun will be sensitive to this class of models.
Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure
The feasibility of canine rabies elimination in Africa: dispelling doubts with data
<p><b>Background:</b> Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.</p>
<p><b>Methodology/Principal Findings:</b> This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention.</p>
<p><b>Conclusions/Significance:</b> We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.</p>
Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice
INTRODUCTION: Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. METHOD: Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. RESULTS: The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4–6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at multiple sites simultaneously. Ex vivo imaging data from sampled tissues verified both skeletal and multiple soft tissue tumor metastasis. CONCLUSION: This study characterized two new bioluminescent MDA-MB-231-luc human breast carcinoma cell lines with enhanced tumor growth and widespread metastasis in mice. Their application to current xenograft models of breast cancer offers rapid and highly sensitive detection options for preclinical assessment of anticancer therapies in vivo
Evaluation of preoperative intra-aortic balloon pump in coronary patients with severe left ventricular dysfunction undergoing OPCAB surgery: early and mid-term outcomes
<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to evaluate the safety and the cost-effectiveness of using preoperative IABP as support compared with postoperative IABP treatment in coronary patients with severe left ventricular dysfunction (SLVD) who is undergoing off-pump coronary artery bypass surgery (OPCAB), including early outcomes, hospital mortality and morbidity, and mid-term follow-up outcomes.</p> <p>Methods</p> <p>Between March 2000 and December 2008, we prospectively and randomly studied the insertion of preoperative IABP in 115 (7.4%) and postoperative IABP in 106 (6.8%) of the 1560 consecutive patients. Group A is preoperative IABP therapy. Group B is postoperative IABP therapy.</p> <p>Results</p> <p>There was no significant difference in the number of grafts used between the two groups. Completeness of revascularization did not differ between the two groups. The statistically significant difference was hospital mortality (2.6% in group A vs. 3.8% in group B) (<it>p </it>< 0.05). And there was significant reduction in postoperative low cardiac output, malignant arrhythmia, acute renal failure and length of stay in ICU in group A, compared with group B (<it>p </it>< 0.05). In the two groups, six-, 12-, 24- and 48-month survival rates were similar. In the study the degree of improvement in angina and quality of life did not differ significantly between the two groups.</p> <p>Conclusion</p> <p>The use of preoperative IABP in SLVD patients undergoing OPCAB is of safety and effectiveness. The combined use of preoperative IABP and OPCAB allows complete revascularization in SLVD patients with an important reduction in operative mortality and excellent mid-term results.</p
Overexpression of Nrdp1 in the Heart Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice
BACKGROUND: Cardiac cell death and generation of oxidative stress contribute to doxorubicin (DOX)-induced cardiac dysfunction. E3 ligase Nrdp1 plays a critical role in the regulation of cell apoptosis, inflammation and production of reactive oxygen species (ROS), which may contribute to heart failure. However, the role of Nrdp1 in DOX-induced cardiac injury remains to be determined. METHODS AND RESULTS: We examined the effect of Nrdp1 overexpression with DOX treatment in rat neonatal cardiomyocytes and mouse heart tissue. Cardiomyocytes were infected with adenovirus containing GFP (Ad-GFP), Nrdp1 wild-type (Ad-Nrdp1) or the dominant-negative form of Nrdp1 (Ad-Dn-Nrdp1), then treated with DOX for 24 hr. DOX treatment increased cell death and apoptosis, with Ad-Nrdp1 infection enhancing these actions but Ad-Dn-Nrdp1 infection attenuating these effects. Furthermore, 5 days after a single injection of DOX (20 mg/kg, intraperitoneally), Nrdp1 transgenic mice (TG) showed decreased cardiac function and increased apoptosis, autophagy and oxidative stress as compared with wild-type (WT) mice (P<0.01). Survival rate was significantly lower in Nrdp1 TG mice than in WT mice 10 days after DOX injection (P<0.01). CONCLUSIONS/SIGNIFICANCE: These results were associated with decreased activation of Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. Nrdp1 may be a key mediator in the development of cardiac dysfunction after DOX treatment and associated with inhibition of Akt, ERK1/2 and STAT3. Nrdp1 may be a new therapeutic target in protecting against the cardiotoxic effects of DOX
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