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1.
Phys Rev Lett ; 131(5): 051201, 2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37595214

ABSTRACT

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

2.
Phys Rev Lett ; 124(13): 131101, 2020 Apr 03.
Article in English | MEDLINE | ID: mdl-32302173

ABSTRACT

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

3.
Oncogene ; 35(32): 4269-81, 2016 08 11.
Article in English | MEDLINE | ID: mdl-26776161

ABSTRACT

Constitutive activation of the antiapoptotic nuclear factor-κB (NF-κB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of ß-catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3ß to oncogenic CARMA1. Recruitment of the ß-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-κB activation and promoted the stabilization of ß-catenin. The ß-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated ß-catenin expression. In line, ß-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased ß-catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF-dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, ß-catenin enhanced expression of immunosuppressive interleukin-10 and suppressed antitumoral CCL3, indicating that ß-catenin can induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and ß-catenin signaling by gain-of-function mutations in CARMA1 augments WNT stimulation and is required for regulating the expression of distinct NF-κB target genes to trigger cell-intrinsic and extrinsic processes that promote DLBCL lymphomagenesis.


Subject(s)
CARD Signaling Adaptor Proteins/genetics , CARD Signaling Adaptor Proteins/metabolism , Carcinogenesis , Guanylate Cyclase/genetics , Guanylate Cyclase/metabolism , Lymphoma, Large B-Cell, Diffuse/metabolism , NF-kappa B/metabolism , Signal Transduction , beta Catenin/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Mutation , Protein Stability , TCF Transcription Factors/metabolism , rho GTP-Binding Proteins/metabolism
4.
Br J Surg ; 100(1): 130-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23132620

ABSTRACT

BACKGROUND: Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy. METHODS: Data for patients who had liver resection for HCC without cirrhosis between January 1996 and March 2011 were retrieved retrospectively using a prospective database containing information on all patients who underwent hepatectomy for HCC. Patient and tumour characteristics were analysed for influence on overall and disease-free survival to identify prognostic factors by univariable and multivariable analysis. RESULTS: The 1-, 3- and 5-year overall survival rates after resection with curative intent for HCC without cirrhosis were 84, 66 and 50 per cent respectively. Disease-free survival rates were 69, 53 and 42 per cent respectively. The 90-day mortality rate was 4·5 per cent (5 of 110 patients). Surgical radicality and growth pattern of the tumour were independent prognostic factors for overall survival. Disease-free survival after resection with curative intent was independently affected by growth pattern and by the number and size of tumour nodules. CONCLUSION: Liver resection for HCC without cirrhosis carries a low perioperative risk and excellent long-term outcome if radical resection is achieved.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/mortality , Liver Neoplasms/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/secondary , Disease-Free Survival , Female , Follow-Up Studies , Humans , Liver/surgery , Liver Cirrhosis/complications , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Lymphatic Metastasis , Male , Multivariate Analysis , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Rate , Treatment Outcome
5.
Phys Rev Lett ; 101(22): 221101, 2008 Nov 28.
Article in English | MEDLINE | ID: mdl-19113471

ABSTRACT

The 7 year data set of the Milagro TeV observatory contains 2.2 x 10(11) events of which most are due to hadronic cosmic rays. These data are searched for evidence of intermediate scale structure. Excess emission on angular scales of approximately 10 degrees has been found in two localized regions of unknown origin with greater than 12sigma significance. Both regions are inconsistent with pure gamma-ray emission with high confidence. One of the regions has a different energy spectrum than the isotropic cosmic-ray flux at a level of 4.6sigma, and it is consistent with hard spectrum protons with an exponential cutoff, with the most significant excess at approximately 10 TeV. Potential causes of these excesses are explored, but no compelling explanations are found.

6.
Phys Rev Lett ; 95(25): 251103, 2005 Dec 16.
Article in English | MEDLINE | ID: mdl-16384445

ABSTRACT

Gamma-ray emission from a narrow band at the galactic equator has previously been detected up to 30 GeV. We report evidence for a TeV gamma-ray signal from a region of the galactic plane by Milagro, a large-field-of-view water Cherenkov detector for extensive air showers. An excess with a significance of 4.5 standard deviations has been observed from the region of galactic longitude l E (40 degrees, 100 degrees) and latitude /b/ < 5 degrees. Under the assumption of a simple power law spectrum, with no cutoff in the EGRET-Milagro energy range, the measured integral flux is phi gamma(>3.5 TeV) = (6.4 +/- 1.4 +/- 2.1) x 10(-11) cm(-2) s(-1) sr(-1). This flux is consistent with an extrapolation of the EGRET spectrum between 1 and 30 GeV in this galactic region.

7.
J Oral Rehabil ; 30(11): 1053-61, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14641668

ABSTRACT

The purpose of this in vitro study was to evaluate crown retention after using different sealing systems on prepared dentine. Ca(OH)2 suspension was used in comparison with three adhesive bonding systems (Gluma Desensitizer, Optibond FL, Prompt L-Pop). Extracted human premolars were uniformly prepared with the use of a special parallelometer (11 degrees taper, 4 mm axial length). Groups of 20 teeth each were treated with each sealing system. Then crowns were fabricated and temporarily cemented twice. Finally the abutments were cleaned and the crowns were cemented with a glass-ionomer cement Ketac-Cem. Subgroups of 10 crowns were removed with a universal testing machine following storage in distilled water either for 3 days or for 150 days. Prior to dislodging, the crowns of both groups were subjected to chewing simulation. The mean dislodgement stresses in MPa were between 4.9 and 6.9. A range test of Student-Newmann-Keuls revealed significant differences between Ca(OH)2 and Optibond FL (P < 0.05), while the storage time had no significant effect. The level of microleakage increased significantly with storage time (P < 0.05). It is concluded, that the use of Gluma Desensitizer and Prompt L-Pop did not affect crown retention as compared with Ca(OH)2, thus may be used in combination with glass-ionomer cement to desensitize prepared teeth.


Subject(s)
Calcium Hydroxide/pharmacology , Crowns , Dental Prosthesis Retention , Dentin Sensitivity/drug therapy , Dentin-Bonding Agents/pharmacology , Fatty Acids/pharmacology , Analysis of Variance , Bicuspid , Dental Bonding/methods , Dental Cements/pharmacology , Dental Restoration Failure , Dentin , Glass Ionomer Cements , Glutaral/pharmacology , Humans , Methacrylates/pharmacology , Resin Cements/pharmacology , Stress, Mechanical
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