CP Violation in B and K Decays: 2003

These lectures give a brief description of CP violation in B and K meson decays with particular emphasize put on the determination of the CKM matrix. The following topics will be discussed: i) The CKM matrix, the unitarity triangle and general aspects of the theoretical framework, ii) Particle-antiparticle mixing and various types of CP violation, iii) Standard analysis of the unitarity triangle, iv) The ratio epsilon^prime/epsilon, v) The most important strategies for the determination of the angles $\alpha$, $\beta$ and $\gamma$ from B decays, vi) Rare decays $K^+\to\pi^+\nu\bar\nu$ and $K_L\to\pi^0\nu\bar\nu$ vii) Models with minimal flavour violation.Comment: Schladming lectures 2003, Main latex-file, 8 figures, 51 page

PERMANENT MAGNET QUADRUPOLE FOR THE 1-ST TANK OF LINAC-4 *

Abstract A rare-earth (REPM) ∅60 mm diameter, 45 mm long quadrupole for the LINAC-4 focusing channel with an integrated gradient of 2.3 T is described. Thin side washers are used for tuning the quad into specified gradient integral with ±0.5 % accuracy. The single washer contribution calculations are discussed. A method for limiting to 30 μm the magnetic axis offset in the REPM quad is discussed to exclude its compensation by the outer diameter machining before inserting into the drift tube. Nonlinearity of the field is less than 1 % in the reference range of 75 % of beam aperture at the central crosssection near the quad axis. The angular quadrupole arrangement in the drift tube will be provided by machining the main groove on the quad surface in the median plane with 1 mrad accuracy. Calculations of the longitudinal gradient distribution between two neighbour quadrupoles showed that some percents should be added to the nominal gradient in the beginning of the LINAC-4 focusing channel because of partial field compensation

Extracellular Vesicles Released by Cardiomyocytes in a Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers of Early Cardiac Injury

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury. Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content. Results—Treatment with DOX caused a significant increase in circulating EVs (DOX_EV) compared with saline-treated controls. DOX_EVs exhibited a higher level of 4-hydroxynonenal adducted proteins, a lipid peroxidation product linked to DOX-induced cardiotoxicity. Proteomic profiling of DOX_EVs revealed the distinctive presence of brain/heart, muscle, and liver isoforms of glycogen phosphorylase (GP), and their origins were verified to be heart, skeletal muscle, and liver, respectively. The presence of brain/heart GP (PYGB) in DOX_EVs correlated with a reduction of PYGB in heart, but not brain tissues. Manganese superoxide dismutase (MnSOD) overexpression, as well as pretreatment with cardioprotective agents and MnSOD mimetics, resulted in a reduction of EV-associated PYGB in mice treated with DOX. Kinetic studies indicated that EVs containing PYGB were released prior to the rise of cardiac troponin in the blood after DOX treatment, suggesting that PYGB is an early indicator of cardiac injury. Conclusion—EVs containing PYGB are an early and sensitive biomarker of cardiac injury

LASER PHYSICS LETTERS

Abstract: Raman spectroscopy offers a powerful alternative analytical method for the detection and identification of lipids/oil in biological samples, such as algae and fish. Recent research in the authors' groups, and experimental data only very recently published by us and a few other groups suggest that Raman spectroscopy can be exploited in instances where fast and accurate determination of the iodine value (associated with the degree of lipid unsaturation) is required. Here the current status of Raman spectroscopy applications on algae is reviewed, and particular attention is given to the efforts of identifying and selecting oil-rich algal strains for the potential mass production of commercial biofuels and for utilization in the food industry. Normalized intensity, a.u

A phase II study of glembatumumab vedotin for metastatic uveal melanoma

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease \u3e100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5-5.6), and the median overall survival was 11.9 months (95% CI 9.0-16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release

PACS: 32.30.-r, 32.60.+i, 32.70

Abstract: We have measured light shifts, also known as AC Stark shifts, as a function of laser intensity in cold Rubidium atoms by observing sub-natural linewidth gain and loss features in the transmission spectrum of a weak probe beam passing through the atomic sample. The observed energy-level shifts for atoms in a magneto-optical trap (MOT) are found to be consistently higher than that obtained in optical molasses (i.e., when the magnetic field gradient in the MOT is turned off). Using a simple model of a multilevel Rubidium atom interacting with pump and probe beams, we have calculated the theoretical light shift as a function of intensity. A comparison of these calculated values with the light shift data obtained for molasses reveals good agreement between experiment and theory. Further, our model elucidates the role of the Zeeman shifts arising from the magnetic field gradient in the observed probe transmission spectrum for the MOT. A qualitative plot of the transmission spectrum of a probe beam through a fictitious sample of cold J = 1 → J = 2 atoms showing probe absorption at the sum of the pump frequency ω pump and δ , where δ is the difference of the light shifts between the |J = 1,mJ = 0 and the |J = 1,mJ = ± 1 ground state Zeeman sublevels. Probe gain is depicted at ω pump -δ . Se

Neutrinoless Double Beta Decay in Gauge Theories

Neutrinoless double beta decay is a very important process both from the particle and nuclear physics point of view. Its observation will severely constrain the existing models and signal that the neutrinos are massive Majorana particles. From the elementary particle point of view it pops up in almost every model. In addition to the traditional mechanisms, like the neutrino mass, the admixture of right handed currents etc, it may occur due to the R-parity violating supersymmetric (SUSY) interactions. From the nuclear physics point of view it is challenging, because: 1) The relevant nuclei have complicated nuclear structure. 2) The energetically allowed transitions are exhaust a small part of all the strength. 3) One must cope with the short distance behavior of the transition operators, especially when the intermediate particles are heavy (eg in SUSY models). Thus novel effects, like the double beta decay of pions in flight between nucleons, have to be considered. 4) The intermediate momenta involved are about 100 MeV. Thus one has to take into account possible momentum dependent terms in the nucleon current. We find that, for the mass mechanism, such modifications of the nucleon current for light neutrinos reduce the nuclear matrix elements by about 25 per cent, almost regardless of the nuclear model. In the case of heavy neutrinos the effect is much larger and model dependent. Taking the above effects into account, the available nuclear matrix elements for the experimentally interesting nuclei A = 76, 82, 96, 100, 116, 128, 130, 136 and 150 and the experimental limits on the life times we have extracted new stringent limits on the average neutrino mass and on the R-parity violating coupling for various SUSY models.Comment: Latex, 24 pages, 1 postscript figure, uses iopconf.st

Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier

<p>Abstract</p> <p>Background</p> <p>Methotrexate (MTX) uptake is mediated by the reduced folate carrier (RFC). Defective drug uptake in association with decreased RFC expression is a common mechanism of MTX resistance in many tumor types. Heavy promoter methylation was previously identified as a basis for the complete silencing of RFC in MDA-MB-231 breast cancer cells, its role and prevalence in RFC transcription regulation are, however, not widely studied.</p> <p>Methods</p> <p>In the current study, RFC promoter methylation was assessed using methylation specific PCR in a panel of malignant cell lines (n = 8), including MDA-MB-231, and M805, a MTX resistant cell line directly established from the specimen of a patient with malignant fibrohistocytoma, whom received multiple doses of MTX. A quantitative approach of real-time PCR for measuring the extent of RFC promoter methylation was developed, and was validated by direct bisulfite genomic sequencing. RFC mRNA levels were determined by quantitative real-time RT-PCR and were related to the extent of promoter methylation in these cell lines.</p> <p>Results</p> <p>A partial promoter methylation and RFC mRNA down-regulation were observed in M805. Using the quantitative approach, a reverse correlation (correlation coefficient = -0.59, <it>p </it>< 0.05) was identified between the promoter methylation and RFC mRNA levels in this a panel of malignant cell lines.</p> <p>Conclusion</p> <p>This study further suggests that promoter methylation is a potential basis for MTX resistance. The quantitative correlation identified in this study implies that promoter methylation is possibly a mechanism involved in the fine regulation of RFC transcription.</p