β-lapachone induces growth inhibition and apoptosis in bladder cancer cells by modulation of BCL-2 family and activation of caspases

Aim: To study in vitro the molecular mechanism of apoptosis caused by b-lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae). Materials and Methods: The study was carried out on human bladder carcinoma T24 cell line. Determination of cell viability was done using trypan blue exclusion method, apoptosis quantitative estimation — by DAPI staining and agarose gel electrophoresis for DNA fragmentation. Flow cytometry analysis, RT-PCR and Western blot analysis, colorimetric assay of caspase activity were applied as well. Results: It was found that in micromolar range of concentrations b-lapachone inhibited the viability of T24 cells by inducing apoptosis, which could be proved by formation of apoptotic bodies and DNA fragmentation. Treatment of T24 cells with b-lapachone resulted in a down-regulation of Bcl-2 expression and up-regulation of Bax expression. b-lapachone-induced apoptosis was also associated with activation of caspase-3 and caspase-9, inhibition of IAP expression, and degradation of poly (ADP-ribose) polymerase, phospholipase C-g1 and b-catenin proteins. At the same time Fas and FasL levels were inhibited upon treatment with b-lapachone in a concentration-dependent manner. Conclusion: b-lapachone-induced apoptosis in T24 cells is mediated, at least in part, by the mitochondrial-signaling pathway.Цель: изучить механизмы апоптоза клеток карциномы мочевого пузыря человека Т24 при действии β-лапакона, хинона из коры дерева Tabebuia avellanedae. Материалы и методы: для определения жизнеспособности клеток использовали окраску трипановым синим; окрашивание DAPI и электрофоретический анализ фрагментации ДНК в агарозном геле, метод проточной цитометрии (для количественной оценки апоптоза); полимеразную цепную реакцию в режиме реального времени (РВ-ПЦР) и Вестерн блот-анализ (для оценки уровня экспрессии генов и белков), а также колориметрический анализ активности каспаз. Результаты: выявлено, что в микромолярных концентрациях β-лапакон понижает жизне- способность клеток линии Т24 путем активации апоптоза, что подтверждается формированием апоптотических тел и фрагментацией ДНК. Результаты РВ-ПЦР и иммуноблоттинга указывают на то, что обработка клеток β-лапаконом приводит к снижению экспрессии Bcl-2 и к активации Bax. Апоптоз, индуцированный β-лапаконом, также сопровож- дается активацией каспаз -3­­ и -9, ингибированием экспрессии семейства IAP, а также деградацией поли-(ADP-рибозо) полимеразы, фосфатазы C-γ1 и β-катенина. Тем не менее, уровень экспрессии Fas и FasL снижался при увеличении концентрации β-лапакона. Выводы: апоптоз, индуцированный при действии β-лапакона в клетках Т24, может быть час- тично опосредован митохондриальным сигнальным каскадом

Specific Heat Discontinuity in Impure Two-Band Superconductors

The Ginzburg-Landau coefficients, and the jump of the specific heat are calculated for a disordered two-band superconductor. We start with the analysis of a more general case arbitrary anisotropy. While the specific heat discontinuity at the critical temperature T_c decreases with increasing disorder, its ratio to the normal state specific heat at T_c increases and slowly converges to the isotropic value. For a strong disorder the deviation from the isotropic value is proportional to the elastic electron scattering time. In the case of a two-band superconductor we apply a simplified model of the interaction independent on momentum within a band. In the framework of this model all thermodynamic values can be found explicitly at any value of the scattering rate. This solution explains the sample dependence of the specific heat discontinuity in MgB_2 and the influence of the disorder on the critical temperature.Comment: New results relate to two-band superconductors, 9 pages, 2 figure

Ginzburg-Landau theory of vortices in a multi-gap superconductor

The Ginzburg-Landau functional for a two-gap superconductor is derived within the weak-coupling BCS model. The two-gap Ginzburg-Landau theory is, then, applied to investigate various magnetic properties of MgB2 including an upturn temperature dependence of the transverse upper critical field and a core structure of an isolated vortex. Orientation of vortex lattice relative to crystallographic axes is studied for magnetic fields parallel to the c-axis. A peculiar 30-degree rotation of the vortex lattice with increasing strength of an applied field observed by neutron scattering is attributed to the multi-gap nature of superconductivity in MgB2.Comment: 11 page

Can R-parity violation explain the LSND data as well?

The recent Super-Kamiokande data now admit only one type of mass hierarchy in a framework with three active and one sterile neutrinos. We show that neutrino masses and mixings generated by R-parity-violating couplings, with values within their experimental upper limits, are capable of reproducing this hierarchy, explaining all neutrino data particularly after including the LSND results.Comment: 7 pages, Latex, 3 PS figures; in v2 a few clarifying remarks included and two references added (to appear in Physical Review D

Supersymmetric Seesaw without Singlet Neutrinos: Neutrino Masses and Lepton-Flavour Violation

We consider the supersymmetric seesaw mechanism induced by the exchange of heavy SU(2)_W triplet states, rather than `right-handed' neutrino singlets, to generate neutrino masses. We show that in this scenario the neutrino flavour structure tested at low-energy in the atmospheric and solar neutrino experiments is directly inherited from the neutrino Yukawa couplings to the triplets. This allows us to predict the ratio of the tau --> mu gamma (or tau --> e gamma) and mu --> e gamma decay rates in terms of the low-energy neutrino parameters. Moreover, once the model is embedded in a grand unified model, quark-flavour violation can be linked to lepton-flavour violation.Comment: 26 LaTeX pages, 10 postscript figures, uses epsfig and axodraw. Comments and references adde

Phenomenology of flavor-mediated supersymmetry breaking

The phenomenology of a new economical SUSY model that utilizes dynamical SUSY breaking and gauge-mediation (GM) for the generation of the sparticle spectrum and the hierarchy of fermion masses is discussed. Similarities between the communication of SUSY breaking through a messenger sector, and the generation of flavor using the Froggatt-Nielsen (FN) mechanism are exploited, leading to the identification of vector-like messenger fields with FN fields, and the messenger U(1) as a flavor symmetry. An immediate consequence is that the first and second generation scalars acquire flavor-dependent masses, but do not violate FCNC bounds since their mass scale, consistent with effective SUSY, is of order 10 TeV. We define and advocate a minimal flavor-mediated model (MFMM), recently introduced in the literature, that successfully accommodates the small flavor-breaking parameters of the standard model using order one couplings and ratios of flavon field vevs. The mediation of SUSY breaking occurs via two-loop log-enhanced GM contributions, as well as several one-loop and two-loop Yukawa-mediated contributions for which we provide analytical expressions. The MFMM is parameterized by a small set of masses and couplings, with values restricted by several model constraints and experimental data. The next-to-lightest sparticle (NLSP) always has a decay length that is larger than the scale of a detector, and is either the lightest stau or the lightest neutralino. Similar to ordinary GM models, the best collider search strategies are, respectively, inclusive production of at least one highly ionizing track, or events with many taus plus missing energy. In addition, D^0 - \bar{D}^0 mixing is also a generic low energy signal. Finally, the dynamical generation of the neutrino masses is briefly discussed.Comment: 54 pages, LaTeX, 8 figure

Newly uncovered physics of MHD instabilities using 2-D electron cyclotron emission imaging system in toroidal plasmas

Validation of physics models using the newly uncovered physics with a 2-D electron cyclotron emission imaging (ECEi) system for magnetic fusion plasmas has either enhanced the confidence or substantially improved the modeling capability. The discarded "full reconnection model" in sawtooth instability is vindicated and established that symmetry and magnetic shear of the 1/1 kink mode are critical parameters in sawtooth instability. For the 2/1 instability, it is demonstrated that the 2-D data can determine critical physics parameters with a high confidence and the measured anisotropic distribution of the turbulence and its flow in presence of the 2/1 island is validated by the modelled potential and gyro-kinetic calculation. The validation process of the measured reversed-shear Alfveneigenmode (RSAE) structures has improved deficiencies of prior models. The 2-D images of internal structure of the ELMs and turbulence induced by the resonant magnetic perturbation (RMP) have provided an opportunity to establish firm physics basis of the ELM instability and role of RMPs. The importance of symmetry in determining the reconnection time scale and role of magnetic shear of the 1/1 kink mode in sawtooth instability may be relevant to the underlying physics of the violent kink instability of the filament ropes in a solar flare

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)

New Medical Device and Therapeutic Approvals in Otolaryngology: State of the Art Review of 2021

Objective To evaluate new medical devices and drugs pertinent to otolaryngology-head and neck surgery that were approved by the Food and Drug Administration (FDA) in 2021.Data SourcesPublicly available FDA device and drug approvals from ENT (ear, nose, and throat), anesthesia, neurosurgery, plastic surgery, and general surgery FDA committees. Review Methods FDA device and therapeutic approvals were identified and reviewed by members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee. Two independent reviewers assessed the relevance of devices and drugs to otolaryngologists. Medical devices and drugs were then allocated to their respective subspecialty fields for critical review based on available scientific literature. Conclusions The Medical Devices and Drugs Committee reviewed 1153 devices and 52 novel drugs that received FDA approval in 2021 (67 ENT, 106 anesthesia, 618 general surgery and plastic surgery, 362 neurosurgery). Twenty-three devices and 1 therapeutic agent relevant to otolaryngology were included in the state of the art review. Advances spanned all subspecialties, including over-the-counter hearing aid options in otology, expanding treatment options for rhinitis in rhinology, innovative laser-safe endotracheal tubes in laryngology, novel facial rejuvenation and implant technology in facial plastic surgery, and advances in noninvasive and surgical treatment options for obstructive sleep apnea. Implications for Practice FDA approvals for new technology and pharmaceuticals present new opportunities across subspecialties in otolaryngology. Clinicians? nuanced understanding of the safety, advantages, and limitations of these innovations ensures ongoing progress in patient care