Curability of Multiple Myeloma

Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987–1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12–22 years). These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure

Screening Masses of Hot SU(2) Gauge Theory from the 3D Adjoint Higgs Model

We study the Landau gauge propagators of the lattice SU(2) 3d adjoint Higgs model, considered as an effective theory of high temperature 4d SU(2) gauge theory. From the long distance behaviour of the propagators we extract the screening masses. It is shown that the pole masses extracted from the propagators agree well with the screening masses obtained recently in finite temperature SU(2) theory. The relation of the propagator masses to the masses extracted from gauge invariant correlators is also discussed. In so-called lambda gauges non-perturbative evidence is given for the gauge independence of pole masses within this class of gauges.Comment: Talk given at SEWM98 Conference, Copenhagen, December 199

The magnetic mass of transverse gluon, the B-meson weak decay vertex and the triality symmetry of octonion

With an assumption that in the Yang-Mills Lagrangian, a left-handed fermion and a right-handed fermion both expressed as quaternion make an octonion which possesses the triality symmetry, I calculate the magnetic mass of the transverse self-dual gluon from three loop diagram, in which a heavy quark pair is created and two self-dual gluons are interchanged. The magnetic mass of the transverse gluon depends on the mass of the pair created quarks, and in the case of charmed quark pair creation, the magnetic mass $m_{mag}$ becomes approximately equal to $T_c$ at $T=T_c\sim 1.14\Lambda_{\bar{MS}}\sim 260$MeV. A possible time-like magnetic gluon mass from two self-dual gluon exchange is derived, and corrections in the B-meson weak decay vertices from the two self-dual gluon exchange are also evaluated.Comment: 22 pages, 9 figure

NNLO hard-thermal-loop thermodynamics for QCD

We calculate the thermodynamic functions of a quark-gluon plasma for general N_c and N_f to three-loop order using hard-thermal-loop perturbation theory. At this order, all the ultraviolet divergences can be absorbed into renormalizations of the vacuum, the HTL mass parameters, and the strong coupling constant.We show that at three loops, the results for the pressure and trace anomaly are in very good agreement with recent lattice data down to temperatures T~2T_c.Comment: 8 pages, 2 fig

Bodeker's Effective Theory: From Langevin Dynamics to Dyson-Schwinger Equations

The dynamics of weakly coupled, non-abelian gauge fields at high temperature is non-perturbative if the characteristic momentum scale is of order |k|~ g^2 T. Such a situation is typical for the processes of electroweak baryon number violation in the early Universe. Bodeker has derived an effective theory that describes the dynamics of the soft field modes by means of a Langevin equation. This effective theory has been used for lattice calculations so far. In this work we provide a complementary, more analytic approach based on Dyson-Schwinger equations. Using methods known from stochastic quantisation, we recast Bodeker's Langevin equation in the form of a field theoretic path integral. We introduce gauge ghosts in order to help control possible gauge artefacts that might appear after truncation, and which leads to a BRST symmetric formulation and to corresponding Ward identities. A second set of Ward identities, reflecting the origin of the theory in a stochastic differential equation, is also obtained. Finally Dyson-Schwinger equations are derived.Comment: 56 page

Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs

Aim Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. Methods and results We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. Conclusion These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clini

The long noncoding RNA Wisper controls cardiac fibrosis and remodeling

Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of cardiac development and disease. However, our understanding of the importance of these molecules in cardiac fibrosis is limited. Using an integrated genomic screen, we identified Wisper (Wisp2 super-enhancer–associated RNA) as a cardiac fibroblast–enriched lncRNA that regulates cardiac fibrosis after injury. Wisper expression was correlated with cardiac fibrosis both in a murine model of myocardial infarction (MI) and in heart tissue from human patients suffering from aortic stenosis. Loss-of-function approaches in vitro using modified antisense oligonucleotides (ASOs) demonstrated that Wisper is a specific regulator of cardiac fibroblast proliferation, migration, and survival. Accordingly, ASO-mediated silencing of Wisper in vivo attenuated MI-induced fibrosis and cardiac dysfunction. Functionally, Wisper regulates cardiac fibroblast gene expression programs critical for cell identity, extracellular matrix deposition, proliferation, and survival. In addition, its association with TIA1-related protein allows it to control the expression of a profibrotic form of lysyl hydroxylase 2, implicated in collagen cross-linking and stabilization of the matrix. Together, our findings identify Wisper as a cardiac fibroblast–enriched super-enhancer–associated lncRNA that represents an attractive therapeutic target to reduce the pathological development of cardiac fibrosis in response to MI and prevent adverse remodeling in the damaged heart

Palladium-catalyzed heteroallylation of unactivated alkenes – synthesis of citalopram

A palladium-catalyzed difunctionalization of unactivated alkenes with tethered nucleophiles is reported. The versatile reaction occurs with simple allylic halides and can be carried out under air. The methodology provides rapid access to a wide array of desirable heterocyclic targets, as illustrated by a concise synthesis of the widely prescribed antidepressant citalopram

The Finite Temperature SU(2) Savvidy Model with a Non-trivial Polyakov Loop

We calculate the complete one-loop effective potential for SU(2) gauge bosons at temperature T as a function of two variables: phi, the angle associated with a non-trivial Polyakov loop, and H, a constant background chromomagnetic field. Using techniques broadly applicable to finite temperature field theories, we develop both low and high temperature expansions. At low temperatures, the real part of the effective potential V_R indicates a rich phase structure, with a discontinuous alternation between confined (phi=pi) and deconfined phases (phi=0). The background field H moves slowly upward from its zero-temperature value as T increases, in such a way that sqrt(gH)/(pi T) is approximately an integer. Beyond a certain temperature on the order of sqrt(gH), the deconfined phase is always preferred. At high temperatures, where asymptotic freedom applies, the deconfined phase phi=0 is always preferred, and sqrt(gH) is of order g^2(T)T. The imaginary part of the effective potential is non-zero at the global minimum of V_R for all temperatures. A non-perturbative magnetic screening mass of the form M_m = cg^2(T)T with a sufficiently large coefficient c removes this instability at high temperature, leading to a stable high-temperature phase with phi=0 and H=0, characteristic of a weakly-interacting gas of gauge particles. The value of M_m obtained is comparable with lattice estimates.Comment: 28 pages, 5 eps figures; RevTeX 3 with graphic

A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma

BACKGROUND Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria ofthe European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS Of 193 patients who could be evaluated, 92 percent had been treated with three or more ofthe major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immuno-fixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy