Fluctuations in granular gases

A driven granular material, e.g. a vibrated box full of sand, is a stationary system which may be very far from equilibrium. The standard equilibrium statistical mechanics is therefore inadequate to describe fluctuations in such a system. Here we present numerical and analytical results concerning energy and injected power fluctuations. In the first part we explain how the study of the probability density function (pdf) of the fluctuations of total energy is related to the characterization of velocity correlations. Two different regimes are addressed: the gas driven at the boundaries and the homogeneously driven gas. In a granular gas, due to non-Gaussianity of the velocity pdf or lack of homogeneity in hydrodynamics profiles, even in the absence of velocity correlations, the fluctuations of total energy are non-trivial and may lead to erroneous conclusions about the role of correlations. In the second part of the chapter we take into consideration the fluctuations of injected power in driven granular gas models. Recently, real and numerical experiments have been interpreted as evidence that the fluctuations of power injection seem to satisfy the Gallavotti-Cohen Fluctuation Relation. We will discuss an alternative interpretation of such results which invalidates the Gallavotti-Cohen symmetry. Moreover, starting from the Liouville equation and using techniques from large deviation theory, the general validity of a Fluctuation Relation for power injection in driven granular gases is questioned. Finally a functional is defined using the Lebowitz-Spohn approach for Markov processes applied to the linear inelastic Boltzmann equation relevant to describe the motion of a tracer particle. Such a functional results to be different from injected power and to satisfy a Fluctuation Relation.Comment: 40 pages, 18 figure

Cancer treatment: the combination of vaccination with other therapies

Harnessing of the immune system by the development of ‘therapeutic’ vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending on the specific chemotherapeutics. Also, chemotherapy represents one of several options available for clearance of CD4+ Foxp3+ regulatory T cells. Moreover, therapies based on monoclonal antibodies may have synergistic potential in combination with vaccination, both when used for targeting of tumor cells and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

Interplay of LFV and slepton mass splittings at the LHC as a probe of the SUSY seesaw

We study the impact of a type-I SUSY seesaw concerning lepton flavour violation (LFV) both at low-energies and at the LHC. The study of the di-lepton invariant mass distribution at the LHC allows to reconstruct some of the masses of the different sparticles involved in a decay chain. In particular, the combination with other observables renders feasible the reconstruction of the masses of the intermediate sleptons involved in $\chi_2^0\to \tilde \ell \,\ell \to \ell \,\ell\,\chi_1^0$ decays. Slepton mass splittings can be either interpreted as a signal of non-universality in the SUSY soft breaking-terms (signalling a deviation from constrained scenarios as the cMSSM) or as being due to the violation of lepton flavour. In the latter case, in addition to these high-energy processes, one expects further low-energy manifestations of LFV such as radiative and three-body lepton decays. Under the assumption of a type-I seesaw as the source of neutrino masses and mixings, all these LFV observables are related. Working in the framework of the cMSSM extended by three right-handed neutrino superfields, we conduct a systematic analysis addressing the simultaneous implications of the SUSY seesaw for both high- and low-energy lepton flavour violation. We discuss how the confrontation of slepton mass splittings as observed at the LHC and low-energy LFV observables may provide important information about the underlying mechanism of LFV.Comment: 50 pages, 42 eps Figures, typos correcte

Defense Against Cannibalism: The SdpI Family of Bacterial Immunity/Signal Transduction Proteins

The SdpI family consists of putative bacterial toxin immunity and signal transduction proteins. One member of the family in Bacillus subtilis, SdpI, provides immunity to cells from cannibalism in times of nutrient limitation. SdpI family members are transmembrane proteins with 3, 4, 5, 6, 7, 8, or 12 putative transmembrane α-helical segments (TMSs). These varied topologies appear to be genuine rather than artifacts due to sequencing or annotation errors. The basic and most frequently occurring element of the SdpI family has 6 TMSs. Homologues of all topological types were aligned to determine the homologous TMSs and loop regions, and the positive-inside rule was used to determine sidedness. The two most conserved motifs were identified between TMSs 1 and 2 and TMSs 4 and 5 of the 6 TMS proteins. These showed significant sequence similarity, leading us to suggest that the primordial precursor of these proteins was a 3 TMS–encoding genetic element that underwent intragenic duplication. Various deletional and fusional events, as well as intragenic duplications and inversions, may have yielded SdpI homologues with topologies of varying numbers and positions of TMSs. We propose a specific evolutionary pathway that could have given rise to these distantly related bacterial immunity proteins. We further show that genes encoding SdpI homologues often appear in operons with genes for homologues of SdpR, SdpI’s autorepressor. Our analyses allow us to propose structure–function relationships that may be applicable to most family members

Beyond the standard seesaw: neutrino masses from Kahler operators and broken supersymmetry

We investigate supersymmetric scenarios in which neutrino masses are generated by effective d=6 operators in the Kahler potential, rather than by the standard d=5 superpotential operator. First, we discuss some general features of such effective operators, also including SUSY-breaking insertions, and compute the relevant renormalization group equations. Contributions to neutrino masses arise at low energy both at the tree level and through finite threshold corrections. In the second part we present simple explicit realizations in which those Kahler operators arise by integrating out heavy SU(2)_W triplets, as in the type II seesaw. Distinct scenarios emerge, depending on the mechanism and the scale of SUSY-breaking mediation. In particular, we propose an appealing and economical picture in which the heavy seesaw mediators are also messengers of SUSY breaking. In this case, strong correlations exist among neutrino parameters, sparticle and Higgs masses, as well as lepton flavour violating processes. Hence, this scenario can be tested at high-energy colliders, such as the LHC, and at lower energy experiments that measure neutrino parameters or search for rare lepton decays.Comment: LaTeX, 34 pages; some corrections in Section

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Childhood trauma fatality and resource allocation in injury control programs in a developing country

BACKGROUND: Only a few studies have addressed the trimodal distribution of childhood trauma fatalities in lesser developed countries. We conducted this study to evaluate pre-hospital, Emergency Department (ED) and in-hospital distribution of childhood injury-related death for each mechanism of injury in Tehran, Iran. This information will be used for the efficient allocation of the limited injury control resources in the city. METHODS: We used Tehran's Legal Medicine Organization (LMO) database. This is the largest and the most complete database that receives information about trauma fatalities from more than 100 small and large hospitals in Tehran. We reviewed all the medical records and legal documents of the deceased registered in LMO from September 1999 to September 2000. Demographic and injury related characteristics of the children 15 years old or younger were extracted from the records. RESULTS: Ten percent of the 4,233 trauma deaths registered in LMO occurred among children 15 years old or younger. Motor vehicle crashes (MVCs) (50%), burns (18%), falls (6%) and poisonings (6%) were the most common mechanisms of unintentional fatal injuries. Prehospital, emergency department and hospital deaths comprised 42%, 20% and 37% of the trauma fatalities, respectively. While, more than 80% of fatal injuries due to poisoning and drowning occurred in prehospital setting, 92% of burn-related fatalities happened after hospital admission. CONCLUSION: Injury prevention is the single most important solution for controlling trauma fatalities due to poisoning and drowning. Improvements in the quality of care in hospitals and intensive care units might substantially alleviate the magnitude of the problem due to burns. Improvements in prehospital and ED care might significantly decrease MVC and falls-related fatalities

Shifting boundaries between the normal and the pathological:the case of mild intellectual disability

When disorders fade into normality, how can the threshold between normality and disorder be determined? In considering mild intellectual disability, I argue that economic factors partly determine thresholds. We tend to assume that the relationship between disorder, need and services is such that: first, a cut-off point between the disordered and the normal is determined; second, a needy population is identified; and third, resources are found (or at least should be found) to meet this need. However, the changing definitions of intellectual disability can best be understood if we think of this happening in reverse. That is, first, certain resources are thought obtainable, and then a cut-off point for disorder is selected which supplies an appropriately sized ‘needy population’