Lady Gaga as (dis)simulacrum of monstrosity

Lady Gaga’s celebrity DNA revolves around the notion of monstrosity, an extensively researched concept in postmodern cultural studies. The analysis that is offered in this paper is largely informed by Deleuze and Guattari’s notion of monstrosity, as well as by their approach to the study of sign-systems that was deployed in A Thousand Plateaus. By drawing on biographical and archival visual data, with a focus on the relatively underexplored live show, an elucidation is afforded of what is really monstrous about Lady Gaga. The main argument put forward is that monstrosity as sign seeks to appropriate the horizon of unlimited semiosis as radical alterity and openness to signifying possibilities. In this context it is held that Gaga effectively delimits her unique semioscape; however, any claims to monstrosity are undercut by the inherent limits of a representationalist approach in sufficiently engulfing this concept. Gaga is monstrous for her community insofar as she demands of her fans to project their semiosic horizon onto her as a simulacrum of infinite semiosis. However, this simulacrum may only be evinced in a feigned manner as a (dis)simulacrum. The analysis of imagery from seminal live shows during 2011–2012 shows that Gaga’s presumed monstrosity is more akin to hyperdifferentiation as simultaneous employment of heterogeneous and potentially dissonant inter pares cultural representations. The article concludes with a problematisation of audience effects in the light of Gaga’s adoption of a schematic and post-representationalist strategy in the event of her strategy’s emulation by competitive artists

Horus: Interference-Aware and Prediction-Based Scheduling in Deep Learning Systems

To accelerate the training of Deep Learning (DL) models, clusters of machines equipped with hardware accelerators such as GPUs are leveraged to reduce execution time. State-of-the-art resource managers are needed to increase GPU utilization and maximize throughput. While co-locating DL jobs on the same GPU has been shown to be effective, this can incur interference causing slowdown. In this article we propose Horus: an interference-aware and prediction-based resource manager for DL systems. Horus proactively predicts GPU utilization of heterogeneous DL jobs extrapolated from the DL model’s computation graph features, removing the need for online profiling and isolated reserved GPUs. Through micro-benchmarks and job co-location combinations across heterogeneous GPU hardware, we identify GPU utilization as a general proxy metric to determine good placement decisions, in contrast to current approaches which reserve isolated GPUs to perform online profiling and directly measure GPU utilization for each unique submitted job. Our approach promotes high resource utilization and makespan reduction; via real-world experimentation and large-scale trace driven simulation, we demonstrate that Horus outperforms other DL resource managers by up to 61.5 percent for GPU resource utilization, 23.7–30.7 percent for makespan reduction and 68.3 percent in job wait time reduction

Rictor Phosphorylation on the THR-1135 Site Does Not Require Mammalian Target of Rapamycin Complex 2

available in PMC 2012 January 1.In animal cells, growth factors coordinate cell proliferation and survival by regulating the phosphoinositide 3-kinase/Akt signaling pathway. Deregulation of this signaling pathway is common in a variety of human cancers. The PI3K-dependent signaling kinase complex defined as mammalian target of rapamycin complex 2 (mTORC2) functions as a regulatory Ser-473 kinase of Akt. We find that activation of mTORC2 by growth factor signaling is linked to the specific phosphorylation of its component rictor on Thr-1135. The phosphorylation of this site is induced by the growth factor stimulation and expression of the oncogenic forms of ras or PI3K. Rictor phosphorylation is sensitive to the inhibition of PI3K, mTOR, or expression of integrin-linked kinase. The substitution of wild-type rictor with its specific phospho-mutants in rictor null mouse embryonic fibroblasts did not alter the growth factor–dependent phosphorylation of Akt, indicating that the rictor Thr-1135 phosphorylation is not critical in the regulation of the mTORC2 kinase activity. We found that this rictor phosphorylation takes place in the mTORC2-deficient cells, suggesting that this modification might play a role in the regulation of not only mTORC2 but also the mTORC2-independent function of rictor. Mol Cancer Res; 8(6); 896–906.University of Texas M.D. Anderson Cancer Center (Fellow Trust fund)American Cancer Society (M.D. Anderson Cancer Center Breast Specialized Programs of Research Excellence (RSG-09-026-01CCG01))National Institutes of Health (U.S.) (NIH grant CA133522)National Institutes of Health (U.S.) (NIH grant AI104389

Intracellular Electric Field and pH Optimize Protein Localization and Movement

Mammalian cell function requires timely and accurate transmission of information from the cell membrane (CM) to the nucleus (N). These pathways have been intensively investigated and many critical components and interactions have been identified. However, the physical forces that control movement of these proteins have received scant attention. Thus, transduction pathways are typically presented schematically with little regard to spatial constraints that might affect the underlying dynamics necessary for protein-protein interactions and molecular movement from the CM to the N. We propose messenger protein localization and movements are highly regulated and governed by Coulomb interactions between: 1. A recently discovered, radially directed E-field from the NM into the CM and 2. Net protein charge determined by its isoelectric point, phosphorylation state, and the cytosolic pH. These interactions, which are widely applied in elecrophoresis, provide a previously unknown mechanism for localization of messenger proteins within the cytoplasm as well as rapid shuttling between the CM and N. Here we show these dynamics optimize the speed, accuracy and efficiency of transduction pathways even allowing measurement of the location and timing of ligand binding at the CM –previously unknown components of intracellular information flow that are, nevertheless, likely necessary for detecting spatial gradients and temporal fluctuations in ligand concentrations within the environment. The model has been applied to the RAF-MEK-ERK pathway and scaffolding protein KSR1 using computer simulations and in-vitro experiments. The computer simulations predicted distinct distributions of phosphorylated and unphosphorylated components of this transduction pathway which were experimentally confirmed in normal breast epithelial cells (HMEC)

Synergy between inhibitors of androgen receptor and MEK has therapeutic implications in estrogen receptor-negative breast cancer

Introduction: Estrogen receptor-negative (ER-) breast cancer is a heterogeneous disease with limited therapeutic options. The molecular apocrine subtype constitutes 50% of ER-tumors and is characterized by overexpression of steroid response genes including androgen receptor (AR). We have recently identified a positive feedback loop between the AR and extracellular signal-regulated kinase (ERK) signaling pathways in the molecular apocrine subtype. In this feedback loop, AR regulates ERK phosphorylation through the mediation of ErbB2 and, in turn, ERK-CREB1 signaling regulates the transcription of AR in molecular apocrine cells. In this study, we investigated the therapeutic implications of the AR-ERK feedback loop in molecular apocrine breast cancer.Methods: We examined a synergy between the AR inhibitor flutamide and the MEK inhibitor CI-1040 in the molecular apocrine cell lines MDA-MB-453, HCC-1954 and HCC-202 using MTT cell viability and annexin V apoptosis assays. Synergy was measured using the combination index (CI) method. Furthermore, we examined in vivo synergy between flutamide and the MEK inhibitor PD0325901 in a xenograft model of the molecular apocrine subtype. The effects of in vivo therapies on tumor growth, cell proliferation and angiogenesis were assessed.Results: We demonstrate synergistic CI values for combination therapy with flutamide and CI-1040 across three molecular apocrine cell lines at four dose combinations using both cell viability and apoptosis assays. Furthermore, we show in vivo that combination therapy with flutamide and MEK inhibitor PD0325901 has a significantly higher therapeutic efficacy in reducing tumor growth, cellular proliferation and angiogenesis than monotherapy with these agents. Moreover, our data suggested that flutamide and CI-1040 have synergy in trastuzumab resistance models of the molecular apocrine subtype. Notably, the therapeutic effect of combination therapy in trastuzumab-resistant cells was associated with the abrogation of an increased level of ERK phosphorylation that was developed in the process of trastuzumab resistance.Conclusions: In this study, we demonstrate in vitro and in vivo synergies between AR and MEK inhibitors in molecular apocrine breast cancer. Furthermore, we show that combination therapy with these inhibitors can overcome trastuzumab resistance in molecular apocrine cells. Therefore, a combination therapy strategy with AR and MEK inhibitors may provide an attractive therapeutic option for the ER-/AR+ subtype of breast cancer

After the epidemic: Zika virus projections for Latin America and the Caribbean

Background: Zika is one of the most challenging emergent vector-borne diseases, yet its future public health impact remains unclear. Zika was of little public health concern until recent reports of its association with congenital syndromes. By 3 August 2017 ~217,000 Zika cases and ~3,400 cases of associated congenital syndrome were reported in Latin America and the Caribbean. Some modelling exercises suggest that Zika virus infection could become endemic in agreement with recent declarations from the The World Health Organisation. Methodology/Principal findings: We produced high-resolution spatially-explicit projections of Zika cases, associated congenital syndromes and monetary costs for Latin America and the Caribbean now that the epidemic phase of the disease appears to be over. In contrast to previous studies which have adopted a modelling approach to map Zika potential, we project case numbers using a statistical approach based upon reported dengue case data as a Zika surrogate. Our results indicate that ~12.3 (0.7–162.3) million Zika cases could be expected across Latin America and the Caribbean every year, leading to ~64.4 (0.2–5159.3) thousand cases of Guillain-Barré syndrome and ~4.7 (0.0–116.3) thousand cases of microcephaly. The economic burden of these neurological sequelae are estimated to be USD ~2.3 (USD 0–159.3) billion per annum. Conclusions/Significance: Zika is likely to have significant public health consequences across Latin America and the Caribbean in years to come. Our projections inform regional and federal health authorities, offering an opportunity to adapt to this public health challenge

A multifaceted intervention to improve syphilis screening and treatment in pregnant women in Kinshasa, Democratic Republic of the Congo and in Lusaka, Zambia: a cluster randomised controlled trial

Background: Despite international recommendations, coverage of syphilis testing in pregnant women and treatment of those found seropositive remains limited in sub-Saharan Africa. We assessed whether combining the provision of supplies with a behavioural intervention was more effective than providing supplies only, to improve syphilis screening and treatment during antenatal care. Methods: In this 18-month, cluster randomised controlled trial, we randomly assigned (1:1) 26 urban antenatal care clinics in Kinshasa, Democratic Republic of the Congo, and Lusaka, Zambia, to receive a behavioural intervention (opinion leader selection, academic detailing visits, reminders, audits and feedback, and supportive supervision) plus supplies for syphilis testing and treatment (intervention group) or to receive supplies only (control group). The primary outcomes were proportion of pregnant women who had syphilis screening out of the total who attended the clinic; and the proportion of women who had treatment with benzathine benzylpenicillin out of those who tested positive for syphilis at their first antenatal care visit. This trial is registered at ClinicalTrials.gov, number NCT02353117. Findings: The 18-month study period was Feb 1, 2016, to July 14, 2017. 18 357 women were enrolled at the 13 intervention clinics and 17 679 women were enrolled at the 13 control clinics at their first antenatal care visit. Syphilis screening was done in a median of 99·9% (IQR 99·0–100·0) of women in the intervention clinics and 93·8% (85·0–98·9) in the control clinics (absolute difference 6·1% [95% CI 1·1–14·1]; p=0·00092). Syphilis treatment at the first visit was done in a median of 100% (IQR 99·7–100·0) of seropositive women in intervention clinics and 43·2% (2·6–83·2) of seropositive women in control clinics (absolute difference 56·8% [12·8–99·0]; p=0·0028). Interpretation: A behavioural intervention, together with the provision of supplies, can lead to more than 95% of women being screened and treated for syphilis. The sole provision of supplies is sufficient to reach such levels of screening coverage but is not sufficient to ensure high levels of treatment. Funding: Bill & Melinda Gates Foundation.Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina. Organizacion Mundial de la Salud; ArgentinaFil: Chomba, Elwyn. University Teaching Hospital of Lusaka; ZambiaFil: Tshefu, Antoinette K. University of Kinshasa; República Democrática del CongoFil: Banda, Ernest. University Teaching Hospital of Lusaka; ZambiaFil: Belizán, María Melina Eleonora. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Berrueta, Amanda Mabel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Bertrand, Jane. University of Tulane; Estados UnidosFil: Bose, Carl. University of North Carolina; Estados UnidosFil: Cafferata, Maria Luisa. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Carlo, Waldemar A. University of Alabama at Birmingahm; Estados UnidosFil: Ciganda, Alvaro. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Donnay, France. University of Tulane; Estados UnidosFil: Garcia Elorrio, Ezequiel. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Klein, Karen. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Liljestrand, Jerker. Bill And Melinda Gates Foundation; Estados UnidosFil: Lusamba, Paul D. University of Kinshasa; República Democrática del CongoFil: Mavila, Arlette K. University of Kinshasa; República Democrática del CongoFil: Mazzoni, Agustina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Nkamba, Dalau M. University of Kinshasa; República Democrática del CongoFil: Mwanakalanga, Friday H. University Teaching Hospital Lusaka; ZambiaFil: Mwapule Tembo, Abigail. University Teaching Hospital Lusaka; ZambiaFil: Mwenechanya, Musaku. University Teaching Hospital Lusaka; ZambiaFil: Pyne Mercier, Lee. Bill And Melinda Gates Foundation; Estados UnidosFil: Spira, Cintia. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Wetshikoy, Jean D. University of Kinshasa; República Democrática del CongoFil: Xiong, Xu. University of Tulane; Estados UnidosFil: Buekens, Pierre. University of Tulane; Estados Unido

Quantifying soil hydrology to explain the development of vegetation at an ex-arable wetland restoration site

Wetland restoration frequently sets well-defined vegetation targets, but where restoration occurs on highly degraded land such targets are not practical and setting looser targets may be more appropriate. Where this more ‘open-ended’ approach to restoration is adopted, surveillance methods that can track developing wetland habitats need to be established. Water regime and soil structure are known to influence the distribution and composition of developing wetland vegetation, and may be quantified using Sum Exceedence Values (SEV), calculated using the position of the water table and knowledge of soil stress thresholds. Use of SEV to explain patterns in naturally colonizing vegetation on restored, ex-arable land was tested at Wicken Fen (UK). Analysis of values from ten locations showed that soil structure was highly heterogeneous. Five locations had shallow aeration stress thresholds and so had the potential to support diverse wetland assemblages. Deep aeration stress thresholds at other locations precluded the establishment of a diverse wetland flora, but identified areas where species-poor wetland assemblages may develop. SEV was found to be a useful tool for the surveillance of sites where restoration targets are not specified in detail at the outset and may help predict likely habitat outcomes at sites using an open-ended restoration approach