Elucidation of the RamA Regulon in Klebsiella pneumoniae Reveals a Role in LPS Regulation

Klebsiella pneumoniae is a significant human pathogen, in part due to high rates of multidrug resistance. RamA is an intrinsic regulator in K. pneumoniae established to be important for the bacterial response to antimicrobial challenge; however, little is known about its possible wider regulatory role in this organism during infection. In this work, we demonstrate that RamA is a global transcriptional regulator that significantly perturbs the transcriptional landscape of K. pneumoniae, resulting in altered microbe-drug or microbe-host response. This is largely due to the direct regulation of 68 genes associated with a myriad of cellular functions. Importantly, RamA directly binds and activates the lpxC, lpxL-2 and lpxO genes associated with lipid A biosynthesis, thus resulting in modifications within the lipid A moiety of the lipopolysaccharide. RamA-mediated alterations decrease susceptibility to colistin E, polymyxin B and human cationic antimicrobial peptide LL-37. Increased RamA levels reduce K. pneumoniae adhesion and uptake into macrophages, which is supported by in vivo infection studies, that demonstrate increased systemic dissemination of ramA overexpressing K. pneumoniae. These data establish that RamA-mediated regulation directly perturbs microbial surface properties, including lipid A biosynthesis, which facilitate evasion from the innate host response. This highlights RamA as a global regulator that confers pathoadaptive phenotypes with implications for our understanding of the pathogenesis of Enterobacter, Salmonella and Citrobacter spp. that express orthologous RamA proteins

Modeling interest rate dynamics: an infinite-dimensional approach

We present a family of models for the term structure of interest rates which describe the interest rate curve as a stochastic process in a Hilbert space. We start by decomposing the deformations of the term structure into the variations of the short rate, the long rate and the fluctuations of the curve around its average shape. This fluctuation is then described as a solution of a stochastic evolution equation in an infinite dimensional space. In the case where deformations are local in maturity, this equation reduces to a stochastic PDE, of which we give the simplest example. We discuss the properties of the solutions and show that they capture in a parsimonious manner the essential features of yield curve dynamics: imperfect correlation between maturities, mean reversion of interest rates and the structure of principal components of term structure deformations. Finally, we discuss calibration issues and show that the model parameters have a natural interpretation in terms of empirically observed quantities.Comment: Keywords: interest rates, stochastic PDE, term structure models, stochastic processes in Hilbert space. Other related works may be retrieved on http://www.eleves.ens.fr:8080/home/cont/papers.htm

Binaries without borders : performing genders in Ghalib Halasa’s “Al-Bish’ah”

Jordanian author Ghalib Halasa lived the majority of his adult life in transit, being exiled from many counties to do his political beliefs. This exile, however, provided him with a unique perspective with which to represent Jordanian and Arab culture more generally. His short story,"Al-Bish’ah,” written earlier in his life, critiques traditional gender roles and binaries, as well as traditional practices which determine honour and justice. Through his telling of a traditional ritual through a powerful mother-figure, Halasa distorts local depictions of gender, and instead inscribes a gender fluidity informed by his lifetime in exile, allowing for a closer depiction of society as he sees it. In this report, I will demonstrate the ways in which Halasa deconstructs traditional gender binaries and traditions through close examination of characters’ gender performance, informed by the work of Goffman and Butler. Additionally, I will connect his destabilizing of gender and traditional rituals to his own life and experience, placing the story within the context of his life and Arab culture at large.Comparative Literatur