Use of the KlADH4 promoter for ethanol-dependent production of recombinant human serum albumine in Kluyveromyces lactis

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity which is specifically induced by ethanol. The promoter of this gene was used for the expression of heterologous proteins in K. lactis, a very promising organism which can be used as an alternative host to Saccharomyces cerevisiae due to its good secretory properties. In this paper we report the ethanol-driven expression in K. lactis of the bacterial beta-glucuronidase and of the human serum albumin (HSA) genes under the control of the KlADH4 promoter. In particular, we studied the extracellular production of recombinant HSA (rHSA) with integrative and replicative vectors and obtained a significant increase in the amount of the protein with multicopy vectors, showing that no limitation of KlADH4 trans-acting factors occurred in the cells. By deletion analysis of the promoter, we identified an element (UASE) which is sufficient for the induction of KlADH4 by ethanol and, when inserted in the respective promoters, allows ethanol-dependent activation of other yeast genes, such as PGK and LAC4. We also analyzed the effect of medium composition on cell growth and protein secretion. A clear improvement in the production of the recombinant protein was achieved by shifting from batch cultures (0.3 g/liter) to fed-batch cultures (1 g/liter) with ethanol as the preferred carbon source

Matrix sketching for supervised classification with imbalanced classes

The presence of imbalanced classes is more and more common in practical applications and it is known to heavily compromise the learning process. In this paper we propose a new method aimed at addressing this issue in binary supervised classification. Re-balancing the class sizes has turned out to be a fruitful strategy to overcome this problem. Our proposal performs re-balancing through matrix sketching. Matrix sketching is a recently developed data compression technique that is characterized by the property of preserving most of the linear information that is present in the data. Such property is guaranteed by the Johnson-Lindenstrauss’ Lemma (1984) and allows to embed an n-dimensional space into a reduced one without distorting, within an ϵ-size interval, the distances between any pair of points. We propose to use matrix sketching as an alternative to the standard re-balancing strategies that are based on random under-sampling the majority class or random over-sampling the minority one. We assess the properties of our method when combined with linear discriminant analysis (LDA), classification trees (C4.5) and Support Vector Machines (SVM) on simulated and real data. Results show that sketching can represent a sound alternative to the most widely used rebalancing methods

Fermion masses and mixings in gauge theories

The recent evidence for neutrino oscillations stimulate us to discuss again the problem of fermion masses and mixings in gauge theories. In the standard model, several forms for quark mass matrices are equivalent. They become ansatze within most extensions of the standard model, where also relations between quark and lepton sectors may hold. In a seesaw framework, these relations can constrain the scale of heavy neutrino mass, which is often related to the scale of intermediate or unification gauge symmetry. As a consequence, two main scenarios arise. Hierarchies of masses and mixings may be explained by broken horizontal symmetries.Comment: 25 pages, RevTex, no figures. Few misprints corrected and two references adde

Leptogenesis and Low-energy Observables

We relate leptogenesis in a class of theories to low-energy experimental observables: quark and lepton masses and mixings. With reasonable assumptions motivated by grand unification, one can show that the CP-asymmetry parameter takes a universal form. Furthermore the dilution mass is related to the light neutrino masses. Overall, these models offer a natural explanation for a lepton asymmetry in the early universe.Comment: 10 pages, revised discussion on light neutrino masse

Fully-automated Runtime Enforcement of Component-based Systems with Formal and Sound Recovery

International audienceWe introduce runtime enforcement of specifications on component-based systems (CBS) modeled in the BIP (Behavior, Interaction and Priority) framework. Runtime enforcement is an increasingly popular and effective dynamic validation technique aiming to ensure the correct runtime behavior (w.r.t. a formal specification) of a system using a so-called enforcement monitor. BIP is a powerful and expressive component-based framework for the formal construction of heterogeneous systems. Because of BIP expressiveness however , it is difficult to enforce complex behavioral properties at design-time. We first introduce a theoretical runtime enforcement framework for component-based systems where we delineate a hierarchy of enforceable properties (i.e., properties that can be enforced) according to the number of observational steps a system is allowed to deviate from the property (i.e., the notion of k-step enforceability). To ensure the observational equivalence between the correct executions of the initial system and the monitored system, we show that i) only stutter-invariant properties should be enforced on CBS with our monitors, and ii) safety properties are 1-step enforceable. Second, given an abstract enforcement monitor for some 1-step enforceable property, we define a series of formal transformations to instrument (at relevant locations) a CBS described in the BIP framework to integrate the monitor. At runtime, the monitor observes and automatically avoids any error in the behavior of the system w.r.t. the property. Third, our approach is fully implemented in RE-BIP, an available tool integrated in the BIP tool suite. Fourth, to validate our approach, we use RE-BIP to i) enforce deadlock-freedom on a dining philosophers benchmark, and ii) ensure the correct placement of robots on a map

Electronic structure of warm dense copper studied by ultrafast x-ray absorption spectroscopy

We use time-resolved x-ray absorption spectroscopy to investigate the unoccupied electronic density of states of warm dense copper that is produced isochorically through the absorption of an ultrafast optical pulse. The temperature of the superheated electron-hole plasma, which ranges from 4000 to 10 000 K, was determined by comparing the measured x-ray absorption spectrum with a simulation. The electronic structure of warm dense copper is adequately described with the high temperature electronic density of state calculated by the density functional theory. The dynamics of the electron temperature is consistent with a two-temperature model, while a temperature-dependent electron-phonon coupling parameter is necessary

Involvement of vascular endothelial growth factor in schizophrenia

Vascular endothelial growth factor (VEGF), which acts as an angiogenic and neurotrophic factor, is involved the regulation of cerebral blood volume and flow in Schizophrenia (SCZ). Several evidence indicates that modification of brain blood circulation due to alterations in the VEGF system affects cognitive performance and brain function in patients with SCZ. The aim of this study is: 1) To analyze the literature data concerning the role of VEGF in modulating the angiogenic response in SCZ. These data are controversial because some studies found elevated VEGF serum levels of VEGF in patients with SCZ, whereas others demonstrated no significant differences between SCZ patients and controls. 2)To analyze the role of VEGF as a predictive factor on the effects of antipsychotics agents used in the treatment of SCZ. In this context, high VEGF levels, associated to better responses to antipsychotics, might be predictive of the use of first generation antipsycotic drugs, whereas low VEGF levels, expression of resistance to therapy, might be predictive for the use of second generation antipsycotic drugs

Seesaw mechanism, baryon asymmetry and neutrinoless double beta decay

A simplified but very instructive analysis of the seesaw mechanism is here performed. Assuming a nearly diagonal Dirac neutrino mass matrix, we study the forms of the Majorana mass matrix of right-handed neutrinos, which reproduce the effective mass matrix of left-handed neutrinos. As a further step, the important effect of a non diagonal Dirac neutrino mass matrix is explored. The corresponding implications for the baryogenesis via leptogenesis and for the neutrinoless double beta decay are reviewed. We propose two distinct models where the baryon asymmetry is enhanced.Comment: 21 pages, RevTex. Revise

Screening masses in the SU(3) pure gauge theory and universality

We determine from Polyakov loop correlators the screening masses in the deconfined phase of the (3+1)d SU(3) pure gauge theory at finite temperature near the transition, for two different channels of angular momentum and parity. Their ratio is compared with that of the massive excitations with the same quantum numbers in the 3d 3-state Potts model in the broken phase near the transition point at zero magnetic field. Moreover we study the inverse decay length of the correlation between the real parts and between the imaginary parts of the Polyakov loop and compare the results with expectations from perturbation theory and mean-field Polyakov loop models.Comment: 19 pages, 9 figures; version to appear on Nuclear Physics B (Section 3.1 revisited; a few comments, a table and a reference added; fit results included in Fig. 8

Subpicosecond Thomson Scattering Measurements of Optically Ionized Helium Plasmas

We present the first subpicosecond time-resolved temperature measurements of plasmas produced by high-intensity optical ionization. Thomson scattering is used to measure electron and ion temperatures of helium plasmas created by 125 fs, 800 nm laser pulses focused to an intensity of 2 × 1017 W/cm2. We find that the electron temperature is accurately predicted by a tunneling ionization model. The measured ion temperature is consistent with direct heating by the laser pulse