Time-Dependent Quantum-Mechanical Approaches to the Continuous Spectrum: Scattering Resonances in a Finite Box

Several novel aspects of scattering resonances are studied. An expression, valid for a finite box, relating the continuum phase shift with the energy shift and unperturbed level separation is proposed and applied to obtain the resonance parameters. The effect of the resonance on propagating a wavepacket in imaginary time is studied. It is observed that the resonance strongly affects the cumulants of the energy distribution. In particular, a local minimum of the first derivative of the energy with respect to time (proportional to the second cumulant) serves to estimate the resonance energy and wavefunction. Once the estimate is known, the autocorrelation function is used to evaluate the resonance width. Alternatively, a new iterative approach is developed that is capable of selectively yielding an arbitrary band of energy eigenvalues and eigenfunctions on a grid. This method is applied to give those energy levels that are of interest for the discrete computation of the resonant phase shift, i.e., those close to resonance. Exact (analytical) and approximate results are in good agreement for a particular separable potential model in one dimension. These methods can be extended to realistic potentials in higher dimensions.     

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Early-Life Development of the Bifidobacterial Community in the Infant Gut

The establishment of the gut microbiota poses implications for short and long-term health. Bifidobacterium is an important taxon in early life, being one of the most abundant genera in the infant intestinal microbiota and carrying out key functions for maintaining host-homeostasis. Recent metagenomic studies have shown that different factors, such as gestational age, delivery mode, or feeding habits, affect the gut microbiota establishment at high phylogenetic levels. However, their impact on the specific bifidobacterial populations is not yet well understood. Here we studied the impact of these factors on the different Bifidobacterium species and subspecies at both the quantitative and qualitative levels. Fecal samples were taken from 85 neonates at 2, 10, 30, 90 days of life, and the relative proportions of the different bifidobacterial populations were assessed by 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing. Absolute levels of the main species were determined by q-PCR. Our results showed that the bifidobacterial population establishment is affected by gestational age, delivery mode, and infant feeding, as it is evidenced by qualitative and quantitative changes. These data underline the need for understanding the impact of perinatal factors on the gut microbiota also at low taxonomic levels, especially in the case of relevant microbial populations such as Bifidobacterium. The data obtained provide indications for the selection of the species best suited for the development of bifidobacteria-based products for different groups of neonates and will help to develop rational strategies for favoring a healthy early microbiota development when this process is challenged.     

Mechanochemical tuning of molecular weight distribution of styrene homopolymers as postpolymerization modification in solvent-free solid-state

Mechanochemical degradation by planetary ball milling (PM) is used for postpolymerization modification of styrene homopolymers (PS). A complete factorial design was chosen to study the effect of radical scavengers, milling time, initial molecular weight, and revolution radius (R_p), on the shape of molecular weight distributions (MWDs) of PS. Size-exclusion chromatography analysis shows the feasibility of fine-tuning MWD of PS at up to 40% conversion. Distributions ranged from unimodal to bimodal in a PM with R_p = 150 mm at different stage of milling, whereas in a PM with R_p of 60.8 mm the adjustment of unimodal distributions is achieved. Initial polydispersity is more important to develop bimodal distributions when compared with initial molecular weight. Fourier transform infrared and X-ray electron spectrometry analysis show some suppression of PS degradation and complete oxidation inhibition of macromolecular radicals with the incorporation of radical scavengers, which we considered as additional aids when adjusting the MWDs.     

Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors

Previous studies aimed at exploring the SAR of C2-functionalized S-DABOs demonstrated that the substituent at this position plays a key role in the inhibition of both wild-type RT and drug-resistant enzymes, particularly the K103N mutant form. The introduction of a cyclopropyl group led us to the discovery of a potent inhibitor with picomolar activity against wild-type RT and nanomolar activity against many key mutant forms such as K103N. Despite its excellent antiviral profile, this compound suffers from a suboptimal ADME profile typical of many S-DABO analogues, but it could, however, represent a promising candidate as an anti-HIV microbicide. In the present work, a new series of S-DABO/N-DABO derivatives were synthesized to obtain additional SAR information on the C2-position and in particular to improve ADME properties while maintaining a good activity profile against HIV-1 RT. In vitro ADME properties (PAMPA permeation, water solubility, and metabolic stability) were also experimentally evaluated for the most interesting compounds to obtain a reliable indication of their plasma levels after oral administration.     

Supertoughness in Polysulfone/Poly(ethylene‐octene) Blends

Summary: Poly(sulfone of Bisphenol A) (PSU) based blends were obtained by melt blending PSU with up to 15 wt.‐% poly(ethylene‐octene) either modified with maleic anhydride (mPEO) or not (PEO). The dispersed particle size was small and similar in blends with PEO or mPEO. These facts indicated respectively that the interfacial tension was low and the lack of compatibilizing effect of mPEO. Some preferential presence of PEO in the outer surface of the specimens was observed, and was attributed to the large viscosity difference between the two components of the blends. This had no effect on the modulus of elasticity, but speeded up both the yield stress and ductility decreases at rubber contents above 3.25 wt.‐%. However, despite the immiscibility of the components, and thanks to the small particle size of the blends, super‐toughness was attained in the unmodified PSU/PEO blends. This was at PEO contents (3.25 wt.‐%) at which the modulus, yield stress and ductility of the blends were almost as good as those of pure PSU. It appeared that a change of the chemical nature of the rubber did not influence by itself super‐toughness, unless it was accompanied by either a morphological or adhesion change.

Impact strength of PSU‐based blends vs. PEO (○) or mPEO (?) content.     

Determination of fermentative volatile compounds in aged red wines by near infrared spectroscopy

The purpose of this work was to study the possibility of determination of fermentative volatile compounds in aged red wines using NIR spectroscopy. To achieve this, 240 wines belonging to different geographic zones and elaborated with one or two varieties were analyzed. The volatile compounds were quantified by SBSE-GC–MS. Spectra obtained by NIR were co-related with these values using partial least square (PLS) regression. Calibration and validation statistics showed the quality of the model, after all when is done separately for each of the four geographic zones, and in the case of wines elaborated with two varieties. Consequently, near infrared spectroscopy can be used as an easy and rapid tool to determine fermentative volatile compounds in aged red wines.     

A differential inclusion approach for modeling and analysis of dynamical systems under uncertainty

In this paper we deal with the application of differential inclusions to modeling nonlinear dynamical systems under uncertainty in parameters. In this case, differential inclusions seem to be better suited to modeling practical situations under uncertainty and imprecision than formulations by means of fuzzy differential equations. We develop a practical algorithm to approximate the reachable sets of a class of nonlinear differential inclusion, which eludes the computational problems of a previous set-valued version of the Heun’s method. Our algorithm is based on a complete discretization (time and state space) of the differential inclusion and it suits hardware features, handling the memory used by the method in a controlled fashion during all iterations. As a case of study, we formulate a differential inclusion to model an epidemic outbreak of dengue fever under Cuban conditions. The model takes into account interaction of human and mosquito populations as well as vertical transmission in the mosquito population. It is studied from the theoretical point of view to apply the Practical Algorithm. Also, we estimate the temporal evolution of the different human and mosquito populations given by the model in the Dengue 3 epidemic in Havana 2001, through the computation of the reachable sets using the Practical Algorithm.     

Challenges for integrated design (ID) in sustainable buildings

It is often argued that integrated design (ID) is a powerful way to enhance collaboration in construction projects. This collaboration is seen as a way of improving innovation to create more sustainable buildings. Contrary to the traditional silo-type and linear design process, ID is based on upfront stakeholder involvement and a holistic approach to project decision-making. Although ID’s premises are theoretically-founded, a close empirical look at its practices shows that numerous challenges compromise its results and efficiency. This study examines the ID process through an iterative process that includes the construction of a conceptual framework and its empirical validation. We examine three green construction projects in Canada. Based on the analysis of 26 interviews with key project stakeholders and more than 198 construction documents, the study assembles – and ultimately applies – a multi-lens framework based on four themes: the fragmented nature of construction; risk perception; stakeholders’ commitment; and efficiency in the design process. Results show that three tensions arise in ID practices: between collaboration and process efficiency, between short-term and long-term goals, and between integrated methods and traditional ones. The study sheds light on ID limits and reveals how stakeholders can improve their interactions to design more sustainable buildings.