Miracle-dz/UniFAR-FTUs huggingface dataset:
Linear and Branched Chitosan Oligomers as Delivery Systems for pDNA and siRNA In Vitro and In Vivo

In this thesis, chitosan, a biocompatible polysaccharide that has been approved as a food additive was selected as a platform for the development of safe, efficient non-viral gene delivery systems to mammalian cells. Previously, chitosan-based gene formulations had been generally associated with high molecular weight chitosans, which were poorly characterised in terms of molecular weight distribution and degree of acetylation. Therefore, in order to improve the properties of chitosan-based gene formulations, the research associated with this thesis focused on establishing the structure-property relationships of well-defined, low molecular weight chitosans (chitosan oligomers) as delivery systems for nucleic acids (pDNA and siRNA) in vitro and after lung administration in vivo. pDNA dissociated more easily from chitosan oligomers than from conventional high molecular weight chitosans, resulting in a faster onset and higher levels of in vivo gene expression, comparable to those mediated by polyethyleneimine (PEI), one of the most efficient non-viral delivery systems. Coupling of a trisaccharide branch to the chitosan oligomers so as to target extracellular lectins resulted in a significant improvement in transfection efficiency because of enhanced cellular uptake and colloidal stability. In contrast to pDNA, longer linear chitosan oligomers were required to form physically-stable nanoparticles with siRNA that mediated efficient, sustained gene silencing in vitro. Finally, the use of an optimised catheter device for the nebulisation of small volumes of pDNA formulations resulted in improved dose precision and lung distribution in vivo compared with conventional intratracheal instillation. In conclusion, chitosan oligomers are interesting and viable alternatives to other non-viral gene delivery systems.
The humerus of Eusthenopteron: a puzzling organization presaging the establishment of tetrapod limb bone marrow

Because of its close relationship to tetrapods, Eusthenopteron is an important taxon for understanding the establishment of the tetrapod body plan. Notably, it is one of the earliest sarcopterygians in which the humerus of the pectoral fin skeleton is preserved. The microanatomical and histological organization of this humerus provides important data for understanding the evolutionary steps that built up the distinctive architecture of tetrapod limb bones. Previous histological studies showed that Eusthenopteron's long-bone organization was established through typical tetrapod ossification modalities. Based on a three-dimensional reconstruction of the inner microstructure of Eusthenopteron's humerus, obtained from propagation phase-contrast X-ray synchrotron microtomography, we are now able to show that, despite ossification mechanisms and growth patterns similar to those of tetrapods, it also retains plesiomorphic characters such as a large medullary cavity, partly resulting from the perichondral ossification around a large cartilaginous bud as in actinopterygians. It also exhibits a distinctive tubular organization of bone-marrow processes. The connection between these processes and epiphyseal structures highlights their close functional relationship, suggesting that either bone marrow played a crucial role in the long-bone elongation processes or that trabecular bone resulting from the erosion of hypertrophied cartilage created a microenvironment for haematopoietic stem cell niches.
Future Grid Business Model Innovation: Distributed Energy Resources Services Platform for Renewable Energy Integration

This paper proposes a Distributed Energy Resources Services Platform as an electric grid Business Model Innovation Framework (BMIF) for coordination of distributed energy resources and renewable energy integration. The platform is based on a decentralized and layered architecture and is centered on the concept of electricity prosumers -economically motivated agents (residential, commercial, industrial) - that can produce, store or consume energy. The platform consists of six layers, including: the physical layer, local control layer, cyber layer, system control layer (economic dispatch and real-time control), market transactive layer and business layer. The main objective of the platform is to provide a framework for the coordination of several spatially distributed and heterogeneous subsystems containing energy resources at different time scales and horizons in order to conduct economic emissions dispatch and reserve scheduling to integrate higher amounts of renewable energy, while dynamically maintaining and adapting to user level of service requirements and system level constraints. Using the structure provided by the platform, the benefits of flexible distributed energy resources for different scenarios of renewable energy integration are quantified. The results show that using the platform for coordination of flexible energy, offers the opportunity to integrate higher amounts of renewable energy, reduce carbon emissions and operational costs.
Structure and Behavior of Human α-Thrombin upon Ligand Recognition: Thermodynamic and Molecular Dynamics Studies

Thrombin is a serine proteinase that plays a fundamental role in coagulation. In this study, we address the effects of ligand site recognition by alpha-thrombin on conformation and energetics in solution. Active site occupation induces large changes in secondary structure content in thrombin as shown by circular dichroism. Thrombin-D-Phe-Pro-Arg-chloromethyl ketone (PPACK) exhibits enhanced equilibrium and kinetic stability compared to free thrombin, whose difference is rooted in the unfolding step. Small-angle X-ray scattering (SAXS) measurements in solution reveal an overall similarity in the molecular envelope of thrombin and thrombin-PPACK, which differs from the crystal structure of thrombin. Molecular dynamics simulations performed with thrombin lead to different conformations than the one observed in the crystal structure. These data shed light on the diversity of thrombin conformers not previously observed in crystal structures with distinguished catalytic and conformational behaviors, which might have direct implications on novel strategies to design direct thrombin inhibitors.
Electronic cigarette use and smoking initiation among youth: a longitudinal cohort study

BACKGROUND: The influence of e-cigarette use on smoking initiation is a highly controversial issue, with limited longitudinal data available for examining temporal associations. We examined e-cigarette use and its association with cigarette-smoking initiation at 1-year follow-up within a large cohort of Canadian secondary school students. METHODS: We analyzed data from students in grades 9–12 who participated in 2 waves of COMPASS, a cohort study of purposefully sampled secondary schools in Ontario and Alberta, Canada, at baseline (2013/14) and 1-year follow-up (2014/15). We assessed cigarette smoking and e-cigarette use at baseline and follow-up using self-completed surveys. We used generalized linear mixed-effects models to examine correlates of past 30-day e-cigarette use at baseline and smoking initiation between waves within the longitudinal sample. RESULTS: Past 30-day e-cigarette use increased from 2013/14 to 2014/15 (7.2% v. 9.7%, p < 0.001), whereas past 30-day cigarette smoking decreased slightly (11.4% v. 10.8%, p = 0.02). Among the 44 163 students evaluated at baseline, past 30-day e-cigarette use was strongly associated with smoking status and smoking susceptibility. In the longitudinal sample (n = 19 130), past 30-day use of e-cigarettes at baseline was associated with initiation of smoking a whole cigarette (adjusted odds ratio [OR] 2.12, 95% confidence interval [CI] 1.68–2.66) and with initiation of daily smoking (adjusted OR 1.79, 95% CI 1.41–2.28) at follow-up. INTERPRETATION: E-cigarette use was strongly associated with cigarette smoking behaviour, including smoking initiation at follow-up. The causal nature of this association remains unclear, because common factors underlying the use of both e-cigarettes and conventional cigarettes may also account for the temporal order of initiation.
Multipollutant markets

I study the optimal design of marketable permit systems to regulate various pollutants (e.g., air pollution in urban areas) when the regulator lives in a real world of imperfect information and incomplete enforcement. I show that the regulator should have pollution markets integrated through optimal exchange rates when the marginal-abatement cost curves in the different markets are steeper than the marginal-benefit curves; otherwise he should keep markets separated. I also find that incomplete enforcement reduces the advantage of market integration.
Baroreflex contribution to blood pressure and heart rate oscillations: time scales, time-variant characteristics and nonlinearities

The aim of this paper is to highlight the aspects of the baroreflex control of the cardiovascular system that could be relevant to the analysis and modelling of cardiovascular oscillations and regulation. In particular, complex and/or controversial issues of the baroreflex control are addressed on the basis of results obtained in previous studies by others as well as by our group. Attention has been focused on time-variant and nonlinear characteristics of the baroreflex function and on the influence of this physiological mechanism on different frequency regions of blood pressure and heart rate spectra.
Researching protective and promotive factors in mental health.

This issue of the Journal features two cohort studies which show a marked excess of schizophrenia in African Americans, and a dose–response relationship between perceived discrimination and excess rates of schizophrenia in different minority groups in The Netherlands. These studies mirror one another, and numerous other studies carried out in developed countries, in inferring that minority groups are at elevated risk for schizophrenia, and that social factors—particularly discriminationrelated disadvantages—are partially responsible. That these elevated rates have been the subject of scientific investigations is fully justified—if the higher rate of schizophrenia in minority groups were ignored, we would feel rightly outraged. Likewise, we believe ignoring the mental health needs of other disadvantaged groups—for example, women or conflict-affected people—is both scientifically and morally indefensible. It is scientifically indefensible because these groups are particularly vulnerable to suffering from poor mental health. It is morally indefensible because in the context of other important disadvantages across multiple axes, attempting to understand and address mental health inequalities becomes still more pressing as a matter of social justice. Nevertheless, in this editorial we add our voices to those who call for a broadening of the research agenda beyond the risk factors for poor mental health and the mental health problems of socially vulnerable groups. Instead, we propose that more attention needs to be paid to the protective factors which decrease the probability of suffering mental health problems, and to the promotive factors which actively enhance positive psychological well-being. Our argument is that protective and promotive factor epidemiology is not simply the converse of risk factor epidemiology, either conceptually, methodologically or in its potential public health benefits; and that a failure to investigate protective and promotive factors rigorously may therefore hamper our ability to understand mental health problems and to promote good mental health. Investigating protective factors at the group level
Food insecurity, stressful life events and symptoms of anxiety and depression in east Africa: evidence from the Gilgel Gibe growth and development study

Objectives: Common mental disorders are a major contributor to the burden of disease in developing countries. An assessment was carried out of whether food insecurity and exposure to stressful life events, two common features of life in sub-Saharan Africa (SSA), are associated with symptoms of mental disorders among adults. Methods: The Gilgel Gibe Growth and Development Study (GGGDS) is an ongoing cohort study in rural Ethiopia. Participants of the GGGDS were randomly selected from households from a complete census of persons living in the area. The Hopkins Symptom Checklist and the Harvard Trauma Questionnaire were used to assess anxiety and depression and post-traumatic stress symptoms. Results: Among 902 adult participants, food insecurity, stressful life events and symptoms of common mental disorders were highly prevalent. In separate multivariate models adjusting for potential confounders, food insecurity and stressful life events were independently associated with high symptoms of depression, anxiety and post-traumatic stress. Conclusions: Potentially modifiable stressors may influence variation in common mental disorders in Ethiopia, and SSA more generally. These findings suggest that the negative effects of food insecurity extend beyond nutritional outcomes and that interventions that promote food security may also positively influence adult mental health in the region.
Structure-dependent mobility of a dry aqueous foam flowing along two parallel channels.

The velocity of a two-dimensional aqueous foam has been measured as it flows through two parallel channels, at a constant overall volumetric flow rate. The flux distribution between the two channels is studied as a function of the ratio of their widths. A peculiar dependence of the velocity ratio on the width ratio is observed when the foam structure in the narrower channel is either single staircase or bamboo. In particular, discontinuities in the velocity ratios are observed at the transitions between double and single staircase and between single staircase and bamboo. A theoretical model accounting for the viscous dissipation at the solid wall and the capillary pressure across a film pinned at the channel outlet predicts the observed non-monotonic evolution of the velocity ratio as a function of the width ratio. It also predicts quantitatively the intermittent temporal evolution of the velocity in the narrower channel when it is so narrow that film pinning at its outlet repeatedly brings the flow to a near stop.
Growth Rate Pattern and Economic Traits of Silkworm, Bombyx Mori LUnder the Influence of Folic Acid Administration

Influence of oral administration of folic acid to 5th instar silkworm larvae of a popular Indian bivoltine hybrid (CSR2 x CSR4) was studied. Folic acid solution spraying on mulberry leaf and feeding to silkworm significantly improved larval weight, silk gland weight and growth rate. Higher larval and silk gland weight subsequently improved the economic parameters like cocoon weight, shell weight and shell ratio of folic acid treated batches.
Antioxidant Property of Coffee Components: Assessment of Methods that Define Mechanisms of Action

Coffee is a rich source of dietary antioxidants, and this property, coupled with the fact that coffee is one of the world’s most popular beverages, has led to the understanding that coffee is a major contributor to dietary antioxidant intake. Brewed coffee is a complex food matrix with numerous phytochemical components that have antioxidant activity capable of scavenging free radicals, donating hydrogen and electrons, providing reducing activity and also acting as metal ion pro-oxidant chelators. More recent studies have shown that coffee components can trigger tissue antioxidant gene expression and protect against gastrointestinal oxidative stress. This paper will describe different in vitro, cell-free and cell-based assays that both characterize and compare the antioxidant capacity and mechanism of action of coffee and its bioactive constituents. Moreover, evidence of cellular antioxidant activity and correlated specific genomic events induced by coffee components, which are relevant to antioxidant function in both animal and human studies, will be discussed.
The cylindrical bending of composite plates with piezoelectric and SMA layers

A laminated plate with orthotropic piezoelectric layers undergoing cylindrical bending under the application of electromechanical loading is considered. A known elasticity solution is extended to the coupled electroelastic field case by introducing, in addition to an Airy stress function, the electric potential for every layer. The validity of the way electric boundary conditions are applied in classical beam or plate theories is discussed. The electroelastic solution is applied to the non-linear case of a hybrid composite plate with piezoelectric layers attached to shape memory alloy (SMA) thin strips. An incremental piecewise elastic formation of the problem incorporates both stiffness changes and transformation strains in the SMA layers. The study of a laminated plate with PZT layers attached on both sides of an NiTi SMA layer shows that a full loading-unloading cycle in the applied electric field leads to energy dissipation in the laminated plate due to the dissipative process of stress induced martensitic phase transformation.
The biosynthetic gene cluster for coronamic acid, an ethylcyclopropyl amino acid, contains genes homologous to amino acid-activating enzymes and thioesterases

Coronamic acid (CMA), an ethylcyclopropyl amino acid derived from isoleucine, functions as an intermediate in the biosynthesis of coronatine, a chlorosis-inducing phytotoxin produced by Pseudomonas syringae pv. glycinea PG4180. The DNA required for CMA biosynthesis (6.9 kb) was sequenced, revealing three distinct open reading frames (ORFs) which share a common orientation for transcription. The deduced amino acid sequence of a 2.7-kb ORF designated cmaA contained six core sequences and two conserved motifs which are present in a variety of amino acid-activating enzymes, including nonribosomal peptide synthetases. Furthermore, CmaA contained a spatial arrangement of histidine, aspartate, and arginine residues which are conserved in the ferrous active site of some nonheme iron(II) enzymes which catalyze oxidative cyclizations. The deduced amino acid sequence of a 1.2-kb ORF designated cmaT was related to thioesterases of both procaryotic and eucaryotic origins. These data suggest that CMA assembly is similar to the thiotemplate mechanism of nonribosomal peptide synthesis. No significant similarities between a 0.9-kb ORF designated cmaU and other database entries were found. The start sites of two transcripts required for CMA biosynthesis were identified in the present study. pRG960sd, a vector containing a promoterless glucuronidase gene, was used to localize and study the promoter regions upstream of the two transcripts. Data obtained in the present study indicate that CMA biosynthesis is regulated at the transcriptional level by temperature.
Quality of life in patients with hepatocellular carcinoma received surgical resection

Hepatocellular carcinoma (HCC) is one the most common malignancies in the world. As the prognosis for HCC patients is poor, the quality of life (QOL) is becoming more important on the outcome assessments. The aim of this study was to evaluate QOL in HCC patients.
Improved Iterative MIMO Signal Detection Accounting for Channel-Estimation Errors

For the case of imperfect channel estimation, we propose an improved detector for multiple-input-multiple-output (MIMO) systems using an iterative receiver. We consider two iterative detectors based on maximum a posteriori and soft parallel-interference cancellation and propose, for each case, modifications to the MIMO detector by taking into account the channel-estimation errors. Considering training-based channel estimation, we present some numerical results for the case of Rayleigh block fading, which demonstrate an interesting performance improvement, compared with the classically used mismatched detectors. This improvement is obtained without a considerable increase in receiver complexity. It is more advantageous when few pilots are used for channel estimation. Thus, the proposed improved detectors are of particular interest under relatively fast-fading conditions, where it is important to reduce the number of pilots to avoid a significant loss in data rate.
Supersymmetric Kaluza-Klein reductions of M2 and M5-branes

We classify and construct all the smooth Kaluza–Klein reductions to ten dimensions of the M2- and M5-brane configurations which preserve some of the supersymmetry. In this way we obtain a wealth of new supersymmetric IIA backgrounds describing composite configurations of D-branes, NS-branes and flux/nullbranes; bound states of D2-branes and strings, D4-branes and NS5-branes, as well as some novel configurations in which the quotient involves nowhere-vanishing transverse rotations to the brane twisted by a timelike or lightlike translation. From these results there also follow novel M-theory backgrounds locally isometric to the M-branes, some of which are time-dependent and all of which are asymptotic to discrete quotients of eleven-dimensional Minkowski spacetime. We emphasise the universality of the formalism by briefly discussing analogous analyses in type IIA/IIB dual to the ones mentioned above. Some comments on the dual gauge theory description of some of our configurations are also included.
Embryo‐maternal dialogue during pregnancy establishment and implantation in the pig

Porcine conceptuses secrete pregnancy‐recognition signals (estrogens, including estradiol‐17β) that inhibit luteolysis, thereby prolonging progesterone production by corpora lutea. The supportive mechanism by which the conceptus also inhibits luteolysis is by shifting endometrial prostaglandin (PG) synthesis to luteoprotective PGE2. Progesterone stimulates endometrial production of factors that are essential for conceptus development. Priming the uterus by progesterone and loss of progesterone receptors from the uterine epithelium by D1ay 10–12 after estrus are key for achieving endometrial receptivity for implantation. Conceptus implantation involves a series of events, many resembling the inflammatory reaction, that are greatly influenced by cytokines, growth factors, and prostaglandins. We herein present a novel, dual role for PGF2α in corpora lutea that depends on the acquisition of luteolytic sensitivity, based on the knowledge that PGF2α triggers pathways involved in luteolysis during the estrous cycle or/and may have an alternative function in maintaining progesterone synthesis during pregnancy. We also point out a new role for PGF2α that, together with PGE2, can act as embryonic signal mediators. PGF2α, which until recently was considered undesirable for promoting pregnancy, is now known to stimulate conceptus‐maternal interactions and angiogenesis in the endometrium. This function is in line with other important prostaglandin functions, such as stimulating adhesion of trophoblasts (PGE2, PGI2) as well as endometrial vascular functions and trophoblast cell proliferation (PGI2). Finally, microRNAs have emerged as important post‐transcriptional regulators of gene function, adding a new area of investigation that may enhance understanding of conceptus‐endometrial interactions.
LIM kinase and Diaphanous cooperate to regulate serum response factor and actin dynamics

The small GTPase RhoA controls activity of serum response factor (SRF) by inducing changes in actin dynamics. We show that in PC12 cells, activation of SRF after serum stimulation is RhoA dependent, requiring both actin polymerization and the Rho kinase (ROCK)–LIM kinase (LIMK)–cofilin signaling pathway, previously shown to control F-actin turnover. Activation of SRF by overexpression of wild-type LIMK or ROCK-insensitive LIMK mutants also requires functional RhoA, indicating that a second RhoA-dependent signal is involved. This is provided by the RhoA effector mDia: dominant interfering mDia1 derivatives inhibit both serum- and LIMK-induced SRF activation and reduce the ability of LIMK to induce F-actin accumulation. These results demonstrate a role for LIMK in SRF activation, and functional cooperation between RhoA-controlled LIMK and mDia effector pathways.