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Excitonic/electronic coupling and cooperative interactions in self-assembled lead halide perovskite nanocrystals were reported to give rise to a collective low energy emission peak with accelerated dynamics. Here we report that similar spectroscopic features could appear as a result of the nanocrystal reactivity within the self-assembled superlattices. This is demonstrated by using CsPbBr3 nanocrystal superlattices under room temperature and cryogenic micro-photoluminescence spectroscopy. It is shown that keeping such structures under vacuum, a gradual contraction of the superlattices and subsequent coalescence of the nanocrystals occurs over several days. As a result, a narrow, low energy emission peak is observed at 4 K with a concomitant shortening of the photoluminescence lifetime due to the energy transfer between nanocrystals. When exposed to air, self-assembled CsPbBr3 nanocrystals develop bulk-like CsPbBr3 particles on top of the superlattices. At 4 K, these particles produce a distribution of narrow, low energy emission peaks with short lifetimes and excitation fluence-dependent, oscillatory decays, resembling the features of superfluorescence. Overall, the reactivity of CsPbBr3 nanocrystals dramatically alters the emission of their assemblies, which should not be overlooked when studying collective optoelectronic properties nor confused with superfluorescence effects., 50 pages, 26 figures

The paraphrasis of Feynman's statement is used to highlight the inherent relevance of surfaces -- and interfaces -- at the nanoscale. Here, the marked impact of the surface chemistry on the light absorption by colloidal inorganic semiconductor nanocrystals is discussed and demonstrated as general. Chemical species at the surface (ligands) of colloidal metal chalcogenide quantum dots (QDs) are shown to induce broadband absorption enhancement and band gap reduction. A comprehensive library of chalcogenol(ate) ligands is exploited to infer the role of surface chemistry on the QD optical absorption properties: ligand chalcogen binding atoms mainly determine band gap reduction, related to np occupied orbital contribution to the valence band edge, and mediates broadband absorption enhancement, fostered by the conjugation of the ligand pendant moiety, with further contribution from electron donor substituents. These findings point to a description of colloidal QDs that may conceive ligands as part of the overall QD electronic structure, beyond common models derived from analogies with core/shell heterostructures depicting ligands as mere perturbation to the core properties.

Chemists deal with matter and its transformations. They create chemical species into an infinite variety of combinations, at least until they have imagination. Some of them hold chemical species together trying to gain control on increasing matter complexity. Supermolecules are organized entities resulting from the self-assembly of two or more chemical species held together by intermolecular forces, thus representing a further step towards complexity compared to molecules as the latter do to atoms. Novel properties peculiar of the supramolecular systems thus arise and do not result from the simple superposition of those of the component units. Self-assembly of chemical species by weak, non covalent interactions is a widespread concept to Nature's forms and functions and is attracting increasing interest in artificial systems conceived to control mechanical movements, process information, and harvest sunlight. The present PhD thesis studies some supramolecular photoactive systems that act as antennas capable of collecting incident light and transfer excitation energy or electrons from one molecular component to another.

Healthcare managers are more and more interested in the role of general practitioners (GP) in the treatment of cardiovascular diseases. Continuing adjustments of the health organization are the old/new challenge in improving patient care. The European Society of Cardiology guidelines recommend a disease-management program for heart failure (HF); moreover, observational studies and randomized controlled trials have reported better patient outcomes if patients are in charge of cardiologists rather than GPs or other physicians. Patients with chronic HF are often very old and affected by multiple comorbid conditions, by themselves associated with high rates of morbidity and mortality. Furthermore, too many patients receive neither a correct diagnosis nor treatment until advanced disease occurs. New treatment approaches, some of them requiring the expertise of well-trained cardiologists, are ongoing to improve the clinical outcomes. The optimal management of patients with HF needs teamwork, i.e. GPs, cardiologists, nurses and caregivers, since a multidisciplinary program, only, can embody the best answer for outpatients with chronic HF. Currently, the Cardiovascular Center in Trieste is performing an experimental trial, so far never attempted before, in treating patients with chronic HF using a thorough approach with the full involvement of local cardiologists, GPs and nurses. Such approach is, at the same time, as well a challenge as an opportunity: a challenge because conventional clinical habits must be changed; an opportunity because patients can benefit from a proper whole care-group, aimed at prolonging life and reducing morbidity and symptoms.

Healthcare managers are more and more interested in the role of general practitioners (GP) in the treatment of cardiovascular diseases. Continuing adjustments of the health organization are the old/new challenge in improving patient care. The European Society of Cardiology guidelines recommend a disease-management program for heart failure (HF); moreover, observational studies and randomized controlled trials have reported better patient outcomes if patients are in charge of cardiologists rather than GPs or other physicians. Patients with chronic HF are often very old and affected by multiple comorbid conditions, by themselves associated with high rates of morbidity and mortality. Furthermore, too many patients receive neither a correct diagnosis nor treatment until advanced disease occurs. New treatment approaches, some of them requiring the expertise of well-trained cardiologists, are ongoing to improve the clinical outcomes. The optimal management of patients with HF needs teamwork, i.e. GPs, cardiologists, nurses and caregivers, since a multidisciplinary program, only, can embody the best answer for outpatients with chronic HF. Currently, the Cardiovascular Center in Trieste is performing an experimental trial, so far never attempted before, in treating patients with chronic HF using a thorough approach with the full involvement of local cardiologists, GPs and nurses. Such approach is, at the same time, as well a challenge as an opportunity: a challenge because conventional clinical habits must be changed; an opportunity because patients can benefit from a proper whole care-group, aimed at prolonging life and reducing morbidity and symptoms.

SummaryMiliary tuberculosis refers to the clinical disease resulting from the hematogenous dissemination of Mycobacterium tuberculosis. A tuberculous aneurysm of the aorta is exceedingly rare. Contiguous tuberculosis in the form of lymphadenitis is generally responsible for the aortic involvement. We report a case of tuberculous mycotic aneurysm in patient with miliary disease, not affected by a cellular immunodeficiency and with no other common risk factor for infection. He received anti-tubercular therapy and endovascular stenting before the identification of Mycobacterium tuberculosis in lung, lymph nodes, and gastric lavage. The clinician should be aware that a mycotic abdominal aortic aneurysm could be caused by M. tuberculosis, even if microbiological confirmation is lacking or is negative, especially if a contiguous focus of tubercular infection is detected.

Semiconductor quantum dots have been recently employed as luminescent probes for the detection of hazardous nitroaromatic compounds. Despite the high sensitivity, such detection systems involve laboratory procedures and employ complex instrumentation. Here, we demonstrate the use of colloidal PbS quantum dots as the main component of a chemiresistor for the detection of nitroaromatic compounds. The proposed device is low-cost, reusable, and produces an electric signal that can be acquired with off-the-shelf electronic components. In this paper, we demonstrate the operation of the proposed device and we discuss its sensing mechanism. We also show the sensor’s response to nitrobenzene in the 65 ppb–16 ppm range, estimating a theoretical detection limit of 2 ppb.

Here we present a colloidal approach to synthesize bismuth chalcohalide nanocrystals (BiEX NCs, in which E=S, Se and X=Cl, Br, I). Our method yields orthorhombic elongated BiEX NCs, with BiSCl crystallizing in a previously unknown polymorph. The BiEX NCs display a composition-dependent band gap spanning the visible spectral range and absorption coefficients exceeding 105 cm-1 . The BiEX NCs show chemical stability at standard laboratory conditions and form colloidal inks in different solvents. These features enable the solution processing of the NCs into robust solid films yielding stable photoelectrochemical current densities under solar-simulated irradiation. Overall, our versatile synthetic protocol may prove valuable in accessing colloidal metal chalcohalide nanomaterials at large and contributes to establish metal chalcohalides as a promising complement to metal chalcogenides and halides for applied nanotechnology.

Nowadays it is well-accepted to attribute bulk-like optical absorption properties to colloidal PbS quantum dots (QDs) at wavelengths above 400 nm. This assumption permits to describe PbS QD light absorption by using bulk optical constants and to determine QD concentration in colloidal solutions from simple spectrophotometric measurements. Here we demonstrate that PbS QDs experience the quantum confinement regime across the entire near UV-vis-NIR spectral range, therefore also between 350 and 400 nm already proposed to be sufficiently far above the band gap to suppress quantum confinement. This effect is particularly relevant for small PbS QDs (with diameter of ≤4 nm) leading to absorption coefficients that largely differ from bulk values (up to ∼40% less). As a result of the broadband quantum confinement and of the high surface-to-volume ratio peculiar of nanocrystals, suitable surface chemical modification of PbS QDs is exploited to achieve a marked, size-dependent enhancement of the absorption coefficients compared to bulk values (up to ∼250%). We provide empirical relations to determine the absorption coefficients at 400 nm of as-synthesized and ligand-exchanged PbS QDs, accounting for the broadband quantum confinement and suggesting a heuristic approach to qualitatively predict the ligand effects on the optical absorption properties of PbS QDs. Our findings go beyond formalisms derived from Maxwell Garnett effective medium theory to describe QD optical properties and permit to spectrophotometrically calculate the concentration of PbS QD solutions avoiding underestimation due to deviations from the bulk. In perspective, we envisage the use of extended π-conjugated ligands bearing electronically active substituents to enhance light-harvesting in QD solids and suggest the inadequacy of the representation of ligands at the QD surface as mere electric dipoles.

PbS colloidal quantum dots (CQDs) are attractive materials for the realization of simple, low-cost, high responsivity near-infrared photodetectors due to the large tunability of their optical properties together with their solution processability. In this work we propose multiple PbS CQD photoconductive devices with different spectral sensitivity realized on silicon substrates. We characterized the devices in terms of dark current, responsivity and response speed. Eventually, we discuss an algorithm for wavelength measurement of a quasi-monochromatic radiation based on linear combination of photocurrents from different photodetectors.

Here we investigate charge carrier generation and extraction processes in hybrid polymer/nanocrystal solar cells by means of time-resolved optical and photoelectrical techniques. We addressed the role of both poly(3-hexylthiophene) and colloidal arenethiolate-capped PbS quantum dots, which constitute the hybrid composite nanomaterial, in the photoinduced processes most relevant to device operation by changing the compositional ratio and applying chemical and thermal postdeposition treatments. The carrier generation processes were found to be wavelength-dependent: excitons generated in the polymer domains led to long-lived weakly bound charge pairs upon electron transfer to PbS nanocrystals; whereas charge carrier generation in the nanocrystal domains is highly efficient, although effective separation required the application of external electric field. Overall, charge carrier generation was found efficient and almost independent of the strength of applied electric field; therefore, competition between separation of electron–hole pairs into free carriers and geminate recombination is the major factor limiting the fill factor of nanocomposite-based solar cells. Device efficiency improvements thus require faster interfacial charge transfer processes, which are deeply related to the refinement of nanocrystal surface chemistry.

Colloidal quantum dots are composed of nanometer-sized crystallites of inorganic semiconductor materials bearing organic molecules at their surface. The organic/inorganic interface markedly affects forms and functions of the quantum dots, therefore its description and control are important for effective application. Herein we demonstrate that archetypal colloidal PbS quantum dots adapt their interface to the surroundings, thus existing in solution phase as equilibrium mixtures with their (metal-)organic ligand and inorganic core components. The interfacial equilibria are dictated by solvent polarity and concentration, show striking size dependence (leading to more stable ligand/core adducts for larger quantum dots), and selectively involve nanocrystal facets. This notion of ligand/core dynamic equilibrium may open novel synthetic paths and refined nanocrystal surface-chemistry strategies.

OBJECTIVES: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. DESIGN:Multicenter prospective study. SETTING: At emergency department admission in five University hospitals. PATIENTS:Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholipase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholipase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. CONCLUSIONS: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome

The RNA interference (RNAi) is a biological process by which a double stranded RNA (dsRNA also called small interfering RNA - siRNA) triggers the sequence-dependent degradation of a target RNA within the cellular environment. Thus siRNAs can be used to combat the expression of deleterious gene(s) causing disease or to destroy invading pathogen RNAs. Despite their enormous therapeutic potential, the use of siRNA as drugs presents two major problems: the difficulties to identify optimal delivery systems and the possible induction of different unwanted side effects. In this review, after presenting an overview about the mechanisms ruling the process of RNAi, we focus the attention on the description of the strategies developed to optimise systemic siRNA delivery; in this sense, considerations about the attempts to improve siRNA stability in the biological environment, the development of synthetic vectors for siRNA delivery, the siRNA bio-distribution and pharmacokinetics together with the selection of siRNA targeted delivery systems, are discussed. Since in the optimisation of the siRNA delivery systems the minimization of siRNA side effects should not be neglected, in the last part of the review we consider the problems related to the possible induction of siRNA mediated side effects focusing on the so called microRNA like off-targeting.

The prevalence of atrial fibrillation (AF) is related to age and is projected to rise exponentially as the populationages and the prevalence of cardiovascular risk factors increases. The risk of ischemic stroke is significantly increasedin AF patients, and there is evidence of a graded increased risk of stroke associated with advancingage. Oral anticoagulation (OAC) is far more effective than antiplatelet agents at reducing stroke risk in patientswith AF. Therefore, increasing numbers of elderly patients are candidates for, and could benefit from, the use ofanticoagulants. However, elderly people with AF are less likely to receive OAC therapy. This is mainly due to concernsabout a higher risk of OAC-associated hemorrhage in the elderly population. Until recently, older patientswere under-represented in randomized controlled trials of OAC versus placebo or antiplatelet therapy, and thereforethe evidence base for the value of OAC in the elderly population was not known. However, analyses of theavailable trial data indicate that the expected net clinical benefit of warfarin therapy is highest among patientswith the highest untreated risk for stroke, which includes the oldest age category. An important caveat with warfarintreatment is maintenance of a therapeutic international normalized ratio, regardless of the age of the patient,where time in therapeutic range should be 65%. Therefore, age alone should not prevent prescription ofOAC in elderly patients, given an appropriate stroke and bleeding risk stratification. (J Am Coll Cardiol 2010;56:827–37) © 2010 by the American College of Cardiology Foundation

For hepatocellular carcinoma (HCC), a leading cause of cancer death world-wide, there is no effective therapy especially for the advanced stage of the disease. Thus, we started the investigations about a novel anti HCC approach based on the depletion of the transcription factor serum response factor (SRF) in HCC cell lines; SRF choice was based on its recently proposed contribution to HCC tissue development and on its important role in cell proliferation. SRF depletion, obtained by a siRNA (siSRF797), was studied in two HCC cell lines, i.e. HepG2 and JHH6 assigned to high and low hepatocytic differentiation grade on the base of the capacity to synthesize albumin. In the HCC cell lines examined, siSRF797 reduced both the mRNA and protein levels of SRF without inducing unspecific interferon response or cytotoxicity. Moreover, SRF depletion induced the reduction of S-phase cells and a decrease in cell number and vitality. Particularly in HepG2, cell growth impairment was paralleled by the decrease of the levels of the transcription factor E2F1 together with some of its regulated genes. In HepG2 but not in JHH6, SRF depletion was associated with apoptosis. Finally, in both HepG2 and JHH6, the combined administration of siSRF797 and bortezomib, a proteasome inhibitor whose therapeutic potential for HCC is considered attractive, further reduced cell viability compared to either siSRF797 or bortezomib treatment alone. In conclusion, SRF depletion affects the expansion of the high and low differentiation grade HCC cells HepG2 and JHH6. These results can pave the way to understand the role of SRF in HCC development and possibly to identify novel anti HCC therapeutic strategies.

Time-resolved confocal fluorescence microscopy is used to image and analyze quantitatively the influence of 1,3,5-trinitrobenzene on the fluorescence of organic nanofibers. These nanofibers are formed by self-assembly of 2,3-didecyloxyanthracene in methanol or from solutions drop-casted onto glass surfaces. Amplification of the fluorescence quenching emerges in the nanofibers as compared to the constituting monomer thus leading to efficient detection of nanomolar concentrations of TNB. The emission of dry nanofibers on glass is also efficiently quenched by vapors of TNB.

Colloidal quantum dots (QDs) stand among the most attractive light-harvesting materials to be exploited for solution-processed optoelectronic applications. To this aim, quantitative replacement of the bulky electrically insulating ligands at the QD surface coming from the synthetic procedure is mandatory. Here we present a conceptually novel approach to design light-harvesting nanomaterials demonstrating that QD surface modification with suitable short conjugated organic molecules permits us to drastically enhance light absorption of QDs, while preserving good long-term colloidal stability. Indeed, rational design of the pendant and anchoring moieties, which constitute the replacing ligand framework leads to a broadband increase of the optical absorbance larger than 300% for colloidal PbS QDs also at high energies (>3.1 eV), which could not be predicted by using formalisms derived from effective medium theory. We attribute such a drastic absorbance increase to ground-state ligand/QD orbital mixing, as inferred by density functional theory calculations; in addition, our findings suggest that the optical band gap reduction commonly observed for PbS QD solids treated with thiol-terminating ligands can be prevalently ascribed to 3p orbitals localized on anchoring sulfur atoms, which mix with the highest occupied states of the QDs. More broadly, we provide evidence that organic ligands and inorganic cores are inherently electronically coupled materials thus yielding peculiar chemical species (the colloidal QDs themselves), which display arising (opto)electronic properties that cannot be merely described as the sum of those of the ligand and core components.\nColloidal quantum dots (QDs) stand among the most attractive light-harvesting materials to be exploited for solution-processed optoelectronic applications. To this aim, quantitative replacement of the bulky electrically insulating ligands at the QD surface coming from the synthetic procedure is mandatory. Here we present a conceptually novel approach to design light-harvesting nanomaterials demonstrating that QD surface modification with suitable short conjugated organic molecules permits us to drastically enhance light absorption of QDs, while preserving good long-term colloidal stability. Indeed, rational design of the pendant and anchoring moieties, which constitute the replacing ligand framework leads to a broadband increase of the optical absorbance larger than 300% for colloidal PbS QDs also at high energies (>3.1 eV), which could not be predicted by using formalisms derived from effective medium theory. We attribute such a drastic absorbance increase to ground-state ligand/QD orbital mixing, as inferred by density functional theory calculations; in addition, our findings suggest that the optical band gap reduction commonly observed for PbS QD solids treated with thiol-terminating ligands can be prevalently ascribed to 3p orbitals localized on anchoring sulfur atoms, which mix with the highest occupied states of the QDs. More broadly, we provide evidence that organic ligands and inorganic cores are inherently electronically coupled materials thus yielding peculiar chemical species (the colloidal QDs themselves), which display arising (opto)electronic properties that cannot be merely described as the sum of those of the ligand and core components.

Hy brid composites obtained upon blending conjugated polymers and colloidal inorganic semiconductor nanocrystals are regarded as attractive photo-active materials for optoelectronic applications. Here we demonstrate that tailoring nanocrystal surface chemistry permits to exert control on non-covalent bonding and electronic interactions between organic and inorganic components. The pendant moieties of organic ligands at the nanocrystal surface do not merely confer colloidal stability while hindering charge separation and transport, but drastically impact morphology of hybrid composites during formation from blend solutions. The relevance of our approach to photovoltaic applications is demonstrated for composites based on poly(3-hexylthiophene) and Pbs nanocrystals, considered as inadequate before the submission of this manuscript, which enable the fabrication of hybrid solar cells displaying a power conversion efficiency that reaches 3 %. Upon (quasi)steady-state and time-resolved analisys of the photo-induced processes in the nanocomposites and their organic and inorganic components, we ascertained that electron transfer occurs at the hybrid interface yielding long-lived separated charge carriers, whereas interfacial hole transfer appears slow. Here we provide a reliable alternative aiming at gaining control over macroscopic optoelectronic properties of polymer/nanocrystal composites by acting at the molecular-level via ligands' pendant moieties, thus opening new possibilities towards efficient solution-processed hybrid solar cells.

We have fabricated UV-sensitive photodetectors based on colloidal CdS nanocrystals and graphene. The nanocrystals act as a sensitizer layer that improves light harvesting leading to high responsivity of the detector. Despite the slow relaxation of the photogenerated charges in the nanocrystal film, faster processes allowed to detect pulses up to a repetition rate of 2 kHz. We have performed time-resolved analysis of the processes occurring in our hybrid system, and discuss possible photo-induced charge transfer mechanisms., Comment: 11 pages, 5 figures

Hybrid nanocomposites (HCs) obtained by blend solutions of conjugated polymers and colloidal semiconductor nanocrystals are among the most promising materials to be exploited in solution-processed photovoltaic applications. The comprehension of the operating principles of solar cells based on HCs thus represents a crucial step toward the rational engineering of high performing photovoltaic devices. Here we investigate the effect of conjugated polymers on hybrid solar cell performances by taking advantage from an optimized morphology of the HCs comprising lead sulfide quantum dots (PbS QDs). Uncommonly, we find that larger photocurrent densities are achieved by HCs incorporating wide-bandgap polymers. A combination of spectroscopic and electro-optical measurements suggests that wide-bandgap polymers promote efficient charge/exciton transfer processes and hinder the population of midgap states on PbS QDs. Our findings underline the key role of the polymer in HC-based solar cells in the activation/deactivation of charge transfer/loss pathways.

Purpose: To assess if a polymorphism (PM) of the microsatellite (CA13–27) in the promoter region of Matrix Metalloproteinase 9 (MMP-9) was associated with the exudative form of age-related macular degeneration (AMD) and to its risk factors. Methods: In 107 patients with AMD (AMD Group) and 223 age- and gender-matched controls (Control Group) with cataract, demographic, clinical data, and MMP-9 PM have been compared. Results: The comparison of allelic frequencies showed a different pattern of CA repeats between AMD and Control Group (P < 0.00005), in particular the prevalence of longer microsatellites (≥ 22 CA repeats) was higher in AMD than in Control Group (O.R. 2.49, 95% CI 1.71 - 3.37, P < 0.001). Analyses of genetic frequencies gave similar results. Logistic regression confirmed that 22 or more CA repeats are associated to AMD. The only association between MMP-9 PM and other risk factors for AMD was with BMI (Spearman’s R = 0.298, P < 0.00005): all patients with both microsatellites ≥ 22 CA repeats were overweight or obese (χ2 test P < 0.0005, compared to other genotypes). Conclusions: Longer microsatellites in the promoter of MMP-9 are associated to the exudative form of AMD and to body mass index, a well-known risk factor for the disease.

A polymorphism (PM) in the microsatellite of the promoter region of matrix metalloproteinase 9 (MMP-9), modulating its expression, could play a role in susceptibility to multiple sclerosis (MS). MMP-9 PM was determined in 95 patients with MS (MS Group) and 95 ageand sex-matched controls (Control Group). Comparison of allelic frequencies showed that a higher number of CA repeats characterized the MS group ( P < 0.0001) and prevalence of carriers of z22 CA repeats was higher in the MS than in the Control Group (OR 3.4, 95% CI: 1.7–6.8, P < 0.0001). An earlier age at disease onset was a characteristic of patients with >22 CA repeats (33F10 vs. 28F10, P= 0.027). No differences were found in the main MRI parameters.

Suitable post-synthesis surface modification of lead-chalcogenide quantum dots (QDs) is crucial to enable their integration in photovoltaic devices. We have developed a solution-phase ligand exchange strategy that exploits arenethiolate anions to replace the pristine oleate ligands on PbS QDs, while preserving the long-term colloidal stability of QDs and allowing their solution-based processability into photoconductive thin-films. Complete QD surface modification is demonstrated by IR spectroscopy analysis, whereas UV-Vis-NIR Absorption Spectroscopy provides quantitative evaluation of stoichiometry and thermodynamic stability of the resulting system. Arenethiolate ligands permit to reduce the inter-particle distance in PbS QD solids, leading to a drastic improvement of the photoinduced charge transport properties. Therefore, smooth dense-packed thin-films of arenethiolate-capped PbS QDs obtained via a single solution-processing step are integrated in heterojunction solar cells: such devices generate remarkable photocurrent densities (14 mA cm(-2)) and overall efficiencies (1.85%), which are outstanding for a single PbS QD layer. Solution-phase surface modification of QDs thus represents an effective intermediate step towards low-cost processing for all-inorganic and hybrid organic/inorganic QD-based photovoltaics. (c) 2013 Elsevier B.V. All rights reserved.

Exciton–polaritons in semiconductors are quasi-particles which have recently shown the capability to undergo phase transition into a coherent hybrid state of light and matter. The observation of such quasi-particles in organic microcavities has attracted increasing attention for their characteristic of reaching condensation at room temperature. In this work, the emission properties of organic polaritons are demonstrated not to depend on the overlap between the absorption and emission states of the molecule and that the emission dynamics are modifi ed in the strong coupling regime, showing a signifi cant enhancement of the photoluminescence intensity as compared to the bare dye. This paves the way to the investigation of molecules with large absorption coeffi cients but poor emission effi ciencies for the realization of polariton condensates and organic electrically injected lasers by exploiting strong exciton-photon coupling regimes.

The objective of the study was to determine the accuracy of phospholipase A2 group II (PLA2-II), interferon-gamma-inducible protein 10 (IP-10), angiopoietin-2 (Ang-2), and procalcitonin (PCT) plasma levels in early ruling in/out of sepsis among systemic inflammatory response syndrome (SIRS) patients. Biomarker levels were determined in 80 SIRS patients during the first 4 h of admission to the medical ward. The final diagnosis of sepsis or non-infective SIRS was issued according to good clinical practice. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for sepsis diagnosis were assessed. The optimal biomarker combinations with clinical variables were investigated by logistic regression and decision tree (CART). PLA2-II, IP-10 and PCT, but not Ang-2, were significantly higher in septic (n = 60) than in non-infective SIRS (n = 20) patients (P ≤ 0.001, 0.027, and 0.002, respectively). PLA2-II PPV and NPV were 88 and 86 %, respectively. The corresponding figures were 100 and 31 % for IP-10, and 93 and 35 % for PCT. Binary logistic regression model had 100 % PPV and NPV, while manual and software-generated CART reached an overall accuracy of 95 and 98 %, respectively, both with 100 % NPV. PLA2-II and IP-10 associated with clinical variables in regression or decision tree heterogeneous models may be valuable biomarkers for sepsis diagnosis in SIRS patients admitted to medical ward (MW). Further studies are needed to introduce them into clinical practice.

Therapy with Vitamin K antagonists (VKA) effectively reduces the thrombosis risk in many clinical conditions. Genetic variants of vitamin K epoxide reductase (VKORC-1) are associated with increased VKA effect and bleeding risk. It is unknown whether these variants could also affect the long-term outcome in patients with high-dosage oral anticoagulation and/or more difficult adherence to the therapeutic INR range. Hundred and twenty-four patients with mechanical heart valve replacement assuming VKA were genotyped for VKORC-1 −1639G>A (Rs9923231) polymorphism. Hemorrhage, venous thrombosis and atherothrombotic events were retrospectively assessed for a 6-year period. Furthermore, stability of their INR in relationship with the VKORC-1 genotype was investigated day-by-day for 3 months. No differences were observed in hemorrhage and venous thrombosis events according to rs 9923231. GG genotype carriers (n = 41) had no atherothrombotic events, while 4 strokes, 4 TIA and 3 AMI were diagnosed in A carriers (n = 83; P = 0.0008). During the daily observation period, A allele carriers had lower VKA requirements (4.7, 3.7, 2.2 mg/day for GG/GA/AA genotype respectively; P = 0.00001), higher mean INR (2.7, 2.8, 2.9; P = 0.05) and a higher number of examinations above the therapeutic range than GG carriers (17 % vs. 0 % in GG genotype, P = 0.036). Conversely, patients with GG genotype had a more stable dosage of VKA (P = 0.006) and a higher percentage of examinations under the therapeutic range (51, 43 and 36 % in GG, GA and AA genotype, respectively, P = 0.040). In patients with high dosage VKA, VKORC-1 polymorphism is associated to a different warfarin dosage, anticoagulation level, time spent outside the therapeutic range and, in the long-term, a different incidence of atherothrombotic events.

Critically ill patients (CIP) are patients who, because of dysfunction or failure of one or more organs/systems, depend on advanced instruments for monitoring and therapy for their survival. Coagulation abnormalities are common in CIP. The most common (35–44%) is thrombocytopenia (platelet count less than 150,000/µl), due to sepsis, disseminated intravascular coagulation (DIC), thrombotic microangiopathy, or induced by drugs, such as heparin. Prolonged global coagulation times, beyond antithrombotic therapy, are also found, and are a result of quantitative defects of coagulation factors, caused by synthesis defects (liver insufficiency), excessive loss (massive hemorrhage), or consumption (DIC), low levels of one or more coagulation factors due to antibodies, antiphospholipid antibodies, or the presence of inhibitors. This chapter provides information on the principles, clinical significance, technology, and open problems in laboratory assessment of hemostasis in critically ill patients.

Background: In prostate adenocarcinoma, the dissection of the expression behaviour of the eukaryotic elongation factors (eEF1A1/2) has not yet fully elucidated. Methods: The EEF1A1/A2 expressions were investigated by real-time PCR, western blotting (cytoplasmic and cytoskeletal/nuclear-enriched fractions) and immunofluorescence in the androgen-responsive LNCaP and the non-responsive DU-145 and PC-3 cells, displaying a low, moderate and high aggressive phenotype, respectively. Targeted experiments were also conducted in the androgen-responsive 22Rv1, a cell line marking the progression towards androgen-refractory tumour. The non-tumourigenic prostate PZHPV-7 cell line was the control. Results: Compared with PZHPV-7, cancer cells showed no major variations in EEF1A1 mRNA; eEF1A1 protein increased only in cytoskeletal/nuclear fraction. On the contrary, a significant rise of EEF1A2 mRNA and protein were found, with the highest levels detected in LNCaP. Eukaryotic elongation factor 1A2 immunostaining confirmed the western blotting results. Pilot evaluation in archive prostate tissues showed the presence of EEF1A2 mRNA in near all neoplastic and perineoplastic but not in normal samples or in benign adenoma; in contrast, EEF1A1 mRNA was everywhere detectable. Conclusion: Eukaryotic elongation factor 1A2 switch-on, observed in cultured tumour prostate cells and in human prostate tumour samples, may represent a feature of prostate cancer; in contrast, a minor involvement is assigned to EEF1A1. These observations suggest to consider EEF1A2 as a marker for prostate cell transformation and/or possibly as a hallmark of cancer progression.

Genetic defects accounting for increased prothrombotic risk are related to antithrombin, prothrombin, protein C, protein S, and factor V. These defects can induce a wide array of clinical relevance and total a few hundred. Suspicion of the defect derives from clinical observation of spontaneous thrombosis either in the deep veins of the leg or in atypical sites (cerebral sinus, mesenteric hepatic veins) and/or at a young age ranging from intrauterine life (hence spontaneous abortion) until 50 years of age. The diagnosis can be frustrating because it requires combined techniques of hemostaseology and molecular biology and is therefore time- and resource-consuming, because only some of the above-mentioned events are associated with genetic defects, and not all identified carriers have the same risk. This reflects on their management, with recommendations for each condition at increased thrombotic risk, such as surgery, immobility, venous or arterial thromboembolism, and pregnancy.

The co-self-assembly of a blue-light emitting organogelator and specifically designed green and red emitting hosts yields light-harvesting nanofibers with tunable emissive properties. In particular, under near-UV excitation white-light emission is achieved in organogels and their constituting nanofibers as demonstrated by confocal fluorescence microspectroscopy. Steady-state and time-resolved emission spectroscopies reveal that color tuning in three component nanofibers is achieved exploiting excitation energy transfers occurring between the blue-emitting anthracene derivative and the green- and red-emitting tetracenes, whereas the latter emission is further sensitized through a cascade blue-to-green-to-red transfer sequence. Moreover, excitation energy migrates through the blue-emitting components by exciton hopping before being transferred to the acceptors, thus contributing to the light-harvesting process.

Aptamer researches applied to the treatment of human cancers have increased since their discovery in 1990. This is due to different factors including: 1) the technical possibility to select, by SELEX-based procedures, specific aptamers targeting virtually any given molecule, 2) the aptamer favorable bio-activity in vivo, 3) the low production costs and 4) the ease synthesis and storage for the marketing. In the field of cancer treatments, aptamers have been studied as tumor-specific agents driving drugs into cancer cells; additionally they have been used as anti-neoplastic agents per se, able to inhibit tumor cell growth and dissemination when administered alone or in combination with conventional anti-neoplastic drugs. Aptamers are gaining an increased interest for pharmaceutical companies and some of them are under clinical evaluation trials. In this review we update the findings about the use of aptamers as “escort" molecules able to drive drugs into the cells and as anti-neoplastic drugs per se. Current anti-neoplastic treatments suffer for the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemiotherapics into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemiotherapics. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use.

Objective: To assess the association of matrix metalloproteinases (MMP) genetic polymorphism (PM) with plaques vulnerability and clinical outcome of acute vascular events. Methods: MMP-1 (-1607 G in/del), MMP-3 (-1171 A in/del), and MMP-9 microsatellite (13–26 CA repeats around -90) PMs have been determined (i) in 204 patients with cerebrovascular disease to assess the association with features of vulnerability in carotid plaques and prevalence of stroke, (ii) in 208 patients with UA/NSTEMI to assess the association with in-hospital clinical outcome. Results: Plaques from carriers of MMP-1 G insertion showed significantly smaller plaques and thicker fibrous cap. In CVD patients carrying such variant, Odds Ratio for previous stroke was 0.27 (95% C.I. 0.13–0.56, P = 0.0002) and, in UA/NSTEMI patients, the risk of Major Adverse Cardiac Events (MACE, persistent angina, NSTEMI, and vascular death) was 0.22 (95% C.I. 0.11–0.44, P < 0.0001).Novariants inMMP-3 PM were associated to differences in either plaque features or clinical outcome. Carriers of MMP-9≥22 repeats in the microsatellite had larger plaques and lipid core. In CVD patients with such variant, Odds Ratio for stroke was 2.2 (95% C.I. 1.1–4.4) and, in UA/NSTEMI patients, MACE risk was 4.1 (95% C.I. 2.3–7.4, P < 0.0001). Persistent angina and NSTEMI separately provided comparable results. Conclusions: Carriers of MMP-1 G insertion show smaller and more stable plaques, as well as better prognosis in acute vascular events, while patients with ≥22 repeats in MMP-9 have larger necrotic core and worse prognosis in UA/NSTEMI.

The self-assembly of a blue-emitting light-harvesting organogelator and specifically designed highly fluorescent tetracenes yields nanofibers with tunable emissive properties. In particular, under near-UV excitation, white light emission is achieved in organogels and dry films of nanofibers. Confocal fluorescence microspectroscopy demonstrates that each individual nanofiber emits white light. A kinetic study shows that an energy transfer (ET) occurs between the blue-emitting anthracene derivative and the green- and red-emitting tetracenes, while inter-tetracene ETs also take place. Moreover, microscopy unravels that the nanofibers emit polarized emission in the blue spectral region, while at wavelengths higher than 500 nm the emission is not significantly polarized.

Background No effective therapy is available for hepatocellular carcinoma. To identify novel therapeutic strategies, we explored the effects of the depletion of E2F1, cyclin E1–E2 whose inter-relationships in hepatocellular carcinoma cell proliferation have never been defined. Methods siRNA-mediated depletion of the targets was studied in the hepatocellular carcinoma cells HepG2, HuH7 and JHH6 characterized by high, medium and low hepatocyte differentiation grade, respectively; a model of normal human hepatocytes was also considered. Results The depletion of each target mRNA reduced the levels of the other two mRNAs, thus demonstrating a close regulatory control, also confirmed by over-expression experiments. At the protein level, an exception to this trend was observed for cyclinE1 whose amount increased upon cyclin E2 (HepG2, HuH7, JHH6) and E2F1 (HepG2) depletion. In HepG2, reduced cyclinE1 proteolysis accounted for this observation. Additionally, cyclin E1–E2–E2F1 targeting decreased the levels of cyclin A2 mRNA and of the hyper-phosphorylated form of pRb thus leading to an S-phase cell decrease; migration was impaired as well. Finally, the model of human hepatocytes used was clearly less affected by target mRNAs depletion than hepatocellular carcinoma cells. Conclusion Our data provide novel mutual relationships amongst cyclin E1–E2–E2F1 and indicate their role in sustaining hepatocellular carcinoma cell proliferation/migration, validating the concept of an anti-cyclin E1–E2–E2F1 therapeutic approach for hepatocellular carcinoma.

Aim. Matrix metalloproteinase 1 (MMP-1) and 9 (MMP-9) are alleged to influence atherosclerotic plaques evolution, vulnerability (tendency to rupture), and development of vascular events. MMPs expression depends on environmental stimuli and functional (i.e. determining differential gene expression) genetic polymorphisms (PM). This study evaluates the relationship between MMP PM and carotid plaque features of vulnerability. Methods. Histopathological traits of plaque instability (plaque and lipid core size, fibrous cap thickness, erosion, thrombosis, macrophages, smooth muscle cells [SMC], and elastic fibers content) have been determined in 31 carotid plaques obtained from thromboendarterectomy and then compared according to a genetic MMP-1 PM (rs1799750, G insertion/deletion at -1607) and MMP-9 PM (rs3222264, CA microsatellite around -90) of the carrier patients. Results. Carriers of MMP-1 G insertion have, on average, a smaller plaque and a thicker fibrous cap (standardized by plaque size) with higher SMC and elastic fibers content. Carriers of more than 21 repeats in MMP-9 microsatellite have plaques with larger lipid core. Conclusions. In carotid plaques, a MMP-1 genetic variant accounting for higher expression is associated with histopathology signs of less vulnerable plaques, while MMP-9 genotypes increasing expression are associated with a trait of plaque vulnerability. MMP-1 and MMP-9 can have an opposite role, protective for the former, causative for the latter, in determining atherosclerotic plaque evolution.

International audience; Selective nucleophilic substitution on a perfluorophenyl unit comprising a BODIPY fluorophore using an alkanethiol or a primary amine offers a quantitative fluorophore labelling strategy, while retaining high photostability and emission quantum yields approaching unity.

Two shape-persistent macrocycles with a hexagonal backbone incorporating two bpy units and two nonchromophoric methoxytetrahydropyran units (M), or two coumarin 2 dyes (C2-M-C2) are highly absorbing and emitting species in dichloromethane solution (epsilon(max) = 1.90 x 10(5) M-1 cm(-1) at 308 nm and 1.92 x 10(5) M-1 cm(-1) at 309 nm; phi(em) = 0.60 and 0.73, tau = 0.76 and 3.6 ns for M and C2-M-C2, respectively). Time-resolved fluorescence anisotropy measurements of M in dichloromethane has given information on the hydrodynamic volume of the free macrocycle in solution, which is close to the molecular volume measured by X-ray crystallographic analysis. M and C2-M-C2 are very good ligands for lanthanide ions (Nd3+ and Gd3+): they form complexes with 1:2, 1:1 and 2:1 (clearly evident only in the case of M) metal to ligand stoichiometry. These complexes are characterised by very high association constants in dichloromethane solution, as demonstrated by significant changes to the photophysical properties of the macrocycles. In the 1:2 and 1:1 complexes, the lanthanide ion is likely sandwiched between two macrocycles and coordinated by two bpy units. The efficiency of energy transfer from the ligand to the lanthanide ion is quite high (73% in the case of the [Nd2M](6+) complex), and it is not sensitive to the presence of oxygen. For the Nd3+ complexes with the C2-M-C2 macrocycle, sensitisation of the lanthanide NIR emission takes place with lower efficiency (ca. 50%), due to a competitive electron transfer process from the coumarin to the complexed macrocycle. Lastly, upon addition of an excess of a competitive ligand, all the absorption and emission spectroscopic changes are completely reversible.

Smooth muscle cells (SMCs) can switch between a differentiated/contractile and an alternative proliferative phenotype. The transcription factor serum response factor (SRF) has been implicated in the regulation of gene expression profiles determining both phenotypes. Whereas strong evidence exists for a role of SRF in SMC differentiation, the contribution of SRF to SMC proliferation is less well defined. For primary human vascular SMCs in particular, existing data are non-conclusive. To study SRF functions in primary human vascular SMCs, we used an siRNA approach. siRNA-mediated SRF suppression affected the expression of established SRF target genes such as smooth muscle alpha-actin (ACTA2) or SM22alpha (TAGLN) and decreased both F-actin formation and cell migration. Furthermore, SRF knockdown caused a cell-cycle arrest in G1 associated with reduced hyperphosphorylated pRB, cyclin A and SKP2 levels, and increased p27(kip1) (CDKN1B) protein levels. SRF-depleted cells expressed senescence-associated beta-galactosidase indicating an irreversible G1 arrest. siRNA-mediated suppression of SKP2 triggered senescence to a similar extent as SRF depletion, indicating that SRF knockdown-induced senescence may be dependent on a decrease in SKP2. Thus, SRF is an essential regulator of primary human vascular SMC proliferation and senescence. Interfering with SRF function may therefore be a promising strategy for the treatment of hyperproliferative SMC disorders such as atherosclerosis and in-stent restenosis.

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The self-assembly of a low molecular weight organic chromophore occurs upon reprecipitation in water and yields 120 nm wide disk-like nanoparticles (NPs), as shown by fluorescence correlation spectroscopy (FCS) and atomic force microscopy (AFM). The NPs are able to incorporate perylene molecules previously present in water at nanomolar concentrations, thus switching ON and sensitizing their fluorescence. The doped NPs display a very high brightness as a result of their significant fluorescence quantum yield (up to 48%), the cumulated molecular absorbance, and the light-harvesting process. Fluorescence polarization spectroscopy also reveals that the efficiency of the donor-to-acceptor energy transfer process is amplified by a donor-to-donor excitation energy migration.

We have investigated the complex formation between dendritic guests and a molecular tweezer host by NMR, absorption, and emission spectroscopy as well as electrochemical techniques. The dendrimers are constituted by an electron-acceptor 4,4'-bipyridinium core appended with one (DnB(2+)) or two (Dn(2)B(2+)) polyaryl-ether dendrons. Tweezer T comprises a naphthalene and four benzene components bridged by four methylene groups. Medium effects on molecular recognition phenomena are discussed and provide insight into the conformation of dendrimers: change in solvent polarity from pure CH(2)Cl(2) to CH(2)Cl(2)/CH(3)CN mixtures and addition of tetrabutylammonium hexafluorophosphate (NBu(4)PF(6), up to 0.15 M), the supporting electrolyte used in the electrochemical measurements, have been investigated. The association constants measured in different media show the following trend: (i) they decrease upon increasing polarity of the solvent, as expected for host-guest complexes stabilized by electron donor-acceptor interactions; (ii) no effect of generation and number of dendrons (one for the DnB(2+) family and two for the Dn(2)B(2+) family) appended to the core is observed in higher polarity media; and (iii) in a low-polarity solvent, like CH(2)Cl(2), the stability of the inclusion complexes is higher for DnB(2+) dendrimers than for Dn(2)B(2+) ones, while within each dendrimer family it increases by decreasing dendron generation, and upon addition of NBu(4)PF(6). The last result has been ascribed to a partial dendron unfolding. Kinetic investigations performed in lower polarity media evidence that the rate constants of complex formation are slower for symmetric Dn(2)B(2+) dendrimers than for the nonsymmetric DnB(2+) ones, and that within the Dn(2)B(2+) family, they decrease by increasing dendron generation. The dependence of the rate constants for the formation and dissociation of the complexes upon addition of NBu(4)PF(6) has also been investigated and discussed.

Hammerhead ribozymes (HRz), catalytic RNA molecules capable of inducing the site-specific cleavage of a phosphodiester bond within an RNA molecule, are typically introduced into target cells by specific constructs (such as viral vectors) able to drive their expression from defined expression cassettes (promoter). This strategy implies the presence of promoter-derived sequences bound to the hammerhead ribozyme structure, a fact which can unpredictably affect HRz cleavage efficiency and eventually the biological effect. We explored the effects of promoter-derived sequences on the cleavage kinetics of an HRz targeted against a relevant cell cycle regulator, i.e. cyclin E1, implicated in the pathogenesis of several human diseases including in-stent restenosis and hepatocellular carcinoma. Sequences derived form the most commonly used promoters (CMV, T7, Pol I and Pol III promoters) were added to the minimal HRz structure and their effects on the cleavage kinetic constants k(cat) and K(m) evaluated in vitro under single turn-over conditions, using a mathematical model we recently developed. The different promoter derived sequences variably affected HRz cleavage efficiency (k(cat)/K(m)) with those derived from the pol III and from a truncated form of T7 promoter (T7-S), impairing maximally and minimally k(cat)/K(m), respectively. Additionally, the extra sequences tend to increase K(m) and to reduce k(cat). The extent of this effect depends both on the secondary RNA structure and on the length of the added sequences. In conclusion, these data, together with further work in cultured cells, can lead to the selection of optimal expression cassettes thus contributing to improve HRz efficacy, bringing these molecules closer to practical applications.