Direct-EI in LC-MS: towards a universal detector for small-molecule applications

This review article will give an up-to-date and exhaustive overview on the efficient use of electron ionization (EI) to couple liquid chromatography and mass spectrometry (LC-MS) with an innovative interface called Direct-EI. EI is based on the gas-phase ionization of the analytes, and it is suitable for many applications in a wide range of LC-amenable compounds. In addition, thanks to its operating principles, it prevents unwelcome matrix effects (ME). In fact, although atmospheric pressure ionization (API) methodologies have boosted the use of LC-MS, the related analytical methods are sometime affected by inaccurate quantitative results, due to unavoidable and unpredictable ME. In addition, API's soft ionization spectra always demand for costly and complex tandem mass spectrometry (MS/MS) instruments, which are essential to acquire an "information-rich" spectrum and to obtain accurate quantitative information. In EI a one-stage analyzer is sufficient for a qualitative investigation and MS/MS detection is only used to improve sensitivity and to cut chemical noise. The technology illustrated here provides a robust and straightforward access to classical, well-characterized EI data for a variety of LC applications, and readily interpretable spectra for a wide range of areas of research. The Direct-EI interface can represent the basis for a forthcoming universal LC-MS detector for small molecules.     

Assessing the potential of SeaWiFS and MODIS for estimating chlorophyll concentration in turbid productive waters using red and near-infrared bands

Bio-optical algorithms for remote estimation of chlorophyll-a concentration (Chl) in case-1 waters exploit the upwelling radiation in the blue and green spectral regions. In turbid productive waters other constituents, that vary independently of Chl, absorb and scatter light in these spectral regions. As a consequence, the accurate estimation of Chl in turbid productive waters has so far not been feasible from satellite sensors. The main purpose of this study was to evaluate the extent to which near-infrared (NIR) to red reflectance ratios could be applied to the Sea Wide Field-of-View Sensor (SeaWiFS) and the Moderate Imaging Spectrometer (MODIS) to estimate Chl in productive turbid waters. To achieve this objective, remote-sensing reflectance spectra and relevant water constituents were collected in 251 stations over lakes and reservoirs with a wide variability in optical parameters (i.e. 4 ≤ Chl ≤ 240 mg m^− 3; 18 ≤ Secchi disk depth ≤ 308 cm). SeaWiFS and MODIS NIR and red reflectances were simulated by using the in-situ hyperspectral data. The proposed algorithms predicted Chl with a relative random uncertainty of approximately 28% (average bias between − 1% and − 4%). The effects of reflectance uncertainties on the predicted Chl were also analyzed. It was found that, for realistic ranges of R_rs uncertainties, Chl could be estimated with a precision better than 40% and an accuracy better than ± 35%. These findings imply that, provided that an atmospheric correction scheme specific for the red-NIR spectral region is available, the extensive database of SeaWiFS and MODIS images could be used to quantitatively monitor Chl in turbid productive waters.     

On‐Chip Magnetic Platform for Single‐Particle Manipulation with Integrated Electrical Feedback

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high‐throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig‐zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1‐μm sized beads is demonstrated.     

Effect of bio-optical parameter variability on the remote estimation of chlorophyll-a concentration in turbid productive waters: experimental results

The analytical development and underlying hypothesis of a three-band algorithm for estimating chlorophyll-a concentration ([Chla]) in turbid productive waters are presented. The sensitivity of the algorithm to the spectral location of the bands used is analyzed. A large set of experimental observations ([Chla] varied between 4 and 217 mg m(-3) and turbidity between 2 and 78 nephelometric turbidity units) was used to calibrate and validate the algorithm. It was found that the variability of the chlorophyll-a fluorescence quantum yield and of the chlorophyll-a specific absorption coefficient can reduce considerably the accuracy of remote predictions of [Chla]. Instead of parameterizing these interferences, their effects were minimized by tuning the spectral regions used in the algorithm. This allowed us to predict [Chla] with a relative root-mean-square error of less than 30%.     

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.     

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η⁶-arene)Ru(N,N′)L][PF₆]₂ containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λ_max = 418 nm) compared with C1 and C2 (λ_max = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC₅₀ = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).     

A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.     

Chelating Polymers for Targeted Decontamination of Actinides: Application of PEI-MP to Hydroxyapatite-Th(IV)

In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.     

Study of relationship between temperature and thermal energy,operating conditions as well as environmental factors in large‐scale lithium‐ion batteries

We have developed a thermal model for a large‐scale lithium‐ion cell and have simulated its thermal behaviors during charge, discharge, and charge–discharge cycles with different current rates by using the software of COMSOL Multiphysics 3.5a. In this work, thermal energy and its distribution were firstly calculated based on experimental data under different operating conditions. A new parameter, called thermal energy conversion efficiency, was proposed to describe relative value of thermal energy in the cell. The thermal energy conversion efficiency and the temperature were plotted in a figure to show their relativity. The temperature variation was also studied systemically when the cell underwent discharge–charge cycles. A low rate charge is validated to be a favorable factor in protecting the cell from overheating during charge–discharge cycles. A connection resistance is proved to be a main factor that accelerates the rise of temperature in the spot near a terminal column, which should be eliminated as much as possible to protect the cell from local overheating. Copyright © 2014 John Wiley & Sons, Ltd.     

The effect of operating and design parameter on bubble column performance: The LOPROX case study

It is known that the performances of multi-phase reactors depend on the operating parameters (the temperature and the pressure of the system), the phase properties, and the design parameters (the aspect ratio (AR), the bubble column diameter, and the gas sparger design). Hence, the precise design and the correct operation of multi-phase reactors depends on the understanding and prediction of the fluid dynamics parameters. This paper contributes to the existing discussion on the effect of operating and design parameter on multi-phase reactors and, in particular, it considers an industrial process (e.g., the LOPROX (low pressure oxidation) case study, which is typical example of two-phase bubble columns). Based on a previously-validated set of correlations, the influence of operating and design parameter on system performances is studied and critically analyzed. First, we studied the effects of the design parameter on the liquid–gas interfacial area, by keeping constant the fluid physical–chemical properties as well as the operating conditions; subsequently, we discussed for a fixed system design, the influence of the liquid phase properties and the operating pressure. In conclusion, this paper is intended to provide guidelines for the design and scale-up of multi-phase reactors.