Replacing dichromate with hydrogen peroxide in the chemical oxygen demand (COD) test

The widely used standard method for chemical oxygen demand (COD) involves hazardous chromium species, and its two-hour heating protocol entails a substantial amount of energy expenditure. In the present work we report a proof of concept for a major modification of this method in the range 10-800 mgCOD/L, whereby H2O2 is proposed as a replacement oxidizer. This modification not only reduces the use of unsafe chromium species but also allows for the use of milder conditions that decrease the total energy outlay. The results are comparable with those obtained either with the standard method or with a commercial Hach? kit.     

Robust quantification of the exposure to operational risk: Bringing economic sense to economic capital

Operational risk is commonly analyzed in terms of the distribution of aggregate yearly losses. Risk measures can then be computed as statistics of this distribution that focus on the region of extreme losses. Assuming independence among the operational risk events and between the likelihood that they occur and their magnitude, separate models are made for the frequency and for the severity of the losses. These are then combined to estimate the distribution of aggregate losses. While the detailed form of the frequency distribution does not significantly affect the risk analysis, the choice of model for the severity often has a significant impact on operational risk measures. For heavy-tailed distributions these measures are dominated by extreme losses, whose probability cannot be reliably extrapolated from the available data. With limited empirical evidence, it is difficult to distinguish among alternative models that produce very different values of the risk measures. Furthermore, the estimates obtained can be unstable and overly sensitive to the presence or absence of single extreme events. Setting a bound on the maximum amount that can be lost in a single event reduces the dependence on the distributional assumptions and improves the robustness and stability of the risk measures, while preserving their sensitivity to changes in the risk profile. This bound should be determined by expert assessment on the basis of economic arguments and validated by the regulator, so that it can be used as a control parameter in the risk analysis.     

Acoustic scattering solver based on single level FMM for multi-GPU systems

In this paper, we present a heterogeneous parallel solver of a high frequency single level Fast Multipole Method (FMM) for the Helmholtz equation applied to acoustic scattering. The developed solution uses multiple GPUs to tackle the compute bound steps of the FMM (aggregation, disaggregation, and near interactions) while the CPU handles a memory bound step (translation) using OpenMP. The proposed solver performance is measured on a workstation with two GPUs (NVIDIA GTX 480) and is compared with that of a distributed memory solver run on a cluster of 32 nodes (HP BL465c) with an Infiniband network. Some energy efficiency results are also presented in this work.     

p21WAF1/Cip1 expression is associated with cell differentiation but not with p53 mutations in squamous cell carcinomas of the larynx

The anti-metastatic effect of Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis, was investigated in mice bearing B16 melanoma cells. Treatment of BF10 mice implanted with high metastatic B16F10 melanoma cells with a 10 mg/kg dose of Z-100 resulted in the reduction of experimental pulmonary metastasis as compared with that of BF10 mice treated with saline. The number of pulmonary metastatic colonies in BF1 mice (mice implanted with low metastatic B16F1 melanoma cells) was greatly increased after the inoculation of CD4+ CD11b+ CD281+ TCR alphabeta+ type 2 T cells (F10-Th2 cells) derived from BF10 mice, while only a few metastatic colonies were demonstrated in lungs of BF1 mice inoculated with naive CD4+ T cells. However, the numbers of metastatic colonies in BF1 mice were not increased when they were inoculated with the F10-Th2 cell fraction derived from Z-100-treated BF10 mice and the generation of F10-Th2 cells in BF10 mice was effectively suppressed by the Z-100 treatment. These results suggest that Z-100 inhibits pulmonary metastasis of B16 melanoma through the regulation of tumor-associated Th2 cells, which are a key cell in the acceleration of tumor metastasis.     

Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort

Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST^® ELISA and Lumipulse G^® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815⁻²⁷). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.     

NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats

Pannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and P2X7R-dependent nociceptive signaling in neuropathic rats require the activation of Panx1 channels to generate spinal central sensitization, as assessed by behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up potentiation) indexes. Administration of either a selective NMDAR agonist i.t. (NMDA, 2 mM) or a P2X7R agonist (BzATP, 150 μM) significantly increased both the mechanical hyperalgesia and the C-reflex wind-up potentiation, effects that were rapidly reversed (minutes) by i.t. administration of a selective pannexin 1 antagonist (10panx peptide, 300 μM), with the scores even reaching values of rats without neuropathy. Accordingly, 300 μM 10panx completely prevented the effects of NMDA and BzATP administered 1 h later, on mechanical hyperalgesia and C-reflex wind-up potentiation. Confocal immunofluorescence imaging revealed coexpression of Panx1 with NeuN protein in intrinsic dorsal horn neurons of neuropathic rats. The results indicate that both NMDAR- and P2X7R-mediated increases in mechanical hyperalgesia and C-reflex wind-up potentiation require neuronal Panx1 channel activation to initiate and maintain nociceptive signaling in neuropathic rats.     

A Review on Current Strategies for Extraction and Purification of Hyaluronic Acid

Since it is known that hyaluronic acid contributes to soft tissue growth, elasticity, and scar reduction, different strategies of producing HA have been explored in order to satisfy the current demand of HA in pharmaceutical products and formulations. The current interest deals with production via bacterial and yeast fermentation and extraction from animal sources; however, the main challenge is the right extraction technique and strategy since the original sources (e.g., fermentation broth) represent a complex system containing a number of components and solutes, which complicates the achievement of high extraction rates and purity. This review sheds light on the main pathways for the production of HA, advantages, and disadvantages, along with the current efforts in extracting and purifying this high-added-value molecule from different sources. Particular emphasis has been placed on specific case studies attempting production and successful recovery. For such works, full details are given together with their relevant outcomes.     

Advances in the Structural Strategies of the Self-Assembly of Photoresponsive Supramolecular Systems

Photosensitive supramolecular systems have garnered attention due to their potential to catalyze highly specific tasks through structural changes triggered by a light stimulus. The tunability of their chemical structure and charge transfer properties provides opportunities for designing and developing smart materials for multidisciplinary applications. This review focuses on the approaches reported in the literature for tailoring properties of the photosensitive supramolecular systems, including MOFs, MOPs, and HOFs. We discuss relevant aspects regarding their chemical structure, action mechanisms, design principles, applications, and future perspectives.     

Collective intelligence as mechanism of medical diagnosis: The iPixel approach

Collective intelligence (CI) is an active field of research, which capitalizes the knowledge of human collectives in order to create, to innovate and to invent. There are two important mechanisms to implement CI: recommender and reputation systems. Recommender systems are used to provide filtered information from a large amount of elements. The recommendations are intended to provide interesting elements to users. Recommendation systems can be developed using different techniques and algorithms where the selection of these techniques depends on the area in which they will be applied. This work presents iPixel Recommender Engine, which is focused on the medical field. iPixel Recommendation Engine supports the process of differential diagnosis by recommending mammographic evaluations. Each mammogram is collectively tagged by the users’ community with a semantic sense; this feature allows iPixel acquires collective knowledge. iPixel can associate more than one feature with each mammogram. This work also presents a qualitative evaluation, where the basic features that a recommendation system should have in the medical field were obtained. Finally, a comparison was carried out with other similar recommender systems in order to know the Pixel advantages.