Anaerobic biodegradation of cassava wastewater under different temperatures and inoculums.

The production of starch generates, as a by-product, the cassava wastewater (manipueira), which can be treated by anaerobic digestion to provide biogas and minimize its polluting potential. The most commonly utilized biomass in the anaerobic digestion is the anaerobic sludge. The literature presents, as an alternative to sludge, bovine manure and ruminal fluids, being scarce the studies with the cassava wastewater. This research evaluated the influence of temperature on the microbial ability of cattle and goat rumen in anaerobically biodegrading the manipueira in substitution to the anaerobic sludge. The cattle and goat rumen specific methanogenic activities (SMA) were compared with that of the anaerobic sludge. Subsequently, by using the inoculum which had the best SMA results, cassava wastewater biodegradability tests were performed, investigating the kinetics of the organic matter removal and methane production at 32 ° C and 39 ° C. The bovine rumen presented better results in the SMA (0,315 g COD-CH4 g VSS.d-1) and methane production (1,026 mL). The temperature of 32 °C did not influence the activity of bovine ruminal inoculum as the kinetics of the biodegradation of the manipueira did not differ for the evaluated temperatures (0.1799 d-1 at 32°C and 0.1781 d-1 at 39°C). Bovine rumen achieved glucose reduction of 76% and 80% and methane yield of 77% and 79% for the tests at 32°C and 39°C, respectively. It is inferred that this type of inoculum might be used in reactors of anaerobic digestion processes for the treatment of the cassava wastewater at the ambient temperature of the semiarid region

All functions are (locally) ss-harmonic (up to a small error) - and applications

The classical and the fractional Laplacians exhibit a number of similarities, but also some rather striking, and sometimes surprising, structural differences. A quite important example of these differences is that any function (regardless of its shape) can be locally approximated by functions with locally vanishing fractional Laplacian, as it was recently proved by Serena Dipierro, Ovidiu Savin and myself. This informal note is an exposition of this result and of some of its consequences

Molecular and clinical characterization of albinism in a large cohort of Italian patients.

PURPOSE: The purpose of this study was to identify the molecular basis of albinism in a large cohort of Italian patients showing typical ocular landmarks of the disease and to provide a full characterization of the clinical ophthalmic manifestations. METHODS: DNA samples from 45 patients with ocular manifestations of albinism were analyzed by direct sequencing analysis of five genes responsible for albinism: TYR, P, TYRP1, SLC45A2 (MATP), and OA1. All patients studied showed a variable degree of skin and hair hypopigmentation. Eighteen patients with distinct mutations in each gene associated with OCA were evaluated by detailed ophthalmic analysis, optical coherence tomography (OCT), and fundus autofluorescence. RESULTS: Disease-causing mutations were identified in more than 95% of analyzed patients with OCA (28/45 [62.2%] cases with two or more mutations; 15/45 [33.3%] cases with one mutation). Thirty-five different mutant alleles were identified of which 15 were novel. Mutations in TYR were the most frequent (73.3%), whereas mutations in P occurred more rarely (13.3%) than previously reported. Novel mutations were also identified in rare loci such as TYRP1 and MATP. Mutations in the OA1 gene were not detected. Clinical assessment revealed that patients with iris and macular pigmentation had significantly higher visual acuity than did severe hypopigmented phenotypes. CONCLUSIONS: TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency than that found in other populations. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation

Revealing a signaling role of phytosphingosine-1-phosphate in yeast

Perturbing metabolic systems of bioactive sphingolipids with genetic approachMultiple types of “omics” data collected from the systemSystems approach for integrating multiple “omics” informationPredicting signal transduction information flow: lipid; TF activation; gene expressio

The synergistic effect of chlorotoxin-mApoE in boosting drug-loaded liposomes across the BBB

We designed liposomes dually functionalized with ApoE-derived peptide (mApoE) and chlorotoxin (ClTx) to improve their blood-brain barrier (BBB) crossing. Our results demonstrated the synergistic activity of ClTx-mApoE in boosting doxorubicin-loaded liposomes across the BBB, keeping the anti-tumour activity of the drug loaded: mApoE acts promoting cellular uptake, while ClTx promotes exocytosis of liposomes

On the Dynamics of solitons in the nonlinear Schroedinger equation

We study the behavior of the soliton solutions of the equation i((\partial{\psi})/(\partialt))=-(1/(2m)){\Delta}{\psi}+(1/2)W_{{\epsilon}}'({\psi})+V(x){\psi} where W_{{\epsilon}}' is a suitable nonlinear term which is singular for {\epsilon}=0. We use the "strong" nonlinearity to obtain results on existence, shape, stability and dynamics of the soliton. The main result of this paper (Theorem 1) shows that for {\epsilon}\to0 the orbit of our soliton approaches the orbit of a classical particle in a potential V(x).Comment: 29 page

Carfilzomib, bendamustine, and dexamethasone in patients with advanced multiple myeloma: The EMN09 phase 1/2 study of the European Myeloma Network

Background: Combined therapy with carfilzomib, bendamustine, and dexamethasone was evaluated in this multicenter phase 1/2 trial conducted within the European Myeloma Network (EMN09 trial). Methods: Sixty-three patients with relapsed/refractory multiple myeloma who had received 652 lines of prior therapy were included. The phase 1 portion of the study determined the maximum tolerated dose of carfilzomib with bendamustine set at 70 mg/m2 on days 1 and 8. After 8 cycles, responding patients received maintenance therapy with carfilzomib and dexamethasone until progression. Results: On the basis of the phase 1 results, the recommended phase 2 dose for carfilzomib was 27 mg/m2 twice weekly in weeks 1, 2, and 3. Fifty-two percent of patients achieved a partial response or better, and 32% reached a very good partial response or better. The clinical benefit rate was 93%. After a median follow-up of 21.9 months, the median progression-free survival was 11.6 months, and the median overall survival was 30.4 months. The reported grade 653 hematologic adverse events (AEs) were lymphopenia (29%), neutropenia (25%), and thrombocytopenia (22%). The main nonhematologic grade 653 AEs were pneumonia, thromboembolic events (10%), cardiac AEs (8%), and hypertension (2%). Conclusions: In heavily pretreated patients who have relapsed/refractory multiple myeloma, combined carfilzomib, bendamustine, and dexamethasone is an effective treatment option administered in the outpatient setting. Infection prophylaxis and attention to patients with cardiovascular predisposition are required

Investigation into the High Voltage Shutdown of the Oxygen Generator System in the International Space Station

The Oxygen Generation System (OGS) Hydrogen Dome Assembly Orbital Replacement Unit (ORU) serial number 00001 suffered a cell stack high-voltage shutdown on July 5, 2010. The Hydrogen Dome Assembly ORU was removed and replaced with the on-board spare ORU serial number 00002 to maintain OGS operation. The Hydrogen Dome Assembly ORU was returned from ISS on STS-133/ULF-5 in March 2011 with test, teardown and evaluation (TT&E) and failure analysis to follow

A novel in-house deep sequencing method for non-invasive disease monitoring in multiple myeloma patients

Background: Novel and more effective treatment strategies have sig- nificantly prolonged multiple myeloma (MM) survival and raised inter- est in the depth of response. This implies the need of highly sensitive assays such as the determination of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) and next generation sequencing (NGS) of immunoglobulin (IGH) gene rearrangements. Ongoing studies are examining circulating cell-free tumor DNA (cfDNA) as a sensitive measure of small amounts of residual cells. In the present study, we de- scribe and analytically validate a simplified in-house deep-sequencing method to identify and quantify residual tumor burden in MM patients from plasma samples. Methods: We retrospectively analyzed 25 MM paired tumor (n=25) and plasma samples (n=48) obtained at diagnosis and at specified time points during treatment. Genomic DNA (gDNA) and cfDNA were extracted from selected CD138+ plasma cells (PC) and from plasma (Qiagen). IGH gene rearrangements were amplified, qual- ity assessed (Agilent hsDNA kit) and sequenced on Ion Torrent PGM. Raw reads were filtered and aligned using IMGT germline database andaggregated into clonotypes. Post-processing analyses were performed using VDJtools and customized R scripts. Results: Our sequencing method successfully identified a IGH MM clonotype in 88% of tumor samples (22/25), subsequently detected in plasma of all 22 cases (me- dian 4.7% of total filtered reads). Levels of the IGH clonotype in cfDNA distinguished between groups of patients with different prognosis: pa- tients with levels >4.7% prior to therapy, had significantly shorter PFS than patients with levels10-5 vs 15\ub15 months for frequencies=10-5 vs 37\ub14 months for frequencies<10- 5). Those patients are in CR and characterized by PC frequencies <10- 5 by MFC, and are therefore defined as MRD-negative. Conclusions: Results of this study support the clinical applicability of quantifying tumor levels by our in-house deep-sequencing of IGH gene rearrange- ments in plasma of MM patients

Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: A pooled analysis of two studies

open20noFunding: The IST-CAR-561 (NCT01857115) study was sponsored by Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON, the Netherlands), in collaboration with Fondazione Neoplasie Sangue ONLUS (Italy). The IST-CAR-506 (NCT01346787) study was sponsored by the HOVON Foundation and co-sponsored by Fondazione Neoplasie Sangue ONLUS. Both trials were supported by funding from AMGEN (Onyx Pharmaceuticals), which had no role in study design, data collection, data analysis, data interpretation, writing of the report or publication of this article. The corresponding author had full access to all the data in the two studies, and had final responsibility for the decision to prepare and submit this manuscript for publication, together with the other authors.Despite remarkable advances in the treatment of multiple myeloma (MM) in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors have been demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with MM receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard-risk versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard-risk versus high-risk patients, we observed similar progression-free survival (PFS) (3-year PFS: 52% vs. 43%, respectively; P=0.50), overall survival (OS) (3-year OS: 78% vs. 73%; P=0.38), and overall response rate (88% vs. 95%; P=0.47), with no statistical differences between the two groups. No difference in terms of PFS was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed MM patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted in similar PFS and OS as in standard-risk patients.noneMina R.; Bonello F.; Petrucci M.T.; Liberati A.M.; Conticello C.; Ballanti S.; Musto P.; Olivieri A.; Benevolo G.; Capra A.; Gilestro M.; Galieni P.; Cavo M.; Siniscalchi A.; Palumbo A.; Montefusco V.; Gaidano G.; Omede P.; Boccadoro M.; Bringhen S.Mina R.; Bonello F.; Petrucci M.T.; Liberati A.M.; Conticello C.; Ballanti S.; Musto P.; Olivieri A.; Benevolo G.; Capra A.; Gilestro M.; Galieni P.; Cavo M.; Siniscalchi A.; Palumbo A.; Montefusco V.; Gaidano G.; Omede P.; Boccadoro M.; Bringhen S