Membrane-Based, Liquid–Liquid Separator with Integrated Pressure Control

We describe the development and application of an improved, membrane-based, liquid–liquid separator. Membrane-based separation relies on the exploitation of surface forces and the use of a membrane wetted by one of the phases; however, successful separation requires accurate control of pressures, making the operation and implementation cumbersome. Here we present an improved separator design that integrates a pressure control element to ensure that adequate operating conditions are always maintained. Additionally, the integrated pressure control decouples the separator from downstream unit operations. A detailed examination of the controlling physical equations shows how to design the device to allow operation across a wide range of conditions. Easy to implement, multistage separations such as solvent swaps and countercurrent extractions are demonstrated. The presented design significantly simplifies applications ranging from multistep synthesis to complex multistage separations.Novartis-MIT Center for Continuous ManufacturingUnited States. Defense Advanced Research Projects Agency (Grant N66001-11-C-4147

Land fragmentation index for drip-irrigated field systems in the Mediterranean: A case study from Ricote (Murcia, SE Spain)

Land fragmentation is widespread in traditional field systems of the Mediterranean region. A typical case for high fragmented properties is the Valley of Ricote. It is dominated by smallholder agriculture. To promote smart sustainable development in rural areas it is important to address the specific needs of these small agricultural producers; especially considering that agriculture is the most important consumer of water worldwide and that the great majority of farms are small production units extending over <2 ha. Indeed, high land fragmentation, resulting from traditional land inheritance and transmission systems, may cause loss of water and productive land, entropic governance and superfluous emissions. In particular, drip-irrigated systems suffer from higher costs for irrigation due to high land fragmentation. In this study, we develop a Fragmentation Index for Drip Irrigation and Distance Assessment (FIDIDA) using Geographic Information Systems. FIDIDA quantifies farms considering their transaction costs. Based on these costs, FIDIDA brings together mean plot size, degree of separation and degree of dispersion of land parcels on farm level. The index can be used to compare the individual fragmentation of farms or the land fragmentation between different study areas. The definition of FIDIDA aims at supporting the management of reasonable land fragmentation thresholds in the context of communities made of traditional small farms, while suggesting possible pathways for a gradual inversion of high land fragmentation trends through agreed plot fusion where necessary.This work was supported with funding from the Humboldt Foundation, through an Experienced Researcher Fellowship awarded to AB (Project: Adaptive Resilience in Drylands - ARiD) and from the Cluster of Excellence “Integrated Climate System Analysis and Prediction” (CliSAP - EXC177), through the German Science Foundation (DFG). Further funding was provided by the Centre for a Sustainable University (KNU) of the University of Hamburg (Project: Sustainable rural development for water-scarce regions. Traditional knowledge for smart solutions in the Mediterranean, (funding channel 1, round 3, project 1))

Uso de radón-222 para determinar el flujo de agua en una laguna freática de la llanura medanosa de San Luis (Argentina)

In the southeastern portion of San Luis Province (33°53’10’’-34°19’00’’ S and 65°42’00’’-65°20’00’’ W), the sand dune landscape hosts a lacustrine system with more than 200 water bodies, where the water table reaches the surface and fills the deepest depressions. The aim of this study is to analyze surface-groundwater interactions using the radioactive isotope radon-222 (222Rn) in a lake known as “Los Pocitos”. During September 2017, in situ222Rn determinations were performed in the air; in the water/sediment interface and in surface waters at 6 sampling stations, as well as in 4 groundwater samples collected in the dune and the lake mudflat using the RAD-7 equipment (Durridge Co.). Surface waters are of the HCO3--Na+-K+ type, with mean pH and electrical conductivity in Lake Los Pocitos of 8.7 and 1232 µS cm-1, respectively, whereas the groundwater is of the HCO3--Ca+2 type, with variable pH and electrical conductivity values. In the northern portion of the lake, concentrations of222Rn in surface water were ~ 70 Bq m-3, one order of magnitude greater than those of the southern sector, which registered values < 5 Bq m-3. By means of a222Rn mass balance model it was possible to determine that the groundwater discharge occurs in the northern sector, with an inflow discharge rate of about 185.3 ± 39.1 m3 d-1, whereas in the southern sector, an outflow from the lake to the surrounding aqui-fers can be detected. The intense groundwater inflow into these lakes may explain their relatively low salinity under a semi-arid climate in which evaporation by far exceeds direct rainfall input.En el sector sureste de la provincia de San Luis (33°53’10’’-34°19’00’’ S y 65°42’00’’-65°20’00’’ O), sobre un paisaje medanoso, se desarrolla un sistema lagunar compuesto por más de 200 depresiones someras en donde los niveles freáticos alcanzan la superficie. El propósito de este trabajo es analizar las interacciones agua superficial-subterránea utilizando el isótopo radioactivo radón-222 (222Rn) en una de estas lagunas, conocida como “Los Pocitos”. Durante septiembre de 2017 se realizaron, in situ, determinaciones de 222Rn utilizando el equipo portátil RAD-7 (Durridge Co.), en el aire, en la interfase agua/sedimento, en 6 estaciones de muestreo alrededor de la laguna, así como también en 4 muestras de agua subterránea tomadas en la duna y en las márgenes de la laguna. Los resultados obtenidos indican que las aguas superficiales son del tipo HCO3 - - Na+ - K+ y tienen un pH y una conductividad eléctrica promedio de 8,7 y 1232 µS cm-1, respectivamente, mientras que las aguas subterráneas son HCO3 - - Ca+2 y tienen un pH y una conductividad eléctrica variable. En el sector norte se presentan las mayores concentraciones de 222Rn en el agua superficial, de aproximadamente 70 Bq m-3, un orden de magnitud mayor que en el sector sur, donde se registraron concentraciones < 5 Bq m-3. Mediante un modelo de balance de masa de 222Rn se estimó que la descarga de agua subterránea ocurre en el sector norte, con un caudal de 185,3 ± 39,1 m3 d-1. Por el contrario, en el sector sur hay un aporte de agua desde la laguna hacia los acuíferos circundantes. Este flujo de agua subterránea hacia las lagunas podría explicar su relativa baja salinidad en un clima semiárido en el que la evaporación supera a las precipitaciones en el balance hídrico.Fil: Echegoyen, Cecilia Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Lecomte, Karina Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Campodonico, Verena Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Yaciuk, Pablo Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Jobbágy, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaFil: Heider, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaFil: Sepúlveda, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Pasquini, Andrea Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: de Micco, Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comision Nacional de Energia Atomica. Gerencia Complejo Tecnológico Pilcaniyeu. División Cinética Química; ArgentinaFil: Bohe, Ana Ester. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Comahue; Argentina. Comision Nacional de Energia Atomica. Gerencia Complejo Tecnológico Pilcaniyeu. División Cinética Química; Argentin

Compound heterozygosity for loss‐of‐function FARSB variants in a patient with classic features of recessive aminoacyl‐tRNA synthetase‐related disease

Aminoacyl‐tRNA synthetases (ARSs) are ubiquitously expressed enzymes that ligate amino acids onto tRNA molecules. Genes encoding ARSs have been implicated in phenotypically diverse dominant and recessive human diseases. The charging of tRNAPHE with phenylalanine is performed by a tetrameric enzyme that contains two alpha (FARSA) and two beta (FARSB) subunits. To date, mutations in the genes encoding these subunits (FARSA and FARSB) have not been implicated in any human disease. Here, we describe a patient with a severe, lethal, multisystem, developmental phenotype who was compound heterozygous for FARSB variants: p.Thr256Met and p.His496Lysfs*14. Expression studies using fibroblasts isolated from the proband revealed a severe depletion of both FARSB and FARSA protein levels. These data indicate that the FARSB variants destabilize total phenylalanyl‐tRNA synthetase levels, thus causing a loss‐of‐function effect. Importantly, our patient shows strong phenotypic overlap with patients that have recessive diseases associated with other ARS loci; these observations strongly support the pathogenicity of the identified FARSB variants and are consistent with the essential function of phenylalanyl‐tRNA synthetase in human cells. In sum, our clinical, genetic, and functional analyses revealed the first FARSB variants associated with a human disease phenotype and expand the locus heterogeneity of ARS‐related human disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144241/1/humu23424_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144241/2/humu23424.pd

Phase II Trial with Carboplatin and Bendamustine in Patients with Extensive Stage Small-Cell Lung Cancer

Background:Bendamustine is an alkylating agent with hybrid activity and proven efficacy in small-cell lung cancer associated with a favorable toxicity rate. This phase II study of carboplatin/bendamustine was conducted to evaluate the efficacy of this combination in patients with extensive disease small-cell lung cancer (ED-SCLC).Methods:Fifty-six untreated patients with ED-SCLC were enrolled. Their median age was 63 years. Sixty-seven percent of patients were male and 18% had a World Health Organization performance status of 2. Bendamustine was administered as a 30- to 60-minute infusion at a dose of 80 mg/m2 on days 1 and 2, and carboplatin was given at an area under the curve of 5 on day 1 of a 21-day cycle.Results:Fifty-five patients were assessable for response and toxicity. The overall response rate was 72.7% (95% confidence interval: 59%–84%), with one complete remission (1.8%). The median time to progression was 5.2 months (95% confidence interval: 4.2–5.6). At the time of evaluation, 71% of the patients had died. The median survival time reached 8.3 months (95% confidence interval: 6.6–9.9). The major toxicity of this regimen was myelosuppression, including grade 3 or 4 neutropenia (46%), thrombopenia (26%), anemia (15%), and infections (11%). Toxic death was recorded in two patients (3.6%).Conclusions:The carboplatin/bendamustine regimen is a well-tolerated cytostatic combination in ED-SCLC with activity comparable with that of other platinum-based regimens. Further investigations, such as a phase III trial, are currently planned

Rapid Flow-Based Peptide Synthesis

A flow-based solid-phase peptide synthesis methodology that enables the incorporation of an amino acid residue every 1.8 min under automatic control or every 3 min under manual control is described. This is accomplished by passing a stream of reagent through a heat exchanger into a low volume, low backpressure reaction vessel, and through a UV detector. These features enable continuous delivery of heated solvents and reagents to the solid support at high flow rate, thereby maintaining maximal concentration of reagents in the reaction vessel, quickly exchanging reagents, and eliminating the need to rapidly heat reagents after they have been added to the vessel. The UV detector enables continuous monitoring of the process. To demonstrate the broad applicability and reliability of this method, it was employed in the total synthesis of a small protein, as well as dozens of peptides. The quality of the material obtained with this method is comparable to that for traditional batch methods, and, in all cases, the desired material was readily purifiable by RP-HPLC. The application of this method to the synthesis of the 113-residue Bacillus amyloliquefaciens RNase and the 130-residue DARPin pE59 is described in the accompanying manuscript.MIT Faculty Start-up FundMassachusetts Institute of Technology (Charles E. Reed Faculty Initiative Fund)Deshpande Center for Technological InnovationDamon Runyon-Rachleff (Innovation Award)Sontag Foundation (Distinguished Scientist Award)C. P. Chu and Y. Lai FellowshipDaniel S. Kemp Summer FellowshipNational Institute of General Medical Sciences (U.S.). Biotechnology Training Program (Grant 5T32GM008334-25)National Institutes of Health (U.S.) (Fellowship F32GM101762

Symptoms and Needs of Patients with Advanced Lung Cancer: Early Prevalence Assessment

Background: Little is known on symptom burden, psychosocial needs, and perception of prognosis in advanced lung cancer patients at the time of diagnosis, although early assessment is strongly recommended within the setting of daily routine care. Methods: Twelve study sites cross-sectionally assessed symptoms and psychosocial needs of patients suffering from newly diagnosed incurable lung cancer. Assessment comprised NCCN distress thermometer, FACT-L, SEIQoL-Q, PHQ-4, and shortened and modified SCNS-SF-34 questionnaires. Additional prognostic information from both patients and physicians were collected. Results: A total of 208 patients were evaluated. Mean age was 63.6 years, 58% were male, 84% suffered from stage IV lung cancer, and 71% had an ECOG performance status of 0–1. Mean distress level was 5.4 (SD 2.5), FACT-L total score was 86 (21.5), and TOI 50.5 (14.9). PHQ-4 was 4.6 (3.3), and shortened and modified SCNS-SF-34 showed 9 (8.7) unmet needs per patient. According to their physicians’ perspective, 98.1% of patients were reflecting on and 85.2% were accepting incurability, while 26.5% of patients considered the treatment to be of curative intent. Conclusion: Our findings emphasize substantial domains of symptom burden seen in newly diagnosed, incurable lung cancer patients. Oncologists should be aware of these features and address prognostic issues early in the disease trajectory to facilitate opportunities to improve coping, advance care planning, and appropriate integration of palliative care, thus improving quality of life

Degree correlations in signed social networks

We investigate degree correlations in two online social networks where users are connected through different types of links. We find that, while subnetworks in which links have a positive connotation, such as endorsement and trust, are characterized by assortative mixing by degree, networks in which links have a negative connotation, such as disapproval and distrust, are characterized by disassortative patterns. We introduce a class of simple theoretical models to analyze the interplay between network topology and the superimposed structure based on the sign of links. Results uncover the conditions that underpin the emergence of the patterns observed in the data, namely the assortativity of positive subnetworks and the disassortativity of negative ones. We discuss the implications of our study for the analysis of signed complex networks

Arsenic in lakes from South Eastern San Luis (Argentina)

La planicie arenosa del sureste de la provincia de San Luis alberga más de 200 lagunas someras. Este sistema presenta aguas del tipo sódicas, claramente alcalinas con valores de pH entre 8,6 y 9,3 y con conductividades entre 1.232 y 2.243 μS/cm. Se ha detectado en la zona la presencia de arsénico en aguas naturales en concentraciones superiores a los valores límite establecidos por la CAA y OMS para el consumo humano. La concentración de arsénico varía entre 6,9 y 150,0 μg/L (promedio 83,8 μg/L), por encima de las concentraciones medias de las aguas superficiales (0,8 μg/L). El resto de los elementos traza presentan un comportamiento similar al promedio de los ríos prístinos del mundo.Centro de Investigaciones Geológica

ATF3 is a novel nuclear marker for migrating ependymal stem cells in the rat spinal cord

The present study identified ATF3 as a novel dynamic marker for ependymal stem/progenitor cells (nestin, vimentin and SOX2 positive) around the central canal of the neonatal or adult rat spinal cord. While quiescent ependymal cells showed cytoplasmic ATF3 expression, during 6-24. h in vitro these cells mobilized and acquired intense nuclear ATF3 staining. Their migratory pattern followed a centrifugal pathway toward the dorsal and ventral funiculi, reminiscent of the rostral migratory stream of the brain subventricular stem cells. Thus, the chain cell formation was, by analogy, termed funicular migratory stream (FMS). The FMS process preceded the strong proliferation of ependymal cells occurring only after 24. h in vitro. Pharmacological inhibition of MAPK-p38 and JNK/c-Jun (upstream effectors of ATF3 activation) prevented the FMS mobilization of ATF3 nuclear-positive cells. Excitotoxicity or ischemia-like conditions, reported to evoke neuronal and glial injury, did not further enhance migration of ependymal cells at 24. h, suggesting that, at this early stage of damage, the FMS phenomenon had peaked and that more extensive repair processes are delayed beyond this time point. ATF3 is, therefore, useful to identify activation and migration of endogenous stem cells of the rat spinal cord in vitro. \ua9 2014