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Silica scaling of RO membranes was evaluated via real-time direct surface imaging demonstrating a capability for detecting the onset of silica scale formation and its evolution. Silica scaling was detected significantly earlier than by traditional flux decline measurements. The observed rate of silica particle nucleation followed classical nucleation theory while the growth of individual silica particles, at the early stages of silica scaling, was governed by diffusional growth. SEM and optical images of the membrane surface suggest that silica scaling occurs through the formation of both primary silica particles and their agglomerates (~1–30 µm), as well as a gel-like silica film embedded with silica particles both of which contribute to permeate flux decline. At low silica saturation index at the membrane surface (SIm≤1.93) silica gel film formation resulted in a smoother and less porous film than at higher silica saturation (SIm≥2.72). At the higher silica saturation levels (SIm=2.72–3.50), silica scaling resulted in larger observed particles as well as rapid permeate flux decline. The silica scale layer thickness was in the range of ~0.1–3.5 µm, with surface roughness being higher by a factor of 2.6–8.3 relative to the native membrane. Results of the present study suggest that there is merit in exploring the application of the present approach for early detection and monitoring of silica scaling in RO plants in support of strategies for silica scale mitigation.

In this paper we present a new method for automatic transliteration and segmentation of Unicode cuneiform glyphs using Natural Language Processing (NLP) techniques. Cuneiform is one of the earliest known writing system in the world, which documents millennia of human civilizations in the ancient Near East. Hundreds of thousands of cuneiform texts were found in the nineteenth and twentieth centuries CE, most of which are written in Akkadian. However, there are still tens of thousands of texts to be published. We use models based on machine learning algorithms such as recurrent neural networks (RNN) with an accuracy reaching up to 97% for automatically transliterating and segmenting standard Unicode cuneiform glyphs into words. Therefore, our method and results form a major step towards creating a human-machine interface for creating digitized editions. Our code, Akkademia, is made publicly available for use via a web application, a python package, and a github repository.

Prediction of chemical bioactivity and physical properties has been one of the most important applications of statistical and more recently, machine learning and artificial intelligence methods in chemical sciences. This field of research, broadly known as quantitative structure-activity relationships (QSAR) modeling, has developed many important algorithms and has found a broad range of applications in physical organic and medicinal chemistry in the past 55+ years. This Perspective summarizes recent technological advances in QSAR modeling but it also highlights the applicability of algorithms, modeling methods, and validation practices developed in QSAR to a wide range of research areas outside of traditional QSAR boundaries including synthesis planning, nanotechnology, materials science, biomaterials, and clinical informatics. As modern research methods generate rapidly increasing amounts of data, the knowledge of robust data-driven modelling methods professed within the QSAR field can become essential for scientists working both within and outside of chemical research. We hope that this contribution highlighting the generalizable components of QSAR modeling will serve to address this challenge.

Modification of inorganic oxide surfaces is used in a variety of practical applications and in the study of interfacial phenomena. There are a multitude of surface modification methods, including modification by reactive polymer interlayers, diblock copolymerization, and polymer adsorption. Although various polymers can be used to modify an inorganic oxide substrate, this chapter focuses on poly(vinylpyrrolidone) (PVP) and poly(vinyl acetate). PVP grafting can be used to form a nontoxic surface that possesses superior hydrophilic and biocompatible properties. Free-radical graft polymerization in solution is relatively simple to carry out experimentally. The grafted polymer is covalently bonded to the surface through two concurrent mechanisms: polymer grafting and graft polymerization. Surface pretreatment is a crucial step which determines the surface activity for the subsequent graft polymerization. The use of vinyl alkoxysilanes with two or three alkoxy groups is particularly useful when the graft polymerization process is conducted in an aqueous solution.

Mapping average axon diameter (AAD) and axon diameter distribution (ADD) in neuronal tissues non-invasively is a challenging task that may have a tremendous effect on our understanding of the normal and diseased central nervous system (CNS). Water diffusion is used to probe microstructure in neuronal tissues, however, the different water populations and barriers that are present in these tissues turn this into a complex task. Therefore, it is not surprising that recently we have witnessed a burst in the development of new approaches and models that attempt to obtain, non-invasively, detailed microstructural information in the CNS. In this work, we aim at challenging and comparing the microstructural information obtained from single diffusion encoding (SDE) with double diffusion encoding (DDE) MRI. We first applied SDE and DDE MR spectroscopy (MRS) on microcapillary phantoms and then applied SDE and DDE MRI on an ex vivo porcine spinal cord (SC), using similar experimental conditions. The obtained diffusion MRI data were fitted by the same theoretical model, assuming that the signal in every voxel can be approximated as the superposition of a Gaussian-diffusing component and a series of restricted components having infinite cylindrical geometries. The diffusion MRI results were then compared with histological findings. We found a good agreement between the fittings and the experimental data in white matter (WM) voxels of the SC in both diffusion MRI methods. The microstructural information and apparent AADs extracted from SDE MRI were found to be similar or somewhat larger than those extracted from DDE MRI especially when the diffusion time was set to 40 ms. The apparent ADDs extracted from SDE and DDE MRI show reasonable agreement but somewhat weaker correspondence was observed between the diffusion MRI results and histology. The apparent subtle differences between the microstructural information obtained from SDE and DDE MRI are briefly discussed.

Significance Many studies have investigated secondary formamides as mixtures of cis and trans isomers. They are widespread in nature, but relatively low energetic barriers to interconversion prevent the isolation and characterization of the pure isomers. Here, we determine hydrophilic differences between the isomers by binding in a water-soluble, synthetic molecular container. The container offers a range of environments from hydrophilic to hydrophobic and distinguishes subtle differences in the polarities of formamide isomers. Using NMR methods, we find that cis formamides are more hydrophobic than the corresponding trans isomers. The conclusion holds for diformamides, where we staged an intramolecular competition between cis and trans formamides within the container. Stable and isolable compounds are not required for the determination with this method.

Purpose: To test the frequency of single-nucleotide polymorphisms in the IL-10, IL23R-IL12RB2 genes in patients with Behcet's uveitis. Methods: Blood samples were collected from 89 Israeli and Turkish patients, and from healthy control subjects of different origins. Genomic DNA was extracted from peripheral blood leukocytes and genotyped. Results: The risk allele, A, in rs1800871, of IL-10 gene was highly prevalent in Behcet's uveitis and healthy control samples alike; highest among the Turkish groups. Prevalence of G allele, in rs1495965, in the IL23R-IL12RB2 gene was high in Behcet's uveitis patients, and among healthy Turkish and Israelis of Middle Eastern origin, while lower among the other Israeli control group (77.9%, 78.9%, 27.8%, respectively, P < 0.001). Conclusion: Our findings highlight the differences between populations and may account for the increased prevalence of the disease among Turkish and Israelis of Middle Eastern origin. Further studies are required to map other healthy and affected populations.

We aim to retrospectively evaluate the role of increasing the gonadotropin daily dose from 450 IU/day to 300 IU twice a day on IVF-ET outcome in poor responder patients. All consecutive women admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU, followed by an IVF cycle using 300 IU twice a day, were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate was assessed. Twenty-three patients undergoing both cycles were evaluated. While there was no between-group difference in the duration of COH, number of 2PN embryos, fertilization rate and number of embryos transferred, patients receiving daily gonadotropin 300 IU twice a day achieved a significantly higher peak estradiol levels (3350.39 ± 2364.26 vs. 2223.74 ± 1299.91

Women who carry the FMR1 premutation may suffer from ongoing deterioration of ovarian function. The lucidity of the molecular mechanism of FXTAS is emerging and findings from research in the field of FXTAS could elucidate the pathogenesis of FXPOI. To date there are three possible mechanisms for ovarian dysfunction in FMR1 permutation carriers. The first is the RNA toxic gain-of-function mechanism initiating loss of function of over 30 specific RNA-binding proteins. The second is associated to the formation of an abnormal polyglycine-containing protein (FMRpolyG), and the third is related to novel lncRNAs, named FMR4 and FMR6. Herein we describe our laboratory methodology, focusing on the culturing and manipulation of granulosa cells from human female premutation carriers, trying to reveal the actual possible mechanisms liable to FXPOI. Detecting the precise pathways in premutation carrier might facilitate in offering these women the opportunity to make an informed decision regarding their reproductive and family planning.

Hydraulic permeability and molecular weight cutoff (MWCO) performance tuning of polysulfone (PSf) ultrafiltration (UF) membrane was attained via surface modification with a tethered layer of poly(acrylic acid) (PAA). Surface nano-structured (SNS) PAA layer was synthesized onto base PSf UF membranes by atmospheric pressure plasma (APP) surface activation followed by graft polymerization (GP) of acrylic acid (AA). Through a systematic study, it was shown that effective SNS-PAA-PSf UF membrane performance tuning was feasible by adjustments of APP and graft polymerization conditions. It was shown, for the first time, that SNS-PAA-PSf membranes can be synthesized with a range of hydraulic permeability (spanning a factor of 1.1–2.6 in magnitude) for a given MWCO, or a range of MWCO (spanning a factor of 1.5–2.3 in magnitude) for a given hydraulic permeability, thereby overcoming the hydraulic permeability-MWCO tradeoff.

The feasibility of a continuous chemically-enhanced seeded precipitation (CCESP) process was evaluated for desupersaturation of primary reverse osmosis (PRO) concentrate generated from RO desalting of inland agricultural drainage (AD) water with high gypsum scaling potential. The CCESP approach, comprised of partial lime treatment (PLT) followed by gypsum seeded precipitation (GSP), was assessed via laboratory and field tests, along with model simulations. PLT effectiveness was confirmed for residual antiscalant removal from the PRO concentrate, which otherwise would suppress gypsum crystallization. GSP was carried out in a fluidized bed crystallizer (FBC) demonstrating the feasibility of continuous PRO concentrate desupersaturation with suitable solids management. FBC operation was stable, with respect to desupersaturation performance, when operating over a sequence of periodic solids purge-only mode with intermittent seeds replenishment. The study suggests that CCESP integration with primary and secondary RO desalting (i.e., PRO-CCESP-SRO) can provide for significant enhancement of product water recovery for inland water of high gypsum scaling propensity. For example, source water of high salinity (14,347 mg/L total dissolved solid) AD water, nearly saturated with respect to gypsum, could be desalted up to a recovery of 88-96% (relative to merely 66% recovery feasible via PRO desalting. Moreover, net salt harvesting of 2.6-3.6 kg per m3 RO concentrate (with concentrate recycle) can be obtained from high recovery desalting of the above PRO concentrate.

Power generation via pressure retarded osmosis (PRO) was explored based on a detailed two dimensional finite-element (2-D-FEM) PRO model. Using the numerical model, an approach is presented for determining the draw and feed crossflow velocities for maximizing peak power generation. The dependence of PRO power generation on channel dimensions, membrane transport parameters were then evaluated, followed by assessing the impact of frictional pressure losses and pumping and energy recovery device (ERD) efficiencies. Illustrative test cases are presented for three different draw/feed streams representing seawater/brackish water (SW/BW), seawater RO-brine/brackish water (SWB/BW), and Dead Sea water/Seawater RO-brine (DSW/SWB). The maximum peak power density attainable via PRO was for DSW/SWB (35.3 W/m2), followed by SWB/BW (7.29 W/m2) and SW/BW (3.53 W/m2) for the case of ideal pumps and ERD. For the optimistic Power generation from DSW/SWB PRO, high efficiency pumps (98%) and ERD (96%) would be required for peak power density to approach ~ 12 W/m2 and 1.6 W/m2 for the cases of DSW/SWB and SWB/BW, respectively, while net positive power generation is not expected for SW/BW. Higher permeability membranes could provide somewhat increased PRO performance; however, frictional pressure loses and less than ideal pumps and ERDs present a barrier for PRO as a viable approach for energy generation.

Real-time self-adaptive approach to in-line UF coagulant dosing was developed and field demonstrated for integrated UF-RO seawater desalination. A novel coagulant dose controller was designed and successfully implemented in a pilot UF-RO seawater desalination plant. The coagulant controller, which tracks the UF resistance during filtration and backwash, adjusts coagulant dose to the UF feed with the objective of reducing the incremental cycle-to-cycle UF post-backwash (PB) resistance change (i.e., Δn). Real-time tracking the above UF resistance metrics, as well as the rate of change of Δn with coagulant dose, enabled the controller to quantify the progression of both irreversible fouling and UF backwash effectiveness. The above information was then utilized by the controller to make the appropriate coagulant adjustment. Field tests of the proposed self-adaptive coagulant dosing approach demonstrated measurable coagulant dose reduction while maintaining robust UF operation even during periods of both mild and severe water quality degradation. The approach to real-time coagulant dose control developed in the present work should be suitable for both seawater and brackish water UF treatment and has the potential of providing both effective UF operation as well as reduction in coagulant use.

An approach is presented describing the development of a Bayesian network (BN) based tool for rapid assessment of the distribution of engineered nanomaterials (ENMs). The methodology was demonstrated via the construction of a BN model for estimating the exposure concentrations of nanomaterials (BN-nanoExpo) based on simulation data derived from a mechanistic multimedia compartmental fate and transport model. The results of simulations of the distribution of six ENMs in eight different regions were generated for a broad range of geographical and meteorological parameters as well as ENM release rates to the air, water and soil major compartments. Test cases with the constructed BN-nanoExpo demonstrated the capability of the BN based model to portray a wide range of simulation results that can be obtained with the mechanistic fate and transport model. Moreover, BN-nanoExpo is shown to be a suitable tool for estimating both ENM concentrations and release rates given partial information, while also enabling assessment of the impact of uncertainties in input data on the predicted outcomes. The results of the current study suggest that there is merit in exploring the utility of the approach to more complex models, which would provide decision makers with powerful tools for rapid assessment of the behavior of nanomaterials in the environment.

Ultrafiltration as a pretreatment for RO feedwater with enhanced UF backwash, which combines continuous with pulse backwash, was investigated in a novel UF-RO process integration. Direct supply of RO concentrate to the UF module served for UF backwash which was further enhanced with pulse backwash generated using bladder-type hydraulic accumulators. Model analysis of the hydraulic accumulator operation, which was validated via a series of field experiments, demonstrated a capability for accumulator charging directly from the RO concentrate stream within a period of 30–40 s. Moreover, pulse backwash over a short period (~5 s) which was added to the continuous UF backwash (directly from the RO brine stream), enabled peak UF backwash flux up to a factor of 4.2–4.6 higher than the normal filtration flux. The above mode of UF operation with multiple consecutive backwash pulses was more effective than with a single pulse, while inline coagulation further increased the UF performance. Relatively long-term field operation (over eight days where) of the UF-RO system with self-adaptive triggering of UF backwash, whereby the number of consecutive pulses increased when a higher membrane fouling resistance was encountered, was highly effective in enabling stable UF operation over a wider range of water quality conditions and without the need for chemical cleaning. These encouraging results suggest that direct UF-RO integration with enhanced pulse UF backwash is an effective approach for dead-end UF filtration without sacrificing water productivity.

Reverse osmosis (RO) polyamide (PA) membrane integrity loss, performance degradation, and alteration of surface properties due to exposure to chlorine were evaluated experimentally via a fluorescent marker (uranine) based method, water permeability and salt flux measurements, and surface characterization via XPS, AFM and contact angle measurements. Membrane exposure to chlorine (4–200 mg/L NaOCl solutions) revealed that although membrane surface roughness increased with chlorine exposure intensity (ppm-h), surface hydrophilicity increased as inferred by the decline (up to 5.2–9.6%) of the surface energy of hydration. Comparative analysis of marker transport for membranes that have undergone chlorine exposure of 125–2000 ppm-h demonstrated that the membrane marker permeability coefficient (B) increased by up to a factor of ~5 relative to the intact membrane. While the severity of membrane integrity loss/performance degradation correlated to a reasonable degree with ppm-h of chlorine exposure, the severity of membrane integrity loss, at the same chlorine ppm-h, was greater for higher exposure concentration. Membrane integrity loss, over the same exposure levels, was quantified by an equivalent cylindrical breach that was in the range of about 14–40 µm, increasing in size with the intensity of chlorine exposure.

Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as "carrier" were proven to be actually full mutation. The mean years of education were 14 (±1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.

© 2016 American Chemical Society. Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations - where observing outcomes is difficult - versus higher ENM doses, where responses are observable. What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review. As a result, three main recommendations emerged. First, researchers should improve ecotoxicology of ENMs by choosing test end points, duration, and study conditions - including ENM test concentrations - that align with realistic exposure scenarios. Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization. Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.

The phosphoinositide 3-kinase (PIK3)/v-akt murine thymoma (AKT) oncogene pathway and the RAS/RAF pathway are involved in regulating the signalling of multiple biological processes, including apoptosis, metabolism, cell proliferation, and cell growth. Mutations in the genes within these pathways are frequently found in several tumours. The aim of this study was to investigate the frequency of mutations in the PIK3CA, BRAF, and KRAS genes in cases of malignant salivary gland tumours. Mutational analysis of the PIK3CA, KRAS, and BRAF genes was performed by direct sequencing of material from 21 patients with malignant salivary gland tumours who underwent surgery between 1992 and 2001. No mutations were found in the KRAS exon 2, BRAF exon 15, or PIK3CA exon 9 genes. However, an unpublished mutation of the PIK3CA gene in exon 20 (W1051 stop mutation) was found in one case of adenocarcinoma NOS. The impact of this mutation on the biological behaviour of the tumour has yet to be explored, however the patient with adenocarcinoma NOS harbouring this mutation has survived for over 20 years following surgery despite a high stage at presentation. Further studies with more homogeneous patient cohorts are needed to address whether this mutation reflects a different clinical presentation and may benefit from targeted treatment strategies.

Angular double-pulsed-field gradient (d-PFG) MR methodology is increasingly used to non-invasively obtain pore sizes in opaque chemical and biological systems. In such MR experiments, the angular dependency of the signal at zero mixing time, through modeling, can be used to extract the pore size. In many systems not only the pore sizes but also their directions are of importance. Before applying d-PFG NMR to complex systems, it is of value to challenge the ability of the methodology to extract these microstructural parameters in samples where the ground truth is known. In the present study we explored whether modeling of the signal in angular d-PFG NMR experiments at zero mixing time, can simultaneously provide the size and the direction of tilted compartments with little prior knowledge. We showed that the angular d-PFG MR methodology enables simultaneous extraction of the pore size and the direction of mono-dispersed phantoms and of phantoms where the restricted compartments have different pore sizes. However, we found that in phantoms with two or more pore sizes, only averaged pore sizes were extracted for large azimuthal and polar angles.

A novel design for a reverse osmosis (RO) desalination system directly integrated with an ultrafiltration (UF) pre-treatment unit was developed. The integration involves direct RO feed from the UF filtrate and UF backwash using the RO concentrate. This alignment reduces overall plant footprint, while the use of RO concentrate for UF backwash allows 100% UF recovery and implementation of flexible backwash strategies. The present system design utilizes a control scheme, whereby RO productivity can be prescribed independently of the UF system which self-adjusts to provide the RO system with its required feed flow rate at the specified RO pump inlet pressure. UF backwash, achieved via direct RO concentrate flow from the RO system provided a continuous flow for sequential UF backwash which was additionally integrated with pulse backwash using a hydraulic accumulator. Seawater desalination field studies with a UF–RO pilot system of 12,000 gal/day permeate production capacity successfully demonstrated the advantage of RO concentrate UF backwash that was triggered based on a membrane resistance threshold. The above self-adaptive UF backwash strategy significantly extended the projected UF operation period (by a factor of nine) to the threshold of required chemical cleaning.

Tetraalkylammonium salts were found, contrary to literature reports, to be encapsulated into hexameric capsules of pyrogallol[4]arene in benzene solution. The guest affinity depended on the length of the alkyl chain, the counteranion, the solvent used, the ammonium concentration, and most importantly, the pyrogallol[4]arene to ammonium salt ratio. At high ammonium salt to pyrogallol[4]arene ratios no encapsulation was observed, presumably since the high salt destabilized the formed hexamers.

A web-based resource for meta-analysis of nanomaterials toxicity is developed whereby the utility of Bayesian networks (BNs) is illustrated for exploring the cellular toxicity of Cd-containing quantum dots (QDs). BN models are developed based on a dataset compiled from 517 publications comprising 3028 cell viability data samples and 837 IC50 values. BN QD toxicity (BN-QDTox) models are developed using both continuous (i.e., numerical) and categorical attributes. Using these models, the most relevant attributes identified for correlating IC50 are: QD diameter, exposure time, surface ligand, shell, assay type, surface modification, and surface charge, with the addition of QD concentration for the cell viability analysis. Data exploration via BN models further enables identification of possible association rules for QDs cellular toxicity. The BN models as web-based applications can be used for rapid intelligent query of the available body of evidence for a given nanomaterial and can be readily updated as the body of knowledge expands.

We describe the preparation of the first water-soluble pH-responsive supramolecular hexagonal boxes (SHBs) based on multiple charge-assisted hydrogen bonds between peramino-pillar[6]arenes 2 with the molecular "lid" mellitic acid (1 a). The interaction between 2 and 1 a, as well as the other "lids" pyromellitic and trimesic acids (1 b and 1 c, respecively) were studied by a combination of experimental and computational methods. Interestingly, the addition of 1 a to the complexes of the protonated form of pillar[6]arene 2, that is, 3, with bis-sulfonate 4 a or 4 b, immediately led to guest escape along with the formation of closed 1 a2 2 supramolecular boxes. Moreover, the process of the openning and closing of the supramolecular boxes along with threading and escaping of the guests, respectively, was found to be reversible and pH-responsive. This study paves the way for the easy and modular preparation of different SHBs that may have myriad applications.

Polyamide (PA) thin film composite (TFC) BWRO and SWRO membranes were surface nano-structured (SNS) with tethered hydrophilic poly(acrylic acid) (PAA) layers. BWRO and SWRO membranes having water (Lp) and salt (B) permeability coefficients in the ranges of 2.3–3.4 L m−2 h−1·bar−1 and 0.15–0.54 L m−2 h−1, respectively, were utilized as base membranes onto which tethered PAA layers were synthesized via acrylic acid (AA) graft polymerization (GP), post-membrane surface activation with atmospheric pressure plasma (APP). Both APP surface activation and GP conditions impacted SNS-PAA-PA membrane performance evaluated in terms of the membrane Lp and B parameters. Surface structuring with a tethered PAA layer enabled tuning of membrane performance (in terms of Lp and B) to achieve water/salt selectivity (evaluated as Lp:B ratio) that was significantly higher (by up to 56%) relative to the base PA membranes. Depending on APP surface activation and AA graft polymerization conditions, membranes could be tuned to have essentially the same salt rejection over a range of permeability or a given permeability over a range of salt rejection. It was also shown that a membrane performance could be achieved that overcomes the permselectivity tradeoff.

Filter-Exchange NMR Spectroscopy (FEXSY) is a method for measurement of apparent transmembranal water exchange rates. The experiment is comprised of two co-linear sequential pulsed-field gradient (PFG) blocks, separated by a mixing period in which exchange takes place. The first block remains constant and serves as a diffusion-based filter that removes signal coming from fast-diffusing water. The mixing time and the gradient area (q-value) of the second block are varied on repeated iterations to produce a 2D data set that is analyzed using a bi-compartmental model which assumes that intra- and extra-cellular water are slow and fast diffusing, respectively. Here we suggest a variant of the FEXSY method in which measurements for different mixing times are taken at a constant gradient. This Constant Gradient FEXSY (CG-FEXSY) allows for the determination of the exchange rate by using a smaller 1D data set, so that the same information can be gathered during a considerably shorter scan time. Furthermore, in the limit of high diffusion weighting, such that the extra-cellular water signal is removed while the intra-cellular signal is retained, CG-FEXSY also allows for determination of the intra-cellular mean residence time (MRT). The theoretical results are validated on a living yeast cells sample and on a fixed porcine optic nerve, where the values obtained from the two methods are shown to be in agreement.

The feasibility of wellhead water treatment in small communities for nitrate removal and salinity reduction via a flexible high recovery RO system was evaluated through analysis of treatment options, laboratory and onsite field tests. In small remote communities that rely on septic systems for residential wastewater treatment, discharge of the RO residual stream (containing nitrate) to the community septic tank is shown to be a feasible option. It is demonstrated that RO treatment with a system that employs partial concentrate recycle, integrated with a pressure intensifier, enabled the use of a relatively low-pressure feed pump while allowing high recovery operation. The approach of integrating RO treatment into existing community small water systems is demonstrated to be suitable for providing effective nitrate removal and salinity reduction over wide range of nitrate and salinity levels, while meeting community water demand and regulatory water quality requirements.

Cannabis is one of the most widely used plant drugs in the world today. In spite of the large number of scientific reports on medical marijuana, there still exists much controversy surrounding its use and the potential for abuse due to the undesirable psychotropic effects. However, recent developments in medicinal chemistry of novel non-psychoactive synthetic cannabinoids have indicated that it is possible to separate some of the therapeutic effects from the psychoactivity. We have previously shown that treatment with the endocannabinoid 2-AG, which binds to both CB(1) and CB(2) receptors 1 h after traumatic brain injury in mice, attenuates neurological deficits, edema formation, infarct volume, blood–brain barrier permeability, neuronal cell loss at the CA3 hippocampal region, and neuroinflammation. Recently, we synthesized a set of camphor-resorcinol derivatives, which represent a novel series of CB(2) receptor selective ligands. Most of the novel compounds exhibited potent binding and agonistic properties at the CB(2) receptors with very low affinity for the CB(1) receptor, and some were highly anti-inflammatory. This selective binding correlated with their intrinsic activities. HU-910 and HU-914 were selected in the present study to evaluate their potential effect in the pathophysiology of traumatic brain injury (TBI). In mice and rats subjected to closed-head injury and treated with these novel compounds, we showed enhanced neurobehavioral recovery, inhibition of tumor necrosis factor α production, increased synaptogenesis, and partial recovery of the cortical spinal tract. We propose these CB(2) agonists as potential drugs for development of novel therapeutic modality to TBI.

Abnormalities in the X-linked FMR1 gene are associated with a constellation of disorders, which have broad and profound implications for the person first diagnosed, and extended family members of all ages. The rare and pleiotropic nature of the associated disorders, both common and not, place great burdens on (1) the affected families, (2) their care providers and clinicians, and (3) investigators striving to conduct research on the conditions. Fragile X syndrome, occurring more severely in males, is the leading genetic cause of intellectual disability. Fragile X associated tremor and ataxia syndrome (FXTAS) is a neurodegenerative disorder seen more often in older men. Fragile X associated primary ovarian insufficiency (FXPOI) is a chronic disorder characterized by oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. There may be significant morbidity due to: (1) depression and anxiety related to the loss of reproductive hormones and infertility; (2) reduced bone mineral density; and (3) increased risk of cardiovascular disease related to estrogen deficiency. Here we report the case of a young woman who never established regular menses and yet experienced a 5-year diagnostic odyssey before establishing a diagnosis of FXPOI despite a known family history of fragile X syndrome and early menopause. Also, despite having clearly documented FXPOI the woman conceived spontaneously and delivered two healthy children. We review the pathophysiology and management of FXPOI. As a rare disease, the diagnosis of FXPOI presents special challenges. Connecting patients and community health providers with investigators who have the requisite knowledge and expertise about the FMR1 gene and FXPOI would facilitate both patient care and research. There is a need for an international natural history study on FXPOI. The effort should be coordinated by a global virtual center, which takes full advantage of mobile device communication systems.

At the end of the last century Fragile X syndrome was identified, and the main syndrome characteristics were discovered. The syndrome is caused from a flaw in the number of nucleotide repeats that encodes for a regulatory protein which is critical for neural connectivity and normal brain development. The syndrome is characterized by neurodevelopmental and intellectual disabilities, autism spectrum features and other clinical features associated with the same gene aberration. The number of trinucleotide repeats have a direct effect on the outcome and the need for genetic counseling. We advocate performing genetic tests for every child with developmental delay, learning disabilities, autism spectrum disorders and especially, intellectual impairment. It is also advisable to check the number of nucleotide repeats of the gene, in every woman suffering from infertility or early menopause. In addition, genetic testing should be performed on older adults manifesting early symptoms of Parkinson's disease, balance instability, tremor or cognitive dysfunction with unknown etiology. Due to the tremendous progress in understanding the biological mechanisms of the syndrome, new molecules/drugs have been proposed and are tested, in order to find a way to bypass the defect mechanism underlying the disorder. We will review the most commonly used drugs in the treatment of Fragile X syndrome and many medications that are currently under investigation as a more targeted treatment.

Macrocyclic host structures for generating transiently bound

Labeling of smart PEG–dendron hybrids with fluorinated groups transformed their assemblies into enzyme-responsive micellar probes for 19F-magnetic resonance (MR). Two distinct labeling approaches were used to study the ability of these smart hybrids to be turned OFF at the assembled micellar state and to turn ON their 19F-MR signal upon enzymatic activation.

The use of 2D finite element CFD model and the common film model (FM) for analysis of FO performance data was examined to assess the merits of conclusions derived from the above approaches regarding characterization of membrane and support layer resistances to water and salt permeation. The FM model leads to estimation of porous layer resistivity (K) that implies tortuosity/porosity ratio that is significantly higher than is physically attainable for typical membrane porous supports. Comparative FO data analysis with the 2D CFD model and FM approximation reveals that the latter approach overestimates (by an order of magnitude and greater) the significance of the permeation resistance of the FO membrane support layer. It is also shown that membrane (water and solute) permeabilities extracted from FO operation in the RO mode (FO/RO) are significantly higher than obtained from direct analysis of FO performance data via detailed 2D CFD modeling. The present analysis suggests that improvements in FO water permeability are more likely to emerge from developing higher permeability membrane skin and improved channel hydrodynamics (to decrease external concentration polarization) rather than from more permeable and thinner membrane support layer as has been asserted in various studies.

Stejskal and Tanner's ingenious pulsed field gradient design from 1965 has made diffusion NMR and MRI the mainstay of most studies seeking to resolve microstructural information in porous systems in general and biological systems in particular. Methods extending beyond Stejskal and Tanner's design, such as double diffusion encoding (DDE) NMR and MRI, may provide novel quantifiable metrics that are less easily inferred from conventional diffusion acquisitions. Despite the growing interest on the topic, the terminology for the pulse sequences, their parameters, and the metrics that can be derived from them remains inconsistent and disparate among groups active in DDE. Here, we present a consensus of those groups on terminology for DDE sequences and associated concepts. Furthermore, the regimes in which DDE metrics appear to provide microstructural information that cannot be achieved using more conventional counterparts (in a model-free fashion) are elucidated. We highlight in particular DDE's potential for determining microscopic diffusion anisotropy and microscopic fractional anisotropy, which offer metrics of microscopic features independent of orientation dispersion and thus provide information complementary to the standard, macroscopic, fractional anisotropy conventionally obtained by diffusion MR. Finally, we discuss future vistas and perspectives for DDE.

A cost-benefit analysis of onsite graywater recycling in single-family and multifamily homes was conducted to evaluate the merits of graywater recycling in arid urban regions using the City of Los Angeles as a case study. Onsite graywater recycling reduces potable water demand by 27% and 38% in single family and multifamily homes, respectively. At participation of 10%, the City will be able to reduce water supply and treatment related energy by 43,000 MWh/year, potable water demand by 2% and wastewater treatment load by 3%. Amending local building codes to require new constructions to include plumbing to divert graywater for reuse will be important for lowering the cost and encouraging adoption of graywater recycling. Given the economic benefits to the City, establishing a rebate program for residential graywater recycling could provide a needed incentive for developing an effective residential graywater recycling program. A third-party ownership model could be a viable model for residential graywater recycling program that reduces the upfront system and installation cost barrier as well as relieves residential property owners the responsibility for system operation and maintenance. A City-wide graywater reuse program could also be developed to satisfy regulatory requirements by monitoring system operation and maintenance by certified contractors.

The technical feasibility of graywater treatment, via a semi-batch vertical flow wetland (SB-VFW), was evaluated at a single family home for aboveground water reuse. Graywater treatment was achieved to a quality level that was well within the regulatory compliance limits (e.g., with respect to biochemical oxygen demand (BOD), total suspended solids (TSS) and turbidity) for above ground reuse. System performance over the course of a five-month field study demonstrated that the necessary treatment time was typically ∼3 h for a 300 L batch. The SB-VFW operated in a stable manner owing to the use of a coconut soil substitute that has high hydraulic conductivity and also enabled avoidance of clogging due to excess biofilm growth. The latter was made possible through the use of a bio-based laundry (BBL) detergent which had a lower organic content relative to conventional laundry detergents. The system was able to return to normal operation even after detergent shock loads. Results of the present study are encouraging and suggest that residential level graywater treatment is technically feasible and can thus potentially expand the range of possible water reuse applications.

Real-time membrane integrity monitoring is critically needed in order to ensure that reverse osmosis (RO) treatment and desalination processes provide a reliable barrier against the passage of pathogens for potable reuse applications. A pulsed marker membrane integrity monitoring (PM-MIM) method was developed for real-time assessment of RO membrane integrity. The sensitivity of the PM-MIM method was evaluated, using a fluorescent molecular marker, in a plate-and-frame RO (PFRO) membrane system with intact and compromised membranes (induced mechanically and via chemical oxidation). Analysis of the marker permeate concentration–time profiles, in response to a controlled marker feed pulse, allowed unambiguous detection of marker enhanced passage, which was indicative of membrane integrity loss. The PM-MIM approach, which is capable of demonstrating log removal value (LRV) above 4 for a fluorescent molecular marker (smaller in size than pathogens) should be suitable for providing a conservative estimate of pathogens LRV. However, regulatory acceptability of the present real-time PM-MIM approach will undoubtedly require long-term field evaluation in RO plants in order to establish the level of confidence to satisfy regulatory requirements for RO use in potable water reuse applications.

Introduction Magnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post-poisoning cognitive dysfunction. Methods Sprague–Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 – no central antidotal treatment (n = 10); group 2 – treated with midazolam (MID) at 30 min after poisoning (n = 9), group 3 – treated with a combination of MID and scopolamine (SCOP) at 30 min after poisoning (n = 9) and controls (n = 6). Each animal had a brain MR examination 3 and 24 h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel 1H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology. Results All paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3 h after poisoning. Both MID and MID + SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3 h after exposure (1.1 ± 0.07 and 1.42 ± 0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even 24 h after poisoning. MID and MID + SCOP prevented much of the 3 h NAA/Cr decrease (1.22 ± 0.05 and 1.32 ± 0.1, respectively). Significant correlations were found between imaging findings (brain edema and spectroscopic changes) and clinical outcomes (poor learning, weight loss and pathological score) with correlation coefficients of 0.4–0.75 (p Conclusions MR imaging is a sensitive modality to explore organophosphate-induced brain damage. Delayed treatment with midazolam with or without scopolamine provides only transient neuroprotection with some advantage in adding scopolamine. Early imaging findings were found to correlate with clinical consequences of organophosphate poisoning and could be potentially used in the future to predict long-term prognosis of poisoned casualties.

Quantitative structure-activity relationships (QSARs) were developed, for cellular uptake of nanoparticles (NPs) of the same iron oxide core but with different surface-modifying organic molecules, based on linear and non-linear (epsilon support vector regression (e-SVR)). A linear QSAR provided high prediction accuracy of R 2 =0.751 (coefficient of determination) using 11 descriptors selected from an initial pool of 184 descriptors calculated for the NP surfacemodifying molecules, while a e-SVR based QSAR with only 6 descriptors improved prediction accuracy to R 2 = 0.806. The linear and e-SVR based QSARs both demonstrated good robustness and well spanned applicability domains. It is suggested that the approach of evaluating pertinent descriptors and their significance, via QSAR analysis, to cellular NP uptake could support planning and interpretation of toxicity studies as well as provide guidance for the tailor-design NPs with respect to targeted cellular uptake for various applications.