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PURPOSE To evaluate whether ethnicity affects the risk of full mutation expansion among females heterozygous for FMR1 premutation. METHODS Women who carry the FMR1 premutation alelle of Jewish origin who underwent fragile X prenatal diagnosis between 2011 and 2018 in two medical centers in Israel were included. The heterozygote women and fetuses were analyzed for the number of CGG repeats and AGG interruptions. RESULTS Seven hundred sixty-six subjects were included. Parental ethnicity was fully concordant in 592 cases (Jewish, Ashkenazi, and non-Ashkenazi). Ashkenazi compared with non-Ashkenazi heterozygotes have a significantly higher mean number of CGG repeats (68 ± 8.7, 64 ± 6.4 respectively, P = 0.03) and a lower mean number of AGG interruptions (0.89 ± 0.83, 1.60 ± 1.18 respectively, p = 0.0001). Overall, 56/198 (28.2%) fetuses of Ashkenazi heterozygotes had an expansion to a full mutation compared with 6/98 among the non-Ashkenazi (6.1%) (p = 0.001). Multivariate analysis demonstrated that, in addition to CGG repeats and AGG interruptions (which contributed 68.3% of variance), ethnicity is an independent risk factor for a full mutation expansion (odds ratio [OR] = 2.04, p

PURPOSE: While FMR1 premutation carriers (CGG 55–200) were shown to have reduced success with IVF treatment (lower oocyte yield), studies reporting on the association between the number of CGG repeats and patients’ response to controlled ovarian hyperstimulation (COH) are inconsistent. In the present study, we aim to explore whether the number of CGG repeats in women with premutation in FMR1 gene, undergoing COH for IVF, correlates with COH variables and whether the number of AGG interruptions may function as a “protective factor” by improving the ovarian response to COH. METHODS: Retrospective study, in an academic IVF-PGD unit. Fifty-seven consecutive FMR1 premutation carriers who underwent 285 IVF treatment cycles were included. The numbers of CGG repeats and AGG interruptions were retrieved and correlated to the demographics and COH variables. RESULTS: There were no significant association between the numbers of CGG or the AGG interruptions and the number of oocyte retrieved or the peak estradiol levels. The lack of association was also observed when including all the IVF treatment cycles or only the first or last IVF treatment cycle. Moreover, no associations were found between the number of CGG repeats or AGG interruptions and other COH variables, i.e., duration of stimulation, the total dose of gonadotropin used, or the number of top-quality embryos. CONCLUSIONS: No associations were observed between the number of CGG repeats or AGG interruptions and any of the COH variables. Further studies are required to identify early biomarkers of POI to empower FMR1 premutation carriers with risk assessment tools to consider procedures such as fertility preservation.

Water use patterns were explored for three small communities that are located in proximity to agricultural fields and rely on their local wells for potable water supply. High-resolution water use data, collected over a four-year period, revealed significant temporal variability. Monthly, daily, and hourly water use patterns were well described by autoregressive moving average (ARMA) models. Model development was supported by unsupervised clustering analysis via self-organizing maps (SOMs) that revealed similarities of water use patterns and confirmed the time-series water use model attributes. The inclusion of ambient temperature and rainfall as model attributes improved ARMA model performance for daily and hourly water use from R2 ~0.86–0.87 to 0.94–0.97 and from R2 ~0.85–0.89 to 0.92–0.98, respectively. Water use predictions for an entire year forward in time was feasible demonstrating ARMA models’ performance of (i) R2 ~0.90–0.94 and average absolute relative error (AARE) of ~2.9–4.9% for daily water use, and (ii) R2 ~0.81–0.95 and AARE ~1.9–3.8% for hourly water use. The study suggests that ARMA modeling should be useful for analysis of temporally variable water use in support of water source management, as well as assessing capacity building for small water systems including water treatment needs and wastewater handling.

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 surroun...

A flexible RO (FLERO) membrane desalination configuration employing a pressure intensifier and partial concentrate recycle was investigated with respect to operational flexibility and specific energy consumption (SEC). Decomposition of FLERO configuration and its operation into a membrane processing and concentrate recycle units allows fluid flow regulation at low pressure and adjustable product water recovery. Operational analysis, along with experimental evaluation using a small-scale spiral wound system, demonstrated a desalting capability over a wide range of both permeate recovery and source water salinity. Moreover, in the FLERO configuration a relatively low-pressure pump can be used, even for seawater desalination. However, the SEC for the FLERO configuration is higher, at the same recovery and permeate productivity, relative to conventional single-pass with energy recovery. Nonetheless, given its operational flexibility, in terms of handling both a wide range of source water salinity and recovery and source water salinity and need for low-pressure RO water feed pump. Given the above, FLERO should be ideal for small-scale applications, particularly in remote locations, and field evaluation is warranted to establish its long-term benefits. Large-scale FLERO applications would depend on the availability of suitable energy recovery devices of sufficient efficiency for large desalination capacity.

This chapter provides an overview of Mesopotamian Wisdom Literature. The introduction discusses the origins and distribution of Mesopotamian Wisdom Literature. It moves on to demonstrate how Mesopotamian Wisdom Literature can be approached. The chapter treats four subcategories of Wisdom Literature: proverbs and instructions, Vanity Theme works, existential works, and satire and parody. The conclusion offers an assessment of the nature of Mesopotamian Wisdom Literature and refers to its transmission and diffusion to other literatures of the East Mediterranean basin, the ancient Near East, the biblical Wisdom books, and beyond.

FMR1 premutation (55–200 CGG repeats) results in fragile X-associated primary ovarian insufficiency (FXPOI). We evaluated expression levels of folliculogenesis-related mediators, follicle-stimulating hormone (FSH) receptor and anti-Mullerian hormone (AMH), to gain insights into the mechanisms underlying the reduced ovarian function. Mural granulosa cells (MGCs) were collected from FMR1 premutation carriers and noncarriers undergoing IVF treatments. At baseline, MGCs of carriers demonstrated significantly higher mRNA expression levels of AMH (3.5 ± 2.2, n = 12 and 0.97 ± 0.5, n = 17, respectively; p = 0.0003) and FSH receptor (5.6 ± 2.8 and 2.7 ± 2.8, respectively; p = 0.02) and higher AMH protein expression on immunostaining. Accordingly, FMR1 premutation-transfected COV434 cells exhibited higher AMH protein expression than COV434 cells transfected with 20 CGG repeats. We conclude that FMR1 premutation may lead to dysregulation of AMH expression levels, probably due to a compensatory mechanism. Elucidating the pathophysiology of FXPOI may help in early detection of ovarian dysfunction and tailoring IVF treatments to FMR1 premutation carriers.

PURPOSE: To detect which factors influence decision-making among pregnant FMR1 premutation carriers regarding the preferred mode of genetic diagnosis: IVF-PGT-M (in vitro fertilization with preimplantation genetic testing for monogenic gene diseases), or CVS (chorionic villus sampling), or AC (amniocentesis) after spontaneous conception. METHODS: In Israel FMR1 premutation preconception genetic screening is offered, free of charge, to every woman in her reproductive years. FMR1 premutation carriers with ≥ 70 CGG repeats, or a history of FXS offspring, are offered IVF-PGT-M. This is a historical cohort study including all pregnant FMR1 premutation carriers who underwent prenatal diagnosis between the years 2011 and 2016 at a tertiary medical center. Data were collected from electronic charts and through phone interviews. RESULTS: One hundred seventy-five women with high-risk pregnancies who were offered IVF-PGT-M were evaluated. In 37 pregnancies (21%), the women decided to undergo IVF-PGT-M. Using the generalized estimating equations (GEE) statistical method including seven parameters, we found that previous termination of pregnancy due to FXS and advanced woman’s age were significantly associated with making the decision to undergo IVF-PGT-M. Previously failed IVF was the most significant parameter in a woman’s decision not to undergo IVF-PGT-M. CONCLUSION: The most dominant factor affecting the decision of FMR1 premutation carriers to choose spontaneous conception with prenatal diagnosis versus IVF-PGT-M is a previous experience of failed IVF treatments. Women whose IVF treatments failed in the past tended to try to conceive naturally and later, during the course of the pregnancy, perform CVS or AC. Conversely, women who previously experienced a termination of pregnancy (TOP) due to an affected fetus, and older women, preferred to undergo IVF-PGT-M procedures.

A machine learning approach to describing the dynamics of ultrafiltration performance in pretreatment of seawater reverse osmosis (RO) feedwater was explored via ensemble back propagation neural network (BPNN) model. The BPNN model was developed with Alopex evolutionary algorithm (AEA) optimization and AdaBoost strategy. The progression of ultrafiltration (UF) membrane resistance during both filtration and backwash, along with backwash efficiency were modeled via the ensemble BPNN-AEA approach relying on 422 days of operational data for an integrated SWRO UF-RO system. Model performance, for UF membrane resistance and backwash efficiency, evaluated over a wide range of operating conditions and coagulant dosing strategies, revealed excellent performance with a forecasting capability even for cases of temporally variable water quality. The performance level attained with the current machine learning modeling approach, which is particularly suited for handling the dynamics of UF operation, should prove useful for (a) determining UF performance deviation from intended baseline performance, (b) forecasting expected UF performance due to anticipated changes in water quality, and (c) providing a basis for model-based control of UF operation.

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.

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

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.

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.

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.

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.

Testing for genetic abnormalities in epithelial growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and potentially additional genes is a critical tool in the care of advanced NSCLC. There is conflicting evidence for the role of such tests in early NSCLC. We report a single-institute Sequenom testing for a wide range of mutations and their clinical correlations in early-resected NSCLC specimens.Early NSCLC paraffin-embedded, formalin-fixed (FFPE) specimens were collected, DNA extracted, and using Sequenom-based matrix-assisted laser desorption/ionization-time of flight analysis, mutations in 22 oncogenes and tumor suppressor genes were evaluated. Clinical data was collected retrospectively.The technique was found to be feasible. Thirty-six of 96 patients (37.5%) had any genetic abnormality identified, and 8 (8.3%) had 2 or more mutations. Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR were the most common genes to appear mutated (15.6%); phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) was the gene to be found most commonly in tumors with co-mutations. Transversions were found mostly in KRAS gene mutations and to be nonprognostic. No difference in the spectrum of mutations was found between squamous-cell and non-squamous-cell lung cancers. Ever-smokers showed a trend for worse prognosis, with a similar spectrum of mutations.Sequenom-based mutation screen is feasible using FFPE samples. More than a third of the patients were found to harbor some genetic abnormality, and 8% were found to have more than a single mutated gene. Wide-range gene screens using large sample depositories are required for further insight into the important genes at play in early NSCLC.

STUDY QUESTION: What are the effects of thin ovarian grafts compared with grafts of the standard thickness on follicle loss post-transplantation? SUMMARY ANSWER: Transplantation of reduced-thickness ovarian grafts led to intense activation and 'burn-out' a short time after transplantation resulting in significant folllicle loss. WHAT IS KNOWN ALREADY: Transplantation of fresh and frozen-thawed ovarian tissue has been proved successful, but techniques vary and are not optimised, often resulting in significant follicular loss. Follicle loss is mostly related to the freezing-thawing process and to post-transplantation hypoxia. STUDY DESIGN, SIZE, DURATION: Bovine ovarian tissue strips (n = 55) were prepared in two groups of conventional-thickness strips (1-2 mm) or thin strips (0.5-0.9 mm). Fresh or frozen-thawed samples were xenotransplanted into sterilized immune-deficient mice (n = 49). Non-transplanted conventional size fresh samples were used as controls (n = 6). Grafts from all study groups were recovered after 7 days for analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Morphometric differential counting of follicle classes was performed by two observers. Immunohistochemistry was conducted for proliferation (Ki67), cortical fibrosis (Masson tri-chrome) and blood-vessel density (CD31). Results were expressed as the mean number of dormant or growing follicle (GF) type per section or total follicle counts per graft. Blood-vessel density was calculated per mm(2). P-values

Identification of non-small cell lung carcinoma (NSCLC) patients at high-risk for recurrence after complete resection would potentially direct surveillance frequency and administration of adjuvant treatments. Genetic profiling of tumors could provide clinicians with information regarding recurrence risk. Conflicting evidence exists regarding EGFR, KRAS, and TP53 mutations as prognostic for recurrence. We aimed to test such mutations for prognostic significance in a cohort of early-resected NSCLC specimens. Formalin-fixed paraffin-embedded stage I NSCLC specimens resected in our institute during 1988–2008 were sampled. DNA was extracted and a panel of common EGFR, KRAS, and TP53 mutations was tested using a mass-spectrometry-based technique. Clinical data were extracted from patients’ files. A total of 96 NSCLC stage I patients were included in this study. EGFR mutation frequency of 15.6 %, KRAS mutation frequency of 15.6 %, and a TP53 mutation frequency of 6.2 % were found. A nonsignificant trend for longer relapse-free survival (RFS) was seen for patients with an EGFR mutation, and a nonsignificant trend for worse RFS was found for patients with a KRAS mutation. EGFR mutation and KRAS mutation were not found to be prognostic for RFS in our cohort of early NSCLC. Larger cohorts and a broader genetic screen for mutations are required.

Nanotechnology has become a significant enabling technology for a wide array of industries being integrated across diverse areas such as medicine, electronics, biomaterials, and energy production. For example, nano-scaled systems have been designed and utilized for safe and effective targeted delivery of therapeutic agents, demonstrating the rapid advancements of nanotechnology in medical-treatment and diagnosis. At the same time, there is also mounting concern regarding the potential impact of nanotechnology on the environment and human health. As a result, there is a global drive to ensure that the development of beneficial nanotechnologies is accomplished in a responsible manner so as to avoid adverse impacts on environmental and human health. In order to develop safe-by-design nanomaterials for their various intended applications, large amounts of data are being generated for better understanding and mapping the toxicology and pharmacology of nanomaterials. Nanomaterials data are typically sought regarding their physicochemical and structural properties, environmentally related properties, toxicity behavior, processing information, production levels, environmental releases, and more. Accordingly advanced informatics techniques are urgently required for the collection and curation, management (e.g., achieving and sharing), analysis and modeling of the large amount of data involved with nanotechnology processes and materials (i.e., “nano-data”). In order to address these requirements, nanoinformatics has emerged over the last decade as “The science and practice of determining which information is relevant to the nanoscale science and engineering community, and then developing and implementing effective mechanisms for collecting, validating, storing, sharing, analyzing, modeling, and applying that information.” [1]. At present, nanoinformatics focuses primarily on: nano-data management and database development, nano-data curation, assessment of the value of information in nano-data, literature mining for nano-data collection and meta-analysis, data mining/machine learning of nano-data (e.g., development of quantitative structure–activity relationships (QSARs)), simulation of the fate and transport of nanomaterials, nano-bio interactions, and assessment of potential environmental and health risks associated with nanomaterials. As an interdisciplinary field consisting mainly of nanotechnology and data science, nanoinformatics has significantly advanced over the last decade, playing an increasingly important role in research and development in nanomedicine and environmental health impact assessment of nanomaterials (often termed NanoEHS). In addition, efforts in nanoinformatics research have provided in a multitude of tools and resources that are being made available through nanoinformatics cyberinfrastructures and web platforms (e.g., nanoinfo.org [2] in the US and eNanoMapper [3] in the EU). However, much of the current research and advances in nanoinformatics are not documented in dedicated resources and, given the interdisciplinary nature of nanoinformatics, are dispersed throughout a wide range of sources and journals. As a consequence, researchers and practitioners in other fields of nanotechnology have been at a disadvantage not having easy access to the most recent resources and tools provided by the nanoinformatics research community. Accordingly, this Thematic Series is devoted to bring together the state-of-the-art in nanoinformatics with a particular focus on the latest related developments/applications for environmental health and biomedicine. In this Thematic Series, recent advances in the development of databases are reported. These databases represent a collection of valuable data related to the physicochemical properties and bioactivity of nanomaterials. In one contribution, the latest version of caNanoLab is described along with a critical discussion of the challenges associated with database development for nanomaterials, as well as the needs for nano-data curation and sharing by the biomedical research community [4]. The latest development of the eNanoMapper database for nanomaterial safety information is summarized in another contribution [5], while a third contribution reports on the NanoE-Tox database that is concerned with the ecotoxicity of nanomaterials [6]. In addition, important improvements are reported for the Nanotechnology Consumer Products Inventory that progressively documents the marketing and distribution of nano-enabled products into the commercial marketplace [7]. The progress in nano-data curation is covered in two contributions. One describes the Nanomaterial Data Curation Initiative, a collaborative effort by the nanoinformatics research community for nano-data discovery and extraction, quality assessment, integration, and reuse [8]. Another contribution illustrates key concepts, and discusses current practices and challenges in the field of nano-data curation [9]. In order to facilitate nano-data discovery and extraction, a data collection framework was developed [10] through ISA-TAB-Nano (a set of standardized specifications for nano-data representation). Advances in automating nano-data discovery and extraction is the subject of two other contributions that report on using advanced literature/text mining techniques, such as natural language processing [11] and corpus-based automatic information extraction [12]. In addition, bibliometric and social network analysis is introduced and adopted in the field of nanoinformatics to identify collaboration networks and developmental patterns of nano-enabled drug delivery for brain cancer [13]. As an imported aspect of nanoinformatics, recent advances in data mining/machine learning of nano-data are also reported in this Thematic Series. In one study, the toxicity of ZnO nanoparticles to zebrafish (measured by mortality rate (%)) was correlated to two principal components calculated from nanoparticle size and surface properties using Kriging estimations [14]. Another contribution reports on the development of models to predict the cytotoxicity of PAMAM dendrimers using molecular descriptors [15]. Nanomaterials that have potential to cause disease (e.g., TiO2 nanoparticles, carbon black, and carbon nanotubes) were also identified using biclustering of gene expression data and gene set enrichment analysis methods [16]. Various visual analytical approaches (e.g., bipartite graphs, log-ratio analysis, and multidimensional scaling) are demonstrated in another study for exploring the impact of manufactured nanoparticles (ZnO and TiO2) on soil bacterial communities [17], which is an area of nanoinformatics that is only now receiving increased attention. The present Thematic Series also presents a simulation tool for estimating the release and environmental distribution of nanomaterials, which provides critical information for the environmental impact assessment of nanomaterials [18]. Another contribution addresses the issue of nanomaterial risk assessment and proposes a decision analysis scheme for furthering nanoinformatics work [19]. This work considers an array of decision analysis techniques (e.g., multicriteria decision analysis, value of information, weight of evidence, and portfolio decision analysis) that are potentially capable of assessing and classifying the multitude of available nanomaterial data. Such an approach can serve as the basis for both establich a decision making process and future research priorities in the field. This Thematic Series was made possible by the contribution of numerous authors to whom we owe our gratitude. We appreciate the time and effort of the numerous referees that helped shape this Thematic Series and we are also grateful for the unwavering support of the team at the Beilstein-Institut. We particularly acknowledge and commend the Beilstein Journal of Nanotechnology for its open access policy, which has provided a wonderful incentive for researchers and practitioners to contribute to this journal while is freely available to all scientific and professional communities. Rong Liu and Yoram Cohen Los Angeles, October 2015

Relationships among fourteen different biological responses (including ten signaling pathway activities and four cytotoxicity effects) of murine macrophage (RAW264.7) and bronchial epithelial (BEAS-2B) cells exposed to six metal and metal oxide nanoparticles (NPs) were analyzed using both statistical and data mining approaches. Both the pathway activities and cytotoxicity effects were assessed using high-throughput screening (HTS) over an exposure period of up to 24 h and concentration range of 0.39-200 mg L(-1). HTS data were processed by outlier removal, normalization, and hit-identification (for significantly regulated cellular responses) to arrive at reliable multiparametric bioactivity profiles for the NPs. Association rule mining was then applied to the bioactivity profiles followed by a pruning process to remove redundant rules. The non-redundant association rules indicated that "significant regulation" of one or more cellular responses implies regulation of other (associated) cellular response types. Pairwise correlation analysis (via Pearson's χ(2) test) and self-organizing map clustering of the different cellular response types indicated consistency with the identified non-redundant association rules. Furthermore, in order to explore the potential use of association rules as a tool for data-driven hypothesis generation, specific pathway activity experiments were carried out for ZnO NPs. The experimental results confirmed the association rule identified for the p53 pathway and mitochondrial superoxide levels (via MitoSox reagent) and further revealed that blocking of the transcriptional activity of p53 lowered the MitoSox signal. The present approach of using association rule mining for data-driven hypothesis generation has important implications for streamlining multi-parameter HTS assays, improving the understanding of NP toxicity mechanisms, and selection of endpoints for the development of nanomaterial structure-activity relationships.

A novel model-based control system for the operation of a spiral-wound RO membrane desalination system was developed with a focus on maintaining energy-optimal operation. The control scheme utilized an operational model for spiral-wound RO desalting with a supervisory controller providing real-time updates of membrane permeability and the appropriate feed pressure set-points for maintaining the target permeate productivity at the lowest feasible specific energy consumption. System RO feed pressure and flow rates were controlled by a lower-level RO controller through adjustment of the RO high pressure feed pump, variable frequency drive, and RO concentrate valve. Seawater desalination tests with an RO plant, capable of permeate productivity up to 18 000 gallons/day, demonstrated effective self-adaptive energy-optimal operation, subject to feed salinity fluctuations, constraints imposed by the system’s physical limitations (i.e., minimum and maximum feasible operational pressures and flow rates), and the th...

The development of data-driven RO plant performance models was demonstrated using the support vector regression model building approach. Models of both steady state and unsteady state plant operation were developed based on a wide range of operational data obtained from a fully automated small spiral-wound RO pilot. Single output variable steady state plant models for flow rates and conductivities of the permeate and retentate streams were of high accuracy, with average absolute relative errors (AARE) of 0.70%–2.46%. Performance of a composite support vector regression (SVR) based model (for both streams) for flow rates and conductivities was of comparable accuracy to the single output variable models (AARE of 0.71%–2.54%). The temporal change in conductivity, as a result of transient system operation (induced by perturbation of either system pressure or flow rate), was described by SVR model, which utilizes a time forecasting approach, with performance level of less than 1% AARE for forecasting periods of 2 s to 3.5 min. The high level of performance obtained with the present modeling approach suggests that short-term performance forecasting models that are based on plant data, could be useful for advanced RO plant control algorithms, fault tolerant control and process optimization.

The development of classification nano-structure-activity Relationships (nano-SARs) of nanoparticle (NP) bioactivity is presented with the aim of demonstrating the integration of multiparametric toxicity/bioactivity assays to arrive at statistically meaningful class definitions (i.e., bioactivity/inactivity endpoints), as well as the implications of nano-SAR applicability domains and decision boundaries. Nano-SARs are constructed based on a dataset of 44 iron oxide core nanoparticles (NPs), used in molecular imaging and nano-sensing, containing bioactivity profiles for four cell types and four different assays. Class definitions are developed on the basis of 'hit' (i.e., significant bioactivity) identification analysis and self-organizing map based consensus clustering; these class definitions enable construction of nano-SARs of a high classification accuracy (>78%) with different NP descriptor combinations that include primary size, spin-lattice and spin-spin relaxivities, and zeta potentials. Analysis of the nano-SAR performance for different class definitions suggests that H4 (i.e., class with at least four hits) is a reasonable endpoint (from a 'regulatory' viewpoint) for keeping the level of false negatives (i.e., incorrect labeling of bioactive NPs as inactive) low. The establishment of a quantitative nano-SAR applicability domain is demonstrated, making use of a probability density with the H4 class definition and naive Bayesian classifier (NBC) model (with spin-lattice relaxivity and zeta potential as descriptors). Decision boundaries are determined for the above H4/NBC nano-SAR for different acceptance levels of false negative to false positive predictions, illustrating a practical approach that may assist in regulatory decision making with a consideration of reducing the likelihood of identifying bioactive NPs as being inactive.

The technical feasibility of operating a spiral-wound RO plant in a cyclic mode of feed-flow reversal (FFR) was evaluated for brackish water desalting under conditions of high mineral scaling propensity. Scale-free and continuous permeate productivity was demonstrated, with calcium sulfate as the model scalant, in an automated spiral-wound RO pilot system in which FFR was triggered by scale detection in an external membrane monitor (MeMo). Real-time detection of mineral scaling in an external RO MeMo cell, receiving its feed from the concentrate of the RO plant tail element, enabled cyclic FFR operation in a self-adaptive mode accomplished by feed-back RO plant control in which permeate productivity was maintained. Membrane permeability was restored after each FFR cycle even with the initiation of membrane cleaning (i.e., via FFR) after a measurable level of scale formation in the MeMo and spiral-wound RO pilot. FFR cycle periods varied in length given the stochastic nature of crystal nucleation on the membranes in both the RO plant and in the MeMo RO cell. Scale-free FFR operation was demonstrated, without anticalant addition, with the RO plant operating (up to 81% recovery) such that the gypsum saturation index was up to 3.45 at the membrane surface of the tail element.

The main aim was to develop recommendations on eMental health interventions for the treatment of psychotic disorders. A systematic literature search on eMental health interventions was performed, and 24 articles about interventions in psychotic disorders were retrieved and systematically assessed for their quality. Studies were characterized by a large heterogeneity with regard to study type, sample sizes, interventions and outcome measures. Five graded recommendations were developed dealing with the feasibility of eMental health interventions, beneficial effects of psychoeducation, preliminary results of clinical efficacy, the need of moderation in peer support eMental health groups and the need to develop quality standards.

Because a variety of human-related activities, engineer-ed nanoparticles (ENMs) may be released to various environmental media and may cross environmental boundaries, and thus will be found in most media. Therefore, the potential environmental impacts of ENMs must be assessed from a multimedia perspective and with an integrated risk management approach that considers rapid developments and increasing use of new nanomaterials. Accordingly, this Account presents a rational process for the integration of in silico ENM toxicity and fate and transport analyses for environmental impact assessment. This approach requires knowledge of ENM toxicity and environmental exposure concentrations. Considering the large number of current different types of ENMs and that those numbers are likely to increase, there is an urgent need to accelerate the evaluation of their toxicity and the assessment of their potential distribution in the environment. Developments in high throughput screening (HTS) are now enabling the rapid generation of large data sets for ENM toxicity assessment. However, these analyses require the establishment of reliable toxicity metrics, especially when HTS includes data from multiple assays, cell lines, or organisms. Establishing toxicity metrics with HTS data requires advanced data processing techniques in order to clearly identify significant biological effects associated with exposure to ENMs. HTS data can form the basis for developing and validating in silico toxicity models (e.g., quantitative structure-activity relationships) and for generating data-driven hypotheses to aid in establishing and/or validating possible toxicity mechanisms. To correlate the toxicity of ENMs with their physicochemical properties, researchers will need to develop quantitative structure-activity relationships for nanomaterials (i.e., nano-SARs). However, as nano-SARs are applied in regulatory applications, researchers must consider their applicability and the acceptance level of false positive relative to false negative predictions and the reliability of toxicity data. To establish the environmental impact of ENMs identified as toxic, researchers will need to estimate the potential level of environmental exposure concentration of ENMs in the various media such as air, water, soil, and vegetation. When environmental monitoring data are not available, models of ENMs fate and transport (at various levels of complexity) serve as alternative approaches for estimating exposure concentrations. Risk management decisions regarding the manufacturing, use, and environmental regulations of ENMs would clearly benefit from both the assessment of potential ENMs exposure concentrations and suitable toxicity metrics. The decision process should consider the totality of available information: quantitative and qualitative data and the analysis of nanomaterials toxicity, and fate and transport behavior in the environment. Effective decision-making to address the potential impacts of nanomaterials will require considerations of the relevant environmental, ecological, technological, economic, and sociopolitical factors affecting the complete lifecycle of nanomaterials, while accounting for data and modeling uncertainties. Accordingly, researchers will need to establish standardized data management and analysis tools through nanoinformatics as a basis for the development of rational decision tools.

The JAK2V617F mutation has emerged in recent years as a diagnostic as well as treatment target in patients with polycythemia vera (PV). We analyzed JAK2V617F allele burden (JAK2(V617F)) in a Jewish population with PV. Results were correlated with disease symptoms and complications. Median JAK2(V617F) was 48% and 54% in patients of Ashkenazi and non-Ashkenazi origin, respectively (p =0.75). Higher JAK2(V617F) was seen in patients with imaging-proven splenomegaly (p =0.01). A correlation between JAK2(V617F) and the weekly hydoxyurea dose needed for disease control was found (p =0.043). In addition, a trend for higher allele burden in patients with longer disease duration (p =0.064) and those treated with cytoreductive drugs other than hydroxyurea (p =0.056) was noted. Higher JAK2(V617F) was seen in patients with transformation to myelofibosis (p =0.0001), but not in patients with vascular complications. JAK2(V617F) may assist in prognostic stratification of patients with PV.

Organophosphates are highly toxic substances, which cause severe brain damage. The hallmark of the brain injury is major convulsions. The goal of this study was to assess the spatial and temporal MR changes in the brain of paraoxon intoxicated rats. T2-weighted MRI and ¹H-MR-spectroscopy were conducted before intoxication, 3 h, 24 h, and 8 days postintoxication. T2 prolongation mainly in the thalami and cortex was evident as early as 3 h after intoxication (4-6% increase in T2 values, P 20% decrease, P 15%, P < 0.05). Animals who succumbed had extensive cortical edema, significant higher lactate levels and a significant decrease in NAA/creatine and NAA/choline levels compared to animals which survived the experiment. Organophosphates-induced brain damage is obvious on MR data already 3 h postintoxication. In vivo spectroscopic changes are more sensitive for assessing long-term injury than T2-weighted MR imaging. Early spectroscopic findings might be used as biomarkers for the severity of the intoxication and might predict early survival.

This paper argues that the peripheral recensions of theBallad of Early Rulersreflect Mesopotamian forerunners, and do not represent re-workings by the local scribes. The Ugarit recension is based on an Old Babylonian forerunner, and the Emar recension is based on a Middle Babylonian version that incorporated material from other scholarly sources. To support this contention, the Babylonian literary and scholarly background of the early rulers is discussed, and a reconstruction and analysis is offered of the Mari section of the Sumerian King List, in which two rulers of theBalladappear. The textual history of theBalladcontributes to the general debate regarding the origin, date of composition and transmission of Mesopotamian literature and its reception throughout scribal centers, not only in Ugarit and Emar, but also in Ḫattuša, Canaan and Egypt during the Late Bronze Age. A new copy of the Emar Ballad manuscript by Andrew George is offered at the end of this paper.

An unsupervised feature selection method is proposed for analysis of datasets of high dimensionality. The least square error (LSE) of approximating the complete dataset via a reduced feature subset is proposed as the quality measure for feature selection. Guided by the minimization of the LSE, a kernel least squares forward selection algorithm (KLS-FS) is developed that is capable of both linear and non-linear feature selection. An incremental LSE computation is designed to accelerate the selection process and, therefore, enhances the scalability of KLS-FS to high-dimensional datasets. The superiority of the proposed feature selection algorithm, in terms of keeping principal data structures, learning performances in classification and clustering applications, and robustness, is demonstrated using various real-life datasets of different sizes and dimensions.

This work focuses on the design and implementation of an optimization-based control system on an experimental reverse osmosis (RO) membrane water desalination process in order to facilitate system operation at an energy optimal condition. A dynamic nonlinear lumped-parameter model for the RO process is derived using first principles and the model parameters are computed from experimental data to minimize the error between model predictions and actual system response. This model, along with several equations for reverse osmosis system energy analysis, are combined to form the basis for the design of a nonlinear optimization-based control system. The proposed control system is implemented on UCLA's experimental RO system and its energy optimization capabilities are evaluated.

Various mixing operations between the feed, retentate and permeate streams are studied in this work to determine their effectiveness in decreasing the specific energy consumption (SEC) of single-stage (single-pass), two-pass and two-stage reverse osmosis (RO) processes operated at the limit of the thermodynamic restriction. The results show that in a single-stage RO process, partial retentate recycling to the feed stream does not change the SEC, while partial permeate recycling to the feed stream increases the SEC if targeting the same overall water recovery. Energy optimization of two-pass membrane desalination, with second-pass retentate recycling to the first-pass feed stream and operated at the limit imposed by the thermodynamic restriction, revealed the existence of a critical water recovery. When desalting is accomplished at recoveries above the critical water recovery, two-pass desalination with recycling is always less efficient than single-pass desalination. When desalting is accomplished at recoveries below the critical water recovery, an operational sub-domain exists in which the SEC for a two-pass process with recycling can be lower than for a single-pass counterpart, when the latter is not operated at its globally optimal state. For the two-stage RO process, diverting part of the raw feed to the second stage, in order to dilute the feed to the second-stage RO, does not decrease the minimal achievable SEC of a two-stage RO process. The various mixing approaches, while may provide certain operational or system design advantages (e.g., with respect to achieving target salt rejection for certain solutes or flux balancing), do not provide an advantage from an energy usage perspective.

Purpose: To assess, by MR spectroscopy (MRS) and diffusion weighted imaging (DWI), the ability of electrical stimulation of the sphenopalatine ganglion (SPG) to augment stroke recovery in transient middle cerebral artery occluded (t-MCAO) rats, when treatment is started 18 6 2 h post-occlusion. Materials and Methods: 1 H-MRS imaging ( 1 H-MRSI) and DWI were used to evaluate ischemic brain tissue after SPG stimulation in rats subjected to 2 h of t-MCAO. Rats were examined by 1 H-MRSI, DWI, and behavioral tests at 16 6 2 h, 8 days, and 28 days post-MCAO. Results: N-Acetyl-aspartate (NAA) levels of the stimulated and control rats were the same 16 6 2 h post-MCAO (0.52 6 0.03, 0.54 6 0.03). At 28 days post-occlusion, NAA levels were significantly higher in the treated group (0.60 6 0.04) compared with those of the untreated animals (0.50 6 0.04; P < 0.05). This effect was more pronounced for regions with low NAA values (0.16 6 0.03) that changed to 0.32 6 0.03 (P ¼ 0.04) for the treated group and to 0.10 6 0.03 (P ¼ 0.20) for the controls. DWI data showed better ischemic tissue condition for the treated rats, but the measured parameters showed only a trend of improvement. The MR results were corroborated by behavioral examinations. Conclusion: Our findings suggest that SPG stimulation may ameliorate MR tissue characteristics following t-MCAO even if treatment is started 18 h post-occlusion.

The technical viability of RO desalination technology was demonstrated in the late 1950's by the pioneering work of Sidney Loeb and Srinivasa Sourirajan and a team of researchers at the University of California, Los Angeles (UCLA) led by Professors Joseph McCutchan and Samuel Yuster. Today Reverse osmosis (RO) membrane desalination is a mature process for the production of potable water from seawater and inland brackish water. RO membranes are also now widely used as part of the overall process for the treatment of wastewater for reclamation and reuse for irrigation, industrial, and groundwater recharge applications. RO desalination technology is used worldwide and has made it possible to develop new potable water sources in areas of the world where freshwater water sources are scarce.

Reverse osmosis (RO) water desalination is now well established as a mature water desalination technology. With the current generation of seawater and brackish-water RO membranes, it is now both economically and technically feasible to desalt brackish water and seawater on a large scale. In order to further expand the applications of RO desalting technologies, optimal process conditions must be selected to minimize water production costs associated with energy consumption, membrane replacement costs, chemical usage, and residual brine concentrate management. In the present review, a multi-pronged process-optimization approach for reverse osmosis desalination is presented. A theoretical framework discussed for optimizing energy consumption with and without energy recovery devices (ERDs), considering the impact of membrane replacement and brine management costs. The approach enables quantification of the optimal water recovery of RO desalting, considering various factors including the use of energy recovery...

An analysis of the impact of increasing RO membrane permeability on the reduction in water desalination cost was carried out for RO desalting operated up to the limit imposed by the thermodynamic restriction. The premise of the present assessment is that, the current generation of high permeability RO membranes makes it feasible to carry out RO desalination up to the thermodynamic restriction limit. In this limit, the ratio of membrane to energy cost can be expressed as a function of the water recovery level and a dimensionless cost parameter that accounts for the purchase cost of electrical energy and membrane area, as well as feed water salinity, salt rejection requirement and membrane permeability. The present analysis suggests that, given the present day electrical energy and membrane prices, the benefit of developing membranes of even greater permeability is primarily at low water recoveries for inland brackish water desalting. At low water recoveries, however, there is typically an added cost associated with brine management for inland water desalting. In RO desalting of seawater, on the other hand, the specific cost (i.e., per permeate produced) of energy is much higher relative to the membrane cost, and there is lower economic incentive for developing higher permeability membranes if the objective is to lower the cost of seawater desalination. The analysis suggests that further significant improvement in RO membrane permeability is less likely to be the primary driver for a major reduction in the cost of seawater desalination. However, it is expected that significant reduction in RO water production cost can arise from a variety of other process improvements including, but not limited to, development of improved fouling-resistant membranes, more effective and lower feed pretreatment and brine management costs, optimization of process configuration and control schemes, as well as utilization of low cost renewable energy sources.

The energy optimization of two-pass membrane desalination, at the limit imposed by the thermodynamic restriction, was investigated and compared with a single-pass membrane desalting operation at the equivalent targeted overall salt rejection and permeate product recovery. The analysis considered the effect of pump and energy recovery efficiencies, membrane rejection, and retentate recycling from the second to the first-pass. The optimization results suggest that when the desired overall salt rejection can be achieved via a single-pass, then this process configuration will result in a lower specific energy consumption (SEC) relative to the two-pass membrane desalting process. However, if the desired overall rejection (or specific ion rejection, e.g., boron) cannot be achieved with the highest available rejection membrane in a single-pass, then a two-pass configuration is a feasible solution. In the latter case, the lowest energy consumption will be attained when a membrane of the highest available salt rejection is used in the first-pass. In cases in which desalting is accomplished at recoveries below the critical water recovery (i.e., the optimal recovery for a single stage), an operational sub-domain may exist in which the SEC for a two-pass process can be lower than for a single-pass counterpart, but only if the single-pass process is not operated at its globally optimal state. Retentate recycling from the second-pass to the first-pass feed can reduce the SEC for the two-pass process. However, optimization solution of the two-pass process is always a single-pass process as the optimal desalination process.

The feasibility of operating brackish water reverse osmosis (BWRO) desalination in a feed flow reversal (FFR) mode so as to mitigate mineral scaling was evaluated with feed solutions containing calcium, sodium, sulfate and chloride ions. The premise of the FFR approach is to enable dissolution of surface mineral crystals, that form first at the BWRO plant tail elements, by periodic exposure to the undersaturated feed solution. Automatic triggering of FFR was accomplished by integrating an Ex-situ scale observation detector (EXSOD) with the BWRO plant controller. The EXSOD system consisted of a small high pressure plate-and-frame RO cell, with its membrane surface digitally imaged in real-time, to monitor the onset and development of membrane mineral scaling. During normal feed flow (NFF) operation, the EXSOD monitored a concentrate side-stream from the BWRO plant tail element, signaling the BWRO plant controller to initiate FFR when the specified scaling threshold was reached. Once the plant feed flow was reversed, the EXSOD feed stream was switched from the BWRO plant concentrate to the plant's permeate in order to dissolve mineral crystals formed on the EXSOD membrane during NFF operation. Successful operation of automated FFR, whereby scale formation was prevented, required adjustment of the EXSOD operating conditions such that the saturation index in the EXSOD RO cell was at a level that would not result in scale detection significantly before or after scaling would occur in the RO plant. Although the onset of mineral scaling was detected at the level of appearance of the first observable mineral crystal, the results suggest that it would be more practical to trigger FFR based on a threshold that considers both the mineral crystal number density and fractional surface scale coverage. Current work is continuing to demonstrate the broad applicability of FFR mode of RO mineral scale-free operation (with reduced or no antiscalant addition) over a wide range of solution compositions and operating conditions.

Purpose: To investigate the neuroprotective effect of brimonidine following induction of ischaemic optic neuropathy in rodents (rAION). Methods: Mice were treated with an intraperitoneal injection of brimonidine 48, 24 or 0 h before rAION induction or eye drops for 5 days after rAION induction. Retinal ganglion cell (RGC) loss and expression of genes involved in the angiogenesis (vascular endothelial growth factor [VEGF], pigment epithelium-derived factor [PEDF], The epidermal growth factor homology domains-2 [Tie-2]), ischaemia (haem oxygense-1 [HO-1], hypoxia-inducible factor 1α[HIF-1α], endothelial nitric oxide synthase [eNOS]) and oxidative stress (superoxide dismutase-1 [SOD-1], glutathione peroxidase-1 [GPX-1]) response to ischaemic damage were compared with sham or rAION-untreated mice. Results: No RGC loss was detected in the brimonidine-treated mice. Effect of post-rAION eye drops: day 1 – no decrease in retinal mRNA levels of angiogenesis-related genes, increase in ischaemia- and oxidative stress-related genes except HIF-1α; day 3 – baseline or higher levels of oxidative and ischaemia-related genes except HIF-1α, increase in VEGF, decrease in PEDF; day 21 – no change in angiogenesis-related genes. Effect of pre-rAION injection: baseline levels of angiogenesis-related genes with all injection schedules; increase in ischaemia-related genes with 48-h and 0-h pretreatment; decrease in HO-1 and eNOS with 24-h pretreatment; increase in oxidative-related genes except GPX-1. In optic nerve tissue, HO-1, HIF-1α and SOD-1 decreased on day 1 after topical administration and were still below baseline on day 3. Conclusions: The increase in HO-1 associated with rAION is mitigated with brimonidine treatment, especially when administered intraperitoneally. Topical brimonidine apparently reduces VEGF, Tie-2, HIF-1α and GPX-1 expression on day 21. These results agree with published data and may have therapeutic implications for patients diagnosed with AION in the acute phase.

A neural network-based modeling approach with back-propagation and support vector regression algorithms was investigated as a mean of developing data-driven models for forecasting reverse osmosis (RO) plant performance and for potential use for operational diagnostics. The concept of plant “short-term memory” time-interval was introduced to capture the time-variability of plant performance since both a state of the plant model and standard time-series analyses for both flux decline and salt passage did not result in realistic predictive horizons for practical purposes. Past information of normalized permeate flux and salt passage were introduced as unique input variables along with process operating parameters to capture short-term plant performance variability. Sequential models, where the time-variation within each forecasting time-interval was also taken as input information, and marching forecasting models, where target values were predicted at fixed future times from past plant information, were developed. Models were trained, with normalized permeate flux and salt passage, for various model architectures, memory time-intervals and forecasting times using both back-propagation and support vector regression approaches. State of the plant models (without forecasting) were able to describe the relatively small permeate flux variations but were unable to capture salt passage trends (for any present time condition) since unsteady state phenomena could not be properly described without plant memory information. Forecasting of plant performance, with both sequential and marching models, yielded good predictive accuracy for short-term memory time-intervals in the range of 8–24 h for permeate flux and salt passage for forecasting times up to 24 h. Current work is ongoing to extend the approach for longer time scales and to incorporate data-driven forecasting models of RO plant into control strategies and process diagnostics.