Lower Filtration Rate Research Articles

X-ray endovascular surgery for in-hospital acute ischemic stroke

The OBJECTIVE was to determine the efficacy of endovascular surgery for in-hospital acute ischemic stroke (AIS) and to identify predictors of unfavorable AIS outcome.METHODS AND MATERIALS. We performed 42 endovascular thrombectomies for in-hospital AIS in patients treated in the hospital for another pathology. Neurological defiCIT was determined by NIHSS scale, thrombectomy efficacy was evaluated by the degree of cerebral revascularization by mTICI scale, functional outcome was determined by Rankin scale (mRS). Multivariate analysis with evaluation of clinical and laboratory, neuroimaging data, and analysis of surgical technique was performed to identify factors contributing to adverse stroke outcome.RESULTS. The mean age of patients was 73.8±11.8 years old. Neurological defiCIT before surgery was 12.8±6.7 points by to NIHSS. Thrombolytic therapy was used in one third of cases, thrombectomy in 92.9 %, and carotid artery stent ing in 2 cases. Successful revascularization (mTICI2b-3) was achieved in 83.3 % of cases. The significant reduction in neurological defiCIT after surgery was achieved to NIHSS 6.0±5.9 points, mRS 2.7±2.1. The mortality rate amounted to 16.7 % of cases. Poor functional outcome (mRS3-5) was significantly associated with: female gender, older age, presence of cardiovascular pathology, recurrent stroke, postoperative tachycardia, low renal tubular filtration rate, hypocoagulation, low cardiac ejection fraction, low aortic valve opening amplitude, high pulmonary hypertension, large left atrial volume, initial severe neurological defiCIT, poor collaterals in the area of cerebral ischemia, proximal internal carotid artery occlusion, hemorrhagic saturation, increased operation time, low degree of revascularization (mTICI0-2a).CONCLUSION. Endovascular surgery has demonstrated its safety and high efficacy in the treatment of in-hospital AIS in surgical hospitalized patients. Endovascular thrombectomies allow to significantly reduce neurological defiCIT and decrease mortality in the severe category of patients with cardioembolic AIS. clinical, laboratory, hemodynamic and neuroimaging factors influencing on poor functional outcome of in-hospital AIS have been determined.

NUMERICAL SIMULATION OF GAS AND WATER FILTRATION IN MICROMODEL OF POROUS MEDIUM WITH A FRACTURE AND TRAPS

To select effective displacement agents, in order to limit waterflow to gas wells, it is necessary to understand the behavior of the multiphasesystem at the scale of individual pores, where capillary forces playan important role. In turn, capillary forces depend on interfacial tensionand wettability. As part of this work, computational microfluidics methodsusing the Open FOAM platform were used to analyze the effect of rockwettability on the features of two-phase filtration of water and gas in theporous medium model with fractures and traps.A mathematical model has been chosen that allows you to describe themovement of fluid in a fracture by the Navier-Stokes equations, and in theelements of a porous matrix by Darcy's law. Multivariable analysis ofwater displacement by gas was performed for different flow modes in caseof hydrophobic and hydrophilic surfaces. It has been shown that in thecase of a hydrophilic surface, the displaced water remains in the fracture«traps» in contrast to the hydrophobic surface, where the water is displacedcompletely. It has also been shown that as permeability increases,most of the gas is filtered into the matrix. However, for the hydrophilicsurface in the trap area, no filtration into the formation occurs, which isassociated with water capture in the fracture traps. It has been found thatmore intensive water washout occurs at low filtration rates. By displacingwater with filtration into a porous medium, most of the water can be lefttrapped, as opposed to displacing without filtration into a porous matrix.The proposed approach can be used as a screening technology to select theoptimal filtration modes and use modifiers for wetting the bottomholezone in order to limit water inflow into gas wells.

NUMERICAL SIMULATION OF GAS AND WATER FILTRATION IN POROUS MEDIUM MICROMODELS

To select and justify effective compositions for limiting water inflow into gas wells, an understanding of the behavior of the multiphase system on the scale of individual pores is necessary. In turn, capillary forces depend on the interfacial tension and wettability of the pore surface. As part of this work, computational microfluidics methods were used using the OpenFOAM platform to analyze the effect of rock wettability on the features of two-phase filtration of water and gas in a T-shaped micromodel of a porous medium, which is a crack connected to an element of a porous matrix.
 A mathematical model was chosen that allows you to describe the movement of fluid in a fracture by the Navier-Stokes equation, and in elements of a porous matrix by the Darcy equation. A grid of a T-shaped micromodel of a porous medium was generated using a GMSH grid generator. The displacement of water by gas from the fracture and porous matrix was simulated. Multivariable analysis of water displacement by gas for hydrophobic and hydrophilic surface was carried out by varying wetting angles. The dependencies of the residual water of the micromodel on the contact angle and flow modes were conducted. It has been found that at low filtration rates, water enters the fracture from the porous medium, which blocks the direct flow of gas through the fracture. In the case of a hydrophilic surface, the water inflow from the porous matrix is greater than in the case of a hydrophobic surface, since blocking the fracture results in gas filtration through the porous medium and displacement of water therefrom. The proposed approach can be used to rank effective bottomhole treatment agents and select optimal filtration modes to limit water inflow into gas wells.

One-year variation in quantity and properties of microplastics in mussels (Mytilus galloprovincialis) and cockles (Cerastoderma edule) from Aveiro lagoon

As filter feeders, marine bivalves inhabiting estuarine and coastal areas are directly exposed to microplastics (MPs) in water. To assess whether MPs number, and their shape, size, colour, and polymer type present in mussels (Mytilus galloprovincialis) and cockles (Cerastoderma edule) varied over one year, bivalves were collected over the year of 2019 in the lower part of the coastal Aveiro lagoon, Portugal. After extraction from the bivalve's whole-body soft tissues, a subset of the visually inspected particles was randomly separated for identification using the Fourier-transform mid-infrared (FT-MIR) spectroscopy. A fraction of the inspected particles, 26–32% of particles >100 μm, and 59–100% of smaller ones were confirmed as MPs. Concentrations varied within the intervals of 0.77–4.3 items g−1 in mussels and 0.83–5.1 items g−1 in cockles, with the lowest values observed in January. In winter, the accumulation of large-sized fibers was composed of a mixture of plastic types, which contrasted against the most abundant MPs in summer consisting mainly of polyethylene of diverse size classes and shapes. Temperature decrease registered in winter might have triggered a lower filtration rate, resulting in lower MPs concentrations in the whole-soft body tissues of organisms. Different properties of MPs found in bivalves between January–February and August–September appear to reflect changes in the characteristics of MPs available in the Aveiro lagoon.

The association between visceral adiposity index and decreased renal function: A population-based study.

We aimed to investigate the association of visceral adiposity index (VAI) with decreased renal function in US adults. Cross-sectional data were analyzed for 35,018 adults in the National Health and Nutrition Examination Survey (NHANES) 2005-2018. VAI was determined using waist circumference, body mass index (BMI), triglycerides (TGs) and high-density lipoprotein-cholesterol. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g. A low estimated-glomerular filtration rate (eGFR) was defined as an eGFR lower than 60 ml/min/1.73 m2. Chronic kidney disease (CKD) was defined as either albuminuria or low-eGFR. A multivariable logistic regression analysis was utilized to explore the relationship of VAI with albuminuria, low-eGFR and CKD. Subgroup analysis and interaction tests were also conducted. A total of 35,018 participants were enrolled with albuminuria, low-eGFR, and CKD prevalence rates of 5.18, 6.42, and 10.62%, respectively, which increased with the higher VAI tertiles. After full adjustment, a positive association of VAI with albuminuria (OR = 1.03, 95% CI: 1.00, 1.06) and CKD (OR = 1.04, 95% CI: 1.02, 1.06) was observed. Participants in the highest VAI tertile had a significantly 30% increased risk for albuminuria (OR = 1.30, 95% CI: 1.07, 1.58) and a 27% increased risk for CKD (OR = 1.27, 95% CI: 1.08, 1.49) compared with those in the lowest VAI tertile. No statistically significant association between VAI and low-eGFR was detected. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Visceral adiposity accumulation evaluating by VAI was associated with increased likelihood of the decline in renal function.

Optimization and Performance Evaluation of Foam Acid Systems for Plugging Removal in Low Pressure Oil and Gas Reservoirs

Foam acidization has unique advantages such as low damage, low filtration, low friction, high efficiency, excellent retardation, and fast liquid discharge rate, which is suitable for stimulation and reconstruction of low-pressure oil and gas reservoirs that have been developed over many years. It is obtained that the main chemical components of downhole plugging materials include vegetable oil, fatty acids and their esters, silicone oil, amide polymers, and additional organic components, as well as non-organic components, elemental sulfur, ferrous sulfide, iron disulfide, silicon dioxide, mineral salts, etc. The performance of foam acid was investigated by experiments, including the effective range of action of active acids, reducing filtration, increasing temperature resistance and high-temperature stability of foam acid deep wells. The new foam acid system is developed and optimized to suitable for low-pressure deep well acidification operations. Experimental evaluation optimized the acid foaming agent and foam stabilizer and developed a new foam acid formulation with foam stability, filter loss reduction, temperature resistance, and easy backflow performance. The experimental condition is that the temperature is 90 °C, the foam quality can reach more than 70% when mixed for more than 30 s, the average half-life is 38.75 min, and the liquid separation rate is 19.90 s/mL. Its suspension is better than that of conventional hydrochloric acid, its corrosion rate is 1.872 g/m2·h, and the flowback rate of foam acid residue reaches 97%. Experimental evaluation has shown that the developed foam acid features high surface activity, stable foam, strong temperature resistance, significant speed and corrosion suppression, and excellent drainage assist performance. Dynamical simulation evaluation of reservoir core foam acidification demonstrated that the foam features long-life, strong suspension capacity, excellent rheology, low filtration, and significant acidization and plug removal effects, and can be used in stimulating the medium-deep, high-temperature, and low-pressure oil and gas reservoirs.

Advanced ceramics in radical filtration: TiO2 layer thickness effect on the photocatalytic membrane performance

Membranes with advanced oxidation processes (AOPs) are a promising combination to separate and degrade organic pollutants in a single system. In this work, we describe the fabrication and characteristics of nine membranes with different TiO2 top layer thicknesses (from 0.26 to 21.9 μm), giving attention to the critical catalyst thickness and the formation of defects. We also report the optimum photocatalyst thickness for our single-layer membranes (∼2.74 μm), after which more titanium dioxide does not improve the degradation. However, an increase in degradation for membranes with multiple TiO2 layers was still possible. These results and the comparisons with the literature suggested that the optimal catalyst thickness is closely related to the material morphology. We obtained a maximum degradation at the lower filtration rate (1.6 L m−2 h−1) of 72% with a single layer membrane of 3.4 μm and 82% with a membrane with six layers of 21.9 μm. Furthermore, a 1D mass transport and reaction model that describes the coating thickness effect was developed and fitted with the experimental data. Other parameters are also discussed, such as light penetration limitations, surface area, and surface reaction rate constant. These results and analysis provide a better understanding of the fabrication and optimization of photocatalytic membranes.

Predictors of change in hypoglycemia unawareness among patients with type 1 diabetes.

To analyse predictors of hypoglycemia unawareness (HU) and improvement in Clarke score in clinical practice. We retrospectively identified patients with type 1 diabetes (T1D) at an academic T1D clinic who completed HU surveys 6-12months apart. HU (Clarke score ≥4) and improvement in Clarke score (decrease by ≥1 point or more clinically relevant ≥2 point) were assessed in univariable relationships and using multivariable logistic regression. Of the 300 participants, median diabetes duration was 19years, 47 had HU at baseline, and 91 had an improvement by 1 point while 21 had an improvement by 2 points. Patients with baseline Clarke score ≥4 who had ≥1 or ≥2 point improvement had lower filtration rate (eGFR) than those who did not. After adjustment for other variables, gender (male OR 0.33, 95% CI 0.15, 0.74), log diabetes duration (OR 6.40, 95% CI 2.84, 14.5), and eGFR <60ml/min/1.73m2 (5.56, 95% CI 1.98, 15.6) were independent predictors of baseline HU. Continuous glucose monitoring use (OR 2.04, 95% CI 1.20, 3.48) and log diabetes duration (OR 1.78, 95% CI 1.22, 2.60) were independent predictors of 1 point improvement and eGFR <60ml/min/1.73m2 (OR 10.5, 95% CI 3.64, 30.0) and an education visit (OR 2.64, 95% CI 1.01, 6.89) were independent predictors of 2 point improvement in Clarke score. Diabetes duration, gender, and eGFR were independent predictors of HU. Improvement in Clarke score is possible in patients with long-standing T1D, underscoring the need for additional study.

Comparative Analysis of Dopaminergic and Cholinergic Mechanisms of Sensory and Sensorimotor Gating in Healthy Individuals and in Patients With Schizophrenia.

Sensory and sensorimotor gating provide the early processing of information under conditions of rapid presentation of multiple stimuli. Gating deficiency is observed in various psychopathologies, in particular, in schizophrenia. However, there is also a significant proportion of people in the general population with low filtration rates who do not show any noticeable cognitive decline. The review article presents a comparative analysis of existing data on the peculiarities of cholinergic and dopaminergic mechanisms associated with lowering gating in healthy individuals and in patients with schizophrenia. The differences in gating mechanisms in cohorts of healthy individuals and those with schizophrenia are discussed.

Optimisation of the filter housing dimensions of an automatic flushing strainer-type filter

Filtration is essential in drip irrigation systems to remove physical contaminants carried by water that can clog the emitters, cause wear, or foul components of the system, affecting its performance and lifespan. Automatic flushing strainer-type filters initiate and terminate discrete flushing cycles that are activated automatically by means of differential pressure. The objective of this study is to investigate the hydraulic performance and flow behaviour of an automatic flushing strainer-type filter operated with clean water, using experimental and numerical approaches, to optimise the dimensions of its filter housing and to increase the range of operating flow rates. Pressure drop curves were determined for the filter housing and the filter system equipped with five models of filter elements (woven and non-woven elements). Excessive pressure drop in the filter housing and low filtration rates were identified as the main drawbacks of the original filter system. Numerical simulations enabled the identification of the most critical regions in terms of pressure losses near the transitions between the inlet and outlet segments of the pipe. Four designs of filter housing were simulated to evaluate the possibilities of optimising the filter housing dimensions using a constant filtering area. Larger inlet and outlet diameters combined to a filter housing shorter and wider were improvements in the filter housing dimensions that enabled to decrease the pressure drop in the filter and/or increase the range of operating flow rates. The results provided useful information for enhancing the hydraulic performance of the filtration system.

Technology for obtaining high-pure magnesium compounds using the hydrolytic processes of sedimentation

In nature, magnesium compounds are distributed in the form of such minerals as dolomite, magnesite, serpentinite, brucite, and in the form of such solutions as sea and ocean waters, salt lakes, bischofite. The main popular magnesium compounds are its chloride, hydroxide, and oxide. The most common technology for obtaining magnesium hydroxide is based on the action of alkaline reagents on solutions of magnesium. However, the technology has significant drawbacks. The main issue is that magnesium hydroxide cannot be obtained free of impurity metal ions, and the sediment itself has an extremely low filtration rate from the solution in which it is formed. Magnesium hydroxide is an excellent sorbent collector for the ions of most metals, so it is possible to utilize this property of absorption of magnesium hydroxide to produce other highly pure compounds, for medicine and pharmacopeia. This paper investigates the processes of alkaline hydrolysis of magnesium chloride and the formation of magnesium hydroxide sediment, the kinetics of processes, as well as the properties of sediments. Empirical formulas for sediment production parameters with a high filtration coefficient that exceeds the known values of 1·106have been derived. The study reported here hasrevealed the possibility of obtaining in a relatively simple way highly pure chloride, hydroxide, and magnesium oxide, sodium chlorides, potassium, calcium, in which the impurity 3d metals content does not exceed the value as a percentage of (1‒4)·10-7. Due to the properties of highly pure magnesium compounds to the sorption of metal ions, it is possible to create reference samples of chemical elements for the needs of metrology. For example, to create MR phantoms to verify measurements and check the operation of magnetic resonance imaging (MRI) in medical institutions. Especially pure magnesium hydroxide can be used for instrumental methods of analytical chemistry (X-ray fluorescent, neutron-activation methods) when fabricating chemical references for testing laboratories.

Poly(ionic liquids) based on β-cyclodextrin as fluid loss additive in water-based drilling fluids

Well wall collapse due to massive fluid in water-based drilling fluids (WDFs) intrusion into the reservoir is an urgent issue during oil drilling. In this study, we synthesized the poly(ionic liquids) (PILs) based on β-cyclodextrin and investigated its novel application as fluid loss additive in WDFs. American Petroleum Institute standard filtration tests showed that the PILs exhibited excellent filtration control performance even after hot rolling at 180 °C for 16 h compared to commercial fluid loss additives (Driscal D, PAC-Lv, CMC). Specifically, the fluid loss volumes of Driscal D/WDFs, PAC-Lv/WDFs and CMC/WDFs were 10.4 mL, 12.4 mL and 14.8 mL respectively after hot roll at 180 °C for 16 h, however, the fluid loss of PILs/WDFs was only 2.8 mL. The extremely low filtration rate, thickness and permeability of the PILs/WDFs mud cake resulted in exceptionally low fluid loss volume. Additionally, the mechanism of PILs controlling fluid loss in WDFs was revealed by bentonite particle size measurement and Zeta potential measurement. This work demonstrates that PILs have the promising application as an efficient fluid loss additive in WDFs due to the outstanding filtration loss reduction behavior.

Development of a Weighted Barite-Free Formate Drilling Mud for Well Construction under Complicated Conditions.

Construction of oil and gas wells at offshore fields often involves high formation pressure and the presence of swellable clay rocks in the section. In addition, productivity preservation is also an important aspect. For this purpose, it is necessary to reduce the solids content of the drilling mud. The purpose of this work is to develop, improve, and study compositions of weighted drilling muds with low content of solids, on the basis of organic salts of alkali metals and polymers for the construction of wells prone to rock swelling and/or cavings, as well as drilling fluids for drilling-in the formation. In order to achieve the set goal the following is required: Analysis of existing drilling muds of higher density for drilling wells in unstable rock intervals and for drilling in the productive formation; analysis of experience in using drilling systems on the formic acid salts base and substantiation of requirements for flushing fluids during well construction; development and investigation of drilling mud compositions on the formate base; and the evaluation of inhibiting effect of systems containing organic salts, polymer reagents, and calcium carbonate on clay samples. The developed drilling mud is characterized by a high inhibiting ability that allows minimized mud-weighting by the natural solid phase. This reduces the volume of prepared mud and facilitates the regulation of its properties by reducing the dispersion of drilled cuttings; it eliminates problems related to hydration and the swelling of active clay rocks; and stabilizes unstable argillites prone to caving. The low solids content, low filtration rates, and inhibitory nature of the mud allows high stability of the rheological properties of the mud, and preserves oil and gas reservoir productivity under conditions of elevated formation pressure.

Performance of biological activated carbon (BAC) filtration for the treatment of secondary effluent: A pilot-scale study

In addition to the adsorption capability for organic compounds, granular activated carbon (GAC) can also serve as a good media for the growth of microbial communities in biofilters. Despite its potential, the application of BAC filtration for municipal wastewater treatment has been little addressed in the literature. In this context, this paper aimed to investigate BAC filtration as a post-treatment of anaerobic effluent in pilot scale and its performance in removing organic matter and turbidity. Removal efficiencies during the biofilters run times and along biofilters depth were also evaluated. Three BAC filters were evaluated under different operating conditions of filtration rates (from 13 to 32 m d−1) and empty bed contact time (EBCT) (from 45 to 112 min) during 170 days. The lowest filtration rate (13 m d−1) presented the best performance in terms of dissolved organic carbon (DOC) removal (68.2 ± 4.0%), leading to mean DOC effluent concentration of 6.8 ± 0,9 mg L−1. The BAC reached the stability of biological activity from the 63rd day of operation, however, the adsorption process was still occurring contributing to DOC removal. These DOC removals were higher than those results reported in the literature for BAC filters treating drinking water and municipal wastewater. The DOC removal efficiencies were maintained during the filter run times, showing the robustness of the system even after the interference caused by the backwashing process. BAC filtration was also capable of removing turbidity, with removal efficiencies between 84.5 ± 3.6% and 70.63 ± 6.8% depending on the filtration rate. The results indicated the capability of BAC systems to remove efficiently organic carbon and turbidity from effluents with high organic content, mean of 23.97 (±3.96) mg.L−1, and also valuable support to determine adequate operating parameters for BAC filters application in secondary effluent treatment, such as filtration rate (13 m d−1), EBCT (112 min), and detailed backwashing procedures.

Biological activated carbon filter for greywater post-treatment: Long-term TOC removal with adsorption and biodegradation

Biological activated carbon (BAC) filters can be used to remove residual total organic carbon (TOC) from greywater after a membrane bioreactor. The two main TOC removal processes are adsorption to the granular activated carbon (GAC) and biological degradation. Biodegradation leads to the growth of microorganisms in the filter bed, which can lead to increased pressure loss over the filter bed. However, the roles of sorption and biodegradation in long-term TOC removal and how they complement each other are unclear. We monitored TOC removal from greywater in a BAC filter installed following a membrane bioreactor over more than 900 days. Removal performance depended on the operational time of the BAC filter, the influent TOC concentration, and in the upper part of the filter on the empty bed contact time (EBCT). Across the overall filter, the EBCT did not significantly influence TOC removal, showing that the filter was sufficiently large for the range of flow rates observed. Analysis of the long-term data revealed the equal importance of sorption and biodegradation over the whole operation period and the whole filter bed. Most of the TOC was removed in the upper part of the filter, where biodegradation was the dominant mechanism. In the lower part of the filter, sorption capacity remained and allowed high influent TOC concentrations to be buffered. The generous filter design with low average filtration rates ensured long-term TOC removal. The only maintenance needed was backwashing, which was required only after more than 800 days of operation. Backwashing effectively reduced the pressure loss but had no significant influence on the effluent water quality. Our study shows that BAC filters are a suitable post-treatment step for the treatment of greywater with highly variable flow and TOC concentrations.

The kidney of the Nodularia freshwater mussel has a larger filtration-size and counter-current system with improved water excretion compared with the seawater mussel Mytilus.

ABSTRACTHistological studies and magnetic resonance imaging were employed to analyze the kidney structure and function of the freshwater mussel, Nodularia douglasiae. The Nodularia kidney consists of proximal, intermediate and distal tubules. The epithelia of the renal tubules were composed of a single layer of cuboidal cells. The proximal and distal tubules run in opposite directions underneath the pericardial cavity. Molecular weight cut-off (MWCO) values for the kidney filtration were detected by MR tracer injections: gadolinium-diethylenetriaminepentaacetic acid (GdDTPA) at 0.55 kDa, an oligomer-based contrast agent (CH3-DTPA-Gd) at 2.2 kDa, as well as Gd-DTPA-polylysine at 10, 22, and 110 kDa. The T1w-MRI intensity and T1 relaxation rate (R1) of the pericardial cavity and renal tubules increased with tracers smaller than 10 kDa. The other tracers showed only minimal or no increase. Thus, we concluded that the MWCO of the kidney is 22 kDa, 50 times larger than that for the Mytilus living in seawater. Since the R1 values of the renal tubules were similar to those of the pericardial cavity, the kidney did not concentrate filtrated tracers. The slow decay of the magnetic resonance (MR) tracers from the renal tubules indicated a low filtration rate, suggesting that the counter-current system reabsorbs useful solutes without reabsorption of water. The higher MWCO may be beneficial to maintain the tubular oncotic pressure and allow excretion of excess water. In conclusion, a main renal function of the freshwater mussel is the excretion of water, opposite to that of the seawater mussel and vertebrates, which preserve water.

Investigation of electret and filtering properties of polypropylene-based nonwoven fabrics and its composites with 2 vol% of silicon dioxide inclusions

The electret characteristics of polypropylene (PP) nonwoven fabrics processed by melt-blowing and its composites with 2 vol% of silicon dioxide (SiO 2 ) are studied in this work. The surface potential V e , effective surface charge density a ef and electric field strengths E as well as their filtration efficiency are reported. Improvement of electret properties of PP filled with SiO 2 in comparison with the samples without filler is observed. It is seen that PP samples poled in a corona discharge show lower filtration rate than the non-poled ones. The electret nonwoven fabrics with improved filtration characteristics are obtained on the basis of PP with SiO 2 inclusions.

Abstract 601: Chimeric antigen receptors incorporating novel binding domains targeting CD123 direct potent antitumor activity of T cells: Correlation between affinity and activity

Abstract Unlike the tumor targets associated with initial CAR T cell successes, the vast majority of tumor associated antigens are not unique, but rather expressed at elevated levels compared to normal tissue. For example, while CD123 is overexpressed on many AML tumor cells, concerns regarding on-target, off-tumor toxicities - often associated low-level CD123 expression on normal endothelial cells - has hindered clinical success. Therefore, future generations of CAR T therapies will require novel strategies that have the ability to discriminate between normal and elevated antigen levels - potentially through mechanisms that involve 1) the simultaneous or sequential targeting of multiple tumor associated antigens and 2) agents that contain affinity-tuned targeting domains. Due to the large inventory of validated antibodies against a variety of therapeutic targets, scFv naturally emerged as the obvious and justifiable targeting domain for chimeric antigen receptors. However, many of the characteristics that have made antibodies versatile and effective recombinant therapeutics (e.g., high affinity, bivalency, antibody-dependent cytotoxicity, complement-dependent cytotoxicity, FcRn recycling, and low renal filtration rates) are not advantageous for membrane associated chimeric receptors. Furthermore, scFv are not native protein structures and their development, particularly as it pertains to solubility and aggregation, can be challenging. Therefore, we sought to develop a simple, highly selective targeting domain that could be engineered into complex, potentially multispecific therapeutics. We describe the design and development of non-scFv-derived binding domains. Using phage display and targeted mutagenesis, we identify a series of binding domains that target CD123 with high specificity - as characterized by functional and tissue binding studies. These domains exhibit affinities that range over 2 logs and demonstrate in vitro potencies that correlate with their affinities. CARs comprised of higher affinity binding domains mediate potent T-cell activation and cytolysis of CD123-expressing target cells and induce complete durable remission in two AML xenograft models. We also describe a strategy of engineering less immunogenic binding domains through the identification and removal of putative T cell epitopes and demonstrate that the resultant variants retain biological activity. Finally, we demonstrate further potential of our binding domains by generating functional, bi-specific CARs comprised of a CD123-specific binding domain and a CD19-specific scFv. The ability to incorporate our target-specific binding domains with a range of affinities into complex chimeric receptors, affords a viable alternative to scFv as targeting domains in CAR T cell therapeutics. Citation Format: David W. LaFleur, Haiying Qin, Justin P. Edwards, Liubov Zaritskaya, Ankit Gupta, C. Jenny Mu, Laura K. Richman, Terry J. Fry, David M. Hilbert. Chimeric antigen receptors incorporating novel binding domains targeting CD123 direct potent antitumor activity of T cells: Correlation between affinity and activity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 601.

Symmetrical Analysis of Low-Cost Filter Media and Their Efficiency in Treatment of Water

Separating is a compelling procedure in expelling particles from water because utilization of sand become nowadays is very challenging in filtration process. It is a necessity to find an alternative media which must satisfy the low cost, easy availability, high durable with less zone required and discharge of water. Many ponds are contaminated mostly in high level of turbidity. In this work it is identified the various synthetic filter media taken examined for the replacement sand. The high level of turbid water may contain slit, dissolved organic compounds, and other microscopic organisms. So, in this method all contaminants are removed. The filtration procedure was created to break down and filtration of lab scale arrangement was planned. The performance as concerns lab scale reactor was optimized by using HDPE (High Density Polyethylene) granules are easily available in all polymer industries are used as a filter media. A proportional study of natural filter media sand and synthetic filter media HDPE granules was undergone for investigation. This two-filter media were selected because of its locally available and two different size of media (sand 2.5 mm, HDPE 3.5 mm) were evaluated. Bentonite (20mg/l ≈ 120 NTU). Identified two parameters were influenced the filtration recital i.e. media depth, filtration velocity. The outcomes uncovered to evacuate turbidity in best conditions where start to be low filtration rate (10.62 l/m² min), extended media midst (240mm). The removal of turbidity in sand was 70% and in plastic media was 55%. Nevertheless, headloss was achieved in higher manner comparing to plastic media. The treated water used as agriculture purpose.

Performance Monitoring of Indigenous Household Groundwater Filter for Iron and Fluoride Removal: A Case Study from Assam, India

Groundwater in the north-eastern part of India contains high levels of iron and fluoride. However, due to lack of piped water supply, the rural people in Assam rely on groundwater for meeting their daily water needs. The groundwater is treated using different types of indigenous household groundwater filter units for removal of iron. IHGF units are fabricated based upon past experiences using layers of sand, gravel and sometimes wooden charcoal enclosed within a hollow reinforced cement concrete ring, tin container and plastic bucket. An attempt has been made to assess the levels of iron and fluoride in the groundwater of Amingaon—a selected rural locality for the study, the effectiveness of an IHGF unit in removal of iron and fluoride from the groundwater and suggestions for improving the service life of the unit. During the field survey in the area, groundwater samples collected from ten locations indicate Fe2+ and F− concentrations in the range of 0.0–11.3 mg/L and 0.1–0.7 mg/L, respectively. Monitoring of an IHGF unit over a period of 170 days indicates almost Fe2+ free water with F− removal of 30–40%. Upon continuous use, filter media of the IHGF unit get clogged leading to lower filtration rate requiring dismantling, cleaning of media and refabrication of the unit every 2–3 months. The batch studies indicate iron removal mechanism as oxidation of Fe2+ in the presence of DO to Fe3+ form. The groundwater devoid of DO is pre-treated by turning nine times from one bucket to the other from a height of approximately 1 m, thereby increasing DO levels close to 6 mg/L. The increased DO converts Fe2+ to Fe3+ which settles out easily within 25 min. The pre-treated and settled groundwater contains residual Fe2+ of 0.5–0.6 mg/L and is then applied to the IHGF unit over a period of 129 days producing almost Fe2+ free water. This helps in increasing the longevity of the service period of the unit as accumulation of Fe3+ reduces significantly due to pre-treatment of the groundwater.