cssi/SciSciGPT-SciSciNet huggingface dataset:
Duodenal Helminth Infection Alters Barrier Function of the Colonic Epithelium via Adaptive Immune Activation

Chronic infection with intestinal helminth parasites is a major public health problem, particularly in the developing world, and can have significant effects on host physiology and the immune response to other enteric infections and antigens. The mechanisms underlying these effects are not well understood. In the current study, we investigated the impact of infection with the murine nematode parasite Heligmosomoides polygyrus, which resides in the duodenum, on epithelial barrier function in the colon. We found that H. polygyrus infection produced a significant increase in colonic epithelial permeability, as evidenced by detection of elevated serum levels of the tracer horseradish peroxidase following rectal administration. This loss of normal barrier function was associated with clear ultrastructural changes in the tight junctions of colonic epithelial cells and an alteration in the expression and distribution of the junctional protein E-cadherin. These parasite-induced abnormalities were not observed in SCID mice but did occur in SCID mice that were adoptively transferred with wild-type T cells, indicating a requirement for adaptive immunity. Furthermore, the helminth-induced increase in gut permeability was not seen in STAT6 knockout (KO) mice. Taken together, the results demonstrate that one of the mechanisms by which helminths exert their effects involves the lymphocyte- and STAT6-dependent breakdown of the intestinal epithelial barrier. This increase in epithelial permeability may facilitate the movement of lumenal contents across the mucosa, thus helping to explain how helminth infection can alter the immune response to enteric antigens.
Restriction of a late Neoproterozoic biotope; suspect-microbial structures and trace fossils at the Vendian-Cambrian transition

Wrinkle structures are a class of oddly textured sedimentary structures that are common in Proterozoic-Cambrian marine siliciclastic strata, but uncommon in post-Ordovician subtidal marine facies. Despite a long history of study, there is little agreement on how these structures form, or their role in larger-scale sedimentologic and paleontologic contexts. Based on similarities with morphologic and sedimentologic characteristics of modern microbially dominated communities, it appears that ancient wrinkle structures could have been formed by microbial mats. Microbial genesis for wrinkle structures not only helps explain their ubiquity during the late Neoproterozoic, but also their distinct paleoenvironmental and temporal shifts related to increasing vertically-oriented metazoan bioturbation. The Vendian-Cambrian transition offers a unique opportunity to examine the influence of suspect-microbial communities on the siliciclastic sedimentary record and their relationship with the earliest burrowing, grazing, and locomotive activities of metazoans. Based on outcrops in the Great Basin, USA, metazoans appear to have been moving on, in, and under suspect microbially-bound sediment, and exhibit features that suggest active and passive epifaunal and infaunal sediment ingestion. Together with more intricate horizontal burrow networks, this style of horizontal bioturbation is common in shallow settings of the Vendian-Cambrian transition, and is hypothesized to reflect highly specialized approaches to exploiting mat-mediated organic-rich sediment layers. Post-Ordovician restriction of such bedding-parallel burrowing behavior to deeper settings mirrors a shift of suspect-microbial structures to stressed or deep-sea settings. This restriction suggests replacement (rather than progressive evolution) of metazoans with horizontally specialized ecological strategies by more vertically-oriented bioturbating organisms.
Dexamethasone-Inhibitable Stimulation of Plasma Prorenin by Ketamine in Cats*

Abstract Plasma prorenin in humans is derived from both renal and extrarenal sources, but in the cat most plasma prorenin is normally of renal origin. Sodium depletion and β-adrenergic blockade can increase plasma prorenin in cats, but the effects of sedatives and glucocorticoids are unknown. We examined the effect of ketamine, a centrally acting nonbarbiturate anesthetic, and of the glucocorticoid dexamethasone on plasma prorenin and renin. Intramuscular injection of ketamine (20 mg/kg, three times a day) for 4 days increased plasma prorenin slowly and consistently, from 7.4 ± 1.4 (±SEM) to 11.4 ± 2.2, 17.1 ± 2.5, 20.2 ± 3.0, and 29.2 ± 3.4 ng/ml-h (P < 0.001) on days 1, 2, 3, and 4, respectively, without any effect on plasma active renin. Plasma renin substrate and cortisol were also unchanged. Bilateral nephrectomy reduced both baseline and stimulated plasma prorenin to undetectable levels. Treatment with α-blocker, β-blocker, angiotensin-converting enzyme inhibitor, or Ca2+ antagonist did not affect t...
Disruption of actin cytoskeleton reorganization after fertilization affects cell cycle time in sea urchin eggs

Abstract We have investigated the effects of cytochalasin D on first cleavage of fertilized eggs from the sea urchin Strongylocentrotus purpuratus. Cytochalasin D inhibits the cortical actin filament reorganization that occurs immediately after fertilization in sea urchin eggs, and arrests cell division by preventing normal contractile ring formation which inhibits cytokinesis. In this study, eggs were incubated in 2 or 4 μg/mL cytochalasin D within the first 5 minutes post-fertilization, for 10, 20, or 30 minutes, followed by washout with artificial sea water. At 2 μg/mL, two groups of results were obtained; a 20–25 minute delay in cytokinesis irrespective of exposure time, and a time-dependent response where longer incubation times produced lengthier delays in cytokinesis. The time-dependent delays in cell division also occurred at 4 μg/mL cytochalasin D, along with cytotoxic effects that correlated to the length of drug exposure. The results show that disruption of the normal actin cytoskeleton reorgan...
A comparative study of two regimens of combination chemotherapy in acute leukemia.

A comparative clinical trial of two regimens of combination chemotherapy has been accomplished in acute leukemia by four separate medical and pediatric services. Sixty-five patients were allocated at random to one of two treatment programs. Daily administration of methotrexate with daily 6-mercaptopurine has been compared to methotrexate every third day in the same total dose with daily 6-mercaptopurine. No difference in frequency of remission, extent of remission or toxicity was observed between the two groups. Among those patients who attained remission status, however, duration of remission (P = .05-.10) and of survival (P = <.05) was longer for the continuous group. All remissions in children occurred in acute lymphocytic leukemia, whereas all remission in adults were observed in acute myelocytic leukemia. The duration of remissions was somewhat shorter for children with acute lymphocytic leukemia than for adults with acute myelocytic leukemia. The frequency of remission, either partial or complete, was higher in children, however (36 per cent), than in adults (19 per cent), although the confidence limits for each figure overlap. The duration of acute leukemia in previously untreated patients did not influence response to therapy from the two antimetabolite regimens in this study. In patients who had had prior antimetabolite therapy, however, complete remissions were attained less often than in previously untreated patients. The toxic manifestations encountered during the administration of these antimetabolites are described. Seventeen deaths occurred during this study, of which 8 occurred in the first 10 days, presumably from leukemia and not drug toxicity. Five patients died with hypoplastic marrows ascribed to drug toxicity. The toxic manifestations were qualitatively and proportionately the same in patients who attained remission status, and in those patients who failed to remit, but who lived long enough to recognize the onset of remission if it were going to occur. No indication was obtained, therefore, that patients who attained remission were subjected to a greater toxic hazard, in order to achieve the therapeutic benefits observed, than those who did not remit. The median survival of patients who achieved remission was longer (p <.05) than for patients who did not remit. Since the survival time of remitters from relapse to death was almost identical with the survival time of nonremitters from onset of treatment to death, this difference can be accounted for by the time spent in remission and getting to remission. The median survival time from symptomatic onset for all children in this study was 12 months, and for adults, 7 months. The median in children is similar to that reported from other clinics. This is evidence that a comparative therapeutic trial in acute leukemia can be accomplished without recognizable compromise of patient welfare.
Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation

Global mRNA abundance depends on the balance of synthesis and decay of a population of mRNAs. To account for this balance during activation of T cells, we used metabolic labeling to quantify the contributions of RNA transcription and decay over a 4 h time course during activation of leukemia-derived Jurkat T cells. While prior studies suggested more than half of the changes in mRNA abundance were due to RNA stability, we found a smaller but more interesting population of mRNAs changed stability. These mRNAs clustered into functionally related subpopulations that included replicative histones, ribosomal biogenesis and cell motility functions. We then applied a novel analysis based on integrating global protein-RNA binding with concurrent changes in RNA stability at specific time points following activation. This analysis demonstrated robust stabilization of mRNAs by the HuR RNA-binding protein 4 h after activation. Our unexpected findings demonstrate that the temporal regulation of mRNA stability coordinates vital cellular pathways and is in part controlled by the HuR RNA binding protein in Jurkat T cells following activation.
Abstract 613: Fibroblast Growth Factor 2 Modulates Endotheliogenesis of Human Adipose Tissue Derived Stem Cells

Background: Adipose-derived stem cells (ASCs) are a potential adult mesenchymal stem cell source for restoring endothelial function in critical limb ischemia patients. Fibroblast growth factors (FGF) play a major role in angiogenesis and wound healing. The purpose of this study was to evaluate the effects of FGF and VEGF on human ASCs proliferation, migration and potential endothelial differentiation regards to their use as endothelial cell (EC) substitutes. Methods: ASCs were isolated from clinical lipoaspirates and cultured in M199 medium with FBS (10%), FGF2 (10ng/ml), VEGF (50ng/ml) or combinations of FGF2 and VEGF. Cell proliferation rates, viability, and migration were measured by growth curves, MTT and scratch assays. For cell attachment determinations, ASCs were seeded onto scaffold (small intestinal submucosa) for 5d. Endothelial differentiation capabilities of ASC were confirmed by expression of EC specific markers using qPCR, immunofluorescence staining and cord formation on Matrigel. PD173074,...
Manometry in pleural drainage: essential practice or over-rated gadget?

About 1.5 million people are diagnosed with pleural effusion each year in the USA with approximately 180,000 thoracenteses performed each year. The measurement of pleural pressure during therapeutic thoracentesis has been proposed as a useful benchmark to guide therapeutic thoracentesis. The proposed benefits of pleural manometry include diagnosis of unexpandable lung, prevention of re-expansion pulmonary edema (REPE), and pneumothorax ex vacuo, as well as prediction of successful pleurodesis in malignant effusions. Although pleural manometry undeniably offers insights into pleural space physiology, the paucity of data on improved clinical outcomes and the absence of standardized methodology and teaching opportunities have hampered its widespread adoption by pulmonologists.
Spatial Variation of Pressure in the Lyophilization Product Chamber Part 2: Experimental Measurements and Implications for Scale-up and Batch Uniformity

Product temperature during the primary drying step of freeze-drying is controlled by a set point chamber pressure and shelf temperature. However, recent computational modeling suggests a possible variation in local chamber pressure. The current work presents an experimental verification of the local chamber pressure gradients in a lab-scale freeze-dryer. Pressure differences between the center and the edges of a lab-scale freeze-dryer shelf were measured as a function of sublimation flux and clearance between the sublimation front and the shelf above. A modest 3-mTorr difference in pressure was observed as the sublimation flux was doubled from 0.5 to 1.0 kg·h−1·m−2 at a clearance of 2.6 cm. Further, at a constant sublimation flux of 1.0 kg·h−1·m−2, an 8-fold increase in the pressure drop was observed across the shelf as the clearance was decreased from 4 to 1.6 cm. Scale-up of the pressure variation from lab- to a manufacturing-scale freeze-dryer predicted an increased uniformity in drying rates across the batch for two frequently used pharmaceutical excipients (mannitol and sucrose at 5% w/w). However, at an atypical condition of shelf temperature of +10°C and chamber pressure of 50 mTorr, the product temperature in the center vials was calculated to be a degree higher than the edge vial for a low resistance product, thus reversing the typical edge and center vial behavior. Thus, the effect of local pressure variation is more significant at the manufacturing-scale than at a lab-scale and accounting for the contribution of variations in the local chamber pressures can improve success in scale-up.
Racial Crime Stereotypes and Offender Juvenility: Comparing Public Views About Youth-Specific and Nonyouth-Specific Sanctions

Recent theoretical advancements of the racial threat model of punitiveness suggest that because youthful offending has driven crime trends in recent decades, and because racially exclusive conceptions of childhood have historically structured public opinion on juvenile justice, Black criminal stereotypes may be especially consequential for attitudes toward juvenile punishments. Building on this work, the current study uses national survey data to examine whether the strength of the relationship between Black criminal stereotypes and support for punitive policies varies according to whether punishments are targeted toward juvenile delinquents or criminals in general. We find that Black criminal stereotypes are positively associated with punitive attitudes and that the magnitude of this effect is statistically identical in the cases of youth-specific and nonyouth-specific sanctions. Thus, the results suggest that racialized support for punitive crime policies is not influenced by the juvenility of the offender.
High-performance liquid chromatographic determination of N-n-propylnorapomorphine and its glucuronide metabolite in blood plasma

Rapid HPLC methods are described for the determinations of either free N-n-propylnorapomorphine (NPA) or the free and conjugated NPA in blood plasma. The methods employ a methanol protein-precipitation step that produces relatively good absolute recoveries, while permitting a simple work-up procedure without derivatization. Only 0.25 ml of plasma is required for a single determination at a sensitivity limit of 0.4μg NPA/ml plasma. Satisfactory accuracy and precision are achieved with the proposed assay.
Improving diffraction resolution using a new dehydration method.

The production of high-quality crystals is one of the major obstacles in determining the three-dimensional structure of macromolecules by X-ray crystallography. It is fairly common that a visually well formed crystal diffracts poorly to a resolution that is too low to be suitable for structure determination. Dehydration has proven to be an effective post-crystallization treatment for improving crystal diffraction quality. Several dehydration methods have been developed, but no single one of them is suitable for all crystals. Here, a new convenient and effective dehydration method is reported that makes use of a dehydrating solution that will not dry out in air for several hours. Using this dehydration method, the resolution of Archaeoglobus fulgidus Cas5a crystals has been increased from 3.2 to 1.95 A and the resolution of Escherichia coli LptA crystals has been increased from <5 to 3.4 A.
Metaphyseal chondrodysplasia of Jansen.

1. A case is described for which the name metaphyscal chondrodysplasia of Jansen is suggested. 2. Biochemical changes were found simulating those caused by hyperparathyroidism, but different and distinctive roentgenographic findings were also evident. Parathyroid exploration was negative for hyperplasia or adenoma. 3. It is postulated that the metabolic changes—hypercalcaemia and hypophosphataemia—may have been secondary to the unverlying bone defect.
Coagulation Profile as a Risk Factor for 30-Day Morbidity and Mortality Following Posterior Lumbar Fusion.

Study design A retrospective cohort study. Objective The aim of this study was to identify associations between abnormal coagulation profile and postoperative morbidity and mortality in patients undergoing posterior lumbar fusion (PLF). Summary of background data The literature suggests that abnormal coagulation profile is associated with postoperative complications, notably the need for blood transfusion. However, there is little research that directly addresses the influence of coagulation profile on postoperative complications following PLF. Methods The American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP) was utilized to identify patients undergoing PLF between 2006 and 2013. Nine thousand two hundred ninety-five patients met inclusion criteria. Multivariate analysis was utilized to identify associations between abnormal coagulation profile and postoperative complications. Results Low platelet count was an independent risk factor for organ space surgical site infections (SSIs) [odds ratio (OR) = 6.0, P 48 hours (OR = 4.5, P = 0.002), Acute renal failure (OR = 5.8, P = 0.007), transfusion (OR = 1.6, P 48 hours (OR = 5.6, P = 0.002), cerebrovascular accident (CVA)/stroke with neurological deficit (OR = 5.1, P = 0.011), cardiac arrest (OR = 5.4, P = 0.030), transfusion (OR = 1.5, P = 0.020), and death (OR = 4.5, P = 0.050). High International Normalized Ration (INR) was an independent risk factor for pneumonia (OR = 8.7, P = 0.001), pulmonary embolism (OR = 5.6, P = 0.021), deep venous thrombosis/Thrombophlebitis (OR = 4.8, P = 0.011), septic shock (OR = 8.4, P = 0.048), and death (OR = 9.8, P = 0.034). Bleeding disorder was an independent risk factor for organ space SSI (OR = 5.4, P = 0.01), pneumonia (OR = 3.0, P = 0.023), and sepsis (OR = 4.4, P Conclusion Abnormal coagulation profile was an independent predictor of morbidity and mortality in patients undergoing PLF. As such, it should be considered in preoperative optimization and risk stratification.
Sensor selection and placement in adversarial environment

We study the problem of sensor placement, when the set of sensors are interrogated sequentially to detect a target employing evading actions. We model the sensor management problem as a two stage game between the observer and the target: in the first stage sensor locations are chosen by the observer, in the second stage the observer and the target choose open-loop control strategies to optimize error exponent for the probability of mis-detection with opposing interests. Therefore the observer chooses the sensor locations to optimize the value function of the game played in the second stage. We propose a computationally efficient gradient descent method to iteratively refine the sensor locations for maximizing the value function using the envelope theorem.
Superacidic porous polymer catalyst and its application in esterification of carboxylic acid

Two solid acid catalysts, SAC1 and SAC2, with porous structure obtained from mesoporous hard template were synthesized and characterized by Fourier transform infrared spectroscopy, acid-base titration, nitrogen adsorption/desorption, scanning electron microscopy, and their catalytic activity in esterification of carboxylic acid. Acid-base titration showed that these catalysts have acidic concentration of 1.02–1.10 mmol/g. The catalytic test in esterification of 6-bromohexanoic acid with methanol showed that SAC1 with perfluorinated sulfonic acid is catalytically more active than SAC2 with aryl sulfonic acid. In spite of lower acid loading, SAC1 showed a comparable catalytic activity with commercially available solid acid catalyst Amberlyst 15 with higher acid capacity (4.80 mmol/g) due to high acidity and well-defined pore structure. SAC1 could be recycled up to three times without significant loss in activity.
Theological Formation: Dialogical Interplay Between Barth, Hauerwas, and Bonhoeffer

This chapter theologically analyzes the task of Christian formation by bringing Karl Barth, Dietrich Bonhoeffer, and Stanley Hauerwas into dialogical interplay. While Hauerwas is to be commended for foregrounding formation, it seems that he lacks a pneumatology adequate for the task. This claim is evident when comparing Hauerwas to Barth. If Barth provides a robust account of the Spirit’s agency but lacks an adequate account of the church as the object of formation, Hauerwas errs in the opposite direction by offering a thick account of the church but no Spirit to form it. Bonhoeffer is then presented as a mediating bridge between the two. The chapter concludes by offering constructive theses about Christian formation and by showing how this theological analysis bears upon ecclesial practices.
Biofuels and Municipal Waste Technology an Overview of the DOE Program

Biomass currently contributes about 4% (1.3 million Barrels of Oil Equivalent /day (BOE/D)) of the total annual U.S. energy requirement in the form of residential heat, process heat and steam, and electricity from wood and municipal waste and ethanol from grain crops. These contributions from biomass are significant; however, the potential exists for a much greater impact on U.S. energy supplies. While that potential is difficult to quantify, it seems likely that it could easily exceed 15 quadrillion Btu (Quads) (15 exajoules). Further, biofuels as a domestic, economic, dispersed and comparatively environmentally benign resource meets the DOE goal of a safe, secure, and affordable supply of energy. The Biofuels and Municipal Waste Technology Division’s (BMWTD) strategy for contributing to the nation’s energy supply focuses on research and development of those technologies where the risks are too high and the return on investment too low to attract private sector investment. As technology is developed cooperation with and cost sharing from is sought for eventual commercialization by industry. Outside input and cooperative research is sought at all stages of the federal research program. With a large federal deficit limiting Federal investment in many areas biofuels research, the BMWTD focuses research on a select number of fuel cycles aimed at mid- to long- term processes for liquid and gaseous fuels, the energy products for which the U.S. is most dependent on foreign sources of supply. Each fuel cycle involves a renewable feedstock coupled to a conversion process.
Results of a compact reflex triode with multi cavity adjustment

This study focuses on achieving wide tunability of a compact reflex triode virtual cathode oscillator (vircator). The cathode is of a bimodal carbon fiber (CF) material paired with a pyrolytic graphite anode. These materials display ideal operating characteristics which include but are not limited to, long lifetime > 106 shots, high operating temperatures > 1000 K, and large current densities ~200 A/cm2. A 12 stage, 158 J pulse forming network (PFN) based Marx generator serves to drive the vircator at 350 kV, 4 kA with ~100 ns pulsewidth. The operating frequency of interest is in the range of 1–6 GHz, where tunability is achieved by varying the length of the anode-cathode (A-K) gap, the length from the back wall to the A-K gap, and/or the distance from the bottom of the cavity to the A-K gap. The primary focus in this research was to increase the achievable frequencies by placing a square waveguide within a sealed vacuum tube. This allows the bottom part of the waveguide to be easily adjusted while still maintaining the waveguide integrity. The resulting microwave frequencies are shown along with the system performance.
The one-dimensional line scheme of a family of quadratic quantum P3s

Abstract The attempted classification of regular algebras of global dimension four, so-called quantum P 3 s, has been a driving force for modern research in noncommutative algebra. Inspired by the work of Artin, Tate, and Van den Bergh, geometric methods via schemes of d-linear modules have been developed by various researchers to further their classification. In this work, we compute the line scheme of a certain family of algebras whose defining relations involve a scalar α such that almost all of the algebras in the family are considered candidates for a generic quadratic quantum P 3 . We find that, for almost all α, the algebras have a one-dimensional line scheme consisting of eight curves. Viewing the line scheme as a closed subscheme of P 5 via the Plucker embedding, it is the union of one nonplanar elliptic curve in a P 3 , one nonplanar rational curve with a unique singular point, two planar elliptic curves, and two subschemes, each consisting of the union of a nonsingular conic and a line.
Civil Society Organizations and the Enduring Role of Religion in Promoting Democratic Engagement

As Tocqueville observed the emergence of democracy in the USA, he noted the central role religion played in undergirding democratic life. Nearly 200 years later, it is unclear whether religion continues to possess sufficient capacity to promote democratic engagement. This study links organizational theory with research on the structural and cultural characteristics of civil society organizations (CSOs) to assess the current impact of religion on democracy. It analyzes original data from a national study of politically oriented CSOs to determine whether drawing on structural characteristics of religious congregations and cultural elements of religion helps the organizations promote democratic engagement. The analysis finds a positive relationship between organizations that incorporate structural and cultural forms of religion and their organizing capacity, political access, and mobilizing capacity. These findings suggest that religion, mediated by congregations and religious culture, retains sufficient civic vitality to help politically oriented CSOs foster democratic engagement.
Retinal vasculitis associated with CREST syndrome

Abstract Purpose To report two cases of retinal vasculitis associated with CREST syndrome, a novel ocular finding. Observations We report two cases of patients with CREST syndrome with ocular inflammatory disease. Patient 1 presented with a right unilateral panuveitis with extensive retinal vasculitis and evidence of prior uveitis in the contralateral eye. Patient 2 presented with a left branch retinal artery occlusion and bilateral retinal vasculitis. Both patients underwent treatment with prednisone and mycophenolate motefil. Conclusions and importance Retinal vasculitis has not been previously reported in CREST syndrome. Prompt therapy with immunomodulatory therapy can potentially minimize ocular morbidity.
Prenatal Material Hardships and Infant Regulatory Capacity at 10 Months Old in Low-Income Hispanic Mother-Infant Pairs.

Abstract Objective Prenatal maternal stresses have been associated with infant temperament patterns linked to later behavioral difficulties. Material hardships, defined as inability to meet basic needs, are important prenatal stressors. Our objective was to determine the associations between prenatal material hardships and infant temperament at 10 months. Methods This was a longitudinal study of mother-infant pairs in a randomized controlled trial of a primary care-based early obesity prevention program (Starting Early). Independent variables representing material hardship were: housing disrepair, food insecurity, difficulty paying bills, and neighborhood stress (neighborhood safety). Dependent variables representing infant temperament were assessed using questions from 3 subscales of the Infant Behavior Questionnaire: orienting/regulatory capacity, negative affect, and surgency/extraversion. We used linear regression to investigate associations between individual and cumulative hardships and each temperament domain, adjusting for confounders, and testing for depression as a moderator. Results Four hundred twelve mother-infant pairs completed 10-month assessments. Thirty-two percent reported food insecurity, 26% difficulty paying bills, 35% housing disrepair, and 9% neighborhood stress. In adjusted analyses, food insecurity was associated with lower orienting/regulatory capacity scores (β = −0.25; 95% confidence interval [CI], −0.47 to −0.04), as were neighborhood stress (β = −0.50; 95% CI, −0.83 to −0.16) and experiencing 3 to 4 hardships (compared with none; β = −0.54; 95% CI, −0.83 to −0.21). For neighborhood stress, the association was stronger among infants of mothers with prenatal depressive symptoms (interaction term P = .06). Conclusion Prenatal material hardships were associated with lower orienting/regulatory capacity. These findings support the need for further research exploring how temperament relates to child behavior, and for policies to reduce prenatal material hardships.
A splice junction-targeted CRISPR approach (spJCRISPR) reveals human FOXO3B to be a protein-coding gene

The rapid development of CRISPR technology is revolutionizing molecular approaches to the dissection of complex biological phenomena. Here we describe an alternative generally applicable implementation of the CRISPR-Cas9 system that allows for selective knockdown of extremely homologous genes. This strategy employs the lentiviral delivery of paired sgRNAs and nickase Cas9 (Cas9D10A) to achieve targeted deletion of splice junctions. This general strategy offers several advantages over standard single-guide exon-targeting CRISPR-Cas9 such as greatly reduced off-target effects, more restricted genomic editing, routine disruption of target gene mRNA expression and the ability to differentiate between closely related genes. Here we demonstrate the utility of this strategy by achieving selective knockdown of the highly homologous human genes FOXO3A and suspected pseudogene FOXO3B. We find the spJCRISPR strategy to efficiently and selectively disrupt FOXO3A and FOXO3B mRNA and protein expression; thus revealing that the human FOXO3B locus encodes a bona fide human gene. Unlike FOXO3A, we find the FOXO3B protein to be cytosolically localized in both the presence and absence of active Akt. The ability to selectively target and efficiently disrupt the expression of the closely-related FOXO3A and FOXO3B genes demonstrates the efficacy of the spJCRISPR approach.
Genetic perspectives on brain development and complexity.

The detection and identification of macromolecular species amidst a vastly complex background is a major problem in neurobiology. Therefore, we wish to begin by making a few introductory remarks pertaining to present estimates of macromolecular complexity of the brain. Genes and their transcripts are the first and second orders respectively of the vast molecular complexity of the brain. The first measurements relevant to estimating the extent to which “single” copy DNA (scDNA or DNA which encodes most of the different proteins) is transcribed in mammalian organs were made about 14 years ago (Hahn, 1970; Hahn & Laird, 1971). These initial measurements, although confirmed by others (Brown & Church, 1971; Grouse, Chilton, & McCarthy, 1972; reviewed by Kaplan & Finch, 1982), were underestimates. But they nonetheless showed that very complex arrays of RNA species are present in eukaryotic cells and organs. We now know that in the mammalian brain (mouse and rat) at least 18–20% of the scDNA is transcribed as nuclear RNA (=~40% of the haploid coding capacity) (Bantle & Hahn, 1976; Chikaraishi, Deeb & Sueoka, 1978). Most of these different transcripts apparently reside in the nuclear RNA of neurons (Ozawa, Kushiya & Takahashi, 1980).
Husserl VS. Jerusalem

To the extent that these thoughts coincide with those of R. Avenarius and E. Mach, we have no differences; I gladly agree with them. I am genuinely convinced, in particular, that we owe a vast amount of logical illumination to the historical-methodological labors of Ernst Mach, and that this is the case where one cannot fully agree with his conclusions. Mach, unfortunately, does not appear to me to have tackled what are the most fruitful problems of the economy of thought, problems I tried to formulate above in a somewhat brief but quite sufficient fashion. His failure to do this is, in any case, partly due to the epistemological misinterpretations that he thought of as necessary foundations for his investigations. Mach’s writings have, however, had an immense influence with respect to these very misinterpretations. This is the side of his thought that he shares with Richard Avenarius, and it is in respect to this which I must here oppose him.
Effect of fabric washing on the presumptive identification of bloodstains

The purpose of this study was to investigate the retention of blood stains on twelve different types of fabrics after washing at various drying times. The findings of this study, supported by chi-square analysis, indicate that the retention of bloodstains on washed fabrics depends upon the particular fiber composition of the fabric, the specific blood screening test used, and whether or not a detergent was used in the wash. The results of this research did not reveal a significant effect of the drying time on the retention of bloodstains, as tested during the 48-h limit of this experiment. The author concludes that the forensic serologist should consider the factors investigated in this study before rendering an opinion on the retention of bloodstains on washed garments.
Mechanism of Enyzmatic Phosphotriester Hydrolysis

There are numerous reports from various sources of crude enzyme systems that appear to be capable of hydrolyzing organophosphotriesters (1–8). Unfortunately, none of these enzymes has ever thoroughly been characterized or purified to homogeneity. However, we have recently succeeded in the first isolation and characterization of a phosphotriesterase from Pseudomonas diminuta and this enzyme is the focus of this presentation.
Anaerobic Biotreatment of Municipal Sewage Sludge

As the world population grows, waste generated by human activities becomes an urgent environmental problem. Enormous amounts of sewage sludge are generated around the world, as wastewater created by humans is treated to avoid environmental pollution, protect human health, and preserve water resources. The beneficial properties of sludge, such as its high calorific value and nutrient content, along with stringent regulations on sludge disposal, provide incentives to viewing sludge as a resource rather than waste. Along these lines, anaerobic digestion is considered to be an attractive sludge-management practice because it offers waste reduction, greenhouse gas mitigation, and renewable energy production opportunities while stabilizing the sludge. In this article, after a brief discussion of the principles and theory of anaerobic digestion, the current status of anaerobic sludge digestion is presented. In addition, up-and-coming technologies to improve the efficiency of this process are discussed.
Abstract 4107: Tumor multifunctional targeting polymeric nanomicelles with polypharmacy payload for effective therapy and imaging of resistant renal cell carcinoma

Renal cell carcinoma (RCC) is very difficult to treat as the cells are mostly resistant to many current therapies. Therefore, newer treatments including better ways of drug delivery are urgently needed to fight this malignant disease efficiently. The ongoing work was done by generating and characterizing RCC cells that are resistant to everolimus, a front-line mTOR-targeted therapy, and tested whether a class of CARP-1 functional mimetic (CFM) compounds inhibits parental and everolimus-resistant RCCs in combination with sorafenib. CFMs inhibited RCC cell viability in a dose-dependent manner that was comparable to everolimus treatments as well as the combination with sorafenib. CFM-4.16 inhibited viabilities of everolimus-resistant RCC cells, albeit CFM-4.16 combined with sorafenib was more effective than CFM-4.16 alone. CFM-dependent loss of RCC cell viabilities was due in part to reduced cyclin B1 levels, activation of pro-apoptotic, stress-activated protein kinases (SAPKs), and apoptosis. However, CFMs and sorafenib are hydrophobic, and their dose escalation for in vivo studies remains challenging. We addressed the solubility and delivery concerns of CFM-4.16 and sorafenib by utilizing a nanotechnology-based approach. Our data thus far revealed that we have been successful in overcoming the solubility concerns of CFM-4.16 and sorafenib by encapsulating it in water-soluble vitamin E TPGS-based micellar nanoformulation that enables high drug loading and affords its intravenous administration for animal testing. We also use our polymeric NPs formulation for in vitro efficacy in parental, wild-type and everolimus-resistant RCC. After confirming the anticancer activity of CFM-4.16-loaded nanoformulations in vitro, we finally examined the intravenous (i.v.) administration of the CFM-4.16-loaded polymeric NPs in a clinically relevant RCC mouse model. The CFM-4.16 formulation inhibited the viability of parental and everolimus-resistant RCC cells in vitro and suppressed the growth of parental A498 RCC-cell-derived xenografts (RCC animal model), in part by stimulating apoptosis. After optimizing its potency and biologic stability, we performed imaging of animal inoculated with RCC tumor and PDX model by conjugation with NIR dye. The results showed high binding affinity and specific tumor uptake, faster normal tissue clearance and less non-target organ uptake. These findings make CFM-4.16 an important potential therapeutic in combination with sorafenib using nanoformulation in the treatment of RCCs. Citation Format: Hashem O. Alsaab, Samaresh Sau, Vino T. Cheriyan, Ulka Vaishampayan, Arun K. Rishi, Arun K. Iyer. Tumor multifunctional targeting polymeric nanomicelles with polypharmacy payload for effective therapy and imaging of resistant renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4107.
Ultrafast all-optical switching in a continuous layer gap plasmon metasurface (Conference Presentation)

All-optical nanophotonic switches, not bound by the inherent RC delays of electronic circuits, have the potential to push data-processing speeds beyond the limits of Moore’s Law. This has lead to the investigation of light-matter interactions in nanostructured materials in several all-optical data processing applications. To have a true impact on the field of ultrafast data-transfer, it is important to demonstrate switching in the telecom frequency range. We have designed a continuous layer gap plasmon metasurface, comprising a layer of gold nanodisk resonators on a 20 nm film of ZnO deposited on an optically thick gold layer. The performance of the metasurface has been investigated through numerical studies, using the optical properties of as-grown gold and zinc oxide, characterized by ellipsometry. An on-off ratio of 10.6 dB has been observed in simulations. Experimental studies are underway. The findings of this research work will pave the pathway to the design of ultra-compact and ultrafast optical switches employing ultrafast, dynamically tunable metasurfaces.
In Situ Imaging of Fluorescent Nipah Virus Respiratory and Neurological Tissue Tropism in the Syrian Hamster Model

Using a recombinant Nipah virus expressing a fluorescent protein (ZsG), we visualized virus tropism in the Syrian hamster model. We found that anatomical localization of fluorescence correlated to clinical signs; signal was primarily visualized in the respiratory tract in animals with acute-onset terminal disease, whereas central nervous system localization was seen in animals that succumbed with delayed disease onset. While polymerase chain reaction (PCR) detection corresponded well to ZsG signal, virus was only isolated from some lung, brain, liver, and kidney samples that were ZsG and/or PCR positive, and only from animals euthanized on or before 15 days post infection.
Electrooxidation of short and long chain perfluorocarboxylic acids using boron doped diamond electrodes.

Abstract This study investigates electrooxidation of short (C3–C6) and long (C7–C-18) chain perfluorocarboxylic acids (PFCAs) including perfluorooctane sulfonate (PFOA) using Si/BDD electrode. The effect of operational parameters (supporting electrolyte type, applied current density, and initial pH) were explored for PFOA removal. At the optimized conditions, 74% TOC removal and 37% defluorination ratio were gained for 10 mg L−1 of PFOA solution which evidences that the shorter chain PFCAs were formed. The PFOA degradation pathway followed one direct electron transfer from PFOA molecule to anode surface. Then two different degradation pathways were proposed. The first proposed degradation mechanism involved the reaction of perfluoroheptyl radical and hydroxyl radical, the release of HF and hydrolysis. The second mechanism involved the reaction between perfluoroheptyl radical and O2, formation of C7F15O and perfluorohexyl radical with releasing COF2. The removal of short- (C3–C6) and long-chain PFCAs (C7–C18) was also characterized. More than 95% of removal efficiency was gained for all long-chain PFCAs, excluding C7. The removal ratios of short-chain PFCAs (C3–C6) were 39%, 41%, 66% and 70% for C3, C4, C5 and C6, respectively. Contrary to long-chain PFCAs, chain-length dependence for short-chain PFCAs were observed. Defluorination ratio of short-chain PFCAs was only 45% signifying that defluorination partially occurred. Water matrix did not significantly affect the degradation of short-chain PFCAs in deionized water (DI), river water and secondary effluent of a wastewater treatment plant (WWTP). In contrast, defluorination ratio of long-chain PFCAs was noticeably affected by water matrix with the order of DI water > WWTP effluent > river water.
Outcome of Early Motion Protocol for Total Hand Replantation: 1- and 2-Year Postoperative Results

Introduction We review the benefits of early motion protocols following replantation of a total right hand amputation at 1 and 2 years after replantation, and provide recommendations for postoperative management. Materials and Methods Replantation of the entire right hand in zone-4 was performed and supported by rigid external fixation spanning the forearm and hand. An early active “place-and-hold” motion protocol was initiated within the first 3 postoperative days. Metacarpophalangeal joint extensors were tethered by the pins, limiting full excursion. This resulted in stiffness and extensor adhesions that required a staged extensor tenolysis; however, all joints remained supple. The early motion protocol prevented the need for significant flexor tenolysis and joint releases. Results Early motion rehabilitation protocols can produce very successful results in complex replantation. The enhanced stability afforded by external fixation of the wrist allowed us to perform aggressive early rehabilitation. Conclusion This case highlights the benefits of early active motion (limiting the need for complex joint and flexor tendon releases) and demonstrates the degree of extensor adhesions caused by even minor extensor tendon tethering. This aggressive rehabilitation approach can produce excellent range of motion, and likely limit the need for secondary tenolysis and joint release procedures.
Factors Associated with Scaphoid Nonunion following Early Open Reduction and Internal Fixation.

Background Nonunion after open reduction and internal fixation (ORIF) of scaphoid fractures is reported in 5 to 30% of cases; however, predictors of nonunion are not clearly defined. Objective The purpose of this study is to determine fracture characteristics and surgical factors which may influence progression to nonunion after scaphoid fracture ORIF. Patients and Methods We performed a retrospective case–control study of scaphoid fractures treated by early ORIF between 2003 and 2017. Inclusion criteria were surgical fixation within 6 months from date of injury and postoperative CT with minimum clinical follow-up of 6 months to evaluate healing. Forty-eight patients were included in this study. Nonunion cases were matched by age, sex, and fracture location to patients who progressed to fracture union in the 1:2 ratio. Results This series of 48 patients matched 16 nonunion cases with 32 cases that progressed to union. Fracture location was proximal pole in 15% (7/48) and waist in 85% (41/48). Multivariate regression demonstrated that shorter length of time from injury to initial ORIF and smaller percent of proximal fracture fragment volume were significantly associated with scaphoid nonunion after ORIF (63 vs. 27 days and 34 vs. 40%, respectively). Receiver operating curve analysis revealed that fracture volume below 38% and time from injury to surgery greater than 31 days were associated with nonunion. Conclusion Increased likelihood for nonunion was found when the fracture was treated greater than 31 days from injury and when fracture volume was less than 38% of the entire scaphoid. Level of Evidence This is a Level III, therapeutic study.
Microstructural analyses of Cr(VI) speciation in chromite ore processing residue from the soda ash process.

Abstract The microstructure of Chromite Ore Processing Residue (COPR) derived from the soda ash roasting process was investigated prior to and after removal of water exchangeable chromate using a host of microscopy and spectroscopy techniques. Soda ash COPR consists mostly of a magnesioferrite (MgFe2O4) matrix that has substantial substitution of trivalent chromium (Cr) for iron. The chromite particles are generally larger than the overall particle size distribution of COPR, containing most of the Cr mass in areas that are greater than 20 μm in diameter; chromite particles are also associated with most of the non-exchangeable hexavalent Cr (Cr(VI)), even though the binding mechanism is not well understood. The remaining non-exchangeable Cr(VI) was found in association with the surrounding Si- and Al-matrix, with spectroscopic evidence of the presence of Cr(VI)-hydrotalcite.
Countering Anti-Semitism: A Catholic Theologian’s Perspective

In this chapter I show how interpretations of certain texts from the New Testament provided raw materials for hostility to Jews and document recent scholarly work to provide interpretations grounded in social-historical and literary contexts. The essay has two major sections. The first explores the complex ways in which Judaism and Christianity interacted in their formative periods. The second section recounts Catholic efforts to confront anti-Semitism, especially its anti-Jewish teachings that arose from failure to grapple with polemical elements in the New Testament and from an arrogant posture toward the religious other. A conclusion includes a brief reflection on implications for mental health practitioners.