cssi/SciSciGPT-SciSciNet huggingface dataset:
Higher order accurate difference solutions of fluid mechanics problems by a compact differencing technique

A general fourth order differencing scheme is developed and applied to three viscous test problems to verify the accuracy and applicability of the technique. The procedure is atypical since only three nodes are necessary to obtain the desired fourth order accuracy. This is accomplished by a differencing technique which considers the function and all necessary derivatives as unknowns. The relations for these derivatives yield simple tridiagonal equations which can be easily solved. Comparisons of the fourth order results with those computed using second order methods are presented for the test problems and clearly indicate that the accuracy achieved by these fourth order computations is always significantly better than current second order procedures.
A New Target for Therapy in Squamous Cell Carcinoma of the Lung

Investigators report the identification of novel somatic mutations in the DDR2 kinase gene in squamous cell carcinoma of the lung. Cellular, biochemical, and human data suggest that tumor cells harboring DDR2 mutations have increased sensitivity to existing tyrosine kinase inhibitors, providing rationale for clinical trials of agents that inhibit DDR2 kinase in the disease.
A 3-D "Super Surface" Combining Modern Intraocular Lens Formulas to Generate a "Super Formula" and Maximize Accuracy.

Importance Cataract surgery is the most common eye surgery. Calculating the most accurate power of the intraocular lens (IOL) is a critical factor in optimizing patient outcomes. Objectives To develop a graphical method for displaying IOL calculation formulas in 3 dimensions, and to describe a method that uses the most accurate and current information on IOL formulas, adjustments, and lens design to create one “super surface” and develop an IOL “super formula.” Design, Setting, and Participants A numerical computing environment was used to create 3-D surfaces of IOL formulas: Hoffer Q, Holladay I, Holladay I with Koch adjustment, Haigis, and SRK/T. The surfaces were then analyzed to determine where the IOL powers calculated by each formula differed by more than 0.5, 1.0, and 1.5 diopters (D) from each of the other formulas. Next, based on the current literature and empirical knowledge, a super surface was rendered that incorporated the ideal portions from 4 of the 5 formulas to generate a super formula. Last, IOL power values of a set of 100 eyes from consecutive patients at an eye institute were calculated using the 5 formulas and super formula. The study was performed from December 11, 2014, to April 20, 2015. Analysis was conducted from February 18 to May 6, 2015. Main Outcomes and Measures Intraocular lens power value in diopters and the magnitude of disparity between an existing individual IOL formula and our super formula. Results In the 100 eyes tested, the super formula localized to the correct portion of the super surface 100% of the time and thus chose the most appropriate IOL power value. The individual formulas deviated from the optimal super formula IOL power values by more than 0.5 D 30% of the time in Hoffer Q, 16% in Holladay I, 22% in Holladay I with Koch adjustment, 48% in Haigis, and 24% in SRK/T. Conclusions and Relevance A novel method was developed to represent IOL formulas in 3 dimensions. An IOL super formula was formulated that incorporates the ideal segments from each of the existing formulas and uses the ideal IOL formula for an individual eye. The expectation is that this method will broaden the conceptual understanding of IOL calculations, improve clinical outcomes for patients, and stimulate further progress in IOL formula research.
Cystic Fibrosis Syndrome: A New Paradigm for Inherited Disorders and Implications for Molecular Diagnostics

In this issue, Castaldo et al. (1) describe the use of denaturing gradient gel electrophoresis to scan the CFTR gene in cystic fibrosis (CF) patients from Southern Italy who were negative for the common CF mutations. As expected, rare mutations were found, five of which were useful in population screening. These findings are particularly important for laboratories in Italy and in areas with families of Italian descent. Advanced molecular techniques provide a double-edged sword because they often detect sequence changes whose deleterious natures are by no means established. In the CFTR gene, such variants may cause classic CF, elicit atypical phenotypes with similarities to CF, or have no consequence to health. Among recent letters in the New England Journal of Medicine on mild phenotypic variants of CF (2)(3)(4), one suggested that “the diagnosis of cystic fibrosis is too nebulous to preserve in clinical practice and that perhaps, as is the case with Cushing’s disease and syndrome, we need to have both a cystic fibrosis ‘disease’. . . and a cystic fibrosis ‘syndrome’ (which would include the pancreatic manifestations, congenital bilateral absence of the vas deferens, or lesser pulmonary manifestations)” (3). As improved mutation detection technologies enter the clinical laboratory and identify rare CFTR mutations, laboratorians and clinicians must be cognizant of the changing nature of genotype-phenotype associations. The severity of the pancreatic and hepatic features of CF is highly variable. The gastrointestinal presentations endured by CF patients take many forms (5). The majority of patients (85–90%) experience pancreatic exocrine insufficiency. Those who retain pancreatic exocrine function (10–15%) typically carry at least one of the CFTR gene mutations that have been associated with residual function. Other CF patients have impaired endocrine insulin production associated with diabetes (10–15% of patients) or liver dysfunction (5), although no specific CFTR …
A phase I and pharmacologic study of DMP 840 administered by 24-hour infusion

Summary Purpose: DMP 840, a novel bisnaphthalimide, has demonstrated promising schedule dependent anti-tumor activity in vitro and in vivo against several tumor cell lines. A phase I study was conducted to evaluate the effect of a 24-hour infusion schedule repeated every three weeks, on the therapeutic efficacy of DMP 840. Patients and methods: Fourteen patients with refractory solid tumor malignancies were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m 2 . Results: A combination of neutropenia, thrombocytopenia and stomatitis were dose-limiting at doses of 50 and 60 mg/m 2 in both minimally- and extensively-pretreated patients. In contrast, all courses at lower dose levels were well tolerated. Pharmacokinetic analysis demonstrated that DMP 840 had a prolonged terminal half life (median 39 hours; range 25-86) and that dose-limiting events were significantly related to several indices of systemic DMP 840 exposure (P < 0.01, Wilcoxon Rank Sum test). Conclusion: The recommended dose of DMP 840 for further disease oriented evaluations is 40 mg/m 2 administered over 24 hours every three weeks. The infusion duration evaluated in this study did not result in a substantial increase in the tolerable dose compared to shorter, less cumbersome schedules.
Lung Vascular Injury from Monocrotaline Pyrrole, a Putative Hepatic Metabolite

The pyrrolizidine alkaloid, monocrotaline (MCT), is a plant toxin that causes injury to the vasculature of the lungs and pulmonary hypertension in animals. To produce lung injury, MCT is bioactivated in the liver by cytochrome P450 monooxygenases to pyrrolic metabolites which travel via the circulation to the lungs, where they cause injury by unknown mechanisms. One putative metabolite of MCT is monocrotaline pyrrole (dehydromonocrotaline, MCTP), a moderately reactive, bifunctional alkylating agent. A single, iv injection of chemically synthesized MCTP into rats causes delayed and progressive lung vascular injury and pulmonary hypertension similar to that caused by MCT itself.
Applications of Strict Pi 1 1 Predicates to Infinitary Logic.

Consider the predicate of natural numbers defined by: where R is recursive. If, as usual, the variable ƒ ranges over ω ω (the set of functions from natural numbers to natural numbers) then this is just the usual normal form for Π 1 1 sets. If, however, ƒ ranges over 2 ω (the set of functions from ω into {0, 1}) then every such predicate is recursively enumerable. 3 Thus the second type of formula is generally ignored. However, the reduction just mentioned requires proof, and the proof uses some form of the Brower-Konig Infinity Lemma.
Functionalization of Metallic Glasses through Hierarchical Patterning

Surface engineering over multiple length scales is critical for electronics, photonics, and enabling multifunctionality in synthetic materials. Here, we demonstrate a sequential embossing technique for building multi-tier patterns in metals by controlling the size-dependent thermoplastic forming of metallic glasses. Sub-100 nm to millimeter sized features are sculpted sequentially to allow an exquisite control of surface properties. The process can be integrated with net-shaping to transfer functional patterns on three-dimensional metal parts.
Pyrite Removal from Several Clays by High Gradient Magnetic Separation Method

Pyrite removal from several clays by high gradient magnetic separation (HGMS) method was investigated. Effects of magnetic susceptibility (MS) values of pyrite and clays, and operation conditions on the pyrite removal were studied. Following results are discussed.(1) MS values of pyrite in the Itaya clay A and Sendatsu clay C were 1.01×10-6 emu/g and 0.64×10-6 emu/g, respectively. In spite of their low SM values, pyrite particles could be separated from clays by HGMS method because of their large particle size.(2) Efficiency of pyrite removal from clays were mainly dependent on the MS values of origin clays, and the good results were naturally obtained for low value clays. Pyrite removal from Itaya clay D (MS =0.08×10-6 emu/g), Itaya clay A (MS =0.63×10-6emu/g) and Sendatsu clay C (MS =1.91×10-6emu/g) was examined under the following condition ; matrix : FW, magnetic field strength : 14.5 kG and linear velocity : 38.4 m/hr. The XRD peak intensities of pyrite (200) in the N-mag clays were 0 cps, 10 cps and 45 cps for Itaya clay D, Itaya clay A and Sendatsu clay C, and their Fe2O3 content were 0.34 wt.%, 0.54 wt.% and 1.92 wt.% respectively.(3) Good results for pyrite removal from Itaya clay A by HGMS method were obtained at the high magnetic field strength (9.7-14.5 kG) and rather low linear velocity (22.1-38.4 m/hr). The matrix FW was best suitable for the pyrite removal.(4) By treating of Itaya clay A at 14.5 kG and 22.1 m/hr with matrix FW, whiteness increased from 80.5 to 87.4 with decreasing Fe2O3 content from 1.46 wt.% to 0.38 wt.%, and N-mag clay yield was 89.00.(5) Also titanium oxide was easily removed from clays under the HGMS conditions which pyrite removal from clays resulted in good success.
Effects of ions on adrenocorticotropin-sensitive adenylate cyclase of rat adrenals.

SummaryThe basal activity of adenylate cyclase in homogenates of normal rat adrenals increased with the concentration of Mg2+ (1.25–10 mM) in the medium. The response of the enzyme to adrenocorticotropin (2 × 10-5M synthetic β1–24 ACTH) and NaF (10 mM) was also determined by the concentration of Mg2+ in the incubation mixture: ACTH was more effective than NaF at low Mg2+ levels (1.25 and 2.5 mM) and less effective at 10 mM Mg2+. Of the monovalent cations tested, Li+ was more potent than Na+ in inhibiting the response of adrenal adenylate cyclase to ACTH. These cation effects were generally greater when medium Mg2+ was lower. The lowest Li+ concentration found to inhibit ACTH action significantly was 25 mM. K+ did not enhance the effect of ACTH on adrenal adenylate cyclase at 5 or 25 mM and depressed it at 100 mM (Mg2+:2.5 mM).
A Direct Proof of the Integral Formula for Arctangent

(1989). A Direct Proof of the Integral Formula for Arctangent. The College Mathematics Journal: Vol. 20, No. 3, pp. 235-237.
A practical method for history matching of production rate and well bottom-hole pressure

This paper proposes a practical method that can be used in quick history matching of production rate and well bottom-hole pressure by combining geostatistical techniques and reservoir simulation.The method is especially suitable for large reservoirs with long production history because it integrates well bottom-hole pressure and production rate simultaneously by limited flow simulation runs and maintains practicality for large complex reservoir geological models.
Cardiopulmonary bypass: Associated hemostatic abnormalities

We prospectively evaluated hemostatic parameters in 11 adults undergoing cardiac operations with cardiopulmonary bypass. Procedures were divided into interval 1 (anesthesia induction and thoracotomy) and interval 2 (bypass and operation). We observed significant prolongations of the prothrombin time (PT) and declines of factors I, II, V, and VII during interval 1. Activated partial thromboplastin time (APTT), thrombin time (TT), and factors VIII, IX, X, XI, and XII were similarly affected but not significantly. During interval 2 the PT, APTT, and TT were all markedly and significantly prolonged. All coagulation factor activities declined significantly. During interval 1 the behavior of factors I, V, and VIII did not differ from that of VII and XI, which are usually stable in acute intravascular coagulation, nor from factors II, VII, IX, X, and XI, which are usually stable in primary fibrinogenolysis. During interval 2, the behavior of factors I and VIII was still similar to these other groups of factors, whereas the decline of factor V was significantly greater. No correlation was noted between plasma hemoglobin and loss of factor I, V, or VIII activity. One patient had circulating fibrin monomers; occasional patients had increases in fibrin degradation products (FDP's) or shortened euglobin lysis times (ELT's). One patient had intravascular coagulation, and another had primary fibrinogenolysis; over-all results suggest at most a minor role for these processes in accounting for the declines in factor activity in most patients. Platelet counts declined significantly during interval 2. No correlation was noted between platelet loss and pump time. Platelet aggregation with adenosine diphosphate (ADP) and collagen was unchanged over interval 1. Over interval 2, aggregation with ADP declined significantly; with collagen, mildly and not significantly. The timing of changes in aggregation suggests that anesthesia and operation per se do not explain the loss of this function. Incubation of normal platelets with postperfusion plasma failed to affect the aggregation of these platelets.
Observations on Fetal Heart Motion by Ultrasound Real Time Imaging

We have found that it is practical to evaluate fetal viability by ultrasound recording of the motion of the heart in utero. To date this has been accomplished in 30 patients. An electronic scanning device consisting of a linear array of 64 independent transducer segments is placed on the abdomen of the pregnant woman, and fetal heart motion is recorded on videotape.
cAMP induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle

Recent studies indicate that vascular smooth muscle cells generate carbon monoxide (CO) via the action of heme oxygenase (HO). Because adenosine 3',5'-cyclic monophosphate (cAMP) is an important intracellular signaling molecule in the regulation of vascular cell function, we examined whether this second messenger modulates the expression of HO and the production of CO by rat aortic smooth muscle cells. Treatment of smooth muscle cells with the membrane-permeable cAMP derivative dibutyryl cAMP or with compounds that increase intracellular cAMP levels (isoproterenol and forskolin) resulted in a concentration- and time-dependent increase in the levels of HO-1 mRNA and protein, whereas the expression of HO-2 remained unchanged. Both actinomycin D and cycloheximide blocked the basal expression of HO-1 mRNA and protein and prevented the cAMP-mediated induction of HO-1. Incubation of platelets with cAMP-treated smooth muscle cells resulted in a significant increase in platelet cGMP concentration that was partially reversed by treatment of smooth muscle cells with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine or the HO blocker zinc protoporphyrin-IX. However, the combined addition of these two inhibitors to cAMP-treated smooth muscle cells or the addition of the CO and NO scavenger hemoglobin to platelets completely blocked the stimulatory effect on platelet cGMP levels. These results demonstrate that cAMP induces the expression of the HO-1 gene and stimulates the formation of CO and NO in vascular smooth muscle cells. The capacity of cAMP to induce the synthesis of guanylate cyclase-stimulatory CO from smooth muscle cells may represent a novel mechanism by which this nucleotide regulates vascular tone.
Markov Processes, Gaussian Processes, and Local Times: Associated Gaussian processes

In Section 7.4 we develop and exploit some special properties of Gaussian processes that are associated with Borel right processes. In this chapter we consider the question of characterizing associated Gaussian processes. In order to present these results in their proper generality, we must leave the familiar framework of Borel right processes and consider local Borel right process, which are introduced in the final sections of Chapter 4. The reader should note that this is the first place in this book, after Chapter 4, that we mention local Borel right processes. We remind the reader that Borel right processes are local Borel right processes, and for compact state spaces, there is no difference between local Borel right processes and Borel right processes. Let S be a locally compact space with a countable base. A Gaussian process { G x ; x ∈ S } is said to be associated with a strongly symmetric transient local Borel right process X on S , with reference measure m , if the covariance Γ = Γ( x, y ) = E( G x G y ) is the 0-potential density of X for all x, y ∈ S . Not all Gaussian processes are associated. It is remarkable that some very elementary observations about the 0-potential density of a strongly symmetric transient Borel right process show what is special about associated Gaussian processes. One obvious condition is that Γ( x, y ) ≥ 0 for all x, y ∈ S , since the 0-potential density of a strongly symmetric transient Borel right process is nonnegative (see Remark (3.3.5)).
Transcriptome analysis of trigeminal ganglia following masseter muscle inflammation in rats

BackgroundChronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptiv...
“What a Boy (or Girl) Wants” in The Turn of the Screw: The Children’s Frankly Expressed Motives for Their Performances

In place of traditional suspicious readings of Henry James’s The Turn of the Screw (1898), I employ Sharon Marcus’s “just reading” to explain the children’s behaviour in terms of their frankly expr...
Immortalized sheep microglial cells are permissive to a diverse range of ruminant viruses.

ABSTRACTBackground: Ruminants, including sheep and goats (small ruminants), are key agricultural animals in many parts of the world. Infectious diseases, including many viral diseases, are significant problems to efficient production of ruminants. Unfortunately, reagents tailored to viruses of ruminants, and especially small ruminants, are lacking compared to other animals more typically used for biomedical research. Objective: The purpose of this study was to determine the permissibility of a stably immortalized, sheep microglial cell line to viruses that are reported to infect ruminants: bovine viral diarrhea virus (BVDV), bovine herpesvirus 1 (BoHV-1), small ruminant lentiviruses (SRLV), and bovine respiratory syncytial virus (BRSV). Methods: Sublines A and H of previously isolated, immortalized, and characterized (CD14-positive) ovine microglial cells were used. Bovine turbinate cells and goat synovial membrane cells were used for comparison. Cytopathic changes were used to confirm infection of indivi...
THE STABILITY AND HYDROLYSIS OF S-ADENOSYL-METHIONINE; ISOLATION OF S-RIBOSYLMETHIONINE

Recent improvements in the methods for biosynthesis and isolation of S-adenosylmethionine (1, 2) have stimulated extensive experimentation with this compound. Detailed information upon its stability under various conditions is a prerequisite to microbiological, nutritional, and enzymatic research involving this substance. Not only is it desirable to have an estimate of the residual amount of X-adenosylmethionine at any given time during an experiment, but in many instances it is necessary also to know what fragments may accrue. Erroneous results may be surmised, especially in microbiological studies with mutants, if the response to hydrolytic products is mistaken for an effect of the parent substance. Experiments were carried out, therefore, on the stability of X-adenosylmethionine under the conditions of biological experimentation. Our study soon revealed that several hydrolytic processes occur simultaneously. To gain insight into the conditions which favor individual reactions, extremes of pH and temperature were included in this investigation. The latter phase of our work revealed conditions for splitting methionine from the molecule and for hydrolysis to adenine and a hitherto unknown fragment, S-ribosylmethionine. Directions for preparation and a description of some of the properties of this new compound are given. Our data extend the earlier observations of Cantoni, (3) and of Baddiley, Cantoni, and Jamieson (3, 4) on the hydrolysis of S-adenosylmethionine; they observed the formation of adenine by acid hydrolysis and of methylthioadenosine and homoserine by heating in neutral solution.
Four Ways to Make CS & IT Curricula More Immersive: Why the Bell Curve Hasn’t Transformed into a Hockey Stick

Our first experiences cement what becomes normal for us. Students should start off seeing a well-run system, dissect it, learn its parts, progressively dig down into the details. Don’t let them see what a badly run system looks like until they have experienced one that is well run. A badly run system should then disgust them.
Microfluidic chip for automated screening of carbon dioxide conditions for microalgal cell growth

This paper reports on a microfluidic device capable of screening carbon dioxide (CO2) conditions for microalgal cell growth. The device mainly consists of a microfluidic cell culture (MCC) unit, a gas concentration gradient generator (CGG), and an in-line cell growth optical measurement unit. The MCC unit is structured with multiple aqueous-filled cell culture channels at the top layer, multiple CO2 flow channels at the bottom layer, and a commercial hydrophobic gas semipermeable membrane sandwiched between the two channel layers. The CGG unit provides different CO2 concentrations to support photosynthesis of microalgae in the culture channels. The integration of the commercial gas semipermeable membrane into the cell culture device allows rapid mass transport and uniform distribution of CO2 inside the culture medium without using conventional agitation-assisted convection methods, because the diffusion of CO2 from the gas flow channels to the culture channels is fast over a small length scale. In addition, automated in-line monitoring of microalgal cell growth is realized via the optical measurement unit that is able to detect changes in the light intensity transmitted through the cell culture in the culture channels. The microfluidic device also allows a simple grayscale analysis method to quantify the cell growth. The utility of the system is validated by growing Chlamydomonas reinhardtii cells under different low or very-low CO2 levels below the nominal ambient CO2 concentration.
Evaluation of Nondestructiveness of Resonant Column Testing for Characterization of Asphalt Concrete Properties

The resonant column (RC) test has been used as a nondestructive test (NDT) to study dynamic properties of soils for the past few decades. With some modifications, this test can also be employed to characterize properties of asphalt concrete, especially because these properties are strongly dependent on the loading frequency. A conventional RC apparatus was retrofitted to characterize asphalt concrete properties at a range of temperatures from 10°C to 45°C. The RC test is believed to be nondestructive for most soils; however, this must be verified in case of testing asphalt concrete, especially at elevated temperatures. For this purpose, the impact resonance (IR) test, as a purely NDT tool, was used to check the integrity of asphalt concrete specimens before and after RC testing. The modulus values measured before and after RC tests, at each of the testing temperatures, were compared to evaluate the nondestructiveness of RC testing. Strain levels were also monitored to ensure that the material remained within the linear elastic range through the tests. The results show that the specimens exhibited the same modulus before and after RC testing over the full range of temperature and frequency sweep tests.
Microbial proteins for organic material degradation in the deep ocean

Organic material is synthesized in the sunlit surface layer of the oceans and that is where most of it is decomposed back to carbon dioxide and other inorganic constituents. However, a small fraction escapes immediate degradation and makes its way into deeper waters, some as far as the bottom thousands of meters below the surface. This sinking organic material contributes to sequestering atmospheric carbon dioxide and to feeding the biota of the deep ocean. Degradation is carried out by a complex microbial community whose taxonomic composition and metabolic potential vary greatly along the kilometer-long trip to the ocean floor. The metabolic potential of microbial communities has been deduced from metagenomics, genomic information gained by sequencing the entire community. In PNAS, Bergauer et al. (1) use metagenomics and another omic approach to explore changes in microbial communities and metabolism from 100-m to over 4,000-m deep in the Atlantic Ocean. They find many changes, but more surprising were the similarities in the cellular proteins used by microbes to degrade organic material along this depth profile and to support microbial life in the deep ocean. In the surface layer, bacteria use dissolved organic material (DOM) from phytoplankton, either produced directly or indirectly via release by grazers and viral lysis. The source for deep oceanic microbes is less obvious. One source is the organisms and particulate organic detritus produced in the surface layer that then sink to deeper waters. Because the biomass production of microbes on particles is much less than that by their free-living counterparts (2, 3), it is thought that sinking particulate organic material is broken up and solubilized to DOM (4) before being taken up by free-living heterotrophic bacteria and archaea (Fig. 1). Another potential source, albeit smaller than sinking particles, is the export of surface-layer DOM to deeper waters … [↵][1]1Email: kirchman{at}udel.edu. [1]: #xref-corresp-1-1
Stress and the city

Many of us were raised or currently live in an urban environment. A neuroimaging study now reveals how this affects brain function when an individual is faced with a stressful situation.
A multi-factorial approach for middle-of-line design rule validation and optimization in 22FDX®

In order to allow competitive and low-cost designs in the 22nm FD-SOI technology 22FDX®, novel Middle-of-Line (MOL) constructs have been specifically enabled. Single­Diffusion Break and Gate Tie-Down constructs and their specific design-to-process validation requirements are described. In particular, contact punch-through is investigated and validated using electrical and E-beam inspection methods. As a second step, the Gate Tie-down is optimized thanks to layout Design of Experiments to provide optimal performance and density once implemented in Standard Cells.
The safety and efficacy of GM-CSF as an adjuvant in hepatitis B vaccination of chronic hemodialysis patients who have failed primary vaccination

BACKGROUND End-stage renal disease and the need for chronic hemodialysis is an indication for hepatitis B vaccination, but up to half of dialysis patients fail to respond to a 40 microg/dose i.m. three-dose primary series of recombinant hepatitis B vaccine. Only another 10-20% respond to additional boosting doses of vaccine. PATIENTS AND METHODS Since GM-CSF has been shown to be an effective adjuvant for hepatitis B vaccine in healthy subjects and multiple animal vaccine models, we conducted a randomized, double-blind trial of GM-CSF with recombinant hepatitis B vaccine in chronic hemodialysis patients. Patients with negative hepatitis B surface antibody and antigen who had received at least three doses of recombinant hepatitis B vaccine without response (antibody titre < 10 mIU/ml) were randomized to placebo, 40 microg, or 80 microg of GM-CSF given with 40 microg recombinant hepatitis B vaccine i.m. at the same site. Clinical and laboratory studies for safety assessment were done on days 1 and 3, and hepatitis B surface antibody titres were measured at baseline and days 21 and 180 after the study injections. RESULTS No significant local or systemic toxicity was noted from the co-injections. The rates of response and geometric mean titre (GMT) were equivalent among all three study groups: placebo 6/10 developed antibodies, GMT 22.1 mIU/ml; 40 microg GM-CSF 3/10 developed antibodies, GMT 5.4 mIU; and 80 microg GM-CSF 3/8 developed antibodies, GMT 9.7 mIU/ml. Six months after vaccination, antibody titres were available for 11 of the 12 day 21 positive responders; only 4 of these 11 patients remained antibody positive at 6 months. CONCLUSION GM-CSF given in a single 40 microg and 80 microg i.m. dose was not an effective adjuvant with hepatitis B vaccine in chronic hemodialysis patients who had previously failed to respond to hepatitis B immunization.
The Importance of a Race-Critical Perspective in the Classroom

Sociologists have a disciplinary mandate to always consider the relationship between the individual and social forces. This means that what sociology has to offer students in courses about race, that is different from other disciplines, is a focus on the structural nature of race. Because of this unique ability of sociology as a discipline to illuminate the social aspects of race relations, it is crucial that sociologists use the tools available to us to help students break out of individualistic ways of thinking about race. In this chapter I argue that without a structural approach to teaching race relations, we run the risk of confirming the validity of white privilege, normalizing existing race relations, and supporting the myth of an American meritocracy. To avoid this, this chapter develops a model for a race-critical approach to teaching the sociology of race that is focused on structure, historically contextualized, and critical.
Analysis of miRNA Modifications

After transcription, a large number of cellular RNAs employ modifications to increase their diversity and functional potential. Modifications can occur on the base, ribose, or both, and are important steps in the maturation of many RNAs. Our lab recently showed that plant microRNAs (miRNAs) possess a 2'-O-methyl group on the ribose of the 3' terminal nucleotide, and that this methyl group is added after miRNA/miRNA* formation. One function of this modification is to protect miRNAs from 3' terminal uridylation by an unknown enzymatic activity. It is possible that uridylation of miRNAs triggers their degradation. Here we describe a protocol to purify a specific miRNA in order to determine its molecular mass so that the presence of a modification can be inferred, an in vivo method to detect 3' terminal modification of miRNAs, and an (alpha-32P) dATP incorporation assay to study 3' terminal uridylation of miRNAs.
Altered predator/prey behavior in polluted environments: implications for fish conservation

Predator/prey behavior has important consequences for individual survival and recruitment into fish populations, both of which can be affected by stressors such as environmental contaminants. The degree to which prey capture or predator avoidance abilities of a predator or prey species are affected will determine the direction in which the balance will be shifted. In a contaminated estuary we have studied, prey capure and predator avoidance of resident mummichogs, Fundulus heteroclitus, are impaired, which may account for individuals in that estuary having reduced growth and longevity compared with those from uncontaminated sites. Exposure to sediments, water, and grass shrimp from the contaminated site can impair the predatory abilities of mummichogs from a clean site. An important prey species, the grass shrimp, Palaemonetes pugio, has a greater population density and a greater proportion of large individuals at the polluted site, apparently because of reduced predation pressure. Mummichog larvae at the polluted site are initially more active and better at prey capture and predator avoidance than larvae from clean sites, but later they become poorer at both. Differences in predator vulnerability among larvae appear to be due to population differences in behavior, which may be due in part to both genetic and environmentally-caused factors. Conservation of fish populations should consider fish behavior and its interaction with contaminants.
Effects of 2 preparation methods and long-term storage on structural integrity and bacterial loads of equine amnion.

Objective To determine the influence of tissue preparation and long-term storage methods on structural integrity and risk of bacterial contamination of equine amnion. Study design Prospective experimental investigation SAMPLE POPULATION: Amniotic membranes from 8 healthy mares (n = 440 tested samples). Methods Samples for baseline bacteriology and histology were taken after removal of debris. The remaining tissue was divided and processed with 0.05% chlorhexidine or 2% iodine/0.25% acetic acid. Processed amnion samples were assigned to 1 of 9 combinations of storage media (saline, chlorhexidine, acetic acid) and temperature (4 °C, -20 °C, -80 °C). Samples were submitted for quantitative bacteriology and histopathology at 1 week, 4 weeks, and 3, 6, 9, and 12 months. Results Baseline bacterial levels ranged from 150 000 colony-forming units (cfu)/mL. None of the potentially pathogenic bacteria in baseline samples were subsequently cultured throughout the study. Nonpathogenic bacteria (median 20 cfu/mL), most commonly Bacillus sp, were cultured sporadically across storage conditions. Tissue architecture was minimally affected histologically by processing protocol, storage temperature, or storage duration. Conclusion The 2 processing protocols tested here resulted in minimal bacterial contamination or loss of structural integrity of equine amnion stored for up to 12 months at 4 °C, -20 °C, or -80 °C. Clinical significance Amnion collected during the foaling season may be stored for up to 12 months without significant bacterial contamination or structural alterations.
A Genetically Informed Study of Neighborhoods and Health: Results From the MIDUS Twin Sample.

Objectives To examine whether neighborhood income and neighborhood safety concerns influence multi-system physiological risk after adjusting for genetic and environmental selection effects that may have biased previous tests of this association. Methods We used structural equation modeling with a genetically informed sample of 686 male and female twin pairs in the Midlife in the United States Study II (2004). Results Controlling for additive genetic and shared environmental processes that may have biased neighborhood-health links in previous examinations, higher neighborhood safety concerns were associated with less physiological risk among women but not men. Discussion Our findings suggest a possible causal role of neighborhood features for a measure of physiological risk that is associated with the development of disease. Efforts to increase neighborhood safety, perhaps through increased street lighting or neighborhood watch programs, may improve community-level health.
Family connections to local science issues: how scientists use questions to engage families in personally-relevant learning during science-themed workshops

This study investigates how scientist-led educational programs, held in libraries, can make local science issues relevant to families. Given the need for an educated citizenry, it is important to e...
Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young.

Stroke in Young Patients with Covid-19 Five patients younger than 50 years of age with large-vessel stroke and Covid-19 infection presented to a health system in New York City over a 2-week period....
Use of single versus multiple vasodilator agents in the treatment of cerebral vasospasm: is more better than less?

Patients with cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage (aSAH) are often treated with intra-arterial (IA) vasodilator infusion. However, the optimal drug regimen is yet to be elucidated. A retrospective review of patients with aSAH and cerebral vasospasm treated with IA vasodilator infusion was performed. Patients in group 1 (2008–2011) were treated with a single agent, either nicardipine or verapamil, and patients in group 2 (2010–2016) were treated with a regimen of nitroglycerin, verapamil, and nicardipine. The post-infusion improvement ratio (PIIR) was compared between groups. Adjusted multivariate logistic regression models were utilized to determine whether patients treated with multiple vasodilators had an improved functional outcome, defined by the modified Rankin Scale, at discharge and 90-day follow-up. Among 116 patients from group 1 (N = 47) and group 2 (N = 69), the median age was 54.5 years [IQR, 46–53 years] and 78% were female. Use of multiple-agent therapy resulted in a 24.36% improvement in vessel diameter over single-agent therapy (median PIIR: group 1, 10.5% [IQR, 5.3–21.1%] vs group 2, 34.9% [IQR, 21.4–66.0%]; p < 0.0001). In the adjusted multivariate logistic regression, the use of multiple-agent therapy was associated with a better functional outcome at discharge (OR 0.15, 95% CI [0.04–0.55]; p < 0.01) and at 90-day follow-up (OR 0.20, 95% CI [0.05–0.77]; p < 0.05) when compared to single-agent therapy. In this study, we found that patients treated for cerebral vasospasm with IA infusion of multiple vasodilators had an increased vessel response and better functional outcomes compared to those treated with a single agent.
Interplay of Diabetes Mellitus and End-Stage Renal Disease in Open Revascularization for Chronic Limb-Threatening Ischemia.

Background Chronic limb-threatening ischemia (CLTI) in patients with end-stage renal disease (ESRD) confers a significant survival disadvantage and is associated with a high major amputation rate. Moreover, diabetes mellitus (DM) is an independent risk factor for developing CLTI. However, the interplay between end-stage renal disease (ESRD) and DM on outcomes after peripheral revascularization for CLTI is not well established. Our goal was to assess the effect of DM on outcomes after an infrainguinal bypass for CLTI in patients with ESRD. Methods Using the Vascular Quality Initiative dataset from January 2003 to March 2020, records for all primary infrainguinal bypasses for CLTI in patients with ESRD were included for analysis. One-year and perioperative outcomes of all-cause mortality, reintervention, amputation-free survival (AFS), and major adverse limb event (MALE) were compared for patients with DM versus those without DM. Results Of a total of 1,058 patients (66% male) with ESRD, 726 (69%) patients had DM, and 332 patients did not have DM. The DM group was younger (median age, 65 years vs. 68 years; P = 0.002), with higher proportions of obesity (body-mass index>30 kg/m2; 34% vs. 19%; P Conclusions DM and ESRD each independently predict early and late major adverse limb events after an infrainguinal bypass in patients presenting with CLTI. However, in the presence of ESRD, DM may increase perioperative adverse events but does not influence primary patency and AFS at one year. The risk profile associated with ESRD appears to supersede that of DM, with no additive effect.
Brain MRI after critical care admission: A longitudinal imaging study.

Abstract Purpose To investigate the association between episodes of critical care hospitalizations and delirium with structural brain changes in older adults. Materials and methods We included Mayo Clinic Study of Aging participants ≥60 years old at the time of study enrollment (October 29, 2004, through September 11, 2017) with available brain MRI and ‘amyloid’ positron emission tomography (PET) scans. We tested the hypothesis that a) intensive care unit (ICU) admission is associated with greater cortical thinning and atrophy in entorhinal cortex, inferior temporal cortex, middle temporal cortex, and fusiform cortex (Alzheimer’'s disease-signature regions); b) atrophy in hippocampus and corpus callosum; c) delirium accelerates these changes; and d) ICU admission is not associated with increased deposition of cortical amyloid. Results ICU admission was associated with cortical thinning in temporal, frontal, and parietal cortices, and decreases in hippocampal/corpus callosum volumes, but not Alzheimer’'s disease-signature regions. For hippocampal volume, and 10 of 14 cortical thickness measurements, the change following ICU admission was significantly more pronounced for those who experienced delirium. ICU admission was not associated with an increased amyloid burden. Conclusions Critical care hospitalization is associated with accelerated brain atrophy in selected brain regions, without increases in amyloid deposition, suggesting a pathogenesis based on neurodegeneration unrelated to Alzheimer’'s pathway.
Telehealth in primary care: Meeting patient and family needs

Background: Telehealth is a novel way to provide care to patients and families and may be especiallyimportant for families with transportation challenges The COVID-19 pandemic with social distancingrequirements further accelerated the need for the utilization and expansion of telehealth services Objective:To evaluate the feasibility of rapidly scaling primary-care telehealth and its impact on families' location of careand associated transportation costs Methods: A retrospective study was conducted at a large, urban,academic primary care center consisting of 6 primary care sites, with approximately 85% of patients coveredby Medicaid In February 2020, just prior to the COVID-19 pandemic, telehealth was launched for routinefollow-up of chronic medical conditions (e g , ADHD, asthma) and acute complaints (e g , rashes) two half-daysper week Due to COVID-19, rapid escalation of telehealth was necessary and during these telehealth visits,families were asked the location of care they would have chosen if telehealth was not available (in-personprimary care, Emergency Department (ED), Urgent Care (UC), or opt for no care) Miles saved (measured bydistance from family residence zip code to the hospital main campus where the ED, UC, and most primary care sites are located) and cost saved (as measured by federal reimbursement amounts for mileage) weredetermined from demographic information in the electronic health record Results: Five physicians trained anadditional 16 clinicians over 2 weeks, providing the ability to expand telehealth to six days per week FromFebruary-March 2020, 245 unique telehealth encounters were completed Providers asked 60% (n=147) offamilies where they would have sought in-person care if telehealth was not available, with the largest percent(68 7% (n= 101)) indicating a primary care visit In addition, 14 2% (n= 21) of families reported intent to visit theED, 4 8% (n=7) an UC and 12 2% (n=18) would have opted for no care Regarding savings related to distance toan alternative location of care, families saved an average of 16 miles ($9 30) for an in-person primary care visit,13 miles ($7 19) for an ED visit, and 11 4 miles ($6 23) for an urgent care visit Families who would have optedfor no care lived the farthest, with an average 21 miles A substantial percent of families (19%;n=28) reportedthat they would have sought more costly care options (ED or UC) Conclusion: Rapid scaling of primary carebased telehealth was feasible serving a mostly publically insured population The majority of families reportedthat without telehealth, they would have sought in-person visits, but those who lived farthest would not havesought care Telehealth appears to be a cost saving alternative for families and the medical system Next stepsinclude a trial of social risk and mental health screening during telehealth visits
Staufen1 in human neurodegeneration.

OBJECTIVE Mutations in the ATXN2 gene (CAG expansions ≥32 repeats) can be a rare cause of Parkinson's disease and amyotrophic lateral sclerosis (ALS). We recently reported that the stress granule (SG) protein Staufen1 (STAU1) was overabundant in neurodegenerative disorder spinocerebellar ataxia type 2 (SCA2) patient cells, animal models, and ALS-TDP-43 fibroblasts, and provided a link between SG formation and autophagy. We aimed to test if STAU1 overabundance has a role in the pathogenesis of other neurodegenerative diseases. METHODS With multiple neurodegenerative patient-derived cell models, animal models, and human postmortem ALS tissue, we evaluate STAU1 function using biochemical and immunohistological analyses. RESULTS We demonstrate STAU1 overabundance and increased total and phosphorylated mammalian target of rapamycin (mTOR) in fibroblast cells from patients with ALS with mutations in TDP-43, patients with dementia with PSEN1 mutations, a patient with parkinsonism with MAPT mutation, Huntington's disease (HD) mutations, and SCA2 mutations. Increased STAU1 levels and mTOR activity were seen in human ALS spinal cord tissues as well as in animal models. Changes in STAU1 and mTOR protein levels were post-transcriptional. Exogenous expression of STAU1 in wildtype cells was sufficient to activate mTOR and downstream targets and form SGs. Targeting STAU1 by RNAi normalized mTOR, suggesting a potential role for therapy in diseases associated with STAU1 overabundance. INTERPRETATION STAU1 overabundance in neurodegeneration is a common phenomenon associated with hyperactive mTOR. Targeting STAU1 with ASOs or miRNA viral vectors may represent a novel, efficacious therapy for neurodegenerative diseases characterized by overabundant STAU1. ANN NEUROL 2021;89:1114-1128.
Harmonic injection locking of high-power mid-infrared quantum cascade lasers

High-power, high-speed quantum cascade lasers (QCLs) with stable emission in the mid-infrared regime are of great importance for applications in metrology, telecommunication, and fundamental tests of physics. Owing to the intersubband transition, the unique ultrafast gain recovery time of the QCL with picosecond dynamics is expected to overcome the modulation limit of classical semiconductor lasers and bring a revolution for the next generation of ultrahigh-speed optical communication. Therefore, harmonic injection locking, offering the possibility to fast modulate and greatly stabilize the laser emission beyond the rate limited by cavity length, is inherently adapted to QCLs. In this work, we demonstrate for the first time the harmonic injection locking of a mid-infrared QCL with an output power over 1 W in continuous-wave operation at 288 K. Compared with an unlocked laser, the intermode spacing fluctuation of an injection-locked QCL can be considerably reduced by a factor above 1×103, which permits the realization of an ultrastable mid-infrared semiconductor laser with high phase coherence and frequency purity. Despite temperature change, this fluctuation can be still stabilized to hertz level by a microwave modulation up to ∼18 GHz. These results open up the prospect of the applications of mid-infrared QCL technology for frequency comb engineering, metrology, and the next-generation ultrahigh-speed telecommunication. It may also stimulate new schemes for exploring ultrafast mid-infrared pulse generation in QCLs.