cssi/SciSciGPT-SciSciNet huggingface dataset:
Streptomyces buecherae sp. nov., an actinomycete isolated from multiple bat species

A putative novel clade within the genus Streptomyces was discovered following antifungal screening against Pseudogymnoascus destructans, the causative agent of white-nose syndrome, and described using multi-locus sequencing analysis. Swabs from both the cave myotis bat (Myotis velifer) and the Brazilian free-tailed bat (Tadarida brasiliensis) in southern New Mexico bore isolates AC536, AC541T and AC563, which were characterised using phylogenetic, morphological, and phenotypic analyses. Multi-locus sequence analysis positions AC541T with neighbors Streptomyces rubidus (NRRL B-24619T), Streptomyces guanduensis (NRRL B-24617T), and Streptomyces yeochonensis (NRRL B-24245T). A complete genome of the type strain was assembled to determine its taxonomy and secondary metabolite potential. ANI comparisons between all closely related types strains are shown to be well below the 95–96% species delineation. DNA-DNA relatedness between AC541T and its nearest neighbors ranged between 23.7 and 24.1% confirming novelty. Approximately 1.49 Mb or 17.76% of the whole genome is devoted to natural product biosynthesis. The DNA G + C content of the genomic DNA of the type strain is 73.13 mol %. Micromorphology depicts ovoid spores with smooth surfaces in flexuous chains. Strains presented an ivory to yellow hue on most ISP media except inorganic salts-starch agar (ISP4) and can grow on d-glucose, mannitol, and d-fructose, but exhibited little to no growth on l-arabinose, sucrose, d-xylose, inositol, l-rhamnose, d-raffinose, and cellulose. This clade possesses the capability to grow from 10 to 45 °C and 12.5% (w/v) NaCl. There was strain growth variation in pH, but all isolates thrive at alkaline levels. Based on our polyphasic study of AC541T, the strain warrants the assignment to a novel species, for which the name Streptomyces buecherae sp. nov. is proposed. The type strain is AC541T (= JCM 34263T, = ATCC TSD201T).
Why LINQ Matters: Cloud Composability Guaranteed: The benefits of composability are becoming clear in software engineering.

In this article we use LINQ (Language-integrated Query) as the guiding example of composability. LINQ is a specification of higher-order operators designed specifically to be composable. This specification is broadly applicable over anything that fits a loose definition of "collection," from objects in memory to asynchronous data streams to resources distributed in the cloud. With such a design, developers build up complexity by chaining together transforms and filters in various orders and by nesting the chains--that is, by building expression trees of operators.
Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors.

Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities. Yuen Gao et al. characterize deficits in brain morphology, behavior, and gene expression following genetic ablation of the histone methyltransferase, ASH1L, during brain development in mice. Their results provide new insight into links between ASH1L activity and neurodevelopmental disorders.
The Use of Ultrasound in the Diagnosis of Gastroenterological Disease

Ultrasound is high frequency mechanical vibration. As far as is presently known, there are no harmful effects of ultrasound at the energy levels used in currently available commercial ultrasonic scanners. Ultrasonic studies are independent of organ function, are painless, and require no special preparation. Ultrasonic scanning is useful in the diagnosis of pancreatic disease, especially in the detection of complications of pancreatitis such as pancreatic abscess or pseudocyst, and in diagnosing pancreatic carcinoma. Gallstones and dilation of the biliary tree can be detected ultrasonically even when the patient is jaundiced. Primary liver tumors and hepatic metastases can often be demonstrated. Intraabdominal abscesses are better investigated by ultrasound than by any other means currently available. Ultrasonic scanning also provides a sensitive means of detecting ascites. Ultrasonic control of needle placement has been suggested for pancreatic and liver biopsy, for aspiration of intraabdominal fluid collections, and for percutaneous transhepatic cholangiography. Ultrasonic B-mode scans provide undistorted images of cross sections through the abdomen which can be used in radiotherapy planning to localize tumor masses and to place kidney shields accurately. Organ volumes can be estimated from a set of ultrasonic B-mode scans without any assumptions being made as to the shape of the organ.
Remarks on Formal Knot Theory

This paper is an introduction to the state sum model for the Alexander-Conway polynomial that was introduced in the the author's book "Formal Knot Theory" (Princeton University Press, 1983). The article outlines how Alexander's original definition of the polynomial as the determinant of a matrix associated with the link diagram can be reformulated as a state summation over combinatorial configurations of the diagram. Facts about the state model, the Clock Theorem (that makes this model tick) and relations with other state models such as the bracket polynomial, are discussed. The paper includes a miniature introduction to Khovanov homology. This paper will appear in the forthcoming Dover republication of Formal Knot Theory.
Frequency domain system identification when assuming unknown but bounded errors

When performing parameter estimation of dynamical systems, one must evaluate unknown variables given uncertain measurements. Often the problem is approached using a probabilistic description of the uncertainty and statistical estimation theory is applied. Another approach is to make the so-called "set-membership" or "unknown-but-bounded error" (UBBE) assumption. Here it is assumed that the measurements contain errors that are within known bounds. This paper discusses the frequency domain system identification problem under the UBBE assumption. It demonstrates that the set of all possible identifications is a finite union of polyhedra. The paper also shows how the problem of finding one valid identification reduces to finding a feasible solution to a nonlinear system of equations under box constraints. An example of applying the resulting algorithm to actual measurements is given.
Taking the Ratio of Differences Seriously: The Multiple Offender and the Standard of Proof, or, Different Strokes for Serial Folks

This paper analyzes the case for utilizing different standards of proof for trying cases involving, respectively, serial offenders and first-time offenders. It argues that, if we expect the standard in a trial to reflect the costs and benefits of the four possible outcomes at trial, then the empirical data leave no room for doubt that the profiles of all four outcomes -- true and false convictions and true and false acquittals -- are strikingly different for serial offenders than for those without prior convictions. Moreover, it is shown how the phenomenon of widespread and prolonged recidivism poses insuperable problems for those who subscribe to a retributionist or just deserts theory of crime and punishment.
Roadway traffic controller design for automated highway systems

For manual driving, the traffic flow is often irregular, unstable leading to congestion and to low traffic flow rate during minor incidents. These irregularities are due to variation of vehicle speeds and headways that are selected by the individual drivers. It is expected that the congestion could be reduced and traffic flow rate could be increased, if the speed and density of the vehicles along a lane can be properly controlled by a roadway controller. In this paper we propose a roadway controller and investigate the benefits of controlling the density and speed of the vehicles along a lane by using the proposed roadway controller. The roadway controller sends the appropriate speed commands to vehicles in each section of the lane. The vehicles are equipped to follow each other automatically and respond to the roadway commands without any driver intervention. A macroscopic traffic flow model is used for analysis and simulations. Our results demonstrate significant benefits in terms of smooth and stable traffic flow that reduce congestion considerably. >
Prediction Mechanisms That Do Not Incentivize Undesirable Actions

A potential downside of prediction markets is that they may incentivize agents to take undesirable actions in the real world. For example, a prediction market for whether a terrorist attack will happen may incentivize terrorism, and an in-house prediction market for whether a product will be successfully released may incentivize sabotage. In this paper, we study principal-aligned prediction mechanisms---mechanisms that do not incentivize undesirable actions. We characterize all principal-aligned proper scoring rules, and we show an "overpayment" result, which roughly states that with n agents, any prediction mechanism that is principal-aligned will, in the worst case, require the principal to pay ?(n) times as much as a mechanism that is not. We extend our model to allow uncertainties about the principal's utility and restrictions on agents' actions, showing a richer characterization and a similar "overpayment" result.
An affinity label for the anion binding site in ovotransferrin: Implications for iron release to reticulocytes

Bromopyruvate has been found to be an affinity label for the anion binding site in ovotransferrin. Spectral and radioactive labeling studies indicate that the bromopyruvate first forms a reversible ternary complex with ovotransferrin and iron and then reacts to yield the covalently bound product. This derivative is partially resistant to iron loss by protonation and suggests that protonation and loss of anion is a requisite first step for iron release to reticulocytes.
Genetic pathways that regulate ageing in model organisms

Searches for genes involved in the ageing process have been made in genetically tractable model organisms such as yeast, the nematode Caenorhabditis elegans, Drosophila melanogaster fruitflies and mice. These genetic studies have established that ageing is indeed regulated by specific genes, and have allowed an analysis of the pathways involved, linking physiology, signal transduction and gene regulation. Intriguing similarities in the phenotypes of many of these mutants indicate that the mutations may also perturb regulatory systems that control ageing in higher organisms.
Inbreeding Depression and Inferred Deleterious-Mutation Parameters in Daphnia

DENG and LYNCH recently proposed a method for estimating deleterious genomic mutation parameters from changes in the mean and genetic variance of fitness traits upon inbreeding in outcrossing populations. Such observations are readily acquired in cyclical parthenogens. Selfing and life-table experiments were performed for two such Daphnia populations. We observed a significant inbreeding depression and an increase of genetic variance for all traits analyzed. DENG and LYNCH's original procedures were extended to estimate genomic mutation rate (U), mean dominance coefficient (h), mean selection coefficient (s), and scaled genomic mutational variance (V(m)/V(e)). On average, U, h, s and V(m)/V(e) (^ indicates an estimate) are 0.74, 0.30, 0.14 and 4.6E-4, respectively. For the true values, the U and h are lower bounds, and s and V(m)/V(e) upper bounds. The present U, h and V(m)/V(e) are in general concordance with earlier results. The discrepancy between the present s and that from mutation-accumulation experiments in Drosophila (~0.04) is discussed. It is shown that different reproductive modes do not affect gene frequency at mutation-selection equilibrium if mutational effects on fitness are multiplicative and not completely recessive.
Systematic quantification of complex metabolic flux networks using stable isotopes and mass spectrometry.

Metabolic fluxes provide a detailed metric of the cellular metabolic phenotype. Fluxes are estimated indirectly from available measurements and various methods have been developed for this purpose. Of particular interest are methods making use of stable isotopic tracers as they enable the estimation of fluxes at a high resolution. In this paper, we present data validating the use of mass spectrometry (MS) for the quantification of complex metabolic flux networks. In the context of the lysine biosynthesis flux network of Corynebacterium glutamicum (ATCC 21799) under glucose limitation in continuous culture, operating at 0.1·h−1 after the introduction of 50% [1-13C]glucose, we deploy a bioreaction network analysis methodology for flux determination from mass isotopomer measurements of biomass hydrolysates, while thoroughly addressing the issues of measurement accuracy, flux observability and data reconciliation. The analysis enabled the resolution of the involved anaplerotic activity of the microorganism using only one labeled substrate, the determination of the range of most of the exchange fluxes and the validation of the flux estimates through satisfaction of redundancies. Specifically, we determined that phosphoenolpyruvate carboxykinase and synthase do not carry flux at these experimental conditions and identified a high futile cycle between oxaloacetate and pyruvate, indicating a highly active in vivo oxaloacetate decarboxylase. Both results validated previous in vitro activity measurements. The flux estimates obtained passed the χ2 statistical test. This is a very important result considering that prior flux analyses of extensive metabolic networks from isotopic measurements have failed criteria of statistical consistency.
Atomistic and Molecular Effects on the Surface Morphology and Film Conformation of Perfluoropolyether Lubricant Layer

As the head-media spacing of head-disk interface (HDI) is reduced to 7 nm, interfacial configurations of molecularly thin perfluoropolyether (PFPE) lubricant film such as surface morphology and film conformation become critical for the stability of head-disk operation. Therefore, for the stable protection layers in HDI with ultra thin conformation as well as enhanced tribological performance, novel lubricant materials modified by the molecular structure and functionality have been developed. For example, ztetraol multidentate was invented to improve the film stability and conformation by adding hydroxyl functional group in the middle of the chain. Branched PFPEs were developed to enhance the functionality as well as thermal stability by modifying backbone structure. Here, we selected the molecular structure and functionality as the key parameters, which provide the direction of researches on novel lubricant marching forward. In this paper, we investigated the surface morphology and film conformation of PFPE films as interfacial properties by modifying molecular structures with backbone structures and endgroup functionality (Fig. 1). Molecular dynamics simulation using a coarse-grained, bead-spring method was performed to generate the PFPE films from submonolayer to a few layer [1]. We modified PFPE backbone structure by tuning the flexibility of bead-spring chain and the functional groups by tuning functional group-functional group and functional group-carbon surface interactions independently. The force field parameters were calculated based on the ab-initio calculation. To characterize the surface morphology, we introduced the wavelet transform entropy [2] as well as correlation length and the roughness exponent. Different morphological states were found for various oligomers backbones, resulting from strong tethering of functional groups on the solid surface, and as a function of surface coverage (Fig. 2). In addition, the correlations between the surface morphologies, transport properties, and the wavelet entropy were investigated. Our simulation results of the atomistic and molecular structures on the interfacial properties of film will provide the lubricant molecular design criteria, which will be combined to the researches on the HDI including air-bearing design (Fig. 1).
Inducible expression of α1B-adrenoceptors in DDT1 MF-2 cells: comparison of receptor density and response

Hamster DDT1 MF-2 smooth muscle cells natively express alpha 1B-adrenoceptors which are linked to phosphatidylinositol hydrolysis. We studied the relationship between alpha 1B-adrenoceptor density and response in this cell line by stable transfection with an isopropyl-beta-D-thiogalactoside (IPTG)-inducible vector (pOP alpha 1B) containing the hamster alpha 1B-adrenoceptor cDNA. Transfected cells showed a 2-fold increase in receptor density compared to untransfected cells due to constitutive activity of the uninduced vector. Induction of vector expression caused a time-dependent increase in receptor density, reaching a maximum 8-fold increase after 48 h. Exposure to different concentrations of inducing agent for 16 h caused a graded increase in both receptor density and norepinephrine-stimulated [3H]inositol phosphate (InsP) formation. A linear correlation between receptor density and maximum InsP response was observed. Induction of receptor expression did not alter the potency of norepinephrine in stimulating [3H]InsP formation, suggesting that there was no receptor reserve, even at very high expression levels. This inducible expression system should be useful for relating receptor density and responsiveness, and comparing the coupling efficiency of closely related subtypes in activating different signal transduction mechanisms.
Classification of Drug Permeability with a Caco-2 Cell Monolayer Assay

In the absence of an optimized and validated protocol for the Caco-2 cell drug permeability assay, a more general approach is considered to standardize a method within a laboratory. An assay was evaluated using over 20 model drugs to assess its ability to classify drugs as high or low permeability. This cell culture method is considered to be useful as it established a relationship between experimental permeability values and extent of absorption. This represents an application of regulatory specifications to demonstrate that a cell model is able to determine the permeability class of a drug substance.
Ribulose bisphosphate carboxylase/oxygenase (rubisco) from green leaves‐potential as a food protein

Abstract Up to 25% of the total protein in green leaves consists of a single molecular species, the enzyme ribulose bisphosphate carboxylase/oxygenase (rubisco). In C3 plants rubisco molecules are found densely packed within chloroplast stroma at concentrations up to 300 mg/mL. The oligomeric protein (MW 550,000) is composed of eight large and eight small subunits which combine to form a compact, nearly spherical molecule. Rubisco is easily purified from leaf extracts in the laboratory but, as yet, there is no simple, economical method for isolating large (kilogram) quantities of the plant enzyme. The protein appears to have potential as an ingredient in animal and/or human foods. Highly purified rubisco is a tasteless, odorless, white powder with a nutritive value reported to be equal to or superior to that of other food proteins. Rubisco also possesses some desirable functional properties which might enable food processors to successfully incorporate the protein into a number of different food systems. ...
Economy, security slow EEZ work

The goal of a November 17–19, 1987, conference on the U.S. Exclusive Economic Zone (EEZ) was a cooperative scientific plan for the next decade of mapping of and research on the huge expanse of ocean floor lying within 200 nautical miles of U.S. shores. But two hard realities were evident in the speeches, discussions, and recommendations of the participants: Both economics and U.S. national security interests are stalling basic scientific research on the EEZ. The root of these problems, according to the conferees, is the lack of centralized national management of the marine dominion proclaimed by President Reagan in 1983.
Diet in the Pathogenesis and Treatment of Inflammatory Bowel Diseases

Some of the most common symptoms of the inflammatory bowel diseases (IBD, which include ulcerative colitis and Crohn's disease) are abdominal pain, diarrhea, and weight loss. It is therefore not surprising that clinicians and patients have wondered whether dietary patterns influence the onset or course of IBD. The question of what to eat is among the most commonly asked by patients, and among the most difficult to answer for clinicians. There are substantial variations in dietary behaviors of patients and recommendations for them, although clinicians do not routinely endorse specific diets for patients with IBD. Dietary clinical trials have been limited by their inability to include a placebo control, contamination of study groups, and inclusion of patients receiving medical therapies. Additional challenges include accuracy of information on dietary intake, complex interactions between foods consumed, and differences in food metabolism among individuals. We review the roles of diet in the etiology and management of IBD based on plausible mechanisms and clinical evidence. Researchers have learned much about the effects of diet on the mucosal immune system, epithelial function, and the intestinal microbiome; these findings could have significant practical implications. Controlled studies of patients receiving enteral nutrition and observations made from patients on exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD. Additionally, studies in animal models suggested that certain nutrients can reduce intestinal inflammation. In the future, engineered diets that restrict deleterious components but supplement beneficial nutrients could be used to modify the luminal intestinal environment of patients with IBD; these might be used alone or in combination with immunosuppressive agents, or as salvage therapy for patients who do not respond or lose responsiveness to medical therapies. Stricter diets might be required to induce remission, and more sustainable exclusion diets could be used to maintain long-term remission.
War-Zone Trauma and Stress-Related Symptoms in Operation Desert Shield/Storm (ODS) Returnees

A growing literature suggests that human beings are often negatively impacted by participation in military combat, but there have been few attempts to document the psychological effects of war stress in the masses of troops deployed to action. We chose to study the relationship of Operation Desert Shield/Storm (ODS) participation and symptoms of psychological distress in a comparison of 215 Army National Guard and Army Reserve troops who were activated to service in the Persian Gulf and returned to the States without seeking mental health treatment services and 60 troops from these same units who were activated but not deployed overseas. Negative psychological outcomes were measured within four to ten months from homecoming in three domains: negative mood states, symptoms of posttraumatic stress disorder (PTSD), and physical health complaints. Results indicated that as war-zone stress exposure increased, the frequency and severity of psychological symptoms were enhanced, providing correlational evidence of the adverse impact of war stress, at least among a subset of ODS returnees. As many as 16–24% of war zone exposed troops exhibited levels of distress symptomatology sufficiently exaggerated to suggest the presence of mental disorders, specifically clinical depression and PTSD. Psychological symptoms were less frequently reported among troops classified in the lower war-zone stress exposure subset and those activated but not deployed to the Persian Gulf.
Role of process conditions on the microstructure, stoichiometry and functional performance of atmospheric plasma sprayed La(Sr)MnO3 coatings

Abstract Strontium doped lanthanum manganite (LSM) perovskite coatings were produced via atmospheric plasma spray technique to examine their applicability as electrically conductive coatings to protect chromium-poisoning of cathode side metallic interconnects in solid oxide fuel cells. Various plasma spray process conditions were manipulated including plasma power, total gas flow and content of H 2 in the plasma gas in order to understand their effects on coating properties as well as efficacy as a protectant against Cr-poisoning. In-flight temperatures and velocities of spray particles were monitored for the various plasma spray conditions enabling assessment of thermal and kinetic energies of LSM particles. As anticipated, coating density improves with increasing thermal and/or kinetic energies of the LSM particles. However, the LSM particles also experienced significant phase decomposition at higher thermal exposure and longer residence time conditions. Due to preferential loss of oxygen and manganese, La 2 O 3 phase is also formed under certain processing regimes. The resultant mixed-phase coating is ineffective both from electrical transport and as a protective coating for the metallic interconnect. Concomitantly, coatings with limited decomposition show excellent conductivity and protection characteristics demonstrating the need for mechanism driven process optimization for these functional oxide coatings.
RADIOGRAPHIC CHARACTERISTICS OF THE FORELIMB DISTAL PHALANX AND MICROSCOPIC MORPHOLOGY OF THE LATERAL PALMAR PROCESS IN FOALS 3–32 WEEKS OLD

Developmental morphology of the forelimb distal phalanges and lateral palmar processes of 9 Thoroughbred foals aged 3–32 weeks was assessed using radiography, microradiography and histology. For inclusion in the study, all distal phalanges had no pathologic radiographic abnormalities. Vascular channels that are characteristically found in the dorsal region of the distal phalanx were not evident radiographically in the palmar process. The proximal and distal angles of the palmar processes were separated by a lucent line continuous with the incisure in foals only through 12 weeks of age. The distal phalanges were triangular-shaped in foals 3–12 weeks of age, and were oval-shaped in older foals. The palmar aspect of the distal phalanx was the major contributor to growth of the distal phalanx in the sagittal plane, especially between 3 and 12 weeks of age. Growth of the lateral palmar process occurred through the means of endochondral ossification. The body and cortices of the lateral palmar process were composed of coarse cancellous bone. Porosity within the lateral palmar process was greater in regions sampled axial, compared to abaxial, to the parietal sulcus and did not change with age. A fracture was identified microradiographically and/or histologically in 9 of 18 (50%) and 10 of 17 (59%), respectively, of the lateral palmar processes examined. The fracture line was consistently associated with the parietal sulcus on the dorsal cortical surface and was always immediately abaxial to the deep digital flexor tendon attachment. No age-related morphological changes of the lateral palmar processes were identified with microradiography or histological examinations.
Macroscopic examination of the placenta immediately following birth.

Abstract Macroscopic examination of the placenta can be performed readily by the healthcare providers present at the time of birth. It can be accomplished with a basic knowledge of placental pathology and a general understanding of the abnormalities and variations that affecting placenta. These observations can easily be entered into the medical record and may often provide information about intrauterine life that will help the future care of both mother and infant.
Biochemical and Structural Characterization of the Cross-Linked Complex of Nitrogenase: Comparison to the ADP-AlF4--Stabilized Structure†,‡

The transient formation of a complex between the component Fe- and MoFe-proteins of nitrogenase represents a central event in the substrate reduction mechanism of this enzyme. Previously, we have isolated an N-[3-(dimethylamino)propyl]-N‘-ethylcarbodiimide (EDC) cross-linked complex of these proteins stabilized by a covalent isopeptide linkage between Glu 112 and Lys β400 of the Fe-protein and MoFe-protein, respectively [Willing, A., et al. (1989) J. Biol. Chem. 264, 8499−8503; Willing, A., and Howard, J. B. (1990) J. Biol. Chem. 265, 6596−6599]. We report here the biochemical and structural characterization of the cross-linked complex to assess the mechanistic relevance of this species. Glycinamide inhibits the cross-linking reaction, and is found to be specifically incorporated into Glu 112 of the Fe-protein, without detectable modification of either of the neighboring residues (Glu 110 and Glu 111). This modified protein is still competent for substrate reduction, demonstrating that formation of the cr...
Rosemary O'Leary and Lisa Blomgren Bingham (Eds.), The Collaborative Public Manager: New Ideas for the Twenty-First Century

(2010). Rosemary O'Leary and Lisa Blomgren Bingham (Eds.), The Collaborative Public Manager: New Ideas for the Twenty-First Century. Administrative Theory & Praxis: Vol. 32, No. 2, pp. 274-279.
Elemental Mercury Vapour Toxicity, Treatment, and Prognosis After Acute, Intensive Exposure in Chloralkali Plant Workers. Part I: History, Neuropsychological Findings and Chelator effects

Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the 'Symptom Check List 90-Revised' (SCL-90R) and tests of visual-motor function such as 'Trailmaking Parts A and B', 'Finger Tapping', 'Stroop Colour Word Test' and 'Grooved Pegboard.' On day 85 ± 11 (mean±s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents.Rapidly resolving metal fume fever was the earliest ...
662. Retroviral Insertion Site Analysis Following Therapeutic Gene Transfer of CD18 in a Canine Model of Leukocyte Adhesion Deficiency

Retroviral insertion site analysis following the infusion of gene-corrected hematopoietic stem cells has become increasingly important following the development of leukemia in three children with common |[gamma]|-chain severe combined immunodeficiency treated with retroviral gene therapy. This analysis is of particular importance in human gene therapy trials and in gene-transfer studies in disease- specific, large-animal models. We have conducted pre-clinical gene therapy in canine leukocyte adhesion deficiency (CLAD), the canine equivalent of leukocyte adhesion deficiency, type 1 (LAD-1) in humans. Both diseases are characterized by life-threatening bacterial infections and are due to mutations in the leukocyte integrin CD18. We have demonstrated reversal of the disease phenotype in six dogs with CLAD following infusion of autologous CD34+ bone marrow hematopoietic stem cells transduced with the retroviral vector PG13/MSCV-cCD18 after non-myeloablative conditioning with either 200 cGy TBI or 10 mg/kg busulfan. In the six CLAD dogs who were long-term survivors, the level of CD18+ gene corrected leukocytes ranged from 0.72% to 8.37% at 1 |[ndash]| 1.5 years post-transplant. Although no adverse events have occurred during this period of observation, demonstration of polyclonality in the gene-corrected cells and characterization of the genomic sites of retroviral integration remain critical safety issues. To this end, we have demonstrated the polyclonality of contributing retrovirus-transduced cells in all six dogs using linear-amplification mediated PCR (LAM-PCR) with DNA obtained from peripheral blood leukocytes up to 18 months following infusion of gene-corrected cells. Multiple clones were shown to contribute to hematopoiesis; no predominant clones emerged over time. Retroviral insertion sites in four of the six dogs were identified using either LAM-PCR or ligation-mediated PCR (LM-PCR) followed by sequencing of the genomic sequence adjacent to the integrated viral LTR. Mapping of insertion sites was facilitated by the recent completion of the annotated dog genome sequence. To date, we have identified 60 unique retroviral insertion sites from four treated CLAD dogs. The insertions sites appear to be distributed almost equally across all 39 dog chromosomes, with a slight preference for chromosomes 2, 10 and 25. 43% of the sites were located within gene-coding regions of the genome (introns or exons). These observations match previous reports of preferential integration of MLV retroviral vectors near coding sequences. We are continuing to sequence and characterize a large number of retroviral insertion sites from the gene-corrected CLAD dogs. Analysis of these insertion sites should provide considerable insight into the risk of genotoxicity through insertional mutagenesis in a disease-specific large-animal model of a human hematopoietic disease.
Fecal excretion, uptake and metabolism by colon mucosa of diacylglycerol in rats.

Abstract In a previous paper we demonstrated that human fecal bacteria can convert phosphatidylcholine to diacylglycerol (DAG), and activator of protein kinase C. The present study demonstrates that several foods contain appreciable levels of DAG, especially certain vegetable oils. On the other hand, when rats were administered [14C]-labeled DAG by intragastric intubation less than 0.1% of the administered radioactivity was recovered as DAG in the feces. Thus only negligible amounts of dietary DAG actually reach the colon. When [14C]DAG was injected directly into ligated segments of rat colon we found appreciable uptake of the intact DAG by the mucosal cells. The major metabolite was arachidonic acid, suggesting that the DAG lipase pathway is more active than the DAG kinase pathway in these cells. Taken together, these results are consistent with our hypothesis that much of the DAG present in the colonic lumen is produced by the intestinal bacteria and that this DAG can actually enter the colonic mucosal cells, where it might influence their function.
Measurement of ligand-protein binding interactions in a biphasic aqueous polymer system.

Abstract In this paper we introduce a new technique, which we term the method of equilibrium partition, for studies of the interaction of small ligands with macromolecules. The method utilizes a biphasic aqueous solution of the polymers dextran and polyethylene glycol; in this system, proteins tend to partition chiefly into one phase while small ligands are distributed among both phases. The quantity of ligand bound to the protein in the protein-containing phase can be calculated using measurements of ligand concentration in the other phase, if the other phase contains only negligible quantities of protein. Compared with other methods commonly in use for ligand binding studies, the equilibrium partition method has the advantages that it is very rapid (equilibrium is reached within a few minutes) and can easily be scaled down to microliter volumes in order to perform binding studies with the consumption of minimal quantities of protein. However, the method is applicable only to those proteins which exhibit the required partitioning behavior. The equilibrium partition method has been used successfully in studies of nucleotide binding to the enzymes aspartate transcarbamylase and formyltetrahydrofolate synthetase. In the case of ATCase (but not FTHF synthetase) ligand binding affinities measured in the presence of the highly concentrated dextran-polyethylene glycol solutions appear to differ from the corresponding affinities observed in dilute aqueous solutions.
Replacement of serum by hormones permits growth of cells in a defined medium

MOST cell cultures require the addition of serum to synthetic media for their maintenance and growth, and we believe that the primary role of the serum is to provide hormones1. We have been led to this hypothesis by a series of experiments showing that serum depleted of certain hormones no longer supports growth of cells, unless the medium is supplemented with the hormones that were removed2–4. Clear evidence for the validity of this hypothesis has not yet been obtained because it is difficult to grow cells in the absence of serum. Recently, however, we have succeeded in growing an established rat pituitary cell line, GH3, in a defined serum-free medium supplemented with physiological concentrations of four hormones together with the iron transport protein, transferrin. Preliminary investigation shows that serum-free medium supplemented with hormone will also support the growth of several other cell lines.
Training the next generation of child neurologists: a child health-based approach

In the United States, child neurologists continue to value close, historical ties to adult neurology. However, the mandatory year of adult training for American Board of Psychiatry and Neurology certification in "Neurology with Special Qualification in Child Neurology" deprives residents of educational opportunities that would yield greater benefit for children afflicted with neurologic diseases. The need for modernization has been recognized in a Professors of Child Neurology survey in which a majority of program directors favored reducing adult neurology training and changing the certification to "Child Neurology." This article reviews the rationale for an overdue transformation of Child Neurology training.
The telecommunication infrastructure: A model for optimum voice-data coverage

Abstract Since voice and data services can greatly enhance the quality of life of people in rural areas, the expansion of the telecommunication infrastructure is one of the most important planning activities for governments especially in developing nations. This study presents an analytical tool for policy makers to evaluate various alternatives that expand telephone and Internet services to underserved and unserved remote areas. Based on Geographic Information System (GIS) datasets of existing infrastructures, a computer model is developed to generate Telecom-and-Internet access maps of a defined region. The map presents the least-cost plan to provide telephony and Internet services to a given percentage of population in a specified area. A remote area of Bangladesh is selected as a case study. Several scenarios are simulated in order to explore the possibility of extending the reach of telecommunication services to the last-mile customers, and to evaluate pilot projects as building blocks of a nationwide infrastructure.
Photochemical oxidation of halide ions by a nitratochromium(III) complex. Kinetics, mechanism, and intermediates

The 266 nm laser flash photolysis of the title complex in the presence of halide ions X(-) (X = I, Br, and Cl) generates halogen atoms on nanosecond time scales, followed by the known X(*)/X(-) reactions to yield dihalide radical anions, X2(*-). Plots of k(obs) against the concentration of X(-) were linear with zero intercepts, but the yields of X2(*-) increased with increasing concentrations of [X(-)]. This result suggests that a short-lived, strongly oxidizing intermediate reacts with X(-) to generate X(*) in parallel with the decomposition to Cr(aq)O(2+) and (*)NO2, both of which were identified in steady-state photolysis experiments in the presence of selective trapping agents. Bromide was oxidized quantitatively to bromine, and a combination of molecular oxygen and methanol channeled the reaction toward superoxochromium(III) ion, Cr(aq)OO(2+). In the absence of scavengers, nitrite and chromate were produced. The proposed reaction scheme draws additional support from the good agreement between the experimental product yields and those predicted by kinetic simulations.
Sleep Duration From Ages 1 to 10 Years: Variability and Stability in Comparison With Growth

OBJECTIVE. Our goal was to describe the variability of sleep duration (time in bed per 24 hours) in healthy children from 1 to 10 years of age in comparison with growth measures. METHODS. A total of 305 children were followed with structured sleep-related interviews and measurements of height and weight 12, 18, and 24 months after birth and then at annual intervals until 10 years of age. SD scores were calculated, and smooth curves were fitted by smoothing splines through the SD scores. The long-term variability channel within children (units SD score) was defined as the difference between the maximum and the minimum of the smooth curves and the short-term variability channel (units SD score) as the difference of the largest and the smallest deviations of the original SD scores from the smooth curve. RESULTS. Sleep duration remained within a long-term variability channel CONCLUSIONS. Sleep duration during early and middle childhood shows large variability among children, as well as trait-like long-term stability and state-like yearly fluctuations within children. An individual approach to the child9s sleep behavior is needed; expectations in terms of appropriate sleep duration of the child should be adjusted to the individual sleep need.
Psychiatric rehabilitation: A framework for psychiatric home care

Psychiatric home care offers excellent opportunities to help the psychiatric patient achieve positive outcomes. Home care agencies need to develop a treatment model that supports the type of care provided to the psychiatric patient, such as psychiatric rehabilitation. This model purports that mental illness is a biologic illness affected by stress and inadequate problem-solving and coping skills. These patients have inadequate social skills, but they can improve. This article describes interactive tools and methods that the home care staff can use with such patients and their families.
Relationship-focused early intervention with children with pervasive developmental disorders and other disabilities: A comparative study

This study compares the effects of relationship-focused early intervention on toddlers and preschool-age children who were classified as having either pervasive developmental disorders (PDDs) (N = 20) or developmental disabilities (DDs) (N = 30). The intervention was conducted over a 1-year period through weekly individual parent-child sessions. It focused on helping parents use responsive teaching strategies to encourage their children to acquire and use pivotal developmental behaviors that addressed their individualized developmental needs. Before and after comparisons indicated significant increases in parents' responsiveness and children's pivotal behavior. Both groups of children made significant improvements in their cognitive, communication, and socioemotional functioning. However, children with PDDs made statistically greater improvements on the developmental measures than children with DDs. On several developmental measures, children's improvements were related to increases in both their parents' responsiveness and their own pivotal behavior.
Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptor

Abstract We have stably expressed in fibroblasts different pairs of α and non-α subunits of the mouse muscle nicotinic acetylcholine receptor (AChR). The γ and δ, but not the β, subunits associated efficiently with the α subunit, and they extensively modified its binding characteristics. The αγ and αδ complexes formed distinctly different high affinity binding sites for the competitive antagonist d -tubocurarine that, together, completely accounted for the two nonequivalent antagonist binding sites in native AChR. The αδ complex and native AChR had similar affinities for the agonist carbamylcholine. In contrast, although the ay complex contains the higher affinity competitive antagonist binding site, it had an affinity for carbamylcholine that was an order of magnitude less than that of the αδ complex or the AChR. The comparatively low agonist affinity of the αγ complex may represent an allosterically regulated binding site in the native AChR. These data support a model of two nonequivalent binding sites within the AChR and imply that the basis for this nonequivalence is the association of the a subunit with the γ or δ subunit.
Myelinated central vertebrate axon lacks voltage-sensitive potassium conductance

Intracellular recordings were obtained from the goldfish Mauthner cell soma and axon before and after intracellular iontophoresis of drugs that block voltage-sensitive potassium conductance. Analysis of the action potentials generated by the axon hillock-initial segment and by the axon suggest that axonal impulses lack this potassium conductance. Thus, impulse repolarization in the Mauthner axon, and perhaps in other vertebrate central axons, may not involve an active potassium current.
Plate bending at subduction zones: Consequences for the direction of plate motions

Abstract Bending of lithospheric plates at subduction zones is thought to be an important source of dissipation for convection in the Earth's mantle. However, the influence of bending on plate motion is uncertain. Here we use a variational description of mantle convection to show that bending strongly affects the direction of plate motion. Subduction of slabs and subsidence of oceanic lithosphere with age provide the primary driving forces. Dissipation is partitioned between plate bending and various sources of friction at plate boundaries and in the interior of the mantle due to viscous flow. We determine the poles of rotation for the Pacific and Nazca plates by requiring the net work to be stationary with respect to small changes in the direction of motion. The best fit to the observed rotation poles is obtained with an effective lithospheric viscosity of 6 × 1022 Pa s. Bending of the Pacific plate dissipates roughly 40% of the energy released by subduction through the upper mantle.
Distributional properties of d -FCSR sequences

In this paper we study the distribution properties of d-FCSR sequences. These sequences, have efficient generators and have several good statistical properties. We show that for d = 2 the number of occurrences of an fixed size subsequence differs from the average number of occurrences by at most a small constant times the square root of the average.
Staining of human metaphase chromosomes with fluorescent conjugates of polylysine

Abstract The interaction of polylysine and partially substituted dansyl, fluorescein, and quinacrine conjugates of polylysine with cytological preparations of human metaphase chromosomes has been studied by fluorescence microscopy. The fluorescence intensity along chromosomes stained with the dansyl and fluorescein conjugates exhibits little variation, suggesting that regions capable of binding these polycations are nearly evenly distributed. In contrast, the quinacrine derivatives of polylysine stain the chromosomes in a banded fluorescence pattern resembling that observed following quinacrine or quinacrine mustard treatment.