cssi/SciSciGPT-SciSciNet huggingface dataset:
Remote exposure to secondhand tobacco smoke is associated with lower exercise capacity through effects on oxygen pulse- a proxy of cardiac stroke volume

BackgroundProlonged past exposure to secondhand tobacco smoke (SHS) is associated with exercise limitation. Pulmonary factors including air trapping contribute to this limitation but the contribution of cardiovascular factors is unclear. MethodsTo determine contribution of cardiovascular mechanisms to SHS-associated exercise limitation, we examined the cardiovascular responses to maximum effort exercise testing in 166 never-smokers with remote but prolonged occupational exposure to SHS and no known history of cardiovascular disease except nine with medically-controlled hypertension. We estimated the contribution of oxygen-pulse (proxy for cardiac stroke volume) and changes in systolic (SBP) and diastolic blood pressures (DBP) and heart rate (HR) over workload towards exercise capacity, and examined whether the association of SHS with exercise capacity was mediated through these variables. ResultsOxygen consumption (VO2Peak) and oxygen-pulse (O2-PulsePeak) at peak exercise were 1,516{+/-}431mL/min (100{+/-}23 %predicted) and 10.6{+/-}2.8mL/beat (117{+/-}25 %predicted), respectively, with 91 (55%) and 43 (26%) of subjects not being able to achieve their maximum predicted values. Sixty-two percent showed hypertensive response to exercise by at least one established criterion. In adjusted models, VO2Peak was associated directly with O2-Pulse and inversely with rise of SBP and DBP over workload (all P<0.05). Moreover, SHS exposure association with VO2Peak was mainly (84%) mediated through its effect on oxygen-pulse (P=0.034). Notably, although not statistically significant, a large proportion (60%) of air trapping effect on VO2Peak seemed to be mediated through oxygen-pulse (P=0.066). DiscussionIn a never-smoker population with remote prolonged exposure to SHS, abnormal escalation of afterload and an SHS-associated reduction in cardiac output contributed to lower exercise capacity.
A Movement Disorders Paradox: Case Report of a Patient with Gene-Positive Huntington’s Disease Who Presented with DaTScan Positive and Levodopa Responsive Parkinson’s Disease (P3.031)

OBJECTIVE: To report a case of gene positive Huntington’s disease with concomitant idiopathic Parkinson’s disease based on positive DaTScan and levodopa response. BACKGROUND: Traditionally, Huntington’s disease (HD) is the prototypical hyperkinetic movement disorder and Parkinson’s disease (PD) is the prototypical hypokinetic movement disorder. That these diseases are traditionally at the opposite ends of the dopamine spectrum is evidenced by the abundance of literature and clinical experience that dopamine depletion/blockade in the treatment of HD may cause parkinsonism, and dopamine replacement therapy in PD can cause chorea/dyskinesias. DESIGN/METHODS: Case Report RESULTS: A 65 year old male with a family history of HD initially developed paranoia, anxiety, and chorea. At age 62, he had genetic testing and was found to be definitively positive for HD with 41 CAG repeats. He was started on lamotrigine, venlafaxine, and ziprasidone to treat his symptoms. Two years later, he began to note a right upper extremity rest tremor, as well as right-sided bradykinesia and rigidity. On initial movement disorders evaluation at age 65, the patient had right hemiparkinsonism, masked facies, and stooped posture. A DaTScan was ordered and showed decreased I-123 uptake in the bilateral putamen, subtle on the right and prominently on the left, correlating with the patient’s side of worse parkinsonian symptoms. The patient was started on dopamine replacement therapy with carbidopa/levodopa and had improvement in his parkinsonian symptoms without recurrence of chorea. CONCLUSIONS: To our knowledge, this is the first report of concomitant HD and PD, and we present our case to suggest a rethinking of traditional dopamine models of movement disorders. The development of parkinsonian symptoms in HD patients should have consideration of idiopathic PD as a superimposed diagnosis even though it would seem improbable by current understanding of the dopaminergic balance in the basal ganglia. Study Supported by: Disclosure: Dr. Hadden has nothing to disclose. Consulting for Auspex Pharmaceuticals and Lundbeck, Inc.,
Binding, fractionation, and distribution of Cs, Co, and Sr in a US coastal soil under saturated and field capacity moisture regimes

The concerns of the public on safe handling of nuclear energy power facilities have increased due to the recent nuclear plant accidents in Japan and others. Cesium, cobalt, and strontium are a few of the major radionuclides released from nuclear power plant accidents. The objectives of this study are to investigate binding, distribution, fractionation, and transformation of cesium (Cs), cobalt (Co), and strontium (Sr) in a US coastal soil under saturated paste (SP) and field capacity (FC) moisture regimes. There are four major nuclear power plants in the coast region around the northern Gulf of Mexico where coastal soil often undergoes soil moisture change. A coastal soil was taken from the middle region of these major nuclear power plants and spiked with different concentrations of cesium, cobalt, and strontium salts. The sequential selective dissolution technique was used to investigate the transformation and fractionations of these metals in the coastal soils affected by moisture regime, a key factor in the coastal environment. The adsorption kinetics showed that both Co and Sr reached the adsorption plateau even after 5 h of adsorption, indicating a fast initial adsorption process in the coastal soil. Cesium, cobalt, and strontium were dominantly presented in the soluble and exchangeable form (EXC) (Cs > Co and Sr), which linearly increased with the addition levels, possessing the high bioavailability, mobility, and ecotoxicity. Saturated regime significantly reduced the soluble and exchangeable form compared to field capacity moisture regime. The current study provides the fundamental understanding for designing the cost-effective remediation technology to remediate these metals in coastal soil by targeting on the soluble and exchangeable forms and better prepare the USA for future potentially nuclear power plant accidents.
Comparison of isozyme and random amplified polymorphic DNA data for determining intraspecific variation in Cucumis

Variation at isozyme and random amplified polymorphic DNA (RAPD) loci in eight cucumber and seven melon cultivars, breeding lines, and plant introductions were used to determine the utility of these markers for assessing genetic variation among populations of each species. Although dendrograms derived from cluster analyses using species' variation at marker loci were dissimilar, these disparities were consistent with differences in the pedigrees and/or other information (e.g., morphological) known about each accession and species. Empirical estimations of variances associated with each marker type in the cucumber and melon accessions examined indicate that, per band, lower coefficients of variation can be attained in the estimation of genetic difference when using RAPDs compared to isozymes. The disparity between the marker analyses made may be related to the amount of genome coverage characteristic of a particular marker system in a species and its efficiency in sampling variation in a population.
Incomplete division of the atrioventricular canal with patent inter-atrial foramen primum, persistent common atrioventricular ostium; report of five cases and review of the literature.

Abstract This paper is based on a report of five cases ∗ ∗Since the time of preparation of the manuscript of this paper, we have observed a sixth example. The anomaly was found in a stillborn full-term female fetus. Both the septal leaflet of the tricuspid valve and aortic leaflet of the mitral valve were cleft, and a common atrioventricular valve was present. There was patency of the interatrial foramen primum and a defect in the posterior portion of the interventricular septum. In this connection, the atrioventricular junction was virtually identical to that in Cases 1, 2, and 3. There was also an anatomic patency of the foramen ovale. of the congenital cardiac disease termed incomplete division of the atrioventricular canal with patent interatrial foramen primum (persistent common atrioventricular ostium) and on a review of the essential pathologic and clinical features in an additional fifty cases reported in the literature. In the entire group of fifty-five cases, the median age of the patients at the time of death was 10 months. More than half of the patients died before they were 1 year of age. Only five of the patients lived beyond the age of 30 years. The anomaly apparently does not have any predilection for either sex. In the fifty-five cases, it appears that the lesion under consideration acts essentially as does a simple interatrial septal defect. Enlargement of the right side of the heart and widening of the pulmonary artery orifice are common associated secondary lesions. Cyanosis may be present at birth, but is usually acquired. When this manifestation develops, it is a sign of failure of the right side of the heart, pulmonary disease, or both. Cardiac murmurs, usually systolic, are frequently observed; they occurred in twenty-two of twenty-five cases in which an adequate history was given with reference to this sign. Monogolism is a relatively common associated finding in cases of incomplete division of the atrioventricular canal with patent interatrial foramen primum. In those case reports in which there was an adequate history, mongolism was recorded as having been present in seventeen cases and its absence was recorded or could be assumed in eight cases. Bacterial endocarditis was observed in three of the fifty-five cases.
T. S. Eliot: His Life and Age of Transition in Deviated Society

Thomas Stearns Eliot, the man of letters, had an unfathomable religious sensibility. His quest for belief holds together the diversified elements of the modern man’s fragmented being and gives a sense of direction in his life . The paper aims to explore the life span of T. S. Eliot, his work and age which leads to the various stages of social and economic changes in mindset of modern society. His work which is known to be milestone of the literature implies the strong impact on the contemporary writer. His writing generated the interest in the society to blend and open up the thoughts of east and west. It gives the acute sense of divinity which indulge into the ocean of the positivity and peace of mind in the modern but deviated society.
Votes and Violence: Electoral Competition and Ethnic Riots in India

List of figures List of tables Acknowledgments 1. The electoral incentives for ethnic violence 2. Explaining town-level variation in Hindu-Muslim violence 3. State capacity explanations for Hindu-Muslim violence 4. The consociational explanation for Hindu-Muslim violence 5. The electoral incentives for Hindu-Muslim violence 6. Party competition and Hindu-Muslim violence 7. The electoral incentives for ethnic violence in comparative perspective 8. Democracy and ethnic violence Appendices References Index.
Output-input stability and feedback stabilization of multivariable nonlinear control systems

We study the recently introduced notion of output-input stability, which is a robust variant of the minimum-phase property for general smooth nonlinear control systems. This paper develops the theory of output-input stability in the multi-input, multi-output setting. We show that output-input stability is a combination of two system properties, one related to detectability and the other to left-invertibility. For systems affine in controls, we derive a necessary and sufficient condition for output-input stability, which relies on a global version of the nonlinear structure algorithm. This condition leads naturally to a globally asymptotically stabilizing state feedback strategy for affine output-input stable systems.
Nucleotide sequence of the secA gene and secA(Ts) mutations preventing protein export in Escherichia coli.

TheDNA sequence ofthesecAgene, essential forprotein export inEscherichia coli, wasdetermined and found toencode ahydrophic protein of901aminoacid residues with apredicted molecular weight of101,902, consistent withitspreviously determined size andsubcelular location. Sequence analysis of9secA(Ts) mutations conferring general protein export andsecAregulatory defects revealed that these mutations were clustered inthree specific regions within thefirst 170aminoacidresidues oftheSecAprotein andwerethe result ofsingle aminoacidchanges predicted tobeseverely disruptive ofprotein structure andfunction. The DNA sequence immdtelyupstream ofsecAwasshowntoencode apreviously inferred gene, geneX. Sequence analysis ofa conditionally lethal ambermutation, amlO9,previously inferred tobelocated proximally inthesecAgene, revealed that itwaslocated distally ingeneXandwasconditionaly lethal dueto its polar effect onsecAexpression. Thisandadditional evidence arepresented indicating that geneXandsecA arecotranscribed. Biochemical andgenetic approaches havebeenusedto study themolecular mechanisms responsible forprotein localization inprocaryotic andeucaryotic cells. Suchstudies reveal that protein translocation across thebacterial plasma membrane andtheeucaryotic roughendoplasmic reticular membrane occurbyapparently homologous andconserved mechanisms. Sharedfeatures include similar signal sequences andstoptransfer sequences onpresecretory protein precursors that arerequired fortheir correct localization and topology (46), frequent removal ofamino-terminal signal peptides bysignal peptidases ofsimilar specificity (45), a dependence onanenergy source suchasATPorelectrochemical membrane potential formembrane translocation (6,13,14),anda requirement forsometypeofexport machinery (29, 35,44).
A rad-hard, steady state, digital imaging bolometer system for ITER

The concept and design of a new type of bolometer system which can function with excellent spatial resolution and good time resolution in the next generation of long-pulse (or steady-state), harsh-neutron environment, fusion plasmas, is outlined. It uses a cooled pinhole camera design, employing a robust, passive, segmented radiation absorber, cooled from the back-side. Infrared emission from the absorber’s front surface is relayed by metal mirror optics to a shielded, high-resolution IR video camera with 0.01 °C temperature resolution. It can make thousands of simultaneous “pixel” measurements at up to 50–60 Hz, without any signal wires through the vacuum interface.
Oxygen Metabolism in Lactobacillus plantarum

Lactobacillus plantarum, although able to grow in the presence of oxygen, was found to retain a completely anaerobic metabolism. Thus, L. plantarum did not consume detectable amounts of oxygen and did not contain measureable amounts of those enzyme activities which serve to protect anaerobic cells against the lethality of O2− and of H2O2. Superoxide dismutase, catalase, and peroxidase appeared to be absent from these cells. L. plantarum was unusually resistant towards hyperbaric oxygen, indicating that it did not reduce oxygen even when exposed to high concentrations of this gas. A photochemical reaction mixture, known to generate O2−, did kill L. plantarum. The lethality was diminished by superoxide dismutase, catalase, or mannitol and was augmented by H2O2. This suggests that the lethal agent generated in the photochemical system was primarily OH., generated from the reaction of O2− with H2O2.
Anatomical and functional changes in the organization of the cuneate nucleus of adult rats after fetal forelimb amputation

A previous study has shown that fetal forelimb removal in the rat results in an increase in the size of the hindlimb representation in primary somatosensory cortex and suggested that this anomalous cortical organization may have resulted from alterations in the primary afferent innervation of the dorsal column nuclei (Killackey and Dawson, 1989). The present study used both anatomical and electrophysiological techniques to examine the effects of fetal forelimb amputation on the dorsal column nuclei. Rats sustained forelimb removals on embryonic day 16 and were used in terminal experiments when they reached adulthood (> 60 d of age). Analysis of cytochrome oxidase-stained sections demonstrated that the cuneate nucleus ipsilateral to the lesion decreased in volume by an average of 36.7% (N = 7, p < 0.001, paired t test), but there was no corresponding increase in the volume of the gracile fasciculus and nucleus. Bilateral application of HRP to the sciatic nerves demonstrated that axons that innervate only the gracile nucleus on the intact side of the brainstem were present in the cuneate nucleus on the deafferented side. Injection of HRP into the skin overlying the point of the amputation (the stump) indicated that axons innervating this region filled most of the dorsal one-half of the shrunken cuneate nucleus and overlapped with the sciatic nerve afferents innervating the cuneate on this side. Mapping the receptive fields of multiple unit clusters demonstrated that most recording sites in the shrunken cuneate nucleus were activated by inputs from the stump and adjacent skin. In addition, 9.1% (N = 30) of such unit clusters (N = 328) could also be excited by stimulation of the hindlimb. These were observed in only three of the nine experiments. Unit clusters with split receptive fields including the skin overlying the stump and the hindlimb were located throughout the rostrocaudal extent of the cuneate nucleus. These results indicate that fetal forelimb amputation results in anatomical expansion of the central projections of hindlimb afferents into the cuneate nucleus. This anatomical organization appears weakly expressed in the receptive fields of cuneate neurons.
The temperature dependence of thermal expansion for p-type Ce0.9Fe3.5Co0.5Sb12and n-type Co0.95Pd0.05Te0.05Sb3skutterudite thermoelectric materials

During waste heat recovery applications, thermoelectric (TE) materials experience thermal gradients and thermal transients, which produce stresses that scale with the TE material's coefficient of thermal expansion (CTE). Thus, the temperature-dependent CTE is an important parameter for the design of mechanically robust TE generators. For three skutterudite thermoelectric compositions, n-type Co0.95Pd0.05Te0.05Sb3 (with and without 0.1 at. % cerium doping) and p-type Ce0.9Fe3.5Co0.5Sb12, the CTE was measured using two methods, i.e. X-ray diffraction on powder and bulk specimens and dilatometry on bulk specimens. Each bulk specimen was hot pressed using powders milled from cast ingots. Between 300 K and 600 K, the mean CTE values were 9.8–10.3 × 10−6 K−1 for the non-cerium-doped n-type, 11.6 × 10−6 K−1 for the 0.1 at. % cerium-doped n-type and from 12.7 to 13.3 × 10−6 K−1 for the p-type. In the literature, similar CTE values are reported for other Sb-based skutterudites. For temperatures >600 K, an unrecove...
Assisting Older Family Members: Association with Marital and Relationship Satisfaction

Summary.-Based on data from a statewide survey of citizens in Michigan ratings on marital and relationship sacisfaction were not sigmficantly daerent for individuals who assisted older family members and those who did not or for frequency of assistInp dn older person or whether an older person lived with the respondent. It has been recognized that adults who assist older family members may experience conficts with other roles, including work roles (Barling, MacEwen, Kelloway, & Higginbottom, 1994). It is plausible that role conacts may be inversely associated with marital satisfaction. Thus, in the present analysis, the interest was on whether satisfaction with marriage or relationship was associated with providing assistance to older family members. The survey data were collected by the Survey Research Division of the Lnstitute for Public Policy and Social Research at Michigan State University,
Correlation of increased CXCL13 with intrathecal humoral immune responses to HTLV-1 in CSF of patients with HAM/TSP

Intrathecal antibody synthesis is a well-documented phenomenon in infectious neurological diseases as well as in demyelinating diseases. Intrathecal antibody synthesis against HTLV-1 has been reported in HAM/TSP, but little is known about the role of B cells and humoral immune responses in the central nervous systems (CNS) of HAM/TSP patients. Here we demonstrate profiles of HTLV-1-specific antibodies in cerebrospinal fluid (CSF) of HAM/TSP patients. Of 36 HAM/TSP patients, antibody responses against Gag and Tax were detected in CSF of all the patients. CSF/Serum antibody ratio was elevated in anti-Gag (mean 1.20) more than in anti-Tax (mean 0.85), but importantly HAM/TSP patients with lesions or atrophy in spinal cord showed higher CSF/ Serum anti-Gag antibody ratio. Antibody response against Env was detected in CSF of 94.4% of patients, but CSF/ serum anti-Env ratio was significantly lower than those of anti-Gag and anti-Tax (mean 0.18). 19 patients were further studied for oligoclonal band (OCB) specificity to HTLV-1 antigens and all of them were found to have bands specific for at least one antigen studied. Significantly higher proportion of patients had Gag- or Envspecific OCBs than Tax-specific OCBs. Interestingly, CXCL13 (B cell attracting chemokine-1) was increased in CSF of HAM/TSP patients, which was associated with higher HTLV-1-specific antibody responses in CSF and was correlated with decrease of plasma blasts in peripheral blood. These results highlight the importance of the B cell compartment in HAM/TSP where production of HTLV-1-specific antibody may be required to control viral persistence and/or may be associated with HAM/ TSP disease progression.
Behavioral and energetic costs of group membership in a coral reef fish

Animals in social aggregations often spend more time foraging than solitary conspecifics. This may be a product of the relative safety afforded by aggregations: group members can devote more time to foraging and less time to antipredator behaviors than solitary animals (the “risk reduction” effect). All else being equal, risk reduction should result in higher food intake for grouped animals. However, intragroup competition may force group members to spend more time foraging in order to obtain the same food ration as solitary individuals (the “resource competition” effect). We compared these opposing explanations of foraging time allocation in a coral reef fish, bluehead wrasse (Thalassoma bifasciatum). Aggregations of juvenile bluehead wrasse experience safety-in-numbers, and preliminary observations suggested that juveniles in aggregations spent more time foraging for copepods in the water column than solitary juveniles. However, the risk reduction and resource competition hypotheses are indistinguishable on the basis of behavioral observations alone. Therefore, we collected behavioral, dietary, and growth data (using otolith growth rings) for bluehead wrasse at multiple reefs around a Caribbean island. Despite spending more time foraging in the water column, grouped fish did not capture more prey items and had slower growth rates than solitary fish. Thus, the increased foraging time of grouped fish appears to reflect resource competition, not risk reduction. This competition may limit the size and frequency of aggregations among juvenile bluehead wrasse, which have been shown to experience reduced mortality rates in larger groups. Bluehead wrasse recruits also spent less time foraging but grew faster at sites where planktonic copepod prey were more abundant. This suggests the possibility that large-scale spatiotemporal variability in the abundance of planktonic copepods over coral reefs may produce corresponding variability in the dynamics of reef fish populations.
Liquefaction of coal in a petroleum fraction under mild conditions.

Abstract Experimental studies on a mild coal liquefaction process for extending the petroleum fuel supply are presented. In this process, coal is dissolved in bottoms from fluid catalytic cracking (FCC), a thermally stable, highly aromatic refinery stream, without added hydrogen and under mild conditions. After ash removal, the product mixture of coal liquid and FCC bottoms is a pumpable fluid and can be used as a boiler fuel. Further upgrading to turbine fuel may be possible. At 600–800°F, 0.1 to 5 h, and 0–1000 psig, conversion of a bituminous coal to pyridine soluble, gas and water was about 90%, while that of lignite was about 60%. Improved product quality was favored by increased reaction pressure. The operable solvent to coal ratio can be as low as 1.3. This ratio can be further reduced if provisions are made to recycle part of the solvent. However, the efficiency of the recovered solvent decreases with each recycle due to a gradual replacement of labile α hydrogen by β hydrogen.
Genetic adaptive identification and control

Abstract Genetic algorithms are computer programs that are developed to crudely emulate the evolution of biological populations according to Darwin’s theory of natural selection and the concept of inheritance from genetics put forward by Mendel. Suppose that a controller for a plant is viewed as an individual decision-maker that has been chosen from a population of possible decision-makers to generate a control input to the plant. Suppose that in real-time a population of such decision-makers evolves. The “best” decision-maker from the evolving population is chosen at each step to control the plant, and using the principles of inheritance and survival of the fittest, good decision-makers will be more likely to propagate through the population as it evolves. Generally, as the population evolves and the best decision-maker is chosen at each time step, it adapts to its environment (i.e. the controller adapts to the plant and anything that influences it) and enhanced closed-loop system performance can be obtained. Also, even if there are plant parameter variations or disturbances, the population of decision-makers (controllers) will continually adapt to its environment to try to maintain good performance. This paper discusses a variety of such genetic adaptive control methods, and gives an extensive comparative analysis of their performance relative to conventional adaptive control techniques for an illustrative control application.
A Class of 2-(3n7, 3n−17, (3n−17−1)/2) Designs

Generalized Hadamard matrices are used for the construction of a class of quasi-residual nonresolvable BIBD's with parameters . The designs are not embeddable as residual designs into symmetric designs if n is even. The construction yields many nonisomorphic designs for every given n ≥ 2, including more than 1017 nonisomorphic 2-(63,21,10) designs. © 2006 Wiley Periodicals, Inc. J Combin Designs 15: 460–464, 2007
Organic matter and copper mineralization at White Pine, Michigan, U.S.A.☆

Mauk, J.L. and Hieshima, G.B., 1992. Organic matter and copper mineralization at White Pine, Michigan, U.S.A. In: P.A. Meyers. L.M. Pratt and B. Nagy (Guest-Editors), Geochemistry of Metalliferous Black Shales. Chem. Geol., 99: 189211. Indigenous and exogenous organic matter in sediments of the North American Midcontinent Rift were involved in precipitation of Cu-bearing minerals during main- and second-stage mineralization events at White Pine, Michigan. Samples of the Proterozoic Nonesuch Formation from the White Pine mine and adjacent areas were investigated petrographically and geochemically in order to determine the influence of organic matter on the precipitation of Cu and to determine whether mineralization influenced thermal maturity of organic matter. During main-stage mineralization, introduction of cupriferous fluids into the lower Nonesuch Fro. formed Cu-bearing sulfides by replacement of pyrite. Sulfur may have been added to the system via abiogenic sulfate reduction, with organic matter providing a direct source of reducing potential. In basal ore horizons where all sulfide had been incorporated into chalcocite during main-stage mineralization, native Cu also precipitated locally, with organic matter presumably acting as a direct reductant. Later compressional faulting at White Pine provided conduits for additional cupriferous fluids; these fluids deposited second-stage Cu mineralization. Inclusions of liquid petroleum and solid pyrobitumen in veins filling fractures associated with compressional faults record migration of petroleum into the White Pine district from the deeper, hotter, axis of the rift penecontemporaneous with second-stage fluids. Some of this petroleum may have acted as a reductant during precipitation of native Cu in basal ore horizons. Biomarker compositions of bitumens and isotopic compositions of individual n-alkanes from petroleums and bitumens suggest that these materials were all derived from organic matter deposited during sedimentation of the Nonesuch Fro.. Biomarker data demonstrate that bitumens from the White Pine area have significantly higher levels of thermal maturity than bitumens from unmineralized strata outside the mine area. Therefore, Cu mineralization at White Pine coincides with a thermal anomaly. Seep petroleums from the northeast and southwest domains of the mine contain different n-alkane distributions; we propose that this difference reflects elevated thermal maturity of seep petroleums spatially associated with second-stage mineralization in the southwestern domain of the mine.
Inheritance of phenytoin hypometabolism: a kinetic study of one family.

To determine whether the slow p-hydroxylation of phenytoin (PHT) is an inherited train, we studied its kinetics in members of a single family in which the trait was observed and in nonfamily control subjects. Each subject was given 5 mg/kg PHT intravenously; plasma and urine samples collected at various intervals after administration were analyzed for PHT or its major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH). Initially, 1 member of the family was observed for 6 mo on oral PHT. The subject became clinically intoxicated on 4.6 mg/kg/day PHT with a plasma level of 52 μg/ml; less than 50% of the dose was excreted as the major metabolite and after 3 mg/kg PHT intravenously, half-life (t½) was 30.6 hr. The results in all subjects were used to determine t½ and volume of distribution (Vd). The mean t½ for the control population was 18.6 ± 3.4 hr and for the family was 24.2 ± 4.2 hr. Individual members of each population were sufficiently far from the mean to suggest a bimodal t½ distribution. Three members of the kinship had t½ for intravenous PHT more than 2 standard deviations longer than the control population mean. HPPH excretion was extremely low in the 3 family members with long t½ as well as 1 child with a t½ somewhat longer than the mean adult values. Other members of the kinship had normal t½s and normal excretion. Vd for all family members was in the normal range. Since hypometabolism was seen in 3 of 4 generations of the kinship and since a bimodal distribution was observed for PHT metabolism, we conclude that it is an inherited trait. The mode of inheritance is not known at this time. Clinical Pharmacology and Therapeutics (1980) 27, 96–103; doi:10.1038/clpt.1980.15
Association of a macrophage galactoside-binding protein with Mycobacterium-containing phagosomes.

Summary Mycobacteria reside intracellularly in a vacuole that allows it to circumvent the antimicrobial environment of the host macrophage. Although the mycobacterial phagosome exhibits selective fusion with vesicles of the endosomal system, identification of host and bacterial factors associated with phagosome bio-genesis is limited. To identify these potential factors, mAbs were generated to a membrane preparation of mycobacterial phagosomes isolated from M. tuberculosis-infected macrophages. A mAb recognizing a 32–35 kDa macrophage protein associated with the phagosomal membrane of Mycobacterium was identified. N-terminal sequence analysis identified this protein as Mac-2 or galectin-3, a galactoside-binding protein of macrophages. Galectin-3 (gal-3) was shown to accumulate in Mycobacterium-containing phagosomes during the course of infection. This accumu-lation was specific for phagosomes containing live mycobacteria and occurred primarily at the cytosolic face of the phagosome membrane. In addition, bind-ing of gal-3 to mycobacterial phosphatidylinositol mannosides (PIMs) demonstrated a novel interaction between host carbohydrate-binding proteins and released mycobacterial glycolipids. Infection of macrophages from gal-3-deficient mice indicated that the protein did not play a role in infection in vitro. In contrast, infection of gal-3-deficient mice revealed a reduced capacity to clear late but not early infection.
Battling the Hematological Malignancies: The 200 Years' War

The delineation of the hematological malignancies began near the end of the first third of the 19th century with the recognition of the similarity among cases with lymph node tumors and an enlarged spleen (Hodgkin's disease). Descriptions of chronic and acute leukemia and myeloma followed thereafter. In the first years of the 20th century the discovery of x-radiation permitted palliative orthovoltage radiation therapy of Hodgkin's disease. Following World War II, legitimate drug therapy for the hematological malignancies was introduced: nitrogen mustard, adrenocorticotropic hormone and cortisone acetate, and anti-folic acid derivatives, initially aminopterin. Today, about 14 classes of drugs (different mechanisms of action) and >50 individual agents are being used, with others under study. Several examples of agents targeting specific transcription factors or oncoproteins have been introduced. Despite remarkable progress, including the ability to cure acute leukemia in about 70% of children, cure several genetic variants of acute myelogenous leukemia in younger adults, cure some cases of lymphoma in children and younger adults, and induce prolonged remission in many affected persons, the majority of patients face an uncertain outcome and shortened life. Thus, we have much to do in the next several decades. The significant hurdles we must overcome include: the apparent infrequency of an exogenous cause that can be avoided, the exponential increase in incidence rates with age and the dramatic negative effect of aging on the results of treatment, the challenge of one trillion or more disseminated cancer cells among which are a smaller population of cancer stem cells, the profound genetic diversity of the hematological malignancies (apparently hundreds of unique genetic primary lesions), the redundant growth and survival pathways defining the cancer phenotype, the decreasing market for pharmaceutical companies as therapy becomes more specific (fewer target patients) and drug development costs become more expensive, and the significant negative long-term effects of current therapy on both children and adults. These challenges will be gradually overcome, if we (a) develop new models of cooperation among academia, industry, and government, (b) continue the growth of international participation in cancer research (more keen minds to the task), and (c) convince the governments of the world, including that of the U.S., that an investment in minimizing the effects of cancer is as important as defending against other threats to the welfare and longevity of their citizens.
IDENTIFICATION OF A PHOSPHATE REGULATORY SITE AND A LOW AFFINITY BINDING SITE FOR GLUCOSE 6-PHOSPHATE IN THE N-TERMINAL HALF OF HUMAN BRAIN HEXOKINASE

Crystal structures of human hexokinase I reveal identical binding sites for phosphate and the 6-phosphoryl group of glucose 6-phosphate in proximity to Gly87, Ser88, Thr232, and Ser415, a binding site for the pyranose moiety of glucose 6-phosphate in proximity to Asp84, Asp413, and Ser449, and a single salt link involving Arg801 between the N- and C-terminal halves. Purified wild-type and mutant enzymes (Asp84 --> Ala, Gly87 --> Tyr, Ser88 --> Ala, Thr232 --> Ala, Asp413 --> Ala, Ser415 --> Ala, Ser449 --> Ala, and Arg801 --> Ala) were studied by kinetics and circular dichroism spectroscopy. All eight mutant hexokinases have kcat and Km values for substrates similar to those of wild-type hexokinase I. Inhibition of wild-type enzyme by 1,5-anhydroglucitol 6-phosphate is consistent with a high affinity binding site (Ki = 50 microM) and a second, low affinity binding site (Kii = 0.7 mM). The mutations of Asp84, Gly87, and Thr232 listed above eliminate inhibition because of the low affinity site, but none of the eight mutations influence Ki of the high affinity site. Relief of 1,5-anhydroglucitol 6-phosphate inhibition by phosphate for Asp84 --> Ala, Ser88 --> Ala, Ser415 --> Ala, Ser449 --> Ala and Arg801 --> Ala mutant enzymes is substantially less than that of wild-type hexokinase and completely absent in the Gly87 --> Tyr and Thr232 --> Ala mutants. The results support several conclusions. (i) The phosphate regulatory site is at the N-terminal domain as identified in crystal structures. (ii) The glucose 6-phosphate binding site at the N-terminal domain is a low affinity site and not the high affinity site associated with potent product inhibition. (iii) Arg801 participates in the regulatory mechanism of hexokinase I.
Motion capture of stationary lines by apparently moving terminators.

Several studies and observations of a new form of motion capture are reported: frames containing identical rows of evenly spaced vertical lines are alternated in a standard apparent-motion paradigm. However, one vertical line in the first frame has short horizontal ‘terminators’ attached; the terminators are shifted to a different line in the second frame. Alternation that includes an unpatterned, nonzero interstimulus interval results in perceived motion of a vertical line along with the terminators. This motion can ‘cross over’ other stationary vertical lines and persists when light-filled interstimulus intervals and gaps between lines and terminators are introduced. It can also be obtained with different line sizes and spacings. The present motion capture does not appear to rely on a global-frame effect. Alternative explanations are considered.
Investigation of Temperature Dependence and Impurity Content on the Growth Rate of KDP Crystals

Growth rate and effects of doping sodium in potassium dihydrogen phosphate (KDP) solution have been studied in crystals grown by solution evaporation and slow cooling methods. The crystals were grown in a KDP solution doped with different concentrations of sodium ions. The rates of growth along the thickness and width of the crystals were independent of sodium incorporation into the grown crystals and dependent on temperature reduction by a factor of 10. The concentration of sodium in the crystals (Cs) measured by ICP and the concentrations of sodium in the KDP solution (Cl) showed Cs/Cl to be constant.
Quantitation of abdominal aortic wall dynamics in man by gradient echo NMR imaging.

To determine the magnitude of the pulsatile (P), translational (T), and composite (C) aortic wall motion and to predict its effect on endothelial edge definition in vascular NMR imaging, 10 healthy volunteers, mean age 42.5 ± 13 years, were studied. In each subject a series of transverse high-resolution (0.6 × 0.6 mm; TR = 40 ms) gradient echo images spanning the cardiac cycle were generated and the aortic wall motion dynamics were analyzed. The group data expressed as a mean ± SD in millimeters, P = 0.87 ± 0.34 (mm), T = 2.71 ± 1.07, and C = 3.39 51.081, indicate that a significant displacement of the endothelial aortic edge (up to 5.6 pixels in high-resolution imaging) occurs during the cardiac cycle in normotensive healthy volunteers. The displacement of this magnitude suggests that cardiac cycle synchronized aortic NMR imaging should be used to improve endothelial edge definition. © 1990 Academic Press, Inc.
Exact results for the two-dimensional two-component plasma

Abstract The free energy and correlation functions of a two-dimensional two-component plasma are explicitly computed at the special temperature T 0 = e 2 2k B .
Repeated generalized audiogenic seizures induce plastic changes on acoustically evoked neuronal firing in the amygdala

Repetition of audiogenic seizures (AGS) (AGS kindling) results in increases in the duration of convulsive behavior and the emergence of cortical epileptiform EEG activity. These changes involve expansion of the neuronal network subserving these seizures. The amygdala (AMG) is postulated to become involved in this expanded network, but the neurophysiological basis of this process is unknown. The present study examined changes in chronically-recorded extracellular neuronal firing patterns in the lateral nucleus of AMG (LAMG) induced by AGS kindling in behaving genetically epilepsy-prone rats (GEPR-9s). Before AGS kindling, onset-only (36.1%), onset-delayed (50%) and delayed-only (13.9%) patterns of response to acoustic stimuli were observed. Neuronal firing was greatly suppressed following systemically administered uncompetitive NMDA antagonist (ketamine, 30 mg/kg, i.p.) with complete recovery by 4 h. After AGS kindling, LAMG neurons displayed a significantly increased incidence of onset-only patterns (93.3%, at 0.5 Hz), and mean acoustic responsiveness was also significantly increased (516.2% of control). LAMG neurons fired tonically during tonic convulsions and exhibited burst firing during post-tonic clonus. Greater acoustically-induced synchronization of LAMG firing, as indicated by elevated responsiveness and increased concentration of firing near the stimulus onset, may be critical for mediating the behavioral and EEG changes induced by AGS kindling. LAMG neuronal firing increases induced by AGS kindling may initiate these pathophysiological alterations, in part, by enhanced glutamate receptor-mediated excitation. This possibility is supported by the previously observed ability of an NMDA antagonist to reverse AGS kindling when focally microinjected into AMG, and the blockade of LAMG firing by administration of an uncompetitive NMDA antagonist observed in the present study.
Inhibition of Exportin-1 inhibits endothelial cell ICAM expression

Abstract Introduction: Regulation of the export of adaptor proteins that reside in the nucleus may modulate signal transduction. MyD88 is the principal adaptor protein for Toll/IL-1 receptor signaling. We have observed that MyD88 is a predominantly nuclear protein in murine macrophages. Similarly TRADD, an adaptor protein in TNF-a signaling, is found in the nucleus in the basal state. Exportin-1 is a nuclear export protein selectively inhibited by Leptomycin B (LMB). We have previously found that exportin-1 inhibition with LMB attenuates macrophage cytokine production in response to IL-1B. We hypothesized that inhibition of exportin-1 would attenuate Il-1B or TNF-a dependent ICAM expression in human microvascular endothelial cells (HMVECS). Methods: Vehicle or LMB pretreated HMVECS were stimulated by TNF-a or IL-1B. After six hours, the cells were fixed, stained, and examined by confocal microscopy. Results: Inhibition of exportin-1 with LMB significantly reduced the IL-1B stimulated HMVEC expression of ICAM by 94%. ICAM production in LMB pretreated HMVECS stimulated by TNF-a was reduced by 66%. IL-1B caused significant translocation of MyD88 from the nucleus to the cytoplasm; whereas, LMB pretreated endothelial cells failed to demonstrate nuclear to cytoplasmic MyD88 translocation with Il-1B stimulation. Conclusions: These data suggest that nuclear export of the adaptor protein MyD88 via exportin-1 is a critical regulatory mechanism of ICAM expression in response to IL-1B. Alternatively, TNF-a signaling is only partially modified by exportin-1.
Conversion and Trade-offs between Scaled Gaussian Parallel and Hierarchic Analysis Multirate Filter Banks

Abstract Scaled Gaussian analysis multirate filter banks (MRBs) are analysis MRBs whose filters are Gaussians scaled differently in width and height. They are frequently employed in image processing and visual systems modeling. We define generalized scaled Gaussian analysis MRBs for both parallel and hierarchic architectures and derive closed-form equations for conversions between them. The MRBs have arbitrary rational number changes in sampling rate between successive outputs, and arbitrary vertical and horizontal scaling of the Gaussian filters for each output. We calculate the number of multiplications, number of additions, and total number of filter coefficients to compare the parallel and hierarchic architectures as implemented with direct form and time-varying filters. In all cases, the parallel MRB requires considerably more multiplications, additions, and filter coefficients than the equivalent hierarchic MRB. However, the relative differences are far less severe in the time-varying case. We also derive a useful approximation for the discrete time Fourier transform of a Gaussian.
Sources of high-energy protons in Saturn's magnetosphere

The passage of Pioneer 11 through Saturn's magnetosphere revealed an especially intense region of high-energy particle fluxes that places unique constraints on models for sources of high-energy protons in the innermost radiation zones. Of special interest is the flux of protons with energies above 35 MeV which was measured with a fission cell in the innermost magnetosphere between the A ring and the orbit of Mimas. The negative phase space density gradients derived from the proton and electron observations in this region imply that steady-state inward diffusion from the outer magnetosphere is not an adequate source for these high-energy protons. In the present paper, the nature of the Crand source at Saturn is examined, and its significance for injection of high-energy protons into the region inside L = 4 is estimated.
Maternal and fetal parathyroid hormone responsiveness in pregnant primates.

Maternal and fetal parathyroid hormone (PTH)responsiveness to hypocalcemia induced by EDTA infusion (50 mg/kg over 2 h) was studied in rhesus monkeys in late pregnancy. Although baseline serum total calcium (Ca) levels in the fetus exceeded those in the mother(4.83 ±0.13 vs.4.28±0.15 meq/liter; P 0.05).EDTA infusion directly to five fetuses produced significant hypocalcemia (maximal decline averaging 19 ± 2%) and PTH response (maximal increase averaging 46 ±5%).In contrast, in four control studies involving fetal saline infusion, there were no significant changes in fetal Ca or PTH levels. Four maternal control infusions produced no significant changes in either Ca or PTH levelsA comparison of maternal and fetal PTH responses indicated considerable similarity, although fetalPTH levels tended to return to baseline somewhat more gradually after cessation of the hypocalcemic stimulus than did maternal levels. These stu...
Tolerance of intravitreal povidone-iodine in rabbit eyes.

Povidone-iodine is frequently instilled on to the conjunctival surface prior to intraocular surgery in order to prevent septic endophthalmitis. A small amount of povidone-iodine is inevitably introduced into the eye when it is used in this manner. The toxicity of intravitreal povidone-iodine was assessed in rabbit eyes by injecting 0.1 ml of povidone-iodine in concentrations of 0.05%, 0.5% and 5% into the vitreous cavity. The injected eyes were evaluated by clinical examination, anterior segment and fundus photography, endothelial cell counts, electroretinography and histopathology. Compared to control eyes, no changes were observed in all 6 eyes injected with 0.1 ml of 0.05% povidone-iodine solutions. 9 of 10 eyes tolerated a concentration of 0.5% with no detectable adverse changes. One eye developed a temporary mild iritis and mild suppression of the ERG. Intraretinal hemorrhages, edema, arteriolar narrowing and retinal edema were seen one week following injection. Mild retinal necrosis of the same area...