cssi/SciSciGPT-SciSciNet huggingface dataset:
Structure of human deoxyhemoglobin specifically modified with pyridoxal compounds.

Abstract Previous studies (Benesch et al., 1972, 1973, 1975) have shown that a variety of specifically modified hemoglobins having a wide range of functional properties can be prepared by reacting human hemoglobin with different pyridoxal compounds and then reducing the products with sodium borohydride. In particular, the modified hemoglobins (α PLS ‡ ‡ Abbreviations used: PLP, pyridoxal 5′-phosphate; PLS, pyridoxal 5′-sulfate; NFPLP, 2-nor-2-formylpyridoxal 5′-phosphate; DPG, 2,3-diphosphoglycerate; HbXL, αβ-NFPLP-βα hemoglobin. ) 2 β 2 , α 2 (β PLP ) 2 and αβ-NFPLP-βα have been characterized, respectively, as the reduced products of the reactions of pyridoxal 5′-sulfate with the NH2-termini of the α chains, pyridoxal 5′-phosphate with the NH2-termini of the β chains, and 2-nor-2-formylpyridoxal 5′-phosphate (which contains two reactive aldehyde groups) with one amino group from each β chain to form a stable cross-link between the β chains. In this paper, we report the three-dimensional structures of the deoxy forms of these hemoglobins as determined by X-ray diffraction methods. We find the pyridoxal side chains of these hemoglobins to be oriented as follows. 1. (1) The PLS side chains of (αPLS)2β2 are positioned so that each sulfate group replaces a weakly bound inorganic anion to form salt bridges between the newly formed secondary amine of valine 1α and the guanidinium ion of arginine 141 on the opposite α chain. The pyridoxal ring interacts with residues of the H-helix on the same α chain to which it is attached. 2. (2) In α2(βPLP)2, the PLP phosphate groups are located very near the positions occupied by the phosphate groups of 2,3-diphosphoglycerate in the deoxyhemoglobin-DPG complex, and serve as permanently bound counterions for the basic side chains of histidine 143, histidine 2, and lysine 82 of both β subunits. Each pyridoxal ring displaces a firmly bound inorganic anion and interacts with residues of the EF corner on the same β chain to which it is attached. 3. (3) In the case of αβ-NFPLP-βα, we find that the cross-link is asymmetric with the 2′ and 4′ carbons of NFPLP joined to the amino nitrogens of lysine 82β1 and valine 1β2, respectively. The phosphate group replaces the firmly bound inorganic anion mentioned above, and the 3-oxygen of the pyridoxal ring interacts with the imidazole group of histidine 143β1. Relative to the structure of deoxyhemoglobin A, no significant changes in α chain tertiary structure are observed for (αPLS)2β2, only small changes in β chain tertiary structure occur in α2(βPLP)2, but exceptionally large perturbations to the structure of one β chain result from the cross-link in αβ-NFPLP-βα. The relationships between the structures of these hemoglobin derivatives and their functional properties are discussed.
Urban dew: Its composition and influence on dry deposition rates

Abstract The composition of dew collected from a Teflon surface was compared to summer rainwater concentrations at a site in Warren, MI. This comparison showed that natural dew is similar to rainwater with the exception that dew has much higher concentrations of Ca 2+ and Cl − and much lower acidity. Dry deposition rates of several species were measured to artificially-generated dew and a dry surface. It was found that deposition rates were 2–20 times greater to the artificial dew than to the dry surface, indicating that the presence of dew enhances both the retention of dry deposited particles and the absorption of water soluble gases. Measurement of the atmospheric concentrations of the depositing gases permitted the calculation of deposition velocities for particulate Cl − , NO − 3 , SO 2− 4 , Ca 2+ , Mg 2+ , Na + , K + and NH + 4 . Deposition velocities for gaseous HNO 3 , HCl, SO 2 and NH 3 were also determined after correction for particle deposition. These results indicate that acid dew is not a problem at this site. However, the ability of dew to increase the deposition rates of acids and acid precursors to some surfaces suggests that dew may be more acidic at sites with lower deposition rates of basic particles.
A novel high-sensitivity electrochemiluminescence (ECL) sandwich immunoassay for the specific quantitative measurement of plasma glucagon.

Abstract Objectives To develop a novel, dual-monoclonal sandwich immunoassay with superior sensitivity that provides a rapid and convenient method for measuring glucagon. Glucagon is a 29-amino acid polypeptide hormone produced in the pancreas by the α-cells of the islets of Langerhans. Working in concert with insulin, glucagon is involved in regulating circulating glucose concentrations. Design and methods The immunoassay utilizes Meso Scale Discovery (MSD) electrochemiluminescence (ECL) technology and two affinity-optimized monoclonal antibodies. A series of experiments was performed to determine the linear range of the assay and to evaluate sensitivity, accuracy, recovery, precision, and linearity. Results The sandwich assay was specific for glucagon and did not recognize the closely related peptide oxyntomodulin or other incretin peptides. The assay demonstrated excellent recovery, precision, and linearity, and a broad dynamic range of 0.14 pmol/L to 1950 pmol/L. In addition, assay results were highly correlated with those obtained using a previously described competitive RIA employing polyclonal antiserum. Conclusion The use of affinity-optimized monoclonal antibodies in a sandwich immunoassay format provides a robust, sensitive, and convenient method for measuring concentrations of glucagon that is highly sensitive and specific. This immunoassay should help to improve our understanding of the role of glucagon in the regulation of glucose metabolism.
KEYNES AND THE FORCES OF HISTORY: A COMMENT

scientist's duties for enlightenment of the public and, more specifically, his responsibility for utterances that may influence public policy for good or evil. Fundamental to Professor Smithies' outlook is his belief that the social scientist ought to consider constructions that might be placed upon his published views. Should he conclude that influential members of society both in the present and future might construe his words in a manner unfavorable to the best interests of the type of society he desires, the social scientist should be very careful in publicly communicating these views.2 The conclusion is that Keynes's public presentation of his ideas often impeded realization of "the good society" Keynes himself desired. Such a criterion could easily come into conflict with other standards of scientific inquiry which have generally been accepted without question, principally the belief that an investigator should follow an inquiry to the limit of his capabilities, letting "the chips fall where they may." Professor Smithies is careful to distinguish the pursuit of truth from its advocacy, allowing the former free rein, while circumscribing the latter by what might be called "the doctrine of potentially adverse repercussions." We believe, however, that such a distinction is at best unclear and in many instances nonexistent. Ex ante, it would be extremely difficult, often impossible, for an economist to determine who will interpret his original findings in a manner invidious to his own vision of the Good Society. Such a difficulty, moreover, would seem to be independent of the way the investigator chooses to present his findings.3 1. November 1951, pp. 578-601. Further references to Professor Smithies' article will be by page number only. 2. "But did not his [Keynes'sl rare gifts of persuasion carry with them special responsibilities to foresee the consequences of what he said?" P. 590. 3. Ricardo's spare and obscure style could hardly be considered persuasive - yet his writings, the very antithesis of Keynes's usually lucid prose, attracted a massive following. 450
Large earthquake cycles and intermittent criticality on heterogeneous faults due to evolving stress and seismicity

[1] We analyze evolving stress and seismicity generated by three realizations of a discrete model of a strike-slip fault in a three-dimensional (3-D) elastic half space using five functions of stress and five functions of seismicity. The first model (F) has realistic dynamic weakening (static minus dynamic frictions), the second (FC) has zero critical dynamic weakening, and the third (SYS) is constrained to produce only system size events. The results for model F show cyclical development, saturation, and destruction of fluctuations and long-range correlations on the fault, punctuated by the system size events. The development stage involves evolution of stress and seismicity to distributions having broad ranges of scales, evolution of response functions toward scale-invariant behavior, increasing seismicity rate and event sizes, and increasing hypocenter diffusion. Most functions reach asymptotically stable values around 2/3 of the cycle and then fluctuate until one event cascades to become the next large earthquake. In model FC the above evolution is replaced by scale-invariant statistical fluctuations, while in model SYS the signals show simple cyclic behavior. The results suggest that large earthquake cycles on heterogeneous faults with realistic positive dynamic weakening are associated with intermittent criticality, produced by spontaneous evolution of stress heterogeneities toward a critical level of disorder having a broad range of scales. The stress evolution and development of large earthquake cycles may be tracked with seismicity functions.
A general method for biological inference: illustrated by the estimation of gene nucleotide transition probabilities.

Abstract The method of maximum entropy inference developed by Jaynes can be a particularly useful method for obtaining unbiased estimates of biological parameters when the experimental knowledge about a system can be explicitly formulated. Base transition probabilities between genes, though central to evolutionary theory and understanding, present a difficult estimation problem because the ancestral genes are not experimentally accessible. The necessary estimates must therefore be made on the basis of experimental knowledge other than a direct frequency count of base replacements (A→C, for example) between contemporary genes. It is shown how maximum entropy inference together with the experimentally observed fact of compositional fidelity in a given gene family can be used to obtain meaningful gene base transition probabilities at each of the three nucleotide positions within codons. Both symmetric and asymmetric transition probabilities are considered. Tables of these probabilities are given for each codon position for the α-hemoglobin, s-hemoglobin, myoglobin, cytochrome c, and the parvalbumin group genes. Tabular values of the average amino acid composition of these five protein families and the average nucleotide composition of their coding genes at varied codon loci are given. It is thus no longer necessary to assume in theories of evolutionary divergence equimolar base ratios A:C:G:U::1:1:1:1 or that each base has an equal chance of mutating to and being fixed as any one of the other three bases.
Effects of amino acids on the absorption of trivalent chromium and its retention by regions of the rat small intestine

Abstract This study utilized the double perfusion technique to measure the effects of dietary amino acids on the absorption of trivalent chromium (Cr 3+ ) and its retention by regions of the rat small intestine. A nutrient-rich tissue culture medium (TCM) with Cr 3+ was perfused through the intestinal lumen as a test meal. Simultaneously, a modified Krebs-Ringer Bicarbonate buffer was perfused through the intestinal vasculature to replace the intestinal blood supply. In two experimental groups, amino acids were omitted from the test meal; one group received a buffered salt solution, the other a specially formulated TCM without amino acids. With no amino acids in the test meal, chromium transport into the vascular perfusate was less than 50% of control, while significantly more chromium (>200%) was retained by the intestinal mucosa. The retention of chromium was greatest in the proximal small intestine when amino acids were present; in their absence, the region of maximal retention shifted to the distal segment. We postulate that dietary amino acids provide ligands necessary for chromium uptake and its transport into the vasculature. The reasons for the regional specificity of the retained chromium are unknown but may reflect the active transport of ligands, such as amino acids or bile salts, that ligate chromium and other minerals.
Effects of Phosgene Exposure on Lung Arachidonic Acid Metabolism

AbstractPhosgene can acylate macromolecules and may react with and affect enzymes involved in arachidonic acid metabolism. We examined the effects of an acute phosgene exposure in vivo and in vitro on lung arachidonic acid metabolism. Fischer 344 rats were exposed either to air or to phosgene (0.05–7.0 ppm) for 4 h and the lungs were lavaged at 0, 4, 20, and 44 h postexposure. Leukotriene B, (LTBJ, peptide leuko-trienes C4 D4 and E4 (LTC4/D/E4, and prostaglandin E2 (PCE2) were measured in la-vage fluid by radioimmunoassay Phosgene exposure in vivo (0.7–7.0 ppm for 4 b) produced significant decreases in concentrations of PGE, (maximal decrease of 74%), LTB, (maximal decrease of 59%), and LTC4/D4/E4 (maximal decrease of 97%) measured in rat lavage fluid immediately postexposure. Associated with this decrease in eicosa-noid production was a decrease in the number of alveolar macrophages and an increased number of neutrophils recovered in the lavage fluid of phosgene-exposed rats. Lung lavage eicosanoid conce...
The effects of a controlled eating and drinking history on the development of schedule-induced polydipsia

Six rats were reared under conditions in which they never had access to food and water simultaneously or in close succession. Six other rats had access to food and water together throughout the course of the experiment. Tests of differences between means for small samples showed that the two groups did not differ significantly in weight or in the amount of food and water consumed per day in the home cage. After 80 days of such rearing, the rats were reduced in weight and introduced in to a Skinner box in which water was freely available. On a fixed interval 50-sec schedule of food reinforcement, all rats displayed the characteristic behavioral aspects of schedule-induced polydipsia (SIP). This finding mitigates against explanations of SIP which relate alternation between eating and drinking in the test chamber to past feeding experience in the home cage.
Transmissive Olefination Route to Putative "Morinol I" Lignans

A series of morinol-type lignans were rapidly assembled using a Grignard-based transmissive olefination. In combination with palladium-catalyzed arylations, the strategy provides stereoselective access to (7Z,7′E), (7E,7′E), and (7E,7′Z) morinol diastereomers and the (7Z,8′E) and (7E,8′E) conjugated analogues. Critical for the E/Z stereoselectivity is a new, general method for converting alkenenitriles to alkenemethanols that circumvents the enal E/Z isomerization commonly encountered during conventional i-Bu2AlH reduction.
PREFERENTIAL TARGETING OF GLUTI TO GOLGI OF MOUSE MAMMARY EPITHELIAL CELLS DURING LACTATION IS RAPIDLY BUT REVERSIBLY LOST DURING PREMATURE WEANING. ♦ 408

Glucose transport is essential for the synthesis of lactose, the major carbohydrate and osmotic constituent of human milk, in the Golgi of mammary epithelial cells. GLUT1, the mammary gland glucose transporter, is targeted to Golgi in mouse mammary epithelial cells treated with prolactin and dexamethasone. Our purpose was to explore GLUT1 targeting in lactating mice and to determine the effect of premature weaning, at 18 d of life, on GLUT1 targeting in mammary gland. Light mitochondrial pellets from mammary glands were subjected to iodixanol density gradient centrifugation; low density fractions (1.05-1.06 g/cm3) were found to be enriched in Golgi. Western blot analysis with highly specific GLUT1 antibody, directed against the C-terminus, revealed the presence of the normally observed approximately 45 kD form of GLUT1, and also showed a signal at approximately 70 kD. Both forms were enriched in low density fractions. This was also seen after 3 h of weaning. However, after 5 h, levels of GLUT1 and the 70 kD form were selectively decreased in the low density fractions. Also, the total cellular content of the 70 kD form decreased, although GLUT1 content did not change. Returning pups to the mother for 5 h after a 5 h wean restores enrichment of the Golgi by GLUT1. The results of returning pups for 15 h after a 5 h wean, including the reappearance of the 70 kD form, were indistinguishable from the results of normally lactating mothers. We conclude that premature weaning causes a transformation of glucose transporter targeting in the lactating mouse mammary gland. During lactation, there is Golgi enrichment by GLUT1 and by a higher MW form recognized by the GLUT1 antibody. Weaning causes a reversible, transitional state that involves loss of the 70 kD form and the loss of preferential Golgi targeting of GLUT1. By diminishing the availability of free glucose within the Golgi for lactose synthesis, this provides a mechanism that reduces the rate of milk production.
Living non-conjugated polyacetylenes

The non-conjugated poly (3,3-dimethyl-1-butyne) and poly (1-trimethylsilyl)-1-propyne were prepared by metathesis catalysts and the polymerization was monitored for molecular weight by GPC and monomer conversion by GC. Both the 1-(trimethylsilyl)-1-propyne and 3,3-dimethyl-1-butyne gave a linear relationship with number average molecular weight versus conversion and number average molecular weight versus monomer to initiator ratio. The 1-(trimethylsilyl)-1-propyne failed to polymerize beyond 100% conversion. The 3,3-dimethyl-1-butyne, however, gave conversion to 300%, with GPC data clearly showing the continuation of propagation from the living polymer chain. The living character of these polymerizations seems to be the result of both the lack of backbiting which can occur only from a cis-cisoidal growing chain, and the lack of interchain reactions. Both the cis-cisoidal configuration and the interchain reactions are prohibited for steric reasons.
Clotting of hemophilic blood with purified platelet cofactor I, platelet factor 3 and threone.

SummaryPurified platelet cofactor I, purified platelet factor 3 or the two together reduce the clotting time of hemophilic blood or recalcified plasma; but, not to the degree observed with normal blood or plasma. In the concentrations used platelet factor 3 was more effective than platelet cof actor I.
Radiation exposure during standing voiding cystourethrography in women

Abstract Objectives To calculate the total radiation exposure and effective organ doses from standard protocol voiding cystourethrography (VCUG). Methods A prospective series of consecutive, non-neurogenic women underwent a standardized VCUG protocol by the same technologist using a Siemens Sireskop Fluorospot radiographic/fluoroscopic unit. Only studies that followed the protocol were included. The effective dose was calculated using a commercially available dose-modeling program (PCXMC, version 1.5) for risk assessment. Results A total of 119 studies in 118 women (mean age 60 ± 13 years, range 30 to 93) were included. Only 15 patients (13%) were premenopausal with in situ reproductive organs. The mean number of images and fluoroscopic time per study was 12.8 ± 1.4 (lateral images 7.5 ± 1.3) and 35.8 ± 11.2 seconds, respectively. The mean effective dose for a single VCUG study was calculated to be 4.3 mSv, of which 26% was from fluoroscopy (1.1 mSv). The dose to the gonads accounted for 50% of the total effective organ dose. Using whole population radiologic risk factors, the total risk detriment, cancer and hereditary, was about 3 per 10,000 patients or a 99.997% chance of no detriment incurred from the study. The genetic and malignant risks were reduced in this cohort of patients, who were older, with most (87%) having no reproductive potential. Conclusions Using a standard protocol for adult women, a VCUG study is associated with an acceptable radiation risk.
Periodic structure in the flagella and cell walls of a bacterium.

Abstract Electron micrographs of a non-spore forming, gram-positive, motile bacterium show the peritrichous flagella to have an external contour of a counterclockwise double helix and the cell wall to have a rectangular periodic structure clearly visible on the inside surface. The flagella are about 150 A in a diameter and have a well-defined cross structure with a periodicity along the flagella axis of 155 A. The nearly constant angle (27 to 35 degrees) that the striae of this cross structure make with the normal to the flagellar axis requires the external contour of the flagella to be a double rather than a single counterclockwise helix. The periodic structure in the cell wall appears to be caused by a rectangular array of spheres or hemispheres having diameters of about 115 A. The outside of the cell wall shows only a faint suggestion of this periodicity.
BOW FLOWS WITH SURFACE TENSION

Two-dimensional free surface flow past a semi-infinite plate is considered. Surface tension is included in the free surface condition, and the effect of gravity is neglected. The configuration models a bow flow, i.e. the flow occurring at the front of an object moving at a constant velocity at the surface of a fluid. It is shown analytically and numerically that flows with waves do not meet the plate tangentially: there is an angle $\delta \neq $ 0 between the plane of the plate and the free surface at the separation point. The shape of the free surface is computed by a boundary integral equation method as a function of $\delta $. The exact form of the wave in the far field is derived as a function of $\delta $ from the principle of conservation of momentum. In particular it is found that the dimensionless wavelength $\lambda $ = $\pi $(1 + cos $\delta $). The numerical results are shown to be consistent with the exact results.
Cepheids at high angular resolution: recent results obtained by stellar interferometry

We present the latest results obtained by stellar interferometry (SI) in the field of pulsating Cephieds stars. The SI technique is particularly well suited to measure distances using the quasi-geometric pulsation parallax method known as the Baade-Wesselink (BW) method. The improvements in angular resolution and precision in the measurements have led to high precision calibration of the Cepheids period luminosity relation. On the other hand, the assumptions of the BW method can be investigated using SI: we present a calibration of the spectroscopic projection factor and the study of center to limb darkening and circumstellar envelopes. These later studies clearly demonstrate that SI has recently entered a regime where the BW implemetation is no longer limited by the precision of the angular diameter measurements but by the classical assumptions underlying the method itself. This calls for a better understanding of Cepheids, using numerical models and diverse observation techniques, including SI.
Reading to learn and reading to integrate: new tasks for reading comprehension tests?:

To address the concern that most traditional reading comprehension tests only measure basic comprehension, this study designed measures to assess more complex reading tasks: Reading to Learn and Reading to Integrate. The new measures were taken by 251 participants: 105 undergraduate native speakers of English, 106 undergraduate nonnative speakers, and 40 graduate nonnative speakers. The research subproblems included determination of the influence of overall basic reading comprehension level, native language background, medium of presentation, level of education, and computer familiarity on Reading to Learn and Reading to Integrate measures; and the relationships among measures of Basic Comprehension, Reading to Learn, and Reading to Integrate. Results revealed that native language background and level of education had a significant effect on performance on both experimental measures, while other independent variables did not. While all reading measures showed some correlation, Reading to Learn and Reading...
Protein Conformation and Supercharging with DMSO from Aqueous Solution

The efficacy of dimethyl sulfoxide (DMSO) as a supercharging reagent for protein ions formed by electrospray ionization from aqueous solution and the mechanism for supercharging were investigated. Addition of small amounts of DMSO to aqueous solutions containing hen egg white lysozyme or equine myoglobin results in a lowering of charge, whereas a significant increase in charge occurs at higher concentrations. Results from both near-UV circular dichroism spectroscopy and solution-phase hydrogen/deuterium exchange mass spectrometry indicate that DMSO causes a compaction of the native structure of these proteins at low concentration, but significant unfolding occurs at ~63% and ~43% DMSO for lysozyme and myoglobin, respectively. The DMSO concentrations required to denature these two proteins in bulk solution are ~3–5 times higher than the concentrations required for the onset of supercharging, consistent with a significantly increased concentration of this high boiling point supercharging reagent in the ESI droplet as preferential evaporation of water occurs. DMSO is slightly more basic than m-nitrobenzyl alcohol and sulfolane, two other supercharging reagents, based on calculated proton affinity and gas-phase basicity values both at the B3LYP and MP2 levels of theory, and all three of these supercharging reagents are significantly more basic than water. These results provide additional evidence that the origin of supercharging from aqueous solution is the result of chemical and/or thermal denaturation that occurs in the ESI droplet as the concentration of these supercharging reagents increases, and that proton transfer reactivity does not play a significant role in the charge enhancement observed.
Thyroid function: Gestational hypothyroidism--a need for universal screening?

The prevalence of gestational hypothyroidism in the USA is higher than previously estimated, according to findings of a new study in the Journal of Clinical Endocrinology and Metabolism. This surprising result raises the question: should all pregnant women be routinely tested for thyroid dysfunction during pregnancy?
Self‐esteem and self‐certainty: a mediational analysis

Self‐esteem has been found to be related to the certainty with which specific self‐conceptions are held. This study tested a number of competing accounts for this relationship, using a more rigorou...
Quantum field states in nonlinear optical balance

Abstract The general structure of electromagnetic quantum field states (QOBS) generated in nonlinear optical balance (NLOB) is illustrated in examples involving triple harmonic generation and the absence of amplified spontaneous emission with four-wave mixing. The method we employ is generally applicable to any NLOB situation. The resultant Fock-space, photon-number states are fundamental solutions to the general problem of NLOB. Superpositions of these states are found to factorize into a novel variety of multiphoton coherent-state solutions.
New vectors for construction of recombinant high-copy-number yeast acentric-ring plasmids.

Yeast acentric-ring plasmid 1 (YARpl), comprising 1453 bp of entirely yeast chromosomal DNA, is maintained in Saccharomyces cerevisiae as a high-copy, relatively stable plasmid. To determine the feasibility of using YARp1 as a yeast cloning vehicle, we subcloned the GAL1-10 promoter and the URA3 gene into YARp1 at different locations. To facilitate these constructions, a class of permuted YARpl construction vectors was generated which enabled us to use various restriction sites in YARp1 as insertion points. Transformation frequencies, plasmid stabilities, and copy numbers of these YARp1 derivatives remained elevated, comparable to those of YARp1 itself. Also, when OMP decarboxylase was assayed using strains containing URA3-YARp's, specific activities of 100–300 times that of wild type were found. This evidence supports the use of YARpl as a high-copy yeast-expression vector or for analyzing structural and regulatory DNA sequences.
Gender and Regional Differences in Schooling Between Boys and Girls in Malawi

Abstract Recognizing the importance of women and the role female education and autonomy plays in the reduction of infant mortality as well as fertility, this paper explores in greater depth the gender differences in schooling between boys and girls in Malawi. Specifically, the paper examines levels of gender inequality in schooling in Malawi and attempts to highlight some of the informal and formal factors that account for the observed differences in the Malawian context. Two main research questions are addressed: (a) What is the extent of the gender differentials in schooling and are there any discernible regional inequalities in female education and autonomy? (b) What are the main explanatory factors behind these differences? Using data from census publications and annual reports of the Ministry of Education in Malawi, the analysis reveals large gender differentials as well as regional disparities in educational attainment. The data show that educational attainment rates for all age groups are higher fo...
Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines

There is an increasing recognition that mitochondrial dysfunction is associated with autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction and how mitochondrial abnormalities might interact with other physiological disturbances such as oxidative stress. Reserve capacity is a measure of the ability of the mitochondria to respond to physiological stress. In this study, we demonstrate, for the first time, that lymphoblastoid cell lines (LCLs) derived from children with autistic disorder (AD) have an abnormal mitochondrial reserve capacity before and after exposure to reactive oxygen species (ROS). Ten (44%) of 22 AD LCLs exhibited abnormally high reserve capacity at baseline and a sharp depletion of reserve capacity when challenged with ROS. This depletion of reserve capacity was found to be directly related to an atypical simultaneous increase in both proton-leak respiration and adenosine triphosphate-linked respiration in response to increased ROS in this AD LCL subgroup. In this AD LCL subgroup, 48-hour pretreatment with N-acetylcysteine, a glutathione precursor, prevented these abnormalities and improved glutathione metabolism, suggesting a role for altered glutathione metabolism associated with this type of mitochondrial dysfunction. The results of this study suggest that a significant subgroup of AD children may have alterations in mitochondrial function, which could render them more vulnerable to a pro-oxidant microenvironment as well as intrinsic and extrinsic sources of ROS such as immune activation and pro-oxidant environmental toxins. These findings are consistent with the notion that AD is caused by a combination of genetic and environmental factors.
A Stereoselective Synthesis of Phosphinic Acid Phosphapeptides Corresponding to Glutamyl-γ-glutamate and Incorporation into Potent Inhibitors of Folylpoly-γ-glutamyl Synthetase

Radical addition of H3PO2 to N-/C-protected vinyl glycine led to the corresponding H-phosphinic acid in excellent yield. The non-nucleophilic H-phosphinic acid was converted to a nucleophilic PIII species, RP(OTMS)2, which was used in two approaches to the target phosphinic acid containing pseudopeptide. New methodology was developed that led to excellent yields in the reaction of RP(OTMS)2 with unactivated electrophiles, including an acyclic homoallylic bromide. However, en route to the target pseudopeptide, Arbuzov reaction of RP(OTMS)2 with a cyclic homoallylic bromide, (R)-3-(bromomethyl)-cyclopent-1-ene, led to a rearranged allylic phosphinic acid rather than the desired homoallylic derivative, a putative glutarate surrogate. Conjugate addition of RP(OTMS)2 to α-methylene glutarate containing a chiral auxiliary resulted in only modest diastereoselectivity. Purification by flash chromatography provided protected derivatives of both diastereomers of the pseudopeptide. Following global deprotection, cou...
Asymmetric Time Evolution and Reduced Dynamics

When using a time asymmetric quantum theory, one must identify the time evolution parameter with a duration in time rather than with a time coordinate value. This identification restricts the options for the quantum mechanical environment of open quantum systems. The restriction may be important for interpretational questions concerning irreversibility or entanglement, but there is no measurable difference between a reduced dynamics within a time symmetric theory or within a time asymmetric theory.
Precision measurement of the mass of the D * 0 meson and the binding energy of the X ( 3872 ) meson as a D 0 D * 0 ¯ molecule

A precision measurement of the mass difference between the ${D}^{0}$ and ${D}^{*0}$ mesons has been made using $316\text{ }\text{ }{\mathrm{pb}}^{\ensuremath{-}1}$ of ${e}^{+}{e}^{\ensuremath{-}}$ annihilation data taken at $\sqrt{s}=4170\text{ }\text{ }\mathrm{MeV}$ using the CLEO-c detector. We obtain $\mathrm{\ensuremath{\Delta}}M\ensuremath{\equiv}M({D}^{*0})\ensuremath{-}M({D}^{0})=142.007\ifmmode\pm\else\textpm\fi{}0.015(\text{stat})\ifmmode\pm\else\textpm\fi{}0.014(\text{syst})\text{ }\text{ }\mathrm{MeV}$, as the average for the two decays, ${D}^{0}\ensuremath{\rightarrow}{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}$ and ${D}^{0}\ensuremath{\rightarrow}{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}$. The new measurement of $\mathrm{\ensuremath{\Delta}}M$ leads to $M({D}^{*0})=2006.850\ifmmode\pm\else\textpm\fi{}\phantom{\rule{0ex}{0ex}}0.049\text{ }\text{ }\mathrm{MeV}$, and the currently most precise measurement of the binding energy of the ``exotic'' meson X(3872) if interpreted as a ${D}^{0}{D}^{*0}$ hadronic molecule, ${E}_{b}(\mathrm{X}(3872))\ensuremath{\equiv}M({D}^{0}{D}^{*0})\ensuremath{-}M(\mathrm{X}(3872))=\phantom{\rule{0ex}{0ex}}3\ifmmode\pm\else\textpm\fi{}192\text{ }\text{ }\mathrm{keV}$.
Neuroscientific Evidence About the Distinction Between Short- and Long-Term Memory:

What have neuroscientific techniques contributed to the development of psychological theory about short- and long-term memory? We argue that the contributions have been varied: In some cases, data about brain mechanisms have been vital to the advancement of psychological theory; in other cases, neuroscientific data and behavioral data from normal participants have made equal contributions; and in yet other cases, the data from neuroscientific approaches have actually led psychological theory astray. We illustrate these various contributions by focusing on the relationship of short- to long-term memory.
Genome-Wide Mapping Indicates That p73 and p63 Co-Occupy Target Sites and Have Similar DNA-Binding Profiles In Vivo

Background: The p53 homologs, p63 and p73, share, ~85% amino acid identity in their DNA-binding domains, but they have distinct biological functions. Principal Findings: Using chromatin immunoprecipitation and high-resolution tiling arrays covering the human genome, we identify p73 DNA binding sites on a genome-wide level in ME180 human cervical carcinoma cells. Strikingly, the p73 binding profile is indistinguishable from the previously described binding profile for p63 in the same cells. Moreover, the p73:p63 binding ratio is similar at all genomic loci tested, suggesting that there are few, if any, targets that are specific for one of these factors. As assayed by sequential chromatin immunoprecipitation, p63 and p73 co-occupy DNA target sites in vivo, suggesting that p63 and p73 bind primarily as heterotetrameric complexes in ME180 cells. Conclusions: The observation that p63 and p73 associate with the same genomic targets suggest that their distinct biological functions are due to cell-type specific expression and/or protein domains that involve functions other than DNA binding. © 2010 Yang et al.
High School Band Students’ and Directors’ Perceptions of Verbal and Nonverbal Teaching Behaviors

This study was designed to examine the use and perception of selected teaching behaviors of high school band directors. Videotaped rehearsals of six band directors’ top-performing ensembles were an...
ULTRASTRUCTURE OF SARCOPLASMIC RETICULUM PREPARATIONS

Fragmented sarcoplasmic reticulum (FSR) from rabbit muscle was examined by positive staining, negative staining, and freeze-etch electron microscopic techniques in the absence and presence of calcium transport conditions. The existence of 30–40 A particles covering the outer surface of FSR vesicles was confirmed by two different negative stains in unfixed, glutaraldehyde-fixed and osmium tetroxide-fixed material. Freeze-etch microscopy revealed a second type of particle, 80–90 A in diameter, on the fractured surfaces of FSR vesicles. Following calcium oxalate accumulation, negative and positive staining techniques provided evidence for large nodular deposits within FSR vesicles which probably correspond to calcium oxalate crystals and are responsible for increments in turbidity during calcium oxalate accumulation. The most probable configuration of FSR vesicles in solution is spherical. "Tadpole" or tubular configurations were not seen by freeze-etch microscopy, positive staining, or in prefixed negatively stained material.
The Role of Connectedness in Relation to Spirituality and Religion in a Twelve-Step Model

The pervasive nature of substance abuse in the United States dictates that much of the research dollars and time is spent on clinical trials that measure anxiety reduction, medication management and the employing of behavioral models that stress gradual change. While these approaches use controls that can be studied and measured in the empirical sense, they often lack the important personal connections with the research participants. As these trials show less than hoped for efficacy, a new body of research is surfacing including spirituality, along with social supports as ways to aid recovery and reduce relapse. Many 12-step groups incorporate spirituality, as opposed to religion as a mainstay of an individual’s recovery effort. Spirituality is regularly mentioned across most twelve-step programs as an essential part of sustained and ongoing recovery. Practical definitions of spirituality have eluded researchers in part because they struggle to separate it from religion. While it may not be impossible to measure spirituality in an empirical sense, it may be possible to clarify what role spirituality plays in aiding sustained recovery and prevention of relapse into drug using behavior. We will suggest connectedness as an integral component in defining spirituality and demonstrate that in twelve-step recovery spirituality can be defined as gaining knowledge through connectedness to others.
Retroviral oncoprotein Tax induces processing of NF‐κB2/p100 in T cells: evidence for the involvement of IKKα

IκB kinase (IKK) is a key mediator of NF-κB activation induced by various immunological signals. In T cells and most other cell types, the primary target of IKK is a labile inhibitor of NF-κB, IκBα, which is responsible for the canonical NF-κB activation. Here, we show that in T cells infected with the human T-cell leukemia virus (HTLV), IKKα is targeted to a novel signaling pathway that mediates processing of the nfκb2 precursor protein p100, resulting in active production of the NF-κB subunit, p52. This pathogenic action is mediated by the HTLV-encoded oncoprotein Tax, which appears to act by physically recruiting IKKα to p100, triggering phosphorylation-dependent ubiquitylation and processing of p100. These findings suggest a novel mechanism by which Tax modulates the NF-κB signaling pathway.
Behavioral evaluation of the psychological welfare and environmental requirements of agricultural research animals: theory, measurement, ethics, and practical implications.

The welfare of agricultural research animals relies not only on measures of good health but also on the presence of positive emotional states and the absence of aversive or unpleasant subjective states such as fear, frustration, or association with pain. Although subjective states are not inherently observable, their interaction with motivational states can be measured through assessment of motivated behavior, which indicates the priority animals place on obtaining or avoiding specific environmental stimuli and thus allows conclusions regarding the impact of housing, husbandry, and experimental procedures on animal welfare. Preference tests and consumer demand models demonstrate that animal choices are particularly valuable when integrated with other behavioral and physiological measurements. Although descriptive assessments of apparently abnormal behavior such as stereotypies and "vacuum behaviors" provide indications of potentially impoverished environments, they should be used with some caution in drawing welfare conclusions. The development of stereotypies may in some cases be linked to psychiatric dysfunction and reflect underlying neurophysiological impairments, which have implications for the ability to perform flexible behavior and thus the quality of research data provided by this kind of behavioral measurement (e.g., in pharmaceutical research). Environmental modifications, commonly termed "enrichment," can have diverse consequences for cognitive function, physiological responses, health, psychological welfare, and research data. Simple practical modifications of housing, husbandry, and experimental design are suggested to improve the psychological welfare of agricultural research animals in accordance with the principles of refining, reducing, and replacing (the "3Rs"), which underlie US Public Health Service Policy, and prevailing public ethics.
Analysis of hyperspectral data for estimation of temperate forest canopy nitrogen concentration: comparison between an airborne (AVIRIS) and a spaceborne (Hyperion) sensor

Field studies among diverse biomes demonstrate that mass-based nitrogen concentration at leaf and canopy scales is strongly related to carbon uptake and cycling. Combined field and airborne imaging spectrometry studies demonstrate the capacity for accurate empirical estimation of forest canopy N concentration and other biochemical constituents at scales from forest stands to small landscapes. In this paper, we report on the utility of the first space-based imaging spectrometer, Hyperion, for estimation of temperate forest canopy N concentration as compared to that achieved with the airborne high-altitude imaging spectrometer, the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS). Overall accuracy of Hyperion estimates of forest canopy N concentration, as compared with field measurements, were within 0.25% dry mass, and AVIRIS-based estimates were within 0.19% dry mass, each well within the accuracy required to distinguish among forested ecosystems in nitrogen status.
Differentiating Literacy Growth of ELL Students With LD From Other High-Risk Subgroups and General Education Peers: Evidence From Grades 3–10

The authors used a large data set (N = 1,011,549) to examine literacy growth over a single school year comparing general education (GenEd) students to three high-risk subgroups: English language learners (ELL), those with a specific learning disability (LD), and those identified as both LD and ELL (LD-ELL) in students in Grades 3–10. The authors were particularly interested in whether variability existed between initial status and the growth trajectories of the three high-risk groups on measures of spelling, fluency, and reading comprehension across the school year and whether this variability was differentiated because of socioeconomic status (SES) as defined by free and reduced lunch (FRL) status. Results indicate that all high-risk groups began the year at substantially lower levels than their GenEd peers, with the largest differences seen between the LD-ELL students and the other subgroups. Further results suggest that students who are in the high-risk subgroups and also qualify for FRL perform signif...
W-ChIPeaks

Summary: ChIP-based technology is becoming the leading technology to globally profile thousands of transcription factors and elucidate the transcriptional regulation mechanisms in living cells. It has evolved rapidly in recent years, from hybridization with spotted or tiling microarray (ChIP-chip), to pair-end tag sequencing (ChIP-PET), to current massively parallel sequencing (ChIP-seq). Although there are many tools available for identifying binding sites (peaks) for ChIP-chip and ChIP-seq, few of them are available as easy-accessible online web tools for processing both ChIP-chip and ChIP-seq data for the ChIP-based user community. As such, we have developed a comprehensive web application tool for processing ChIP-chip and ChIP-seq data. Our web tool W-ChIPeaks employed a probe-based (or bin-based) enrichment threshold to define peaks and applied statistical methods to control false discovery rate for identified peaks. The web tool includes two different web interfaces: PELT for ChIP-chip, BELT for ChIP-seq, where both were tested on previously published experimental data. The novel features of our tool include a comprehensive output for identified peaks with GFF, BED, bedGraph and.wig formats, annotated genes to which these peaks are related, a graphical interpretation and visualization of the results via a user-friendly web interface. Availability: http://motif.bmi.ohio-state.edu/W-ChIPeaks/. Contact: victor.jin@osumc.edu Supplementary information:Supplementary data are available at Bioinformatics online.
Fast, Accurate Models for Predicting the Compliance of Elastic Flexure-Jointed Robots

Robot manipulators having elastic links or flexure joints have a number of advantages, especially in simplify ing the control of contact with other objects. However, cur rent simplified parametric models of flexure motion do n ot accurately predict the behavior of these mechanisms under large deflections. This paper presents a “smooth curvatur e model” of flexure behavior that describes the curvature of a highly flexible member such as a flexure joint using a basis of thr ee orthogonal polynomials. Using this model, we show that it is p ossible to predict the planar stiffness these mechanisms, even in cases where the deformation of the hinge is too large for the linear Euler-Bernoulli beam bending model. Using both finite element methods and the much less computationally expensive proposed model, numerical results will demonstrate that it i s possible to accurately predict the in-plane compliance of a hig hly flexible mechanism in the presence of an external load. The results of this work are significant because they demonstrate that the behavior of flexure-based robotic mechanisms can be modeled quickly and with few parameters, enabling their use in closedloop control for situations where collision safety is a concern, and rigorous model-based path planning for obstacle avoidance, among other applications.