cssi/SciSciGPT-SciSciNet huggingface dataset:
DNA Repair Mechanisms and Therapeutic Targets in Glioma

This review discusses current and investigative strategies for targeting DNA repair in the management of glioma. Recent strategies in glioma treatment rely on the production of overwhelming DNA damage and inhibition of repair mechanisms, resulting in lethal cytotoxicity. Many strategies are effective in preclinical glioma models while clinical feasibility remains under investigation. The presence of glioma biomarkers, including IDH mutation and/or MGMT promoter methylation, may confer particular susceptibility to DNA damage and inhibition of repair. These biomarkers have been adopted as eligibility criteria in the design of multiple ongoing clinical trials. Targeting DNA repair mechanisms with novel agents or therapeutic combinations is a promising approach to the treatment of glioma. Further investigations are underway to optimize this approach in the clinical setting.
Social position indirectly influences the traits yellow-bellied marmots use to solve problems

Animals adapt to changing environments by behaving flexibly when solving problems. Traits, such as sex and age, and specifically behavioral traits like persistence-the amount of time spent attempting to solve a problem, are positively associated with successful problem-solving. However, individuals face social pressures, such as aggression, which may directly alter an individual's behavior or interact with sex or age, when they attempt to problem-solve. We examined the direct and indirect effects of social position and individual behavioral traits on solving a novel puzzle box in facultatively social yellow-bellied marmots (Marmota flaviventer), using both generalized linear mixed models and confirmatory path analysis. We found strong support that marmots who used a diversity of behaviors were more successful problem-solvers and weak support that those who received more aggression were less successful. Additionally, marmots who received more aggression were less behaviorally diverse, less behaviorally selective and less persistent while trying to open the puzzle box. Thus, we show that aggression indirectly decreases problem-solving success by acting on the behavioral traits that an individual uses. We conclude that specific social relationships, including the type of interaction and whether they are recipients or initiators, influences the ways in which an individual interacts with cognitive tests and should be considered in analysis of individual problem-solving.
Functional diversity of neuronal nicotinic acetylcholine receptors.

Publisher Summary The neuronal nicotinic acetylcholine receptors are likely to be oligomeric proteins composed of five subunits. If these receptors were all homo-oligomers, there might be one unique receptor that corresponded to each pentameric arrangement of each of the available subunits. The situation is more complicated than that because most of the neuronal nicotinic receptors are hetero-oligomers. These hetero-oligomeric receptors contain both alpha and beta subunits. Because individual alpha subunits can participate in the formation of functional receptors with more than one kind of beta subunit, the number of possible receptors is larger. This chapter documents several examples of the functional heterogeneity of the neuronal nicotinic receptors and presents new properties that characterize these receptors. Specifically, it reviews data showing the pharmacological diversity of neuronal nicotinic acetylcholine receptors and shows that these receptors differ from the muscle nicotinic acetylcholine receptors in their permeability to calcium and in their modulation by external calcium ions.
Mechanism of polymer-based separations

Abstract The metal ion affinities of polystyrene-supported phosphinic and phosphonic acid ligands have been examined under a wide variety of solution conditions in order to elucidate the interaction mechanisms displayed by the two polymeric reagents for different metals. Nitrate solutions of Fe(III), Hg(II), Ag(I), and Mn(II) were contacted with the resins. Three variables studied were the pH, ionic strength, and initial metal concentration (viz., 10 −1 to 10 −5 N). It was concluded that: the phosphinic resin is more sensitive to loading effects and its phosphoryl oxygen has a lower H + affinity than the phosphonic resin under highly acidic conditions; the phosphinic resin's recognition mechanism, reduction, intervenes at Hg(II) concentrations ≥ 10 −4 N ; and Ag(I) is reduced to Ag metal by the phosphinic resin only from relatively high metal ion concentrations coupled with low acid solutions. The log D / pH correlations were found to fall into one of four categories from which the relative affinities displayed by the resin for M n+ / H + / Na + could be deduced. The inherent ligand / M n+ affinity is best defined in dilute solutions (10 −5 N) and acid concentrations wherein the ratio of solution H + to polymer ligand is 1:1 or less; the relative coordinative affinity for M n+ / H + displayed by the ligand is best defined in dilute solutions and high acid concentrations (≥ 2 N HNO 3 ). The sensitivity of the polymer to loading effects may then be defined by increasing the initial metal concentration from 10 −5 N to 10 −1 N.
An Algorithm for Labeling Edges of Hierarchical Drawings

Let G(V, E) be a graph, and let Γ be the drawing of G on the plane. We consider the problem of assigning text labels to every edge of G such that the quality of the label assignment is optimal. This problem has been first encountered in automated cartography. Even though much effort has been devoted over the last 15 years in the area of automated drawing of maps, the Edge Label Placement (ELP) problem remains essentially unsolved. In this paper we investigate the ELP problem. We present an algorithm for the ELP problem more suitable for hierarchical drawings of graphs, but it can be adopted to many different drawing styles and still remain effective. Also, we present experimental results of our algorithm that indicate its effectiveness.
Poxviral infection elicits human neutralizing antibodies recognizing diverse epitopes of the major vaccinia virus surface protein D8 (VIR4P.1016)

Immunization with vaccinia virus (VACV) confers cross-protective immunity to variola, the causative agent of smallpox, and other clinically important poxviral species, such as cowpox and monkeypox viruses. Vaccine-mediated protection has been correlated with elicitation of broad neutralizing antibody (Ab) responses, however the specificity of human neutralizing antibodies to poxviruses is poorly understood. We used a highly-optimized human hybridoma technology to generate large panels of anti-VACV monoclonal Abs (mAbs) from vaccinia-immunized subjects or from subjects who had naturally acquired monkeypox infection. Immunologic characterization and DNA sequencing of the panel revealed 16 individual mAbs that recognized the immunodominant surface protein antigen D8. Several of anti-D8 mAbs possessed neutralizing activity against VACV, cowpox and monkeypox viruses. These Abs exhibited mainly a complement-dependent pattern of neutralization and they formed at least four cross-blocking groups, suggesting the existence of several non-overlapping neutralizing epitopes for D8. The results suggest that D8 is an important target for human neutralizing Abs generated following poxviral infection or vaccination, and suggest the existence of novel epitopes targeted by anti-D8 Abs that contribute to cross-protective immunity following smallpox vaccination.
Cooperative Human and Machine Perception in Teleoperated Assembly

This paper presents results on a teleoperator expert assistant — a system that in cooperation with a human operator estimates properties of remote environment objects in order to improve task performance. Specifically, an undersea connector-mating task is investigated in the laboratory using a PHANToM master and WAM remote manipulator. Estimates of socket orientation are obtained during task performance and conveyed to the operator through a graphical display. Task performance, measured by completion time and peak insertion force, is compared for operators using combinations of video images, the graphical display and a shared control mode in which the connector automatically rotates to the estimated socket orientation. The graphical display and automatic orientation controller reduce task completion times and contact forces by over one-third for inclined sockets when the video signal is noisy, e.g., due to water turbidity.
Peripheral Muscle Strength and Correlates of Muscle Weakness in Patients Receiving Mechanical Ventilation

Intensive care unit-acquired weakness (ICUAW), defined as the development of severe paresis related to critical illness,1 is a frequent complication of critical illness due to prolonged immobility and bed rest2 particularly in patients receiving prolonged mechanical ventilatory support.1 Respiratory and limb muscle strength are altered after 7 days of mechanical ventilation leading to delayed extubation and prolonged mechanical ventilation.3 Development of ICUAW can also contribute to physical limitations in patients who recover from critical illness.1,2 Known risk factors for ICUAW include older age, diagnosis of sepsis, electrolyte disturbances, receipt of corticosteroids and neuromuscular blocking agents, illness severity, and immobility, while an indirect link has been proposed for sedation due to reduced mobility of sedated patients.4, p. 1880 In addition, muscle mass and force of muscle contraction decrease with aging, which results in weakness that exceeds what would be expected in the presence of muscle atrophy.5 One study reported that female gender was significantly associated with ICUAW.6 Of these known risk factors, those that are not clinically modifiable include older age, gender, multisystem organ failure, sepsis and the requirement in some patients of medications needed for treatment such as corticosteroids and neuromuscular blocking agents (NMBAs).7 Modifiable risk factors include hyperglycemia and sedative medications.7 Little is known about the pattern of muscle strength during ventilatory support, or if modifiable risk factors might directly influence muscle strength in patients experiencing prolonged mechanical ventilation. Measurement of muscle strength also poses challenges in the critical care unit given that non-invasive methods require alert and cooperative patients. One objective, directly quantifiable measure of peripheral muscle strength is hand-grip dynamometry. Grip strength limited to 1-3 measurements has been used by other ICU researchers1,4 as a marker of impaired functional status with diminished grip strength linked to increased ICU mortality.1 There is a paucity of data documenting serial grip strength assessment over the course of ventilatory support. Thus, the purpose of this longitudinal study was to describe serial peripheral muscle strength measurements and to identify factors that are associated with patterns of peripheral muscle strength during mechanical ventilation.
Lyman alpha radiation in the night-time mesopause and lower thermosphere - II. Measurements of atomic hydrogen and molecular oxygen densities in the night-time atmosphere.

Abstract Measurements of Lyman alpha night airglow made with rocket borne ionisation chambers have been used to derive the atomic hydrogen and molecular oxygen density profiles between 70 and 120 km altitude. The measured profiles are compared with photochemical model and standard atmosphere density profiles respectively.
Aortic expansion rate in patients with dilated post-stenotic ascending aorta submitted only to aortic valve replacement long-term follow-up.

Objectives This study was conceived to describe the evolution of aortic dimensions in patients with moderate post-stenotic ascending aorta dilation (50 to 59 mm) submitted to aortic valve replacement (AVR) alone. Background The appropriate treatment of post-stenotic ascending aorta dilation has been poorly investigated. Methods Ninety-three patients affected by severe isolated calcific aortic valve stenosis in the tricuspid aortic valve accompanied by moderate dilation of the ascending aorta (50 to 59 mm) were submitted to AVR only. All patients were followed for a mean of 14.7 ± 4.8 years by means of periodic clinical evaluations and echocardiography and tomography scans of the thorax. Results Operative mortality was 1.0% (1 patient). During the follow-up, 16 patients died and 2 had to be reoperated for valve dysfunction. No patients experienced acute aortic events (rupture, dissection, pseudoaneurysm), and no patient had to be reoperated on the aorta. There was not a substantial increase in aortic dimensions: mean aortic diameter was 57 ± 11 mm at the end of the follow-up versus 56 ± 02 mm pre-operatively (p = NS). The mean ascending aorta expansion rate was 0.3 ± 0.2 mm/year. Conclusion In the absence of connective tissue disorders, AVR alone is sufficient to prevent further aortic expansion in patients with moderate post-stenotic dilation of the ascending aorta. Aortic replacement can probably be reserved for patients with a long life expectancy.
Labor force migration non-labor force migration and non-employment reasons for migration

Abstract This paper documents the extent and nature of non-employment factors in migration. The labor force status of over 18 million recent interstate migrants in the United States and stated reasons for moving reported in several surveys in the U.S. are examined. Labor force migrants are heterogeneous in terms of the relationships between acquisition of employment and the migration decision, and in terms of the influence of decision makers outside of the migrant household including firms and the government. Numerically important categories of migrants not traditionally captured in migration models exist, including the elderly, the military, and movers from abroad. Whereas non-employment reasons are secondary to employment reasons for a majority of labor force migrants, non-employment factors are singularly important or operate in combination with employment factors for the majority of all migrants. The heterogeneity of migrant types and migration reasons needs to be better captured in migration models.
Distribution and characterization of steroid hormone receptors in human thyroid tissue.

The incidence and molecular characteristics of cytosolic steroid receptors for estrogen (ER), androgen (AR), progesterone (PR), and glucocorticoid (GR) were analyzed in human thyroidectomy specimens. All assays were performed by a protamine sulfate precipitation technique and analyzed by the method of Scatchard. Selected specimens were analyzed by sucrose density gradient. A receptor content over 1 fmol/mg cytosol protein was taken as positive. Estrogen was found in 23 of 45 specimens including 8 of 8 papillary cancers. Mean ER content (Rc) was 29.8 ±6.7 fmol/mg cytosol protein with a dissociation constant (Kd) of 0.23 ±0.09 × 10−10M. The Rc of ER was higher in neoplastic than non-neoplastic thyroid tissue. Androgen was found in 19 of 41 specimens, including 6 of 8 papillary cancers. Mean Rc for AR was 10.6 ± 7.1 fmol/mg cytosol protein with a Kd of 0.17 ± 0.11 × 10−10. The incidence of ER and AR was significantly higher (p<0.05) in neoplastic than in non-neoplastic thyroid tissue. Progesterone was found in 7 of 25 specimens. Mean Rc for PR was 6.2 ± 2.9 fmol/mg cytosol protein with a Kd of 0.03 ± 0.02 × 10−10M. Glucocorticoid was found in 6 of 26 specimens. Rc for GR was 6.3 ± 2.3 fmol/mg cytosol protein with a Kd of 0.11 ± 0.05 × 10−10M. By sucrose density gradient, a 4S and 8S type of ER was identified, while AR was predominately 6S, and GR was predominately 8S. The steroid receptors identified were a single-class, high-affinity, and saturable similar to those found in other steroid hormone dependent tissues. These findings suggest that steroid hormones may influence the development and growth of thyroid tumors.
Texture mapping on surfaces of arbitrary topology using norm preserving-based optimization

A simple and yet highly efficient, high-quality texture mapping method for surfaces of arbitrary topology is presented. The new method projects the given surface from the 3D object space into the 2D texture space to identify the 2D texture structure that will be used to texture the surface. The object space to texture space projection is optimized to ensure minimum distortion of the texture mapping process. The optimization is achieved through a commonly used norm preserving minimization process on edges of the surface. The main difference here is, by using an initial value approach, the optimization problem can be set up as a quadratic programming problem and, consequently, solved by a linear least squares method. Three methods to choose a good initial value are presented. Test cases show that the new method works well on surfaces of arbitrary topology, with the exception of surfaces with exceptionally abnormal curvature distribution. Other advantages of the new method include uniformity and seamlessness of the texture mapping process. The new method is suitable for applications that do not require precise texture mapping results but demand highly efficient mapping process such as computer animation or video games.
Evaluation of mutual radiation impedances between circular pistons by impulse response and asymptotic methods

Abstract A general approach is presented to evaluate the mutual radiation impedance between circular pistons of arbitrary size and spacing in an infinite rigid planar baffle. The impedance is expressed as a Fourier transform of a generalized impulse response which is defined by an integral relationship. Although the integral must, in general, be numerically evaluated, several special cases of interest can readily be evaluated by using asymptotic techniques. Several asymptotic expressions for the mutual radiation impedance are developed and their limitations are noted. Numerical results are then presented for the generalized impulse response and mutual radiation impedance corresponding to pistons of equal size and arbitrary spacing. The time domain characteristics of the generalized impulse responses as a function of spacing are noted and related to the frequency characteristics of the mutual radiation impedances as a function of spacing. In addition, the accuracy of a simple closed form expression for the mutual radiation impedance is presented as a function of normalized frequency and spacing.
Mycorrhiza in the Genus Citrus

RECENT experiment points to a close and direct correspondence between the incidence and character of mycorrhizal infection and differences in the rooting medium. In view of the existence of mycorrhiza as a regular phenomenon in many crop plants, it appears likely, therefore, that intensive study of the soil conditions controlling its development may be a matter of practical importance to growers.
Effect of Continuous Light on the Potency of Plodia interpunctella Males (Lepidoptera: Phycitidae)

Recent studies showed that the egg production of females of the Indian-meal moth, Plodia interpunctella (Hubner), that were mated to males reared under 12-hr light :12-hr dark (LD) cycles was always higher than that of females mated to males reared under continuous light (LL) (Lum and Flaherty 1969). Even though males from either light regime copulated readily and transferred spermatopheres, the percent of females that oviposited was greater in cultures mated with LD males than in cultures mated with LL males. Oviposition in the Indian-meal moth is, therefore, stimulated by neither the physical act of mating nor the presence of a spermatophore in the bursa copulatrix. Because it was previously suspected that the quantity of spermatozoa deposited in some female insects may be the stimulus to oviposition (Norris 1933), the spermathecal contents of females mated to LD males, and females mated to LL males were compared to find the causes leading to differences in egg production and percent females ovipositing.
Low-energy electron-beam patterning of amine-functionalized self-assembled monolayers

Patterned amine-functionalized self-assembled monolayers have potential as a template for the deposition and patterning of a wide variety of materials on silicon surfaces, including biomolecules. Results are presented here for low-energy electron-beam patterning of 2-aminopropyltriethoxysilane and (aminoethylaminomethyl)phenethyltrimethoxysilane self-assembled monolayers on silicon substrates. On these ultrathin (1–2 nm) monolayers, lower electron beam energies (<5 keV) produce higher resolution patterns than high-energy beams. Auger electron spectroscopy indicates that low-energy electron exposure primarily damages the amine groups. At 1 keV, a dose of 40 μC/cm2 is required to make the patterns observable by lateral force microscopy. Features as small as 80 nm were exposed at 2 keV on these monolayers. After exposure, palladium colloids and aldehyde- and protein-coated polystyrene fluorescent spheres adhered only to unexposed areas of the monolayers.
Latency-associated nuclear antigen (LANA) cooperatively binds to two sites within the terminal repeat, and both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication.

Abstract The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus is a multifunctional protein with important roles in both transcriptional regulation and episomal maintenance. LANA is also a DNA-binding protein and has been shown to specifically bind to a region within the terminal repeat. Here, we have performed a detailed analysis of the DNA-binding activity of LANA and show that it binds two sites separated by 22 bp. We used electrophoretic mobility shift assay to quantitatively analyze the binding sites and determined that the K d of the high affinity site is 1.51 ± 0.16 nm. Examination of the contribution of nucleotides near the ends of the site showed that the core binding site consists of 16 bp, 13 of which are conserved between both sites. Analysis of the affinity of each site alone and in tandem revealed that the binding to the second site is primarily due to cooperativity with the first site. Using deletion and point mutations, we show that both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication. In addition, we show that the ability of LANA to carry out these functions is directly proportional to its affinity for the sites in this region. The affinities, spacing, and cooperative binding between the two sites is similar to that of the Epstein-Barr virus dyad symmetry elementoriP, suggesting a requirement for such an element in latent replication of these related DNA tumor viruses.
Age at leaving home in rural Ireland 1901-1911.

Economic historians have stressed the importance of households and household formation but have devoted little attention to the process of leaving home. Leaving home in Ireland is important because of households role in post-Famine demographic patterns. A matched Irish manuscript census sample for 1901 and 1911 shows that Irish males left home later than females. Statistical tests show that much of this reflects an Irish inheritance system that led many males never to leave home. Other economic forces such as labor market opportunities often had opposite impacts on males and females. (EXCERPT)
The potential of high speed UTC-TW photo detectors to generate sub-MM wave signals-predictions by a new analytical model

This study presents a novel model of a high-speed uni-travelling-carrier travelling wave (UTC-TW) photo detector for submillimeter wave signal generation. The model is fully analytical and is intended to be used as a design tool. This newly designed photo detector can operate well above 100 GHz.
Monoterpene synthases of loblolly pine (Pinus taeda) produce pinene isomers and enantiomers.

Abstract The turpentine fraction of conifer oleoresin is a complex mixture of monoterpene olefins and plays important roles in defense and in the mediation of chemical communication between conifer hosts and insect predators. The stereochemistry of the turpentine monoterpenes is critical in these interactions, influencing host recognition, toxicity, and potency of derived pheromones, and the stereochemical composition of these compounds lends insight into their biogenetic origin, with implications for the numbers and types of enzymes responsible and their corresponding genes. Analysis of the oleoresin from several tissues of loblolly pine (Pinus taeda) showed the derived turpentine to consist mainly of (+)-(3R:5R)-α-pinene and (−)-(3S:5S)-β-pinene. Cell-free extracts from xylem tissue yielded three monoterpene synthases which together account for the monoterpene isomer and enantiomer content of the turpentine of this tissue. The major products of these enzymes, produced from the universal precursor of monoterpenes, geranyl diphosphate, were shown to be (+)-α-pinene, (−)-α-pinene, and (−)-β-pinene, respectively. In most properties (molecular mass of ∼60 kDa, Km for geranyl diphosphate of 3 μM, requirement for monovalent and divalent cations), these enzymes resemble other monoterpene synthases from conifer species.
Hospital-based case management for medically fragile infants: Program design

A hospital-based multidisciplinary team is demonstrating services for medically fragile infants which facilitate transition from the hospital to the community and home. The team provides education and counseling for communities and families to overcome barriers to services. With individualized case management, the team facilitates family access to the community services they need in infant health, infant development and family functioning. The team plans the infant's discharge from the hospital and collaborates on the initial Individualized Family Service Plan (IFSP) with the family and local community providers. The initial IFSP details potential outcomes in the areas of infant health, infant development and family functioning for the first year the infant is home. Systematic home visits with the team's nurse or developmental consultant, the family and the local provider continue the education and counseling process during the infant's first year of life. This describes the educational aspect of case management services for medically fragile infants.
Oxygen and pyridine on Ag(110) studied by second harmonic generation: Coexistence of two phases within monolayer pyridine coverage

Abstract The adsorption of oxygen and pyridine on Ag(110) in UHV is studied by second harmonic generation (SHG) from the surface. The adsorption of oxygen at room temperature (atomic) and at 110 K (molecular) causes a monotonic decrease in the second harmonic intensity with coverage which obeys simple Langmuir kinetics. Model fits to the data yield initial sticking coefficients, s0, of 0.0049 and 0.0088 for atomic and molecular oxygen adsorption, respectively. In contrast to oxygen adsorption, the changes in SHG signal induced by the exposure of Ag(110) to pyridine are more complicated and cannot be fit to a single-site Langmuir adsorption model. The SHG measurements indicate the presence of two distinct phases in the pyridine monolayer. A model, which depicts a broad transition from a flat-lying pyridine configuration at low coverages to a stand-up configuration at higher coverages, reproduced both the SHG and the work function measurements. The flat-lying phase dominates at low coverage, but the stand-up phase prevails when the coverage exceeds 0.3 monolayers. s0 for pyridine adsorption at 110 K was determined to be close to unity.
Deep desulfurization of diesel oil oxidized by Fe (VI) systems

Abstract Fe (VI) compound, such as K2FeO4, is a powerful oxidizing agent. Its oxidative potential is higher than KMnO4, O3 and Cl2. Oxidation activity of Fe (VI) compounds can be adjusted by modifying their structure and pH value of media. The reduction of Fe (VI), differing from Cr and Mn, results in a relatively non-toxic by-product Fe (III) compounds, which suggests that Fe (VI) compound is an environmentally friendly oxidant. Oxidation of model sulfur compound and diesel oil by K2FeO4 in water-phase, in organic acid and in the presence of phase-transfer catalysts is investigated, respectively. The results show that the activity of oxidation of benzothiophene (BT) and dibenzothiophene (DBT) is low in water-phase, even adding phase-transfer catalyst to the system, because K2FeO4 reacts rapidly with water to form brown Fe(OH)3 to lose ability of oxidation of organic sulfur compounds. The activity of oxidation of the BT and DBT increases markedly in acetic acid. Moreover, the addition of the solid catalyst to the acetic acid medium promotes very remarkably oxidation of organic sulfur compounds. Conversions of the DBT and BT are 98.4% and 70.1%, respectively, under the condition of room temperature, atmospheric pressure, acetic acid/oil (v/v) = 1.0, K2FeO4/S (mol/mol) = 1.0 and catalyst/K2FeO4 (mol/mol) = 1.0. Under the same condition, diesel oil is oxidized, followed by furfural extraction, the results display sulfur removal rate is 96.7% and sulfur content in diesel oil reduces from 457 ppm to 15.1 ppm.
Musical aptitudes, musical interests and mental retardation

. A modified version of the Bentley scales of musical aptitude was given to a sample of mild and moderately retarded adults chosen on the basis of alleged musical interest or experience. Several comparison groups were also given the assessment battery. The musical nominees generally performed more accurately than both matched retarded subjects with no particular musical interests and a group of normal children matched on (Wechsler) vocabulary scores. The musical nominees showed especially high performance on the subtest assessing voice analysis in chords.
Use of Methionine Alkylation to Prepare Cationic and Zwitterionic Block Copolypeptide Vesicles

We have developed a facile method for preparation of ionic copolypeptide vesicles that requires no protecting groups or expensive components. We prepared amphiphilic copolypeptides containing segments of water-soluble methionine sulfonium residues. These were derived by aqueous phase, direct alkylation of a fully hydrophobic precursor diblock copolypeptide, poly(L-methionine)65-block-poly(L-leucine0.5-stat-L-phenylalanine0.5)20 (M65[L0.5/F0.5]20), with simple alkylating reagents. Methylation of M65(L0.5/F0.5)20 gave the cationic methyl-methionine sulfonium derivative MM65(L0.5/F0.5)20, and carboxymethylation gave the zwitterionic carboxymethyl-methionine sulfonium derivative MC65(L0.5/F0.5)20. Assembly of MM65(L0.5/F0.5)20 or MC65(L0.5/F0.5)20 in water gave rise to vesicles with average diameters of a few microns, which could then be extruded to nanoscale diameters. While the cationic MM-based vesicles were found to be cytotoxic, the zwitterionic MC-based vesicles were found to possess minimal cytotoxicity.
The Roadblock Light Chain Binds a Novel Region of the Cytoplasmic Dynein Intermediate Chain

Cytoplasmic dynein is the major minus-end directed microtubule-based motor in eukaryotic cells. It is composed of a number of different subunits including three light chain families: Tctex1, LC8, and roadblock. The incorporation of the roadblock light chains into the cytoplasmic dynein complex had not been determined. There are two roadblock genes in mammals, ROBL-1 and ROBL-2. We find that both members of the roadblock family bind directly to all of the intermediate chain isoforms of mammalian cytoplasmic dynein. This was determined with three complementary approaches. A yeast two-hybrid assay demonstrated that both roadblock light chains interact with intermediate chain isoforms from the IC74-1 and IC74-2 genes in vivo. This was confirmed in vitro with both a solid phase blot overlay assay and a solution-binding assay. The roadblock-binding domain on the intermediate chain was mapped to an approximately 72 residue region. The binding domain is downstream of each of the two alternative splice sites in the intermediate chains. This location is consistent with the finding that both roadblock-1 and roadblock-2 show no binding specificity for a single IC74-1 or IC74-2 intermediate chain isoform. In addition, this roadblock-binding domain is significantly downstream from both the Tctex1- and LC8-binding sites, supporting the hypothesis that multiple light chain family members can bind to the same intermediate chain.
Filamentous phage morphogenetic signal sequence and orientation of DNA in the virion and gene-V protein complex

The circular single-stranded viral DNA (ssDNA) of filamentous phage is oriented in the virus with a hairpin forming sequence called mos at the leading end of the virion-the end that emerges from the cell first. In the experiments that originally defined mos it was also found to enhance virion production 100-fold, though in other circumstances it has no such effect. Using a new electron-microscopic method, we have ascertained the orientation of ssDNA in phage having mutations involving mos and other viral functions, and also in the intracellular precursor to the virion-a rod-shaped complex between the ssDNA and the phage-encoded gene-V protein, pV. The results show (1) that the ssDNA is oriented in the complex as in the virion, with mos at one end; (2) that orientation is maintained even if assembly is not mediated by the complex; (3) that orientation is manifested in polyphage--abnormal particles in which many unit-length ssDNA molecules are sheathed in a single, extremely long capsid; (4) that orientation is imposed by mos itself (or something very nearby) since it disappears in a mos deletion; and (5) that a 229-base segment including the minus strand of mos is also effective at imposing orientation. On the basis of our findings, we speculate that mos determines orientation in two stages, one imposing an axis on the ssDNA loop during formation of the pV/ssDNA complex, the other imposing a direction on the loop during initiation of particle assembly. The sequence requirements for the two stages may be different.
A formal, stereocontrolled synthesis of (±) estrone employing the trimethylsilylcyanohydrin cope rearrangement

Abstract A new synthetic approach to estrone is discussed which employs control of stereochemistry via the Cope rearrangements.
Effect of a limited-enforcement intelligent tutoring system in dermatopathology on student errors, goals and solution paths

Objectives: Determine effects of a limited-enforcement intelligent tutoring system in dermatopathology on student errors, goals and solution paths. Determine if limited enforcement in a medical tutoring system inhibits students from learning the optimal and most efficient solution path. Describe the type of deviations from the optimal solution path that occur during tutoring, and how these deviations change over time. Determine if the size of the problem-space (domain scope), has an effect on learning gains when using a tutor with limited enforcement. Methods: Analyzed data mined from 44 pathology residents using SlideTutor-a Medical Intelligent Tutoring System in Dermatopathology that teaches histopathologic diagnosis and reporting skills based on commonly used diagnostic algorithms. Two subdomains were included in the study representing sub-algorithms of different sizes and complexities. Effects of the tutoring system on student errors, goal states and solution paths were determined. Results: Students gradually increase the frequency of steps that match the tutoring system's expectation of expert performance. Frequency of errors gradually declines in all categories of error significance. Student performance frequently differs from the tutor-defined optimal path. However, as students continue to be tutored, they approach the optimal solution path. Performance in both subdomains was similar for both errors and goal differences. However, the rate at which students progress toward the optimal solution path differs between the two domains. Tutoring in superficial perivascular dermatitis, the larger and more complex domain was associated with a slower rate of approximation towards the optimal solution path. Conclusions: Students benefit from a limited-enforcement tutoring system that leverages diagnostic algorithms but does not prevent alternative strategies. Even with limited enforcement, students converge toward the optimal solution path.
NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP.

In myometrial strips from near-term non-labouring human uterus, addition of oxytocin (OT) evoked dose-dependent (10 – 3000 nM) phasic contractions that were antagonized by atosiban (1 μM) and relaxed by addition of the nitric oxide donor S-nitroso L-cysteine (Cys-NO). In near-term labouring myometrium, however, addition of OT was ineffective at raising additional tone. In both labouring and non-labouring tissue, Cys-NO mediated relaxation of spontaneous or OT-induced contractions (IC50=1 μM) was unaffected by prior addition of the guanylyl cyclase (GC) inhibitors ODQ (1H-[1,2,4]oxadiazolo[4,3,-α]quinoxalin-1-one; 1 μM), or methylene blue (MB; 10 μM). Elevation of intracellular cyclic GMP accompanying 30 μM Cys-NO addition in non-labouring tissue (7.5 fold) or in labouring tissues (2.5 fold) was completely blocked in tissues that had been pre-treated with ODQ or MB. Charybdotoxin (ChTx), iberiotoxin (IbTx) and kaliotoxin (KalTx) all shifted the Cys-NO inhibition curve to the right and reduced the degree of relaxation produced by maximal Cys-NO treatment (100 μM in non-labouring tissue; in labouring tissue, KalTx prevented Cys-NO mediated relaxation in both stimulated and unstimulated tissue. Addition of the NO-donor S-nitroso N-acetyl penicillamine (SNAP) produced a dose-dependent relaxation of pregnant myometrium while 3-morpholinosyndonimine (SIN-1) did not. The failure of SIN-1 to relax OT-induced contractions was not due to a failure of the donor to stimulate myometrial GC. We demonstrate that despite the ability of NO to stimulate myometrial GC in pregnant uterine muscle, relaxations are independent of cyclic GMP action. Effects of K+-channel inhibitors suggests that NO-induced relaxation in human uterine smooth muscle may be subserved by direct or indirect activation of one or more calcium-activated K+-channels. British Journal of Pharmacology (2001) 134, 206–214; doi:10.1038/sj.bjp.0704226
Ortho and parahydrogen in interstellar material

The ortho/para molecular hydrogen ratio in the interstellar medium is considered. It is shown that the ortho/para ratio will be 3:1 in practically all chemical reactions, even at relatively low temperatures. Two examples of exothermic processes that will result in the formation of a 3:1 ortho:para ratio, corresponding to a high-temperature equilibrium, are examined: H2 formation via three-body or surface recombination and catalytic recombination involving electrons and H(-) ions. Gas-phase scrambling ion reactions are also discussed, and it is suggested that virtually all the H2 equilibrated via scrambling reactions involving H(+) and H3(+) ions should exist as parahydrogen in the J ? 0 quantum state. Arguments are given that deuterium cannot interfere with the long scrambling chain that results in parahydrogen formation.
Quantitative determination of paraquat in meconium by sodium borohydride-nickel chloride chemical reduction and gas chromatography/mass spectrometry (GC/MS)

The objective of this study was to develop a procedure for the GC/MS assay of paraquat in meconium as a biomarker of fetal exposure to paraquat. The method involved a sodium borohydride-nickel chloride reduction procedure, liquid-liquid extraction of the perhydrogenated product, concentration, and GC/MS assay. The method demonstrated good overall recovery (102.56%) with %CV (inter-assay) of less than 13%, and a limit of detection of 0.0156microg/g. Analysis of meconium samples from a study population in the Philippines (n=70) showed a 2.8% prevalence of fetal exposure to paraquat.
Detection of CO2 leakage by eddy covariance during the ZERT project’s CO2 release experiments

Carbon dioxide was released from a shallow horizontal well for ten days at 0.1 t d−1 (Release 1) and for seven days at 0.3 t d−1 (Release 2) during Summer 2007. Net CO2 fluxes (Fc) were continuously monitored by eddy covariance during the summers of 2006 and 2007. To improve leakage detection ability, we removed ecosystem fluxes correlated with changes in soil temperature and light intensity from Fc. The Release 2 leakage signal was enhanced in a time series of upper 95th percentile residual Fc, while the Release 1 signal fell within the variability of unmodeled processes.
Functional Cell Mediated Lympholysis: II. Genetics1,2

The diminished response to secondary stimulation of human lymphocytes primed in bi-directional (BD) mixed lymphocyte culture (MLC) has been demonstrated to be due to cytotoxic destruction of the responder cells by the numerically superior allogeneic stimulating cell population. This phenomenon is called Functional Cell Mediated Lympholysis (F-CML). Matching for HLA-A and B, HLA-DR or for MLC non-responsiveness (HLA-D) in unrelated pairs does not ablate F-CML, indicating that none of these loci serve as the exclusive target for this activity. One locus appears to be centromeric from HLA-A in an A/B recombinant family and a B/D recombinant family demonstrates a target centromeric from HLA-B. A special family with homozygous for HLA-A, B and D provided evidence for an additional locus other than HLA-A, B or D. Thus, genetic studies indicate that at least one target antigen of F-CML may be coded for by a locus that is centromeric from HLA-B and which may be distinct from HLA-D or DR.
The DNA-binding ability of HIVEP3/KRC decreases upon activation of V(D)J recombination

Somatic V(D)J recombination of the immune receptor genes is mediated by the recombination signal sequence (RSS) and the recombination-activating genes RAG1 and RAG2. Previously, proteins binding specifically to the RSS have been characterized in nuclear extracts of T and B lymphocytes. Further elucidation of the role of those RSS-binding proteins in V(D)J recombination, however, has been hampered by the fact that their identities have not been established. Here, we show that the major RSS-binding protein present in the nuclear extracts of B lymphocytes is an M r 135,000 species. Notably, its affinity for the RSS decreased when RAG1 and RAG2 were induced. In immunoblot analyses and gel supershift assays, we showed that KRC antisera react with the M r 135,000 RSS-binding protein. We previously cloned KRC from a thymocyte expression library using 32P-RSS as a ligand and showed that KRC fusion proteins bind specifically to the RSS and to the κB enhancer motif. The lymphoid expression and DNA-binding characteristics suggest that KRC may be involved in lymphocyte development.
The role of vaginal hysterectomy in the treatment of endometrial cancer.

Objective The objective of the study was to evaluate the role of vaginal hysterectomy in the treatment of endometrial cancer. Study Design Medical records were retrospectively reviewed for patients undergoing vaginal hysterectomy for endometrial cancer at the University of South Florida. The medical data were reviewed for medical comorbidities, preoperative and postoperative diagnosis, hospital course, surgical and postoperative complications, adjuvant treatments, and follow-up. Results Sixty-three women underwent vaginal hysterectomy for endometrial carcinoma between May 1987-September 2006. Mean age was 62.1 years and body mass index [BMI] was 40; 73% of patients were obese (BMI ≥30 or greater). Medical comorbidities included hypertension (76.2%), cardiovascular disease (34.9%), diabetes mellitus (31.7%), and pulmonary disease (28.6%). Eighty-one percent of patients had at least 2 and 55.5% had 3 or more comorbid surgical risk factors. Postoperative complications included infection (4.8%), blood transfusion (11.1%), and prolonged hospital stay (6.3%). Of patients with intrauterine pathology, 89.5% had endometrioid adenocarcinoma. Conclusion Vaginal hysterectomy may be appropriate treatment of endometrial carcinoma for select patients.
Semiconductor optoelectronic devices based on interference-induced carrier modulation

Transport of carriers generated under the influence of optically induced spatial modulation is investigated theoretically and experimentally in semiconductors. The resulting transient photocurrent is studied under varied degrees of optical interference. It is shown that strong anisotropic properties describable by an interaction tensor are suitable for device applications. Device properties are characterized and are seen to be useful for the processing of optical signals with picosecond and femtosecond features. Accurate modeling demonstrates the formation of strong nodal fields whose effect is detrimental to the achievement of high current extinction. The manifestation of interference-induced carrier modulation is demonstrated with high-contrast recordings of autocorrelation of picosecond laser pulses in homogeneous materials. In other experiments, monitoring of laser coherence ranging from picoseconds to tens of femtoseconds is shown. >
The electronic structure of small clusters of sodium

Abstract The electronic structures of small clusters of sodium atoms are calculated using the semi-empirical diatomics-in-molecules method.
Broken windows and low adolescent prosociality: not cause and consequence, but co-symptoms of low collective efficacy.

The current study presents a case in which adolescent prosociality is lower in neighborhoods with greater physical disorder. Current theory provides two interpretations for such a pattern: (1) that disorder signals a threatening environment and discourages prosociality (“broken windows theory”); (2) that disorder and low prosociality are both symptoms of a weak community (i.e., low collective efficacy). A survey of 642 students from a small American city was combined with an assessment of the built environment to evaluate these two interpretations. Students were nested in 59 Census block groups. Multilevel models demonstrated that collective efficacy best explained variation in prosociality between neighborhoods, and that perceived collective efficacy best explained variation within neighborhoods. Objective and perceived disorder had no significant relationship with prosociality in these models, suggesting that disorder is not directly responsible for cross-neighborhood variation in prosociality. The paper discusses the implications for place-based interventions promoting prosociality. The results also emphasize the need for measures of social processes (e.g., collective efficacy) when evaluating “broken windows” hypotheses.
Neonatal lead exposure impairs development of rodent barrel field cortex

Childhood exposure to low-level lead can permanently reduce intelligence, but the neurobiologic mechanism for this effect is unknown. We examined the impact of lead exposure on the development of cortical columns, using the rodent barrel field as a model. In all areas of mammalian neocortex, cortical columns constitute a fundamental structural unit subserving information processing. Barrel field cortex contains columnar processing units with distinct clusters of layer IV neurons that receive sensory input from individual whiskers. In this study, rat pups were exposed to 0, 0.2, 1, 1.5, or 2 g/liter lead acetate in their dam's drinking water from birth through postnatal day 10. This treatment, which coincides with the development of segregated columns in the barrel field, produced blood lead concentrations from 1 to 31 μg/dl. On postnatal day 10, the area of the barrel field and of individual barrels was measured. A dose-related reduction in barrel field area was observed (Pearson correlation = −0.740; P < 0.001); mean barrel field area in the highest exposure group was decreased 12% versus controls. Individual barrels in the physiologically more active caudoventral group were affected preferentially. Total cortical area measured in the same sections was not altered significantly by lead exposure. These data support the hypothesis that lead exposure may impair the development of columnar processing units in immature neocortex. We demonstrate that low levels of blood lead, in the range seen in many impoverished inner-city children, cause structural alterations in a neocortical somatosensory map.