cssi/SciSciGPT-SciSciNet huggingface dataset:
Application of Stopped-flow Kinetics Methods to Investigate the Mechanism of Action of a DNA Repair Protein

Transient kinetic analysis is indispensable for understanding the workings of biological macromolecules, since this approach yields mechanistic information including active site concentrations and intrinsic rate constants that govern macromolecular function. In case of enzymes, for example, transient or pre-steady state measurements identify and characterize individual events in the reaction pathway, whereas steady state measurements only yield overall catalytic efficiency and specificity. Individual events such as protein-protein or protein-ligand interactions and rate-limiting conformational changes often occur in the millisecond timescale, and can be measured directly by stopped-flow and chemical-quench flow methods. Given an optical signal such as fluorescence, stopped-flow serves as a powerful and accessible tool for monitoring reaction progress from substrate binding to product release and catalytic turnover(1,2). Here, we report application of stopped-flow kinetics to probe the mechanism of action of Msh2-Msh6, a eukaryotic DNA repair protein that recognizes base-pair mismatches and insertion/deletion loops in DNA and signals mismatch repair (MMR)(3-5). In doing so, Msh2-Msh6 increases the accuracy of DNA replication by three orders of magnitude (error frequency decreases from approximately 10(-6) to 10(-9) bases), and thus helps preserve genomic integrity. Not surprisingly, defective human Msh2-Msh6 function is associated with hereditary non-polyposis colon cancer and other sporadic cancers(6-8). In order to understand the mechanism of action of this critical DNA metabolic protein, we are probing the dynamics of Msh2-Msh6 interaction with mismatched DNA as well as the ATPase activity that fuels its actions in MMR. DNA binding is measured by rapidly mixing Msh2-Msh6 with DNA containing a 2-aminopurine (2-Ap) fluorophore adjacent to a G:T mismatch and monitoring the resulting increase in 2-aminopurine fluorescence in real time. DNA dissociation is measured by mixing pre-formed Msh2-Msh6 G:T(2-Ap) mismatch complex with unlabeled trap DNA and monitoring decrease in fluorescence over time(9). Pre-steady state ATPase kinetics are measured by the change in fluorescence of 7-diethylamino-3-((((2-maleimidyl)ethyl)amino)carbonyl) coumarin)-labeled Phosphate Binding Protein (MDCC-PBP) on binding phosphate (Pi) released by Msh2-Msh6 following ATP hydrolysis(9,10). The data reveal rapid binding of Msh2-Msh6 to a G:T mismatch and formation of a long-lived Msh2-Msh6 G:T complex, which in turn results in suppression of ATP hydrolysis and stabilization of the protein in an ATP-bound form. The reaction kinetics provide clear support for the hypothesis that ATP-bound Msh2-Msh6 signals DNA repair on binding a mismatched base pair in the double helix. F
The oxidation of Ni-20 wt. % Cr-2ThO2

The oxidation of TD NiCr (Ni-20 wt. % Cr-2ThO2) has been investigated between 900 and 1200°C, and the oxidation behavior is compared with Ni-30 wt. % Cr and Co-35 wt. % Cr alloys. All alloys develop Cr2O3 scales but the weight changes obtained for the NiCr and CoCr alloys show an increase with time whereas above 1000° C the TD NiC shows a progressive loss in weight from the evaporation of CrO3 from the scale, and the reaction products appear to be formed mainly at the alloy-scale interface. However, no mechanism for its formation has been established.
The Role of Ultrasonography in the Evaluation of Diffuse Liver Disease

The use of ultrasonography (US) to detect and characterize diffuse liver disease can be challenging, but remains a useful tool for the diagnosis and management of many diffuse parenchymal liver diseases such as cirrhosis, steatosis, and malignancies. Newer techniques, such as elastography, are proving useful for earlier detection of hepatic parenchymal changes. The role of US in the assessment of possible biliary ductal obstruction is well established, and Doppler US may provide additional physiologic information regarding hepatic blood flow. US plays a central role in target selection and guidance of percutaneous liver biopsies.
Moral distress in medical education and training.

Moral distress is the experience of cognitive-emotional dissonance that arises when one feels compelled to act contrary to one’s moral requirements. Moral distress is common, but under-recognized in medical education and training, and this relative inattention may undermine educators’ efforts to promote empathy, ethical practice, and professionalism. Moral distress should be recognized as a feature of the clinical landscape, and addressed in conjunction with the related concerns of negative role modeling and the goals and efficacy of medical ethics curricula.
A numerical elimination method for polynomial computations

A numerical elimination method is presented in this paper for floating-point computation in polynomial algebra. The method is designed to calculate one or more polynomials in an elimination ideal by a sequence of matrix rank/kernel computation. The method is reliable in numerical computation with verifiable stability and a sensitivity measurement. Computational experiment shows that the method possesses significant advantages over classical resultant computation in numerical stability and in producing eliminant polynomials with lower degrees and fewer extraneous factors. The elimination algorithm combined with an approximate GCD finder appears to be effective in solving polynomial systems for positive dimensional solutions.
Anxieties in Children: Dysfunctional Interactional Patterns and an Effective Systemic/Integrative Treatment

After defining the various types of childhood anxieties as “dysfunctional fears,” this article analyzes which interactional patterns and typical beliefs, in a child’s relationships with significant others/adults, appear in relation to the problem-behavior of children who suffer from anxiety. The research conducted in Argentina suggests that children’s fears have a psychosocial nature and that it is possible to obtain a “relational diagnosis” in order to select an appropriate and effective treatment. Finally, and in support of this, a study conducted in Argentina about the effectiveness of a systemic/integrative treatment, in order to change the maintenance-problem system, is included.
Maternal Depletion of Piwi, a Component of the RNAi System, Impacts Heterochromatin Formation in Drosophila

A persistent question in epigenetics is how heterochromatin is targeted for assembly at specific domains, and how that chromatin state is faithfully transmitted. Stable heterochromatin is necessary to silence transposable elements (TEs) and maintain genome integrity. Both the RNAi system and heterochromatin components HP1 (Swi6) and H3K9me2/3 are required for initial establishment of heterochromatin structures in S. pombe. Here we utilize both loss of function alleles and the newly developed Drosophila melanogaster transgenic shRNA lines to deplete proteins of interest at specific development stages to dissect their roles in heterochromatin assembly in early zygotes and in maintenance of the silencing chromatin state during development. Using reporters subject to Position Effect Variegation (PEV), we find that depletion of key proteins in the early embryo can lead to loss of silencing assayed at adult stages. The piRNA component Piwi is required in the early embryo for reporter silencing in non-gonadal somatic cells, but knock-down during larval stages has no impact. This implies that Piwi is involved in targeting HP1a when heterochromatin is established at the late blastoderm stage and possibly also during embryogenesis, but that the silent chromatin state created is transmitted through cell division independent of the piRNA system. In contrast, heterochromatin structural protein HP1a is required for both initial heterochromatin assembly and the following mitotic inheritance. HP1a profiles in piwi mutant animals confirm that Piwi depletion leads to decreased HP1a levels in pericentric heterochromatin, particularly in TEs. The results suggest that the major role of the piRNA system in assembly of heterochromatin in non-gonadal somatic cells occurs in the early embryo during heterochromatin formation, and further demonstrate that failure of heterochromatin formation in the early embryo impacts the phenotype of the adult.
Internal Distribution and Milk Secretion of Polonium-210 After Oral Administration to a Lactating Goat

Abstract A study was made of the distribution of 210 PoO 2 in a lactating goat after a single acute oral administration of 210 P o O 2 . The transfer coefficient (per cent intake per liter of milk) was estimated to be 0.18. This was much higher than the 0.029 reported earlier for PoCl 4 in a lactatifing cow. The concentrations in the organs and selected tissues at 20 days post-ingestion are reported. Highest concentrations in decreasing order were found in hair, kidney, bile, and liver. This experiment was a pilot study for evaluating the hazard which might result from the release of 210 Po from a radioisotope electrical generator designed for space missions.
Relationship between dobutamine-induced regional wall motion abnormalities and coronary flow reserve in heart transplant patients without angiographic coronary artery disease

Abstract Background: Regional wall motion abnormalities (RWMA) demonstrated by dobutamine stress echocardiography (DSE) are a sensitive predictor of coronary artery disease (CAD) in heart transplant recipients. However, RWMA have been shown to occur in patients with angiographically "normal" coronary arteries. The reasons for this are unknown. We sought to determine if abnormal responses to dobutamine in this setting can be explained by microvascular dysfunction in the coronary circulation as detected by decreased coronary flow reserve (CFR). Methods: Twenty-six consecutive heart transplant patients were evaluated prospectively. Five of 26 (19.2%) patients (seven coronary arteries) were excluded for poor acoustic windows on echocardiography. Another three patients were excluded for angiographically apparent CAD. CFR and wall motion score index (WMSI) derived from DSE were measured in the remaining 18 patients and formed the basis of this study. Patients were divided into two groups based on the absence (Group 1; n=5) or presence (Group 2; n=13) of RWMA on DSE. CFR was measured with the Doppler Flo-Wire in 34 coronary arteries (18 patients) and correlated with WMSI. Results: In Group 1 patients, CFR measured in eight coronary arteries was normal (2.6 ± 0.4). In Group 2 patients, CFR measured in 26 coronary arteries also was normal (2.2 ± 0.6; p = NS vs Group 1). In Group 2, CFR was measured in 20 of 24 vessels assigned to segments that developed RWMA. Only 6 of these 20 vessels (30%) had abnormal CFR. Overall, there was no correlation between decreased CFR and the presence of RWMA induced by dobutamine. Conclusions: These data suggest that, in cardiac transplant patients with angiographically "normal" coronary arteries, inducible wall motion abnormalities during DSE cannot be attributed to coronary microvascular dysfunction as manifested by decreased CFR.
Dementia and the Default Mode

Changes in regional activity levels and network connectivity occur across the lifespan within the default mode network (DMN) of resting brain function. Changes with age are noted in most components of the DMN, especially in medial frontal/anterior cingulate and posterior cingulate/precuneus regions. Individuals with age-related disease such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD) demonstrate additional default-related changes particularly in posterior cingulate/precuneus and hippocampal regions. As these regions are areas of known pathologic change in both normal aging and age-related disease, examining DMN activity may allow future studies to more fully assess the relationship between pathology and function in these regions. The ability to form this structure-function link could allow us to determine critical factors involved in the decline or preservation of function in the presence of age-related neuropathology.
On the short-run effects of labor market reforms☆

Abstract While several countries have recognized the need of introducing flexibility to their labor markets, there are different ways of doing so. Using a small open economy with tenure-dependent separation taxes, this paper compares introducing a full reform with two partial alternatives: (1) the introduction of temporary contracts, and (2) the elimination of separation costs from all new hires while freezing them on the workers that were hired prior to the reform. The first alternative can achieve a first-best long run outcome but leads to a sharp initial recession. The second alternative generates a similar long run outcome but avoids the recessionary adjustment.
Replace Band Theory in Introductory Chemistry

Band theory is less helpful than the Mott-Hubbard theory of combined electron excitation and delocalization for explaining conductivity and semiconductivity for introductory students.
In situ heating to improve adhesion for parylene-on-parylene deposition

A new technique of using “in-situ heating” to enhance adhesion for parylene-on-parylene deposition is reported. This method is compared with existing physical or chemical adhesion-enhancing methods and the results show clear advantages of this new technique. The physics is believed to be that the mobility of deposition-involved molecules (including the substrate parylene polymer chains and adsorbed monomers during deposition) is enhanced when deposition temperature rises, especially above the glass transition temperature of the substrate parylene. Each sample is patterned and then soaked in 0.9% saline at 90°C, and the undercut between two parylene layers due to the attack from saline during the soaking test could be observed. The undercut rate is measured to quantify the adhesion strength.
When the neutral's dilemma hits: Routine problems, and the not‐so‐routine repercussions, of common arbitration conflicts

Routine arbitration matters breed potential conflicts for every arbitrator. In the second of two articles, Judith P. Meyer, of Haverford, Pa., presents scenarios that illustrate ethical situations. They provide guidance not only for neutrals, but also for parties dealing with arbitration processes and the problems that arise
Egg-white-specific IgA and IgA2 antibodies in egg-allergic children: is there a role in tolerance induction?

Background Decreased serum food-specific IgA antibodies have been associated with allergic disease in cross-sectional, case–control studies. The purpose of this study was to prospectively compare egg-white-(EW)-specific IgA and IgA2 levels between egg-allergic children and children tolerating egg. Methods Seventeen egg-allergic children were followed prospectively. Total IgA, EW-specific IgA, and EW-specific IgA2 levels were measured in their sera with a sensitive ELISA. As negative controls were used children with no previous history of egg allergy. Egg-allergic children with or without concomitant milk allergy were evaluated as additional controls with measurement of casein-specific IgA. Results After 2.5 ± 0.9 yrs, nine out of the 17 allergic children became tolerant and eight remained allergic to baked egg. Baseline EW-specific IgA2 levels were significantly lower in the egg-allergic subjects (median 23.9 ng/ml) compared with the negative control subjects (99.4 ng/ml) and increased significantly by 28% over the study time period in eight out of the nine allergic children that became tolerant to baked egg. There was no significant change over time in EW-specific IgA in any of the study groups. Non-milk-allergic subjects with concomitant egg allergy had almost threefold higher casein-specific IgA levels than the milk- and egg-allergic subjects (p = 0.025). Conclusions These results suggest a potential role for allergen-specific IgA2 antibodies in the induction of food tolerance. Furthermore, they support the hypothesis that immature or impaired production of allergen-specific IgA2 may be associated with the pathophysiology of food allergy, a defect that seems to be selective for the culprit allergen.
Implementing Cleaner Production Programmes in Changzhou and Nantong, Jiangsu Province

Cleaner Production (CP) has been advocated worldwide as a strategy for companies to obtain environmental and economic benefits simultaneously. This analysis of how city-level CP programmes were implemented in Changzhou and Nantong (Jiangsu Province, China) finds that both cities failed to meet the Province's targets to implement CP at all large- and medium-sized companies by the end of 2000. Ineffective vertical control, weak inter-agency co-ordination, and lack of alignment between CP requirements and the core missions and operating procedures of implementing agencies have impeded CP implementation in the two cities. The relatively few successful CP outcomes at companies are based on the professionalism and skills of individual implementing agents. However, successes that rely exclusively on individual agents may not last, and thus institutional changes will be needed if the government's CP programmes are to lead to broader CP adoption.
Role of polyamines in the synthesis of prolactin-regulated growth factors by experimental breast cancer in culture.

The present experiments were designed to test whether polyamines play an essential role in the synthesis of growth factors induced by ovine prolactin (oPRL), using the N-nitrosomethylurea (NMU)-induced rat mammary tumor cultured in the soft agar clonogenic assay. Conditioned media (CM) obtained from tumors treated with oPRL and the polyamine biosynthesis inhibitor α-difluoromethylornithine (DFMO) (1 mM) no longer exerted the colony-stimulating effect which was observed with oPRL-CM. Such growth-promoting activity was restored with conditioned media obtained from tumors treated with oPRL, DFMO, and increasing concentrations of spermidine from 1 to 500µM. The colony-stimulating effect of the CM employed could not be accounted for by the contaminating presence in the media of oPRL, DFMO, and polyamines. These results indicate that in our system polyamines play an important role in the synthesis of oPRL-regulated growth factors.
An introduction to buddhism for the cognitive-behavioral therapist

Basic concepts in Buddhism are presented for cognitive-behavioral therapists. Buddhist theoretical causes of suffering are presented as extensions of cognitive assumptions of selfhood. The essentialist position is contrasted to the Buddhist perspectives of dialectics and interdependence. The focus on impermanence in Buddhist thought is presented. The synergistic relationship between compassion and mindfulness is examined. Compassion as both behavioral alternative to essentialism as well as precursor to mindfulness is discussed. Additionally, mindfulness meditation from the Buddhist perspective is presented.
The Absence of Extracellular Calcium Potentiates the Killing of Cultured Hepatocytes by Aluminum Maltolate

Dose- and time-dependent killing of cultured rat hepatocytes was produced by aluminum maltolate (AlM), a neutral, water-soluble complex of aluminum 3-hydroxy-2-methyl-4H-pyran-4-one. Treatment with 10 mM AlM for 1 h killed 50% or more of the cells within 3 h. Removal of calcium from the culture medium or treatment with calcium channel blockers (verapamil, nifedipine, diltiazem) potentiated the cell killing. By contrast, inhibition by thapsigargin of the sequestration of intracellular calcium by the endoplasmic reticulum reduced the toxicity of AlM. In turn, activation of protein kinase C with 12-O-tetradecanoylphorbol 13-acetate or activation of protein kinase A with 8-[4-chlorophenyl-thio]adenosine 3',5'-cyclic monophosphate also reduced the toxicity of AlM. By contrast, inhibition of protein kinase activity by staurosporine potentiated the cell killing. Staurosporine, however, did not reverse the protection afforded by thapsigargin. Hepatocytes treated with AlM for 1 h were rescued by adding deferoxamine as late as 90 min following the removal of AlM, whereas pretreatment for 1 h with deferoxamine did not prevent the toxicity of AlM. ATP depletion did not precede loss of viability. Pharmacologic probes excluded oxidative stress as a mechanism of lethal injury by AlM, and inhibition of protein synthesis by cycloheximide did not protect the hepatocytes, thereby excluding activation of a cell death program. These data define a new model in which aluminum kills liver cells by a mechanisms distinct from previously recognized pathways of lethal cell injury. It is hypothesized that aluminum binds to cytoskeletal proteins intimately associated with the plasma membrane. This interaction eventually disrupts the permeability barrier function of the cell membrane, an event that heralds the death of the hepatocyte. The intracellular calcium ion concentration and protein phosphorylation may modify the interaction of aluminum with its critical targets. Alternatively, aluminum may inhibit the phosphorylation of cytoskeletal elements, thereby interfering with their function.
Choosing and Using Videotexts

: Technological developments such as the videocassette recorder/player have facilitated the use of videotaped foreign-language materials in the classroom and such materials are increasingly available to language teachers from a number of sources. If, however, students view foreign-language broadcasts passively, little learning will take place. By carefully selecting and manipulating programs, the teacher can encourage more active viewing and at the same time foster comprehension by serving as a mediator between the learners' imperfect linguistic ability and limited cultural knowledge and the sophisticated videotext. The form provided and discussed in this article will enable the teacher/evaluator to motivate students and to accomplish course goals through a more effective selection and use of videotexts.
Zebrafish Heart as a Model System to Study Structure-Function Relationships

The zebrafish (Danio rerio) has been intensively used in cardiovascular biology mainly for study of heart development. This is a promising cost-effective model system to study structure-function due to the ease of genetic manipulations. However, the basic contractile physiology of zebrafish heart is still incompletely understood. Moreover, the applicability of the fish heart as a model system for study mammalian heart contractility needs to be established.The aim of our work was to establish the zebrafish as a model system to approach structure-function cardiac myocyte biology. Accordingly, we performed experiments with a focus on the Frank-Starling mechanisms at two levels: cellular (intact cells) and myofilament level (permeabilized cells). In single cell experiments we were able to attach a single enzymatically isolated zebrafish ventricular myocytes to myotak coated carbon probes and measure force, intracellular calcium, cell length, and sarcomere length in electrically paced cells over a range (20%) of cell lengths. In skinned cell experiments, we used a single myofibril technique to measure activation/relaxation kinetics and force-Ca2+ relations at short and long sarcomere lengths (2.2 and 2.4 um). Zebrafish intact myocytes displayed robust length induced increase in twitch force in the absence of calcium transient alteration. In skinned zebrafish muscle we found robust myofilament length dependent activation as well as characteristic activation/relaxation dynamics. We conclude that the zebrafish heart is an appropriate model to study cardiac structure-function relationships.
In situ Synthesis of Polyaniline in Poly(dimethylsiloxane) Networks Using an Inverse Emulsion Route

Polyaniline (PANI) was successfully prepared in end‐linked poly(dimethylsiloxane) (PDMS) networks using an inverse emulsion method. Its generation as dispersed particles was confirmed by UV/Vis spectrophotometry, Fourier transform infrared spectrometry, scanning electron microscopy and energy dispersive X‐ray analysis. The content, particle sizes and degrees of dispersion of the PANI particles were studied with regard to the pore dimensions of the PDMS networks, which had known cross‐link densities. Variables such as the nature of oxidants, solvent contents, solubility parameters, miscibility properties, and chemical interactions, etc. were also investigated, and a possible reaction mechanism was proposed.
Francis W. Reichelderfer: Part I: Aerologists and Airdevils

(1981). Francis W. Reichelderfer: Part I: Aerologists and Airdevils. Weatherwise: Vol. 34, No. 2, pp. 52-59.
Hydrothermal preparation of low-rank coal-water fuel slurries

Abstract Lignite and sub-bituminous coals are by nature high in inherent moisture and oxygen content and low in calorific heating value. As-mined low-rank coals when mixed with water generally produce slurries with low solids content and with heating values generally less than 11.6 MJ/kg. These same slurries are usually unstable and form hard-pack sediments quickly, unless chemical additives or constant agitation are added. The low heating value and poor storage and flow characteristics of these coal-water mixtures discourage the use of raw lignite and subbituminous coals for preparation of slurries for fuel purposes. Hydrothermal conditioning, in a water slurry at temperatures above 230 °C and pressures above 552 MPa, is one method that can significantly aid in the preparation of low-rank coal-water fuels. High-pressure hot-water thermal conditioning of lignites and sub-bituminous coals has been found not only to change both the chemical and physical characteristics of the coal but also to alter the coal slurry's rheological properties. These changes are controlled by process variables (i.e. temperature, residence time, particle size, and mode of processing) and result because of decarboxylation, mild pyrolysis, extraction, dehydration, and surface modification; all of which occur during hydrothermal treatment. Using the hydrothermal process, concentrated low-rank coal-water slurries with heating values approaching or exceeding the heating value of the as-mined coal have been achieved with pseudoplastic flow behavior and stability towards settling, without the use of additives. Pilot-scale studies using a 90-kg/hr process development unit (PDU) are currently under way to produce hydrothermally treated low-rank coal fuel slurries for combustion tests in a pilot-scale, slurry-fed test furnace.
Formal structure and pattern length in serial pattern learning by rats

When rats learn to anticipate a sequence of stimulus events, such as a serial pattern of different food quantities, they are sensitive to the rule-based formal structure relating the magnitude of successive stimuli. Earlier research has shown that if formal structure is simple (e.g., if a single “less than” rule relates the size of each successive quantity), patterns are learned faster than if formal structure is complex (e.g., if two or more rules such as “less than” and “greater than” relate successive pattern quantities). Two experiments tested the hypothesis that pattern length modulates the role of pattern complexity. We predicted that pattern length and pattern complexity interact in determining pattern difficulty. That is to say, long complex patterns should be learned more slowly than short complex patterns. However, long simple patterns should be learned faster than short simple patterns. In Experiment 1, rats ran a straight runway to receive repeated sequences of food quantities. The long-monotonic group received a formally simple 18-10-6-3-1-0 pattern, in which each number represents a quantity of food pellets. The long-nonmonotonic group received a formally complex 10-1-3-6-18-0 pattern. Similarly, the short-monotonic and short-nonmonotonic groups received 18-1-0 and 1-18-0 patterns. Pattern tracking—fast and slow running in anticipation of large and small quantities of food, respectively—was taken as an index of pattern learning. In Experiment 2, comparable patterns were used, but rats leverpressed in a discrete-trial procedure; response latencies measured pattern tracking. In both experiments, rats learned formally simple patterns faster than they did formally complex patterns. In Experiments 1 and 2, but less clearly in Experiment 2, the predicted interaction was obtained. The results support and generalize the idea that rats encode and use some representation of the formal rule structure of serial patterns as they learn them.
LXII.—On nomenclatorial and other problems in the systematics of the Coccoidea (Insecta: Homoptera)

(1937). LXII.—On nomenclatorial and other problems in the systematics of the Coccoidea (Insecta: Homoptera). Annals and Magazine of Natural History: Vol. 20, No. 119, pp. 525-530.
Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes

Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) offers safe and effective therapy for certain viral infections and could prove useful in the eradication of tumor cells. Whether or not the infused T cells persist for extended periods, retaining their ability to expand in response to antigenic stimulation, is not known. We now report long-term detection of gene-marked Epstein-Barr virus (EBV)-specific CTLs in immunocompromised patients at risk for the development of EBV lymphoproliferative disease. Infusions of CTLs not only restored cellular immune responses against EBV, but also established populations of CTL precursors that could respond to in vivo or ex vivo challenge with the virus for as long as 18 months. Our findings support wider use of antigen-specific CTLs in adoptive immunotherapy.
Sizing Nanoparticles by Means of Elliptically Polarized Scattered Light: A suggested method

Given the paucity of optical methods for sizing nanoparticles (those between 1 and 100 nm), more methods are needed if, as has been predicted, such particles have a bright future. Linearly polarized light is transformed into elliptically polarized light upon scattering by small spheres at 90°. The resulting circular polarization increases as the fifth power of particle diameter and the shift of the azimuth of the vibration ellipse from the vertical increases as the square if the particles are negligibly absorbing. Titanium dioxide spheres (in air) with diameters between 20 and 120 nm give circular polarizations between about 10−5 and 10−1 for incident light of wavelength 450 nm. The corresponding azimuth shifts (in radians) lie between about 10−2 and 1. These values are within reach of experimental techniques based on polarization modulation. Metallic spheres yield much larger circular polarizations and azimuth shifts (with signs opposite those for negligibly absorbing spheres), both of which increase approximately as the square of particle diameter.
Addition of Amino Acids to Further Stabilize Lyophilized Sucrose-Based Protein Formulations: I. Screening of 15 Amino Acids in Two Model Proteins

In small amounts, the low molecular weight excipients-sorbitol and glycerol-have been shown to stabilize lyophilized sucrose-based protein formulations. The purpose of this study was to explore the use of amino acids as low molecular weight excipients to similarly enhance stability. Model proteins, recombinant human serum albumin and α-chymotrypsin, were formulated with sucrose in combination with one of 15 amino acid additives. Each formulation was lyophilized at 1:1:0.3 (w/w) protein-sucrose-amino acid. Percent total soluble aggregate was measured by size-exclusion chromatography before and after storage at 50 °C for 2 months. Classical thought might suggest that the addition of the amino acids to the sucrose-protein formulations would be destabilizing because of a decrease in the system's glass transition temperature. However, significant improvement in storage stability was observed for almost all formulations at the ratio of amino acid used. Weak correlations were found between the extent of stabilization and both amino acid molar volume and side-chain charge. The addition of amino acids at a modest level generally improves storage stability, often by more than a 50% increase, for lyophilized sucrose-based protein formulations.
Military Leaders and Foreign Policy-Making

A survey of the literature of the last decade in the burgeoning interdisciplinary field which has come to be known—rather imprecisely—as civil-military relations, reveals a large number of descriptive and prescriptive, operational and theoretical studies, but little unity of focus or method. The interested shopper finds himself in a veritable department store filled with a wide assortment—including those in the bargain basement. Spurred on by wartime experiences and Cold War exigencies, historians and social scientists, physical scientists and journalists—above all in the United States—have covered reams of paper with discussions of the relationship between arms and men, war and peace, strategy and policy, defense and diplomacy. Displaying a great variety of analytical depth, breadth and sophistication, some of these studies have advanced our knowledge of civil-military relations—particularly in contemporary America—while others have failed to survive changes in international politics and weapons technology. Some writers, both of conservative and liberal orientation, have focused on the “appropriate” role for the military in state and society; others have sought to remain detached from such normative questions in order to concentrate on micro-descriptive phenomenal studies or more or less abstract macro-analytical theoretical models. Between the earth-bound descriptive and prescriptive studies on the one hand, and the soaring theoretical efforts on the other has loomed a wide gap, all too familiar to students of international relations, comparative politics, and public administration, waiting to be bridged—if bridged it can be—by empirical theories of civil-military relationships.
An introduction to Salud America!: a research network to prevent obesity among Latino children.

e c c Calls for the prevention and control of childhood obesity in theU.S. can seem almost commonplace these days. Media outlets regularly sound alarm over new statistics showing risks to children’s health from being overweight or obese. As a response, some states and cities are regulating or considering regulating sodas and sugary snacks. Restaurants are labeling menus with nutrition information, and in some cases are making changes in what they are offering. Neighborhood stores are making fruits and vegetables more accessible. And First Lady Michelle Obama launched her massive “Let’s Move!” national initiative dedicated to solving the challenge of childhood obesity within a generation. Unfortunately, the limited amount of data available on U.S. Latino children and communities makes it difficult to identify effective strategies for addressing this epidemic. It is within this backdrop that Salud America! investigators were charged with identifying the best approaches for addressing the obesity epidemic within U.S. Latino communities. Addressing the obesity epidemic in the U.S. Latino community is urgent. Latino boys are among the highest at risk (44% overweight or obese), and Latino girls follow closely behind (39%), compared with an average prevalence rate of 31%. As the percentage of Latinos among U.S. children aged 18 years or younger surges (rising from 17% of U.S. children in 1998 to 22% today and a projected 30% by 2025), the impact of these prevalence rates on the healthcare system cannot be ignored. Health risks associated with childhood obesity can reverberate into adulthood and include pulmonary, orthopedic, neurologic, gastroenterologic, endocrine, and cardiovascular problems, as well as other systemic issues. Long-term health consequences include cancer, diabetes, hypertension, sleep apnea, renal failure, and even death.
PET and PET/CT in Pediatric Oncology

18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET/computed tomography (CT) are becoming increasingly important imaging tools in the noninvasive evaluation and monitoring of children with known or suspected malignant diseases. In this review, we discuss the preparation of children undergoing PET studies and review radiation dosimetry and its implications for family and caregivers. We review the normal distribution of 18 F-fluorodeoxyglucose (FDG) in children, common variations of the normal distribution, and various artifacts that may arise. We show that most tumors in children accumulate and retain FDG, allowing high-quality images of their distribution and pathophysiology. We explore the use of FDG-PET in the study of children with the more common malignancies, such as brain neoplasms and lymphomas, and the less-common tumors, including neuroblastomas, bone and soft-tissue sarcomas, Wilms' tumors, and hepatoblastomas. For comparison, other PET tracers are included because they have been applied in pediatric oncology. Multiple multicenter trials are underway that use FDG-PET in the management of children with neoplastic disease; these studies should give us greater insight into the impact FDG-PET can make in their care. PET is emerging as an important diagnostic imaging tool in the evaluation of pediatric cancers. The recent advent of dual-modality PET-computed tomography (PET/CT) imaging systems has added unprecedented diagnostic capability by revealing the precise anatomical localization of metabolic information and metabolic characterization of normal and abnormal structures. The use of CT transmission scanning for attenuation correction has shortened the total acquisition time, which is an especially desirable attribute in pediatric imaging. Moreover, expansion of the regional distribution of the most common PET radiotracer, FDG, and the introduction of mobile PET units have greatly increased access to this powerful diagnostic imaging technology. Here, we review the clinical applications of PET and PET/CT in pediatric oncology. General considerations in patient preparation and radiation dosimetry will be discussed.
Male mice have increased thrombotic potential: sex differences in a mouse model of venous thrombosis.

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). In the United States (U.S.), the high morbidity and mortality rates make VTE a serious health concern. After heart disease and stroke, VTE is the most common vascular disease (1). In the U.S. alone, there is an estimated 900,000 people affected each year, with 300,000 deaths occurring annually (2–3). Venous thrombosis results from a combination of hypercoagulability conditions, blood flow stasis, and endothelial injury (4). Studies have provided evidence that there are sex-specific differences in pharmacokinetics, pharmacodynamics, and physiology for a number of drugs (5). In 1994 the FDA created the Office of Women's Health (OWH). This program has sought out research projects in sex differences in the areas of cardiovascular diseases, autoimmune diseases, and the safety and efficacy of FDA regulated products (6). In 1998, the FDA mandated that new drug applications include data on safety and effectiveness by sex (7). Recently, our laboratory developed a mouse electrolytic inferior vena cava (IVC) model (EIM) of DVT. This model consistently induces IVC thrombogenesis in the presence of continuous blood flow (8). This concept of continuous flow mimics the condition of a partial occlusive DVT in humans. The aim of this study was to determine if sex influences non-occlusive venous thrombogenesis in our animal model of the disease. Our hypothesis was that male and female mice have different inflammatory responses and physiological factors that would directly affect venous thrombogenesis.
Signaling mechanisms in tumor necrosis factor alpha-induced death of microvascular endothelial cells of the corpus luteum

The microvasculature of the corpus luteum (CL), which comprises greater than 50% of the total number of cells in the CL, is thought to be the first structure to undergo degeneration via apoptosis during luteolysis. These studies compared the apoptotic potential of various cytokines (tumor necrosis factor α, TNFα; interferon gamma, IFNγ; soluble Fas ligand, sFasL), a FAS activating antibody (FasAb), and the luteolytic hormone prostaglandin F2α (PGF2α) on CL-derived endothelial (CLENDO) cells. Neither sFasL, FasAb nor PGF2α had any effect on CLENDO cell viability. Utilizing morphological and biochemical parameters it was evident that TNFα and IFNγ initiated apoptosis in long-term cultures. However, TNFα was the most potent stimulus for CLENDO cell apoptosis at early time points. Unlike many other studies described in non-reproductive cell types, TNFα induced apoptosis of CLENDO cells occurs in the absence of inhibitors of protein synthesis. TNFα-induced death is typically associated with acute activation of distinct intracellular signaling pathways (e.g. MAPK and sphingomyelin pathways). Treatment with TNFα for 5–30 min activated MAPKs (ERK, p38, and JNK), and increased ceramide accumulation. Ceramide, a product of sphingomyelin hydrolysis, can serve as an upstream activator of members of the MAPK family independently in numerous cell types, and is a well-established pro-apoptotic second messenger. Like TNFα, treatment of CLENDO cells with exogenous ceramide significantly induced endothelial apoptosis. Ceramide also activated the JNK pathway, but had no effect on ERK and p38 MAPKs. Pretreatment of CLENDO cells with glutathione (GSH), an intracellular reducing agent and known inhibitor of reactive oxygen species (ROS) or TNFα-induced apoptosis, significantly attenuated TNFα-induced apoptosis. It is hypothesized that TNFα kills CLENDO cells through elevation of reactive oxygen species, and intracellular signals that promote apoptosis.
Molecular dynamics simulations and coupled nucleotide substitution experiments indicate the nature of A·A base pairing and a putative structure of the coralyne-induced homo-adenine duplex

Coralyne is an alkaloid drug that binds homo-adenine DNA (and RNA) oligonucleotides more tightly than it does Watson–Crick DNA. Hud’s laboratory has shown that poly(dA) in the presence of coralyne forms an anti-parallel duplex, however attempts to determine the structure by NMR spectroscopy and X-ray crystallography have been unsuccessful. Assuming adenine–adenine hydrogen bonding between the two poly(dA) strands, we constructed 40 hypothetical homo-(dA) anti-parallel duplexes and docked coralyne into the six most favorable duplex structures. The two most stable structures had trans glycosidic bonds, but distinct pairing geometries, i.e. either Watson–Crick Hoogsteen (transWH) or Watson–Crick Watson–Crick (transWW) with stability of transWH > transWW. To narrow down the possibilities, 7-deaza adenine base substitutions (dA→7) were engineered into homo-(dA) sequences. These substitutions significantly reduced the thermal stability of the coralyne-induced homo-(dA) structure. These experiments strongly suggest the involvement of N7 in the coralyne-induced A·A base pairs. Moreover, due to the differential effect on melting as a function of the location of the dA→7 mutations, these results are consistent with the N1–N7 base pairing of the transWH pairs. Together, the simulation and base substitution experiments predict that the coralyne-induced homo-(dA) duplex structure adopts the transWH geometry.
Principles of Qualitative Methodology for Psychology

Since positivistic methods are inadequate for cultural psychology, better methods are required that will reveal the cultural quality of psychological phenomena. Qualitative methods, developed by humanistically oriented social scientists, have the potential to serve this function. This chapter will articulate principles of qualitative methodology, and the next chapter will demonstrate how they can be employed to investigate cultural psychology.
High‐Temperature Thermophysical Properties of Uranium Monocarbide

Thermal conductivity (k), electrical resistivity (p), total hemispherical emittance (et), and normal spectral emittance (e0.65μ) of dense, arc-cast uranium monocarbide (5.3 wt % total carbon) were measured in the temperature range 1150° to 2050°K. The results were as follows: k, 0.057 cal/sec-cm-deg, 1200° < T < 2050°K, probable error ± 0.002; p, 20.4 × 10−6+ 114.8T× 10−9 ohm-cm, 1175° < T < 2050°K, probable error ± 1.7 × 10−6; et0.42, 1250° < T < 1980°K, probable error ± 0.02; e0.65 0.539 – 0.02T× 10−3 1150° < T < 1890°K, probable error ± 0.02. Experimental methods are discussed and error sources are analyzed. Uranium monocarbide exhibited typical metallic behavior in its thermophysical properties.
Angiogenesis and Prostate Cancer: In vivo and In vitro Expression of Angiogenesis Factors by Prostate Cancer Cells

Abstract Objectives. Recently, it was confirmed that angiogenesis is important in the development and spread of a variety of human cancers, including prostate cancer (PCa). Tumor neovascularization is thought to be controlled by chemical signals, known as angiogenic factors (AF). To date, little is known regarding the existence and role of AF in PCa. We previously reported on vascular endothelial growth factor (VEGF) in PCa. Currently, we compare VEGF expression with that of interleukin-8 (IL-8), another putative regulator of angiogenesis. We evaluated the expression of these two important AF in PCa and explored the role of inflammatory cytokines IL-1 and tumor necrosis factor (TNF) in their regulation. Methods. Ex vivo studies involved previously reported immunohistochemical analysis for VEGF and recent evaluation of IL-8 expression and distribution in archival tissue samples of PCa, benign prostatic hyperplasia (BPH), and normal prostate tissue. In vitro studies used PCa cells (DU-145) grown in culture and stimulated with cytokines thought to induce VEGF and IL-8 (ie, IL-1 alpha, IL-1 beta, TNF-alpha, and TNF-beta). After 24 hours, with or without cytokines, cell culture supernatants were analyzed by enzyme-linked immunosorbent assay or radioimmunoassay for VEGF or IL-8 levels. Results. Immunohistochemical studies of prostate tissue showed that PCa cells stained positively for VEGF and IL-8. Benign prostatic hyperplasia and normal prostate cells displayed little staining for either AF. Low levels of VEGF and IL-8 were produced by unstimulated DU-145 cells. Induction of DU-145 cells with cytokines resulted in differential stimulation whereby TNF was the predominant inducer of VEGF, whereas IL-1 was the predominant inducer of IL-8. Conclusions. Our results indicate that significant levels of VEGF and IL-8 are present in PCa, but not BPH or normal prostate cells in vivo. In vitro studies suggest that differential regulation of AF expression occurs in PCa. Because IL-1 and TNF are present in the PCa tumor microenvironment, it is likely that differential regulation of AF also occurs in human PCa and contributes to differential tumor growth and metastasis.
Enzyme‐modified carbon paste: Tetrathiafulvalene electrodes for the determination of acetylcholine

The response characteristics of a new sensor for determining acetylcholine are reported. The sensor is based on a carbon paste electrode containing the enzymes acetylcholinesterase and choline oxidase and the electron transfer mediator tetrathiafulvalene (TTF). TTF is shown to efficiently reoxidize the reduced flavin adenine dinucleotide centers of choline oxidase. Acetylcholine calibration graphs are obtained in the range 10−6 to 10−3 M in pH 7.0 phosphate buffer, and the sensors are shown to operate efficiently at low applied potentials, where electrochemical interference due to oxidation of ascorbic acid is minimized.