cssi/SciSciGPT-SciSciNet huggingface dataset:
Conformationally constrained analogues of diacylglycerol (DAG). 28. DAG-dioxolanones reveal a new additional interaction site in the C1b domain of PKCδ

Diacylglycerol (DAG) lactones have provided a powerful platform for structural exploration of the interactions between ligands and the C1 domains of protein kinase C (PKC). In this study, we report that DAG-dioxolanones, novel derivatives of DAG-lactones, exploit an additional point of contact (glutamine 27) in their binding with the C1b domain of PKCδ. Mutation of this point of contact to glutamate selectively impairs binding of the DAG-dioxolanones compared to that of the corresponding DAG-lactones (1200- to 3000-fold versus 35- to 55-fold, respectively). The differential response of this mutated C1b domain to the DAG-dioxolanones relative to the DAG-lactones provides a unique tool to probe the role of the C1b domain in PKCδ function, where the response to the DAG-lactones affords a positive control for retained function. Using this approach, we show that the C1b domain of PKCδ plays the predominant role in the translocation of PKCδ to the membrane in the presence of DAG.
Increasing incidence of bilateral mastectomies: the patient perspective

BACKGROUND: Numerous studies have reported increasing rates of contralateral prophylactic mastectomies (CPMs). Understanding patient rationale for the surgical choice may provide insight into this trend. METHODS: A questionnaire was mailed to 350 mastectomy patients identified from a community health system tumor registry. RESULTS: Two hundred fifty questionnaires were received; of these, 237 had undergone mastectomy. Fifty-two percent had unilateral mastectomy (UM), and 43% had bilateral mastectomies (BMs) (6% for bilateral disease). Women younger than 60 years of age were more likely to choose BM (P = .0046). Those who had CPM were significantly more likely to make the same surgical decision (P < .0001). Reconstruction was performed in 52%, with BM patients more likely to undergo reconstruction (P = .009). Twenty-three (19%) needed unanticipated reoperation for reconstruction complications. CPM had equivalent rates of unanticipated surgery versus UM (P = .64). CONCLUSIONS: Patients choosing BMs are younger, have equivalent rates of reoperation because of reconstruction complications, and are significantly more satisfied with their decision than those who chose UM.
Building a virtual community of practice for K-12 CS teachers

Bringing educators together and focusing their interests toward improving computer science education in high schools.
Ce Heavy fermion systems: The nearly trivalent limit of the mixed valence regime☆

Abstract Specific heat, magnetic susceptibility, and resistivity data is presented which suggests that the heavy fermion phenomenon in Ce systems corresponds to the nearly trivalent limit of the mixed valence behavior. This correspondence holds for both heavy fermion lattices and diluted heavy fermion systems.
A decomposition of Moran's I for clustering detection

The test statistics I"h, I"c, and I"n are derived by decomposing the numerator of the Moran's I test for high-value clustering, low-value clustering, and negative autocorrelation, respectively. Formulae to compute the means and variances of these test statistics are derived under a random permutation test scheme, and the p-values of the test statistics are computed by asymptotic normality. A set of simulations shows that test statistic I"h is likely to be significant only for high-value clustering, test statistic I"c is likely to be significant only for low-value clustering, and test statistic I"n is likely to be significant only for negatively correlated spatial structures. These test statistics were used to reexamine spatial distributions of sudden infant death syndrome in North Carolina and the pH values of streams in the Great Smoky Mountains. In both analyses, low-value clustering and high-value clustering were shown to exit simultaneously.
2,3,7,8-Tetrachlorodibenzo-p-dioxin Upregulates FoxQ1b in Zebrafish Jaw Primordium

Vertebrate jaw development can be disrupted by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—a potent activator of the aryl hydrocarbon receptor (AHR) transcription factor required for transducing the toxic effects of TCDD. We used zebrafish (Danio rerio) embryos to investigate transcriptional responses to TCDD with the goal of discovering novel, jaw-specific genes affected by TCDD exposure. Our results uncovered a novel target of TCDD-activated Ahr belonging to the evolutionarily conserved family of forkhead box transcription factors. Quantitative real-time polymerase chain reaction analysis demonstrated that FoxQ1b was upregulated by TCDD 7- and 10-fold at 24 and 48 h postfertilization (hpf), respectively. The rate of TCDD-induced FoxQ1b expression was more rapid than that of Cyp1a, a known direct target of TCDD-activated Ahr. TCDD-mediated induction of FoxQ1b was suppressed in the presence of an Ahr antagonist, α-naphthoflavone, as well as following knockdown of Ahr2 expression using an Ahr2-specific morpholino antisense oligonucleotide. In situ hybridization analysis of FoxQ1b expression at 48 hpf demonstrated that FoxQ1b is specifically expressed in the jaw primordium where it discretely outlines a developing jaw structure known as Meckel’s cartilage—a conserved structure in all jawed vertebrates that develops abnormally in the presence of TCDD. These results identify a novel target of TCDD-activated Ahr and suggest that FoxQ1b may play a role in craniofacial abnormalities induced by developmental exposure to TCDD.
Wave functions and properties of massive states in three-dimensional supersymmetric Yang-Mills theory

We apply supersymmetric discrete light-cone quantization (SDLCQ) to the study of supersymmetric Yang-Mills theory on R x S^1 x S^1. One of the compact directions is chosen to be light-like and the other to be space-like. Since the SDLCQ regularization explicitly preserves supersymmetry, this theory is totally finite, and thus we can solve for bound-state wave functions and masses numerically without renormalizing. We present an overview of all the massive states of this theory, and we see that the spectrum divides into two distinct and disjoint sectors. In one sector the SDLCQ approximation is only valid up to intermediate coupling. There we find a well defined and well behaved set of states, and we present a detailed analysis of these states and their properties. In the other sector, which contains a completely different set of states, we present a much more limited analysis for strong coupling only. We find that, while these state have a well defined spectrum, their masses grow with the transverse momentum cutoff. We present an overview of these states and their properties.
Cascade Baryon Production in Photon-Induced Reactions

The reaction ?N ? KK? is studied within a relativistic meson exchange model of hadronic interactions. This is the first theoretical effort in connection to the cascade baryon spectroscopy program initiated recently at the Thomas Jefferson National Accerelator Facility. The basic features of this reaction and their manifestations in some of the observables are presented.
The Fuel Accident Condition Simulator (FACS) furnace system for high temperature performance testing of VHTR fuel

Abstract The AGR-1 irradiation of TRISO-coated particle fuel specimens was recently completed and represents the most successful such irradiation in US history, reaching peak burnups of greater than 19% FIMA with zero failures out of 300,000 particles. An extensive post-irradiation examination (PIE) campaign will be conducted on the AGR-1 fuel in order to characterize the irradiated fuel properties, assess the in-pile fuel performance in terms of coating integrity and fission metals release, and determine the fission product retention behavior during high temperature safety testing. A new furnace system has been designed, built, and tested to perform high temperature accident tests. The Fuel Accident Condition Simulator furnace system is designed to heat fuel specimens at temperatures up to 2000 °C in helium while monitoring the release of volatile fission metals (e.g. Cs, Ag, Sr, and Eu), iodine, and fission gases (Kr, Xe). Fission gases released from the fuel to the sweep gas are monitored in real time using dual cryogenic traps fitted with high purity germanium detectors. Condensable fission products are collected on a plate attached to a water-cooled cold finger that can be exchanged periodically without interrupting the test. Analysis of fission products on the condensation plates involves dry gamma counting followed by chemical analysis of selected isotopes. This paper will describe design and operational details of the Fuel Accident Condition Simulator furnace system and the associated fission gas monitoring system, as well as preliminary system calibration results.
Providing students universal access to a centralized, graphical computing environment

We investigate the use of a thin-client based configuration in providing students with universal access to a centralized, graphical computing environment. The primary goal is to enable students to work effectively from arbitrary locations and computing platforms, while always interacting with the consistent environment seen in tightly controlled labs.
Observed one‐dimensional return stroke propagation speeds in the bottom 170 m of a rocket‐triggered lightning channel

[1] The return-stroke propagation speeds of five strokes from a seven-stroke triggered lightning flash are measured, with a 2 ns sampling interval, using a vertical array of photodiodes. Various methods for determining the reference point to be tracked are explored, and the speed is seen to vary over nearly an order of magnitude depending upon which method is chosen. The speeds are generally in agreement with the values found in the literature. The return-stroke speed appears to increase with height and then decrease with height in four of the five strokes examined.
Parapet Strength and Contribution to Live-Load Response for Superload Passages

The main objective of this study is to evaluate the effects of parapets on the live-load response of slab-on-girder steel bridges subjected to superload vehicles and the effects of these loads on the parapets. A superload is a special permit truck that exceeds the predefined weight limitation. The presence of parapets can result in reduced girder distribution factors (GDFs) for critical girders, and this reserve strength can be considered for passage of a superload truck. This reduction is investigated, as well as the effects of discontinuous parapets and the capacity of parapets. Two steel bridges with significantly different geometric proportions were analyzed to evaluate the sensitivity of the structure to the effects of parapets. It was found that the GDFs can be decreased by as much as 30%, depending on the stiffness of the girders and the transverse truck position if the parapets are included in the analysis. The axial forces and bending moments resisted by the parapets were compared with the capaci...
Measuring aggregate impacts: The case of the conservation reserve program

Abstract This paper uses an aggregate modelling approach to assess the impacts of the Conservation Reserve Program (CRP) on the United States economy, in general, and the agricultural sectors, in particular. The approach consists of a general equilibrium model composed of 12 producing sectors, 13 consuming sectors, six household categories classified by income and a government. The effects of removing 33·9 million acres and 45 million acres of cropland from agricultural production on prices and quantities are examined. The results are revealing. For example, keeping the CRP at 33·9 million acres will result in lower output by the producing sectors (by about $191 million), a decrease in the consumption of goods and services (by about $99 million), and a reduction in welfare (by about $95 million). The government would realize an increase in expenditures of about $77 million. The agricultural sectors would be affected. For example, if the CRP is limited to 33·9 million acres, output in the program crops sector will rise (by $57·1 million), output in the livestock sector will decline (by $22 million), output in the all other agriculture commodities sector will be reduced (by $173 million), and output in the forestry sector will fall (by $2 million). Finally, when subjected to a sensitivity analysis, the results are reasonably robust with regard to the assumption of the values of the substitution elasticities. That is, while the model's equilibrium values do vary in response to different assumptions of the values of these elasticities, the fluctuations are not so enormous to suggest that the model is unrealistically sensitive to these parameters.
Error concealment techniques for an all-digital high-definition television system

Abstract Broadcasting High Definition Television (HDTV) requires the trausmission of an enormous amount of informationwithin a highly restricted bandwidth. Adhering to the transmission constraints, channel errors are inevitable. Thispaper proposes error concealment techniques to remove subjeci;ive effects of transmission errors. Error concealmenttechniques for several data parameters transmitted for the compressed representation of HDTV are considered.Specifically, we address errors in motion vectors and DCT coefficients. The concealment techniques estimate the truevalue of the corrupted parameters by exploiting the spatial an(l temporal correlation within the image sequence. Ingeneral, the error concealment techniques are found to be extremely successful in removing degradations from thedecoded image. 1 Introduction Broadcasting High-Definition Television (HDTV) requires the transmission of an enormous amount of informationwithin a highly restricted bandwidth channel. Adhering to the channel constraints necessitates the use of an efficientcoding scheme to compress the data. Compressing the data significantly increases the effect of channel errors. Inthe uncompressed video representation, a single channel error affects only one pixel in the received image. In thecompressed format, a channel error affects a block of pixels in the reconstructed image, perhaps even the entireframe.One way to combat the effect of channel errors is to add well-structuied redundancy to the data throughchannel coding. Error correction schemes, however, require tran:;rnitting a significant numl)er of overhead bits.
Temperature dependent exciton linewidths in quantum wells

Abstract Calculations have been made of the temperature dependent linewidths of excitons in semiconductor quantum wells due to coupling to LO phonons. The contributions to the linewidth from exciton scattering to both bound and interacting continuum states have been included. The dependences of the linewidth on the quantum well width and on the choice of heavy hole mass is discussed, and comparison is made with available experimental data.
The resolution limit for far-field optical imaging

Using the methods of the information theory, we derive the fundamental limit to the resolution of optical imaging, and demonstrate that in the far-field, contrary to the conventional wisdom, it is not equal or close to one half of the wavelength.
Basis of selectivity of the herbicide rimsulfuron in maize.

Abstract Rimsulfuron, N -((4,6-dimethoxypyrimidin-2-yl)aminocarbonyl)-3-(ethylsulfonyl)-2-pyridinesulfonamide, formerly DPX-E9636, is a sulfonylurea herbicide for postemergence use in maize to control grasses and some broadleaf weeds. Similar to other sulfonylureas, the site of action of rimsulfuron is acetolactate synthase (ALS), an enzyme in branched-chain amino acid biosynthesis. Studies of in vitro inhibition of ALS from sensitive and tolerant species discount differential active site sensitivity as the basis for maize tolerance to this herbicide. However, there was a good correlation between the rate of metabolism of the herbicide and plant tolerance. Plant metabolism studies demonstrated that tolerant maize metabolized rimsulfuron rapidly, with a half-life of Sorghum halapense, Amaranthus retroflexus , and Digitaria sanguinalis metabolized rimsulfuron slowly, with half-lives of 38, > 48, and 27 h, respectively. The initial metabolic pathway for rimsulfuron in maize primarily involves hydroxylation on the pyrimidine ring followed by glucose conjugation. Both of these metabolites are inactive which results in the detoxification of the herbicide. Rimsulfuron was also metabolized in vitro by maize microsomes in a NADPH-dependent reaction to the same hydroxylated product, suggesting involvement of cytochrome P450. Additional studies with maize leaves demonstrated inhibition of rimsulfuron metabolism by terbufos and piperonyl butoxide, which further supports involvement of a cytochrome P450. Metabolism of rimsulfuron in maize is also temperature dependent, having a maximum rate at 25–30°C and lower rates at higher and lower temperatures. It is concluded that the basis of maize tolerance to rimsulfuron is rapid metabolic inactivation.
Multilayer High Reflective Coating Designs Achieving Broadband 90° Phase Change

For non-normal incidence angles, it has been shown that the polarization state may be controlled by reflection through the use of specially designed multilayer coatings. An optimization I has been used to determine layer thickness for a coating design tha. produces a 90° phase shift between the p and s polarization comppnents over a wavelength range of Δλ/λ0 = ± 5%. A particular 20 layer design produces 90° ± 1° phase shift over this spectral range while maintaining an average reflectivity of over 99.9%. A tolerance analysis on this design indicates that the coating layers must be deposited within ± 1% in order to achieve ± 3° phase shift over the spectral range.© (1980) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Enteral Stent Placement and Small Bowel Balloon Dilation Using Double Balloon Enteroscopy

The last decade has seen several advances which have opened the door to diagnostic and therapeutic endoscopy within the small intestine, an area long considered the “final frontier” of endoscopic imaging. The introduction of the double balloon enteroscope into clinical practice has allowed for the application of several therapeutic techniques within the small intestine. This chapter will review two such techniques: enteral stenting and balloon dilation.
Overview of the standard model

A few problem areas in relation to the standard model are discussed: the Kobayashi-Maskawa matrix, CP violation in the neutral kaon system, B-anti B mixing, and tau decays. 50 refs. (LEW)
Environmental Justice: Evidence from Superfund Cleanup Durations

This paper investigates the extent to which cleanup durations at Superfund sites reflect demographic biases incongruent with the principles of Environmental Justice. We argue that the duration of cleanup, conditional on a large number of site characteristics, should be independent of the race and income profile of the neighborhood in which the site is located. Since the demographic composition of a neighborhood changes during the cleanup process, we explore whether cleanup durations are related to neighborhood demographics recorded at the time when the cleanup is initiated. We estimate a semiparametric Bayesian proportional hazard model, which also allows for unobserved site specific heterogeneity, and find that sites located in black, urban and lower educated neighborhoods were discriminated against at the beginning of the program but that the degree of bias diminished over time. Executive Order 12898 of 1994 appears to have re-prioritized resources for the faster cleanup of sites located in less wealthy neighborhoods. We do not find that the litigation process is an impediment in the cleanup process, and support the notion that community involvement plays an important role.
Immune-mediated Neutropenia in the Neonate

Neutropenia is a relatively common finding in ill neonates, occurring in approximately 32,000 infants each year in the United States. In this patient population, immune-mediated neutropenia results from the antibody-mediated destruction of neutrophils and is associated with such disorders as alloimmune neonatal neutropenia, neonatal autoimmune neutropenia, and autoimmune neutropenia of infancy. Such conditions only recently have begun to be understood and often are problematic in terms of clinical identification and laboratory confirmation. This article reviews the clinical presentation, laboratory diagnosis, and treatment options for these three disorders.
Two-dimensional nonstationary causal stochastic model for turbulence/radiation interactions in flames

A new stochastic method is presented to treat turbulence/radiation interactions. In order to simulatethe random field of instantaneous mixture fraction distributions along the radiation path, a two-dimensional (2D) nonstationary causal stochastic model is proposed. The model can account for not only the first-order correlations both in time space and geometric space but also the first-order cross correlation. Also presented is a general proof that in the simulation of the mixture fraction, the contributions from the first-order correlations in time and geometric spaces are important and so is the contribution from the first-order time-geometric space cross correlation. Furthermore, the second- and higher-order correlation terms are proved to be negligibly small. They provide the foundation for the general development of the present two-dimensional and future three-dimensional stochastic models for turbulence-radiation interactions. Finally, application of the proposed two-dimensional causal model to simulate the radiation process in turbulent carbon monoxide/hydrogen/air flames is illustrated. The predicted mean and fluctuating radiation properties are found to be in good agreement with experimental data.
Virus-Host Interactions: From Unbiased Genetic Screens to Function

Deciphering the many interactions that occur between a virus and host cell over the course of infection is paramount to understanding mechanisms of pathogenesis and to the future development of antiviral therapies. Over the past decade, researchers have started to understand these complicated relationships through the development of methodologies, including advances in RNA interference, proteomics, and the development of genetic tools such as haploid cell lines, allowing high-throughput screening to identify critical contact points between virus and host. These advances have produced a wealth of data regarding host factors hijacked by viruses to promote infection, as well as antiviral factors responsible for subverting viral infection. This review highlights findings from virus-host screens and discusses our thoughts on the direction of screening strategies moving forward.
The Influence of Ergonomic Factors and Perceptual-Motor Abilities on Handwriting Performance

Difficulty with handwriting is one of the most frequent reasons that children in the public schools are referred to occupational therapy. Current research on the influence of ergonomic factors, such as pencil grip and pressure, and perceptual-motor factors traditionally believed to affect handwriting, is reviewed. Factors such as visual perception show little relationship to handwriting, whereas tactile-kinesthetic, visual-motor, and motor planning appear to be more closely related to handwriting. By better understanding the ergonomic and perceptual-motor factors that contribute to and influence handwriting, therapists will be better able to design rationally based intervention programs.
The role of suppliers in market intelligence gathering for radical and incremental innovation

Drawing on transaction cost economics theory, this study addresses the following research questions: (1) Does supplier involvement in market intelligence gathering activities have a greater impact on innovation success in predesign or commercialization activities? and (2) Does supplier involvement in market intelligence gathering activities have a greater impact on success in radical or incremental product innovation? Hypotheses are tested using both subjective and objective measures of success from a study of 205 incremental and 110 radical new product development projects. Results from the estimation of a two-group path model suggest that this theoretical framework is useful in providing guidance as to when product developers should emphasize the gathering of market intelligence through suppliers. Consistent with conventional wisdom, the findings suggest that supplier involvement in market intelligence gathering activities are positively related to success in incremental innovations across predesign and commercialization activities. However, supplier involvement in market intelligence gathering activities is found to have no significant impact on market share and is negatively associated with perceived product performance in radical innovations in predesign tasks. Also, while there was no significant difference in market share for supplier involvement in market intelligence gathering activities between radical and incremental innovation in commercialization activities, supplier involvement in these activities did have a greater impact on perceived product performance in radical innovation than it did in incremental innovation. Although current practice suggests that teams allocate fewer resources to the gathering of market intelligence through their suppliers during predesign activities in incremental innovation projects compared with radical innovation projects, the findings in this study suggest that they should do the opposite. Shifting resources allocated for engaging suppliers in market information gathering activities in predesign activities from radical innovation projects to incremental innovation projects could increase the return on these investments. Alternatively, these resources currently allocated to the gathering of market intelligence through suppliers in predesign activities of radical innovation projects could also provide greater benefits if allocated to commercialization activities of radical innovation projects, where they have the greatest positive impact.
Measuring Gender Disparity in the HIV Pandemic: A Cross‐National Investigation of Female Empowerment, Inequality, and Disease in Less‐Developed Nations

Current research recognizes that the HIV pandemic uniquely impacts women, as they are socially and biologically more vulnerable to the infection. However, present measurement strategies focus on assessing the level of HIV infection among women, rather than inequality in the distribution of HIV cases by gender in less-developed nations. In this study, we compare the cross-national determinants of the level of female HIV prevalence to the determinants of the percentage of HIV cases among women. Ordinary least squares (OLS) regressions suggest that the predictors of female HIV differ across the two measures, where aspects of female empowerment and female access to health resources are more influential in explaining the distribution of HIV cases across gender than the level of female HIV prevalence. These results suggest that analyzing the distribution of HIV cases by gender is a more appropriate way to measure gender disparities in the HIV pandemic. Therefore, future research should be cautious to consider the implications of investigating levels of HIV versus the distribution of HIV cases across populations.
Abuse of Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors, like other antidepressants, generally are considered free of risk for abuse. There is, however, some evidence that MAOIs possess dependence and abuse potential for some patients. We will review the available literature and describe three current cases. Recommendations for treatment are discussed briefly.
The implementation of the Itanium 2 microprocessor

This 64-b microprocessor is the second-generation design of the new Itanium architecture, termed explicitly parallel instruction computing (EPIC). The design seeks to extract maximum performance from EPIC by optimizing the memory system and execution resources for a combination of high bandwidth and low latency. This is achieved by tightly coupling microarchitecture choices to innovative circuit designs and the capabilities of the transistors and wires in the 0.18-/spl mu/m bulk Al metal process. The key features of this design are: a short eight-stage pipeline, 11 sustainable issue ports (six integer, four floating point, half-cycle access level-1 caches, 64-GB/s level-2 cache and 3-MB level-3 cache), all integrated on a 421 mm/sup 2/ die. The chip operates at over 1 GHz and is built on significant advances in CMOS circuits and methodologies. After providing an overview of the processor microarchitecture and design, this paper describes a few of these key enabling circuits and design techniques.
Recognizing Action at a Distance

Our goal is to recognize human actions at a distance,at resolutions where a whole person may be, say, 30 pixelstall. We introduce a novel motion descriptor based onoptical flow measurements in a spatio-temporal volume foreach stabilized human figure, and an associated similaritymeasure to be used in a nearest-neighbor framework. Makinguse of noisy optical flow measurements is the key challenge,which is addressed by treating optical flow not asprecise pixel displacements, but rather as a spatial patternof noisy measurements which are carefully smoothed andaggregated to form our spatio-temporal motion descriptor.To classify the action being performed by a human figurein a query sequence, we retrieve nearest neighbor(s) from adatabase of stored, annotated video sequences. We can alsouse these retrieved exemplars to transfer 2D/3D skeletonsonto the figures in the query sequence, as well as two formsof data-based action synthesis "Do as I Do" and "Do as ISay". Results are demonstrated on ballet, tennis as well asfootball datasets.
Application of Statistical-BGK Approach to Modeling of Nozzle Flows in the Near Continuum Regime

Conical nozzle flows are studied for Reynolds numbers of 1,230 and 12,300 using different numerical techniques: DSMC Method, Navier-Stokes with velocity slip and temperature jump boundary conditions, and statistical and deterministic approaches to the solution of the BGK and ES-BGK equations. Detailed comparison of the accuracy and convergence of the employed numerical techniques provides better understanding of their benefits and deficiencies, and assists in selecting the most appropriate technique for a particular nozzle flow application and available computational resources. The deterministic and statistical solutions of the BGK equation were found to be in good agreement with the benchmark DSMC results. The Navier-Stokes solution was found to differ from DSMC in the boundary layer. Statistical BGK and ES-BGK methods are shown to be more efficient methods than DSMC in the continuum and near-continuum regime, and more accurate than the solution of the Navier-Stokes equations in the transition regime.
In utero haematopoietic stem cell transplantation – experimental progress towards clinical application

In utero haematopoietic stem cell transplantation (IUHCT) is a potential therapeutic alternative to postnatal allogeneic bone marrow transplantation (BMT) for congenital haematologic disorders that can be diagnosed early in gestation and can be cured by BMT. The rationale is to take advantage of normal events during haematopoietic and immunologic ontogeny to facilitate allogeneic haematopoietic engraftment. The most important of these is the normal process of thymic processing of self-antigen to create a state of self-tolerance. Introduction of allogeneic antigen in the form of haematopoietic stem cells results in a state of permanent donor specific tolerance, eliminating the need for immunosuppression. Although the rationale remains compelling, IUHCT has only been clinically successful in X-linked severe combined immunodeficiency syndrome, a disease in which a competitive advantage exists for donor lymphoid cells. In other disorders, such as the haemoglobinopathies, where host-cell competition is a major barrier, IUHCT has not yet succeeded. However, great experimental progress has recently been made in pre-clinical animal models. Strategies based on prenatal tolerance induction to facilitate post-natal non-toxic cellular transplantation appear promising and clinical application is likely imminent. Because donor specific tolerance induction requires relatively minimal engraftment, this strategy may hold the key to broad clinical application of IUHCT in the near future.
The proton channel of the energy-transducing nicotinamide nucleotide transhydrogenase of Escherichia coli.

Abstract The nicotinamide nucleotide transhydrogenases of mitochondria and bacteria are proton pumps that couple direct hydride ion transfer between NAD(H) and NADP(H) bound, respectively, to extramembranous domains I and III to proton translocation by the membrane-intercalated domain II. To delineate the proton channel of the enzyme, 25 conserved and semiconserved prototropic amino acid residues of domain II of the Escherichia coli transhydrogenase were mutated, and the mutant enzymes were assayed for transhydrogenation from NADPH to an NAD analogue and for the coupled outward proton translocation. The results confirmed the previous findings of others and ourselves on the essential roles of three amino acid residues and identified another essential residue. Three of these amino acids, His-91, Ser-139, and Asn-222, occur in three separate membrane-spanning α helices of domain II of the β subunit of the enzyme. Another residue, Asp-213, is probably located in a cytosolic-side loop that connects to the α helix bearing Asn-222. It is proposed that the three helices bearing His-91, Ser-139, and Asn-222 come together, possibly with another highly conserved α helix to form a four-helix bundle proton channel and that Asp-213 serves to conduct protons between the channel and domain III where NADPH binding energy is used via protein conformation change to initiate outward proton translocation.
Relational Bureaucracy: Structuring Reciprocal Relationships into Roles

We describe a hybrid relational bureaucratic form with structures that embed three processes of reciprocal interrelating—relational coproduction, relational coordination, and relational leadership—into the roles of customers, workers, and managers. We show how these role-based relationships of shared goals, shared knowledge, and mutual respect foster participants' attentiveness to the situation and to one another, enabling the caring, timely, and knowledgeable responses found in the relational form, along with the scalability, replicability, and sustainability found in the bureaucratic form. Through these role-based relationships, relational bureaucracy promotes universalistic norms of caring for particular others.
Phylogeny of finescale shiners of the genus Lythrurus (Cypriniformes: Cyprinidae) inferred from four mitochondrial genes.

Abstract We infer the phylogenetic relationships of finescale shiners of the genus Lythrurus , a group of 11 species of freshwater minnows widely distributed in eastern North America, using DNA sequences from the ND2 (1047 bp), ATPase8 and 6 (823 bp), and ND3 (421 bp) mitochondrial protein-coding genes. The topologies resulting from maximum parsimony, Bayesian, and maximum likelihood tree building methods are broadly congruent, with two distinct clades within the genus: the L. umbratilis clade ( L. umbratilis + L. lirus + ( L. fasciolaris + ( L . ardens , L. matutinus ))) and the L. bellus clade ( L. fumeus + L. snelsoni + ( L. roseipinnis + ( L. atrapiculus + ( L . bellus , L. algenotus )))). Support is weak at the base of several clades, but strongly supported nodes differ significantly from prior investigations. In particular, our results confirm and extend earlier studies recovering two clades within Lythrurus corresponding to groups with largely “northern” and “southern” geographic distributions. Several species in this genus are listed in the United States as threatened or of special concern due to habitat degradation or limited geographic ranges. In this study, populations assigned to L . roseipinnis show significant genetic divergence suggesting that there is greater genetic diversity within this species than its current taxonomy reflects. A full accounting of the biodiversity of the genus awaits further study.
Influence of feeding Aspergillus oryzae fermentation extract on the milk yields, eating patterns, and body temperatures of lactating cows

Trials were conducted to evaluate effects of a fermentation extract of Aspergillus oryzae (AO) on milk production and composition, diet digestibility, and rectal temperature changes in lactating dairy cows. Treatments were incorporated as a top dressing at the morning feeding and consisted of control (90 g/d of ground sorghum) or AO (3 g of culture + 87 g of ground sorghum daily). Twenty-four mid-lactation Holstein cows were paired for production in Lactation Trial 1 (LT-1). In Lactation Trial 2 (LT-2), 46 cows (20 primiparous and 26 multiparous) in early lactation were used. Trials lasted 12 wk. In LT-1, AO supplementation increased milk yields only at 2 (P less than .05) and 8 wk (P less than .10) of treatment. Rectal temperatures were lower (P less than .05) for cows fed AO for 4 of 10 readings made during summer. Supplementation of AO culture in LT-2 (early lactation cows) increased milk production and feed efficiency (P less than .05). Inner ear temperatures tended to be lower (P less than .11) for cows fed AO. Digestion trials, conducted at the end of lactation trials, used Cr2O3 as an indigestible marker. In Digestion Trial 1, digestibilities were not significantly (P greater than .10) affected by AO supplementation. However, in Digestion Trial 2, AO increased (P less than .05) digestibilities of DM, OM, CP, NDF, and ADF. Length and number of meals were not affected (P greater than .10) by feeding AO. In summary, milk yields, efficiency of milk production, and nutrient digestibilities were higher for early lactation cows fed a high-concentrate diet supplemented with 3 g of AO/d. Mid-lactation cows fed a lower-energy diet were less responsive to AO than early lactation cows, though similar trends were shown.
First Hand: Hand-Picked Music for Kids

FIGURE 1: To the amazement of the clinic staff and the waiting room, Dr. Barry Gainor (mandolin) auditions a rehabilitated fiddler who retrained his 4-finger hand to play the violin again. My father was a pediatrician and musician, so performing musical benefits for the Children’s Hospital at the University of Missouri is a natural connection for me. As a multi-instrumentalist, singer, and Bluegrass band leader, I have been performing for the kids since 1995. Every Sunday afternoon, my band, “Gainor & Friends,” plays at a local microbrewery and all tips are donated to the Children’s Miracle Network. We collect about $1,000 a year in donations from generous patrons who post our songs on You Tube. Since 2004, I have written, produced, and solo-performed 3 compact discs of original music that have netted more than $12,000 in sales for the hospital. The women in my band join me as the “G&F Trio” to sing on the pediatric ward quarterly, especially around holidays. A threesome of operating room nurses sew festive surgeon caps as gifts for the patients and siblings during these songfests. It is easy and fulfilling work, which has not passed unnoticed by the media. My patients love to ask me about my music and upcoming performances. Children sing refrains to me in the clinic from the tunes that I have written and recorded. For years, my band has enjoyed stable membership because the musicians cherish this fun opportunity of community service. Remaining proficient on multiple instruments requires daily practice, even if for just a scant few minutes in a too-busy surgeon’s schedule. My electric bass is outfitted with nylon strings, which give the instrument a mellow acoustic tone but minimize the cyclic microtrauma to my fingertips that would be imparted by conventional heavy steel wound strings. For the same reason, the doubled strings on my mandolin are light-medium gauge, and the strings on my guitar are a pliable silk and steel design. The
Heparin-induced Leukocytosis Requires 6-O-Sulfation and Is Caused by Blockade of Selectin- and CXCL12 Protein-mediated Leukocyte Trafficking in Mice

Leukocytosis refers to an increase in leukocyte count above the normal range in the blood and is a common laboratory finding in patients. In many cases, the mechanisms underlying leukocytosis are not known. In this study, we examined the effects, the structural determinants, and the underlying mechanisms of heparin-induced leukocytosis, a side effect occurring in 0.44% of patients receiving heparin. We observed that heparin induced both lymphocytosis and neutrophilia, and the effects required heparin to be 6-O-sulfated but did not require its anticoagulant activity. Cell mobilization studies revealed that the lymphocytosis was attributable to a combination of blockage of lymphocyte homing and the release of thymocytes from the thymus, whereas the neutrophilia was caused primarily by neutrophil release from the bone marrow and demargination in the vasculature. Mechanistic studies revealed that heparin inhibits L- and P-selectin, as well as the chemokine CXCL12, leading to leukocytosis. Heparin is known to require 6-O-sulfate to inhibit L- and P-selectin function, and in this study we observed that 6-O-sulfate is required for its interaction with CXCL12. We conclude that heparin-induced leukocytosis requires glucosamine 6-O-sulfation and is caused by blockade of L-selectin-, P-selectin-, and CXCL12-mediated leukocyte trafficking.
Pathologic stage migration has slowed in the late PSA era.

Objectives Serum prostate specific antigen (PSA) screening has led to clinical and pathologic stage migration. We examined patients treated by radical prostatectomy between 1987 and 2005 to establish temporal trends in pathologic stage migration as assessed by the proportion of patients with nonorgan-confined disease (NOCD). Methods Step-sectioned prostatectomy specimens of 3364 consecutively treated patients were evaluated by year. The data were modeled by joinpoint regression, and the optimal model was selected by a Bayesian information criterion. Results From 1987 to 2005, the population underwent pathologic stage migration toward more organ-confined tumors (P <0.0001). The proportion of patients with NOCD exhibited changes in trend at 1992 and 1995. After widespread implementation of PSA screening, stage migration accelerated between 1992 and 1995. Since 1995, stage migration has substantially slowed but continues at an annual change of −4.2% (P = 0.0027). Conclusions The presence of NOCD at prostatectomy has declined substantially in the PSA era. Recent slowing in this trend suggests a diminishing effect of PSA screening on pathologic stage migration.
A cytochrome P450 monooxygenase cDNA (CYP71A10) confers resistance to linuron in transgenic Nicotiana tabacum

Abstract The isolation of a Glycine max cytochrome P450 monooxygenase (P450) cDNA designated CYP71A10 that conferred linuron resistance to laboratory-grown, transgenic Nicotiana tabacum seedlings was previously reported. A nonsegregating transgenic N. tabacum line has been established that possesses two independent copies of the G. max CYP71A10 transgene. Five-week-old progeny plants of this selected line were grown in a controlled environmental chamber and treated with linuron using either pretransplant incorporated (PTI) or postemergence (POST) applications. CYP71A10-transformed N. tabacum was more tolerant to linuron than the wild type for both application methods. The transgenic N. tabacum line tolerated an approximately 16-fold and 12-fold higher rate of linuron than wild-type N. tabacum when the herbicide was applied PTI or POST, respectively. These results provide evidence that plant-derived P450 genes can be employed effectively to confer herbicide resistance to transgenic plants. Nomenclature: Cy...
Epidemiology and Culture: Anthropological and Epidemiological Collaboration to Help Communities Become Healthier

The principle that health programs should “start with people as they are and the community as it is” applies both at home and abroad…. The problem is how to implement the principle. The real challenge is to discover just where particular groups of people stand; a willingness to meet them must be matched by a knowledge of the meeting place. (Paul 1955:476–7) Introduction When I awake in foreign hotels late at night with jet lag, I sometimes turn on the television. This often is the best time to watch for official government messages about how to avoid malnutrition, AIDS, malaria, diarrhea, or a host of other modern plagues. Campaigns like these to increase health and reduce disease are an increasingly important part of public health work, although their appearance at 3 a.m. belies their importance relative to other shows and advertisements on television. Where do these messages come from, and why do they often appear when they are least likely to be seen? Organized attempts to influence human thought, motivation, and behavior, and the environment in which that behavior takes place, are called “interventions” in today's public health vocabulary, and “intervention research” is its own domain. World AIDS Day (December 1) is designed to increase awareness of health concerns. Television campaigns to promote exercise, condom use, low-cholesterol diets, or mass immunizations are undertaken to increase behavior thought to prevent disease. Campaigns to reduce smoking or alcohol consumption aim to reduce behavior thought to promote disease.
The craniofacial morphology of Nubian schoolchildren.

Abstract No Abstract Available. From the Department of Orthodontics and Dental Research Institute, University of Michigan, Ann Arbor, Michigan.
Stability Result for Dynamic Inversion Devised to Control Large Flexible Aircraft

High performance aircraft of the future will be designed lighter, more maneuverable, and operate over an ever expanding flight envelope. One of the largest differences from the flight control perspective between current and future advanced aircraft is elasticity. Over the last decade, dynamic inversion methodology has gained considerable popularity in application to highly maneuverable fighter aircraft, which were treated as rigid vehicles. This paper is an initial attempt to establish global stability results for dynamic inversion methodology as applied to a large, flexible aircraft. This work builds on a previous result for rigid fighter aircraft and adds a new level of complexity that is the flexible aircraft dynamics, which cannot be ignored even in the most basic flight control. The results arise from observations of the control laws designed for a new generation of the High-Speed Civil Transport aircraft.
Cardiomyocytes Derived From Embryonic Stem Cells

Self-renewing embryonic stem (ES) cells have been established from early mouse embryos as permanent cell lines. By cultivation in vitro as three-dimensional aggregates called embryoid bodies (EBs), ES cells can differentiate into derivatives of all three primary germ layers, including cardiomyocytes. ES cells thus represent a useful model system for studying cardiomyocyte developmental paradigms. This chapter describes techniques and protocols for the cultivation and maintenance of ES cell lines, and the differentiation of ES cell lines into all specialized cell types of the heart, including atrial-, ventricular-, sinus nodal- and Purkinje-like cardiomyocytes. We also include protocols for the isolation and evaluation (morphological, molecular, and functional) of in vitro-generated cardiomyocytes. We consider these latter techniques to be prerequisites for the successful use of this model system to study cardiomyocyte differentiation. Finally, our objective in writing this chapter is to provide sufficient detail and explanation so that any competent scientist who is new to the field will be able to successfully establish and employ this model system for the analysis of ES cell-derived cardiomyocytes.