cssi/SciSciGPT-SciSciNet huggingface dataset:
Arsenic promotes the COX2/PGE2-SOX2 axis to increase the malignant stemness properties of urothelial cells

Chronic arsenic exposure is associated with the development of urothelial carcinoma of the bladder (UCB). To elucidate the contribution of arsenic exposure to urothelial cancer stem cell (CSC) generation, we established an in vitro stepwise malignant model transformed by chronically exposing human urothelial cells to arsenic. Using this model, we found that chronic arsenic exposure endows urothelial cells with malignant stemness properties including increased expression of stemness-related factors such as SOX2, sphere formation, self-renewal, invasion and chemoresistance. SOX2 was gradually and irreversibly overexpressed in line with acquired sphere-forming and self-renewal abilities. Following gene set enrichment analyses of arsenic-exposed and arsenic-unexposed cells, we found COX2 as an enriched gene for oncogenic signature. Mechanistically, arsenic-induced COX2/PGE2 increases SOX2 expression that eventually promotes malignant stem cell generation and repopulation. In urine samples from 90 subjects exposed to arsenic and 91 control subjects, we found a significant linear correlation between SOX2 and COX2 expression and the potential of SOX2 and COX2 expression as urinary markers to detect subjects exposed to arsenic. Furthermore, the combination marker yielded a high sensitivity for UCB detection in a separate cohort. Finally, our in vitro model exhibits basal-type molecular features and dual inhibition of EGFR and COX2 attenuated stem cell enrichment more efficiently than an EGFR inhibitor alone. In conclusion, the COX2/PGE2-SOX2 axis promotes arsenic-induced malignant stem cell transformation. In addition, our findings indicate the possible use of SOX2 and COX2 expression as urinary markers for the risk stratification and detection of UCB.
Mechanisms of thiol reaction with oxygen: implications for hyperthermic and radiation therapies.

Cysteamine (MEA) and other thiols have been used in research as radioprotecting agents1–4 and anticarcinogens.5–6 More recently MEA has been found to enhance the effects of hyperthermic sterilization? and to protect against the cytotoxicity of misonidazole.8–9 Despite its possible therapeutic potential, MEA is known to be cytotoxic, and it has been shown that low concentrations of MEA (less than 1 mM) kill cells more effectively than higher concentrations. 10,11 MEA toxicity has been attributed to the production of peroxide via the spontaneous reaction with oxygen which is metal ion catalysed.10,12–16 our research purpose was to extend the earlier observations on MEA-linked peroxide production10, 11 because of the possible importance in hyperthermic sterilization as well as in radiation biology. We have measured thiol-linked oxygen uptake and peroxide formation. In addition, we have studied the effects of catalase, superoxide dismutase (SOD), and metal ions on the oxygen uptake and peroxide production for MEA in phosphate buffered saline (PBS).
Exponential Rate Conditions for Dynamical Systems

Publisher Summary This chapter presents a diffeomorphism F : R n → R n , F ( x ) = Ax + f ( x ), where f vanishes together with its first derivative at the origin. This chapter discusses exponential rate conditions for dynamical system. It presents a typical application of exponential rate conditions. A perturbation problem for invariant manifolds is stated in terms of exponential rates, and the study of these rates is the main step in solving the problem.
Elderly Caregivers and Care Receivers

Meeting the needs of families caring for elders at home continues to be a major challenge as we move into the 21st century. The tremendous expansion of the older population will mean that ever more families will be involved in providing some amount of care for aged parents, grandparents, spouses, siblings, and adult children. By 2010 the baby boomers will contribute their mass to the 65 and older group and by 2030 will have a dramatic effect on the numbers of individuals over 85 (Hooyman & Kiyak, 1993). Since fewer members of that generation got married and stayed married, and since many tended to have one or no children, the impact of that generation on society will be great (Dychtwald & Flower, 1988). Initially, “boomers” will be primary caregivers to parents and grandparents. Later, their small families will be their caregivers.
Jury Selection and Trial Consultation

The area of trial consultation including selecting juries is one that has developed over the past 30 years into an important area of forensic psychology. This has occurred despite the skepticism that occurred because of the possibility for unscrupulous attorneys or psychologists to overstep the boundaries of ethical and moral behavior as was portrayed in the Runaway Jury by John Grisham. Everyone likes to think that psychologists can see into people’s minds and use what they learn to be manipulative. While that occasionally can and does happen, in fact, most trial consultants use perfectly acceptable research methods to obtain important information that lawyers can then choose to use or discard.
Impact of short- and long-term heat stress on reproductive potential of Drosophila suzukii Matsumura (Diptera: Drosophilidae).

Abstract Drosophila suzukii Matsumura (Diptera: Drosophilidae) is an invasive vinegar fly of Asian origin now distributed throughout North America. Due to the unique morphology of females, this fly has become one of the most serious pests of thin-skinned fruits including blueberry, blackberry, cherry, raspberry, and strawberry. Prophylactic insecticide applications are commonly used to control this fly. A more sustainable approach to managing this invasive pest may not be possible without a clear understanding of the biology of this species under extreme environmental conditions. Specifically, high temperature is known to interfere with development and reproduction of drosophilids; however, the impact of high temperature on D. suzukii needs to be further investigated. The objective of the present study was to investigate the impact of exposure to constant and relatively short-term heat stress on reproductive success of D. suzukii, and potential for recovery. Results show that the development and reproduction of D. suzukii were negatively affected by constant and relatively short-term heat stress. Under constant heat stress, oviposition rate and adult lifespan decreased as temperature increased from 24 °C to 33 °C and reproduction was completely absent at 33 °C. Under relatively short-term heat stress, oviposition, pupation, and adult eclosion were significantly decreased as temperature increased from 28 °C to 34 °C. The short-term heat stress greatly reduced the fertility of both male and female D. suzukii which was recovered eight days after treatment. This study provides basic information on thermal biology of D. suzukii to help us better understand the trends commonly observed in D. suzukii trap captures in regions with hot summer conditions, and the results can be used in population models to predict its population dynamics in regions where high temperatures prevail during the field season.
Site-Specific Oxidation State Assignments of the Iron Atoms in the [4Fe:4S] 2+/1+/0 States of the Nitrogenase Fe-Protein

The nitrogenase iron protein (Fe-protein) contains an unusual [4Fe:4S] iron-sulphur cluster that is stable in three oxidation states: 2+, 1+, and 0. Here, we use spatially resolved anomalous dispersion (SpReAD) refinement to determine oxidation assignments for the individual irons for each state. Additionally, we report the 1.13-A resolution structure for the ADP bound Fe-protein, the highest resolution Fe-protein structure presently determined. In the dithionite-reduced [4Fe:4S]1+ state, our analysis identifies a solvent exposed, delocalized Fe2.5+ pair and a buried Fe2+ pair. We propose that ATP binding by the Fe-protein promotes an internal redox rearrangement such that the solvent-exposed Fe pair becomes reduced, thereby facilitating electron transfer to the nitrogenase molybdenum iron-protein. In the [4Fe:4S]0 and [4Fe:4S]2+ states, the SpReAD analysis supports oxidation states assignments for all irons in these clusters of Fe2+ and valence delocalized Fe2.5+ , respectively.
HONORING AND PRIVILEGING PERSONAL EXPERIENCE AND KNOWLEDGE: IDEAS FOR A NARRATIVE THERAPY APPROACH TO THE TRAINING AND SUPERVISION OF NEW THERAPISTS

This article discusses an approach for the training and supervision of new therapists built around social constructionist and poststructuralist ideas from a narrative therapy perspective. We briefly discuss some of the pitfalls of current training/supervision in marriage and family therapy (MFT) that are deficit based and/or that disproportionately grant privilege to expert knowledge. We articulate this emerging training approach which utilizes the rite of passage metaphor, centers relationalism, and incorporates the honoring and privileging of new therapists' lived experience, knowledges, skills, talents, ideas, morals, personal ethics, values, beliefs. Concrete practices of experience privileging, re-membering, and creating communities of concern are detailed, and illustrative examples from our supervision work are given.
Using Adaptive Designs to Avoid Selecting the Wrong Arms in Multiarm Comparative Effectiveness Trials

Limited resources are a challenge when planning comparative effectiveness studies of multiple promising treatments, often prompting study planners to reduce the sample size to meet the financial co...
Disappearing Dykes? Post-Lesbian Discourse and Shifting Identities and Communities.

Researchers and activists have argued that the term “lesbian” has been disappearing, in decline for decades, and have focused on tensions around gender and sexual identities as the source of its de...
Who Were the Most Influential Twitter Contributers to #HFSA2018 Related Social Media Conversations?

Introduction Use of social media (SoMe) before, during, and after major medical meetings has become commonplace. While prior studies have demonstrated the marked year-over-year increase in the number of users and the content they produce, little is known about who these specific contributors are. The aim of this study was to describe the most influential Twitter contributors to SoMe conversations related to the 2018 Heart Failure Society of America's Annual Scientific Meeting (September 15-18, 2018). Methods SymplurRank ( https://help.symplur.com/general/symplurrank ) is a proprietary algorithm that orders influential Twitter accounts by measuring the number of quality mentions received as they relate to a specific healthcare conversation (identified by a unique hashtag). The algorithm is designed to address weaknesses found in commonly used simplistic Twitter metrics such as the number of mentions, tweets, and followers. Additionally this algorithm is designed specifically for healthcare and therefore takes into consideration both an account's influence on a specific health topic and what healthcare stakeholder group any account belongs to. By analogy, it is similar to modern impact factor algorithms for academic journals. For the purposes of this study we obtained data from Symplur regarding the top 100 Twitters influencers who used the hashtag #HFSA2018. We manually reviewed these accounts and classified them into standard categories. Results Between June 15, 2018, and November 15, 2018, 507 unique users used the #HFSA2018 hashtag to generate 1839 tweets. The total number of times tweets with this hashtag appeared in users timelines (i.e. “impressions”) was 3,905,884. The top 100 most influential Twitter users who engaged in the #HFSA2018 conversation, as determined by SympurRank score, are shown in the Figure. Physicians represented the largest category of contributors (74 of the top 100), followed by healthcare organizations (11), and journal/media accounts (6). Professional organizations, including HFSA, the Amyloidosis Foundation, and the Cardiovascular Research Foundation, among others, represented a smaller subset of contributors (5 of the top 100) but on average had the highest SoMe healthcare-related influence (mean SymplurRank score 76). Conclusions Physicians were the largest group of influential Twitter contributors to #HFSA2018-related SoMe conversations. Future research needs to focus on how to increase the participation of other highly influential contributors, such as professional organizations, in SoMe conversations related to major medical meetings.
Behavior of Composite Materials and Structures in Low Temperature Arctic Conditions

Advanced composite materials play vital structural roles in automotive, aerospace and marine industries. Drastic reduction in arctic sea ice region over the last three decades has opened new sailing routes which are more efficient and economical. This has resulted in the increased use of marine and naval vessels in extreme low temperature arctic conditions. The fundamental challenge of operating in such cold and harsh environment lies in the understanding of how materials and structures behave and perform in extreme low temperature. In this chapter, the behavior of composite materials and composite sandwich structures in low temperature arctic conditions is presented. Composite sandwich structure far exceeds classical composite laminates in terms of flexural capability and performance. In this work, we experimentally investigate the impact and post-impact compressive and flexural response of Divinycell H-100 foam core sandwich panel with woven carbon fiber reinforced polymer (CFRP) facesheets. Specimens were conditioned and impacted over a temperature range (from room temperature down to −70 °C). Results show that exposure to low temperature inevitably causes more severe damage in the specimens. Post-mortem inspection using x-ray micro-computed tomography revealed complex failure mechanisms in the composite facesheets (such as matrix crack, delamination and fiber breakage) and foam core (core crushing, core shearing and interfacial debonding).
Comparative Uptake and Biological Distribution of[ 18 F]-Labeled C6 and C8 Perfluorinated Alkyl Substancesin Pregnant Mice via Different Routes of Administration

Elevated blood sera concentrations of perfluorinated and polyfluorinated alkyl substances (PFAS) are associated with many adverse human health effects, including lower birth weight children. Yet th...
NOTCH1-driven UBR7 stimulates nucleotide biosynthesis to promote T cell acute lymphoblastic leukemia.

Ubiquitin protein ligase E3 component N-recognin 7 (UBR7) is the most divergent member of UBR box–containing E3 ubiquitin ligases/recognins that mediate the proteasomal degradation of its substrates through the N-end rule. Here, we used a proteomic approach and found phosphoribosyl pyrophosphate synthetases (PRPSs), the essential enzymes for nucleotide biosynthesis, as strong interacting partners of UBR7. UBR7 stabilizes PRPS catalytic subunits by mediating the polyubiquitination-directed degradation of PRPS-associated protein (PRPSAP), the negative regulator of PRPS. Loss of UBR7 leads to nucleotide biosynthesis defects. We define UBR7 as a transcriptional target of NOTCH1 and show that UBR7 is overexpressed in NOTCH1-driven T cell acute lymphoblastic leukemia (T-ALL). Impaired nucleotide biosynthesis caused by UBR7 depletion was concomitant with the attenuated cell proliferation and oncogenic potential of T-ALL. Collectively, these results establish UBR7 as a critical regulator of nucleotide metabolism through the regulation of the PRPS enzyme complex and uncover a metabolic vulnerability in NOTCH1-driven T-ALL.
Interactive identification of individuals with positive treatment effect while controlling false discoveries

Out of the participants in a randomized experiment with anticipated heterogeneous treatment effects, is it possible to identify which ones have a positive treatment effect, even though each has only taken either treatment or control but not both? While subgroup analysis has received attention, claims about individual participants are more challenging. We frame the problem in terms of multiple hypothesis testing: we think of each individual as a null hypothesis (the potential outcomes are equal, for example) and aim to identify individuals for whom the null is false (the treatment potential outcome stochastically dominates the control, for example). We develop a novel algorithm that identifies such a subset, with nonasymptotic control of the false discovery rate (FDR). Our algorithm allows for interaction -- a human data scientist (or a computer program acting on the human's behalf) may adaptively guide the algorithm in a data-dependent manner to gain high identification power. We also propose several extensions: (a) relaxing the null to nonpositive effects, (b) moving from unpaired to paired samples, and (c) subgroup identification. We demonstrate via numerical experiments and theoretical analysis that the proposed method has valid FDR control in finite samples and reasonably high identification power.
Evaluation of radiomics as a predictor of tumor hypoxia and response to anti-PD-1 mab treatment (IO) in recurrent/metastatic HNSCC patients (R/M).

6045Background: There is a great need for non-invasive predictors of the tumor microenvironment and the efficacy of anti-PD-1 mAb treatment (IO) in R/M HNSCC patients. We previously showed that low...
Reflections on Praxis: The Tensions of Disability and Education in Post-Colonial Kenya

In this paper we explore our emerging and evolving critical approaches to inclusive education development work in the postcolonial, global South context of Kenya. We use the concept of vector of similarity and continuity and vector of difference and rupture (Hall, 1990) as a lens to materialize the effects and tensions between the Northern academy and Southern indigenous knowledge in our own work. We present our work not as models of "what to do" or "what not to do" in development work. Rather we offer a reflection on the evolution of our understanding of this work from being "progressive" while still potentially interpellating the logic of colonialism and further exporting Northern theory, toward a more overtly critical and continually self-reflexive understanding. This paper explores these questions: 1) How do able-bodied, white, "Western" educators working in global South contexts promote social justice and simultaneously disrupt learned oppressive educational practices imported and imposed by the global North? 2) How can this type of work evolve over time with a CDS approach? 3) What are the implications of this? 4) What does this evolution look like in practice?
Idiopathic Constipation and Other Motility Disorders

The methods of evaluation of patients with severe constipation including nuclear transit studies, sitz markers, ultrasound, and rectal manometry are critically discussed. The authors offer their original way to evaluate the magnitude of the constipation problem, based on the amount of senna laxative, necessary to empty the colon completely, as radiologically demonstrated.
Assessment of quality of derived macromolecular structures.

Publisher Summary This chapter discusses assessment of quality of derived macromolecular structures. Qualitatively, a structure is certainly good if it allows one to deduce the way the molecule operates. However, some insight can often be readily derived from NMR spectral data without recourse to the relatively troublesome task of “determining a structure.” The NMR data used to determine structures have always included interproton distance related two-dimensional (2D) NOE or possibly (rotating-flame Overhauser effect spectroscopy) cross-peak intensities. This is sometimes augmented by torsion angle-related data from scalar coupling-based spectra. Typically, distances are estimated from 2D NOE spectra along with an estimate of upper and lower bounds to each of the distances. The chapter discusses factors that may affect the quality of the protein structure derived using NMR data. Some of these factors depend on molecular features, some on the structural information extracted from NMR data, and some on the methods employed to determine structure from the experimental information.
Closed-loop nonlinear system identification using the vector optimal parameter search algorithm

The vector optimal parameter search (VOPS) and the constrained optimal parameter search (COPS) are recently developed algorithms for closed-loop linear system identification. We extend both algorithms to be applicable to a closed-loop nonlinear system, which is characterized by a vector nonlinear autoregressive model. Monte Carlo simulations of the nonlinear closed-loop system were performed to compare the performance of the VOPS to the widely utilized vector least squares (VLS), the COPS, and the total least squares (TLS) approaches. The relative error and linear transfer functions are computed to determine the accuracy of each method. The clinical applicability of the two extended methods is examined by applying them to a classical physiological closed-loop system, the heart rate baroreflex.
Determination of carbon and its radioactivity. III. Transfer of small samples of CO2 to counting tubes.

A micromanometric modification of the ninhydrin-CO/sub 2/ method for determining carboxyl CO/sub 2/ of alpha -amino acids is described together with transfer of the CO/sub 2/ to a Bernstein-Ballentine gas counter for counting C/ sup 14/O/sub 2/. The procedure serves for amounts of carboxyl carbon in the range 10 to 30 mu g. When CO/sub 2/ is transferred from a manornetric chamber to a gas counter, a small amount of CO/sub 2/, sufficient to be significant when the sample is less than 2 mg of carbon, may be trapped in the connecting tube between the manometric chamber and the counter. The trapped CO/sub 2/ can be quantitatively washed into the counter by a few milliliters of methane admitted into the mano- metric chamber after the usual transfer operation. (auth)
Enhanced Responsiveness to Novelty and Cocaine Is Associated with Decreased Basal Dopamine Uptake and Release in the Nucleus Accumbens: Quantitative Microdialysis in Rats under Transient Conditions

Male rats were screened for their response to a novel environment and designated as high responders (HRs) or low responders (LRs). They then received daily injections of saline or cocaine (20 mg/kg, i.p.). Basal and cocaine-evoked extracellular dopamine (DAext) levels as well as basal DA uptake rate and cocaine-evoked inhibition of uptake in the nucleus accumbens were determined on abstinence day 3 using quantitative microdialysis under transient conditions. The kinetics of uptake, dopamine transporter (DAT) expression, and [3H](−)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate ([3H]WIN35428) binding were also examined. The locomotor activating effects of cocaine and the magnitude of behavioral sensitization were greater in HRs. Saline-treated HRs had lower basal uptake than LRs. DA uptake after cocaine challenge was also lower in these animals. Although basal DAext did not differ, cocaine-evoked DAext was greater in HRs. The K m and V max of DA uptake were higher in naive HRs than LRs, as were the K d and B max of [3H]WIN35428 binding. DAT protein expression did not differ. Previous cocaine exposure decreased basal DA uptake. It increased cocaine-evoked DAext and decreased the cocaine-induced inhibition of uptake, especially in HRs, indicating greater DA release during cocaine challenge in this phenotype. We hypothesize that lower basal uptake in HRs results from a decrease in DAT binding affinity that is compensated for, in part, by an increased number of plasma membrane binding sites. Basal uptake, but not DAext, was lower in HRs, indicating lower basal DA release in HRs. The finding that cocaine-evoked DAext is higher in naive and cocaine-exposed HRs suggests that the greater responsiveness of DA neurons in HRs may underlie the enhanced behavioral responses that characterize this phenotype.
Detection and Characterization of In Vivo Nitration and Oxidation of Tryptophan Residues in Proteins

Oxygen and nitrogen centered reactive species can cause specific structural modifications in amino acids and proteins, such as the addition of a nitro group onto aromatic residues. Heretofore, studies on protein nitration have mainly focused on the in vitro and in vivo nitro addition to tyrosine residues (3-nitrotyrosine or 3NT), whereas the formation of nitrotryptophan in proteins in vivo and/or its functional significance has remained quite obscure. A novel structural modification, involving the addition of nitro and hydroxy groups to tryptophan, has been detected in the mitochondrial protein succinyl-CoA:3-oxoacid CoA transferase (SCOT) in rat heart. Modified SCOT accumulated progressively with age, which was associated with an elevation of its activity. The specific biochemical properties of this novel amino acid were characterized by a combination of HPLC-electrochemical detection and mass spectrometric analysis. This chapter describes the experimental steps involved in the characterizations and a procedure for the synthesis of nitrohydroxytryptophan. Similar methodology can be applied to the identification of nitrohydroxytryptophan in other proteins.
Optically effective area of particle ensembles in the sea

The optically effective area (OEA) concentration of particles was computed from measured size distributions and concentrations of particles in the upper 100 m of the Pacific Ocean off Baja California and is shown to correspond closely to direct measurements of the volume coefficient of light scattering at an angle of 20°, shown previously to be proportional to total scattering. Plots of OEA as a function of particle diameter exhibit a maximum contribution at about 2 µm diameter at offshore stations and at 3.5 µm at nearshore stations. The roll-off at smaller particle diameters is attributed to diminished optical efficiency rather than to decreased concentrations of smaller particles.
Design of Small-Molecule Smac Mimetics as IAP Antagonists

Smac/DIABLO, discovered in 2000 as a protein released from mitochondria into the cytosol in response to apoptotic stimuli, functions as an endogenous antagonist of X-linked inhibitor of apoptosis protein (XIAP) and several other IAP proteins through direct binding. The interaction between Smac and IAPs involves the AVPI tetrapeptide binding motif on the N-terminus of Smac and a well-defined groove on the surface of these IAP proteins, providing an ideal site for the design of small-molecule Smac mimetics. Potent and cell-permeable small-molecule Smac mimetics have provided powerful pharmacological tools for study of the regulation of apoptosis by IAP proteins, and several such compounds are now in early clinical trials as new anticancer agents.
Should the druggist know the nature of substances he dispenses

While the following article is composed largely of a series of questions, it brings out important thoughts from the active life of pharmacists. Several of these questions, though not new, are worthy of consideration by associations. Confidence is an important factor in every activity, in fact is one of the essentials of business and must be passed along. It is impossible for the average pharmacist to test all the materia medica he handles; if this were necessary, it would certainly reduce the volume of his business and increase the overhead expenses. The reliability of our pharmaceutical and chemical manufacturers is of a high quality, and contributes to the efficiency of pharmacists. The error that is cited in the article, or similar one, may occur, but so rare are these occurrences, that they are impressive because they are unusual. It is almost impossible to employ the same care, in the average pharmacy, for the prevention of errors, as is imperative in manufacturing establishments. What the retailer rightly says to the consumer, „Know whom you are dealing with,” is applicable in buying.—Editor.
The NIMH Research Domain Criteria (RDoC) Project: implications for genetics research

Heterogeneity of disorders, comorbidity across diagnoses, and reification of existing disease classifications are some of the challenges facing psychiatry in the twenty-first century. NIMH’s Research Domain Criteria (RDoC) Project seeks to address these issues by defining basic dimensions of function that cut across disorders as traditionally defined and can be studied across multiple units of analysis, from genes to neural circuits to behaviors. The intent is to translate rapid progress in basic genetic, neurobiological, and behavioral research to an improved integrative understanding of psychopathology. In so doing, RDoC seeks to facilitate the development of new and/or optimally targeted treatments for mental disorders. The RDoC project would not have been possible without NIMH’s long-term investment in basic research. Without the continuation of basic research, both related and unrelated to current RDoC domains and constructs, it will not be possible to sustain the RDoC effort. This article seeks to outline the relationship between RDoC and NIMH’s ongoing support for broad-based basic research, from genetics to behavior.
Union Reform and Labor Law: Miners For Democracy and the Use of the Landrum-Griffin Act

In 1970, Miners For Democracy [MFD], a rank-and-file reform group within the United Mine Workers of America [UMWA], filed suit under the Landrum-Griffin Act to overturn the 1969 UMWA presidential election on grounds of fraud, intimidation, and corruption. Dissatisfied with the government’s prosecution of the case, MFD lawyers filed suit to gain intervenor status in the courtroom. Trbovich v. United Mine Workers of America allowed MFD lawyers to join the prosecution and help win the case, setting an important precedent. The election rules resulting from the Trbovich case created conditions for a fair campaign and an honest count. MFD won the election supervised by the Department of Labor, providing an important case study of the impact of the LMRDA.
Characterization of an inkjet chemical microdispenser for combinatorial library synthesis

Solenoid inkjet valves are characterized and implemented in an automated chemical microdispenser, the ChemJet, to be used for combinatorial library synthesis. A novel high-density format for chemical synthesis and assay is also presented. The “ChemSheet” consists of a 48 × 48 array of 8-μL wells, molded as an 8 1/2-in. × 11-in. sheet of polypropylene. The development of the ChemSheet created the need for high-speed, parallel microdispensing. The ChemJet addresses this need by providing the ability to dispense 8-μL volumes of chemical reagents to the 2304 wells of the ChemSheet in under 10 s, with an average reproducibility of ∼2.2%. Results from both quantitative and qualitative characterization of inkjet solenoid valves are presented. Characterization of the ChemJet instrument is also presented.
Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source

Much of the mortality attributed to influenza virus is due to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae. However, mechanisms underlying this coinfection are incompletely understood. We find that prior influenza infection enhances pneumococcal colonization of the murine nasopharynx, which in turn promotes bacterial spread to the lungs. Influenza accelerates bacterial replication in vivo, and sialic acid, a major component of airway glycoconjugates, is identified as the host-derived metabolite that stimulates pneumococcal proliferation. Influenza infection increases sialic acid and sialylated mucin availability and enhances desialylation of host glycoconjugates. Pneumococcal genes for sialic acid catabolism are required for influenza to promote bacterial growth. Decreasing sialic acid availability in vivo by genetic deletion of the major airway mucin Muc5ac or mucolytic treatment limits influenza-induced pneumococcal replication. Our findings suggest that higher rates of disease during coinfection could stem from influenza-provided sialic acid, which increases pneumococcal proliferation, colonization, and aspiration.
Shear‐wave splitting in Ethiopia: Precambrian mantle anisotropy locally modified by Neogene rifting

[1] Twenty-six broadband seismic stations in an areal array spanning 500 × 500 km across Ethiopia were used for shear-wave splitting studies. Our results show small-to-moderate delay times (0.5–1.7s) with fast-polarization azimuths sub-parallel to the orientation of the East African Rift (NNE-SSW) and also to the Proterozoic tectonic fabric across the entire studied area. Our results imply Ethiopian upper-mantle anisotropy is controlled largely by the Proterozoic accretion of the Mozambique belt, with possible minor effects within the rift due to aligned cracks or melt pockets parallel to the rift axis. Our observations are not consistent with anisotropy created by asthenospheric flow parallel either to the Cenozoic extension direction (NW-SE) or to the modern absolute plate motion direction (NNW-SSE), or to asthenospheric radial flow from the “Afar” plume.
Convergent evolution in law and science: the structure of decision-making under uncertainty

The formal structure of decision-making under uncertainty used in legal trials bears a noteworthy similarity to the structure of decision-making under uncertainty used in hypothesis testing in empirical science. The first purpose of this article was to explicate those similarities. Secondly, the article reviews the historical origins of these decision-making schemes in both law and science, finding that they evolved independent of each other to serve similar functions. Language: en
ActiveGraph: A digital library visualization tool

ActiveGraph is an information visualization tool designed to provide users with a concise, customizable view of objects in a digital library. A set of digital library objects is represented as a data set in a two- or three-dimensional scatter plot. The data set can represent any digital library objects in any medium: books, journals, papers, images, Web resources, or even entire databases. Since ActiveGraph is intended for use in the context of digital libraries, data attributes consist for the most part of metadata fields such as title, author, date of publication, and number of citations. Data attributes are mapped to six visual attributes of the scatter plot: the X-, Y-, and Z-axes, color, size, and shape. The metadata for a selected data point are displayed in a control panel on the right-hand side of the screen. Users can edit the metadata and even add new metadata fields. Thus ActiveGraph allows users to both view and customize the contents of a library. Because of its flexibility in handling digital library objects and metadata of different types, ActiveGraph can be used in a variety of digital library applications. In this paper, we describe two: LibGraph, which is a visualization of a collaborative library, and CiteGraph, which is a visualization of citation statistics. Both applications were designed for use by scientists and engineers, for whom scatter plots are familiar and intuitive visualizations.
SPIN AND ORBITAL ANGULAR MOMENTUM IN THE PROTON

Since the announcement of the proton spin crisis by the European Muon Collaboration there has been considerable progress in unravelling the distribution of spin and orbital angular momentum within the proton. We review the current status of the problem, showing that not only have strong upper limits have been placed on the amount of polarized glue in the proton but that the experimental determination of the spin content has become much more precise. It is now clear that the origin of the discrepancy between experiment and the naive expectation of the fraction of spin carried by the quarks and anti-quarks in the proton lies in the non-perturbative structure of the proton. We explain how the features expected in a modern, relativistic and chirally symmetric description of nucleon structure naturally explain the current data. The consequences of this explanation for the presence of orbital angular momentum on quarks and gluons is reviewed and comparison made with recent results from lattice QCD and experimental data.
Earth tide effects on flows in horizontal permeable elastic layers connected to wells

Summary. The flux between a well and a water-saturated permeable elastic layer caused by an oscillating rigid impermeable overburden is examined for plane and axi-symmetric flows. It is assumed that the overburden height is much greater than the layer thickness. Estimates of the amplitude of the water-level fluctuation in the well are made when the oscillation is caused by a small periodic gravity perturbation describing an Earth tide. It is shown that the maximum possible amplitude is inversely proportional to the layer porosity, and is attained only when the length (radius) of layer influencing the well exceeds a critical length. This critical length is much smaller for axi-symmetric flow than for plane flow. The maximum amplitude can be of order 1 cm or greater for low-porosity layers under an overburden of large depth.
Palaeontology: The 165-Million-Year Itch

New flea-like fossils from China provide a rare, tantalizing glimpse of bizarre insects in the Cretaceous and Jurassic. Possibly the oldest flea-like animals known, they provide a challenge to the functional morphologist to infer which animals they may have targeted.
Inhibition of glucosephosphate isomerase allozymes of the mosquitofish, Gambusia holbrooki, by Mercury

Frequencies of allozyme genotypes are being used as population-level indicators of environmental heavy-metal contamination. A genotype of glucose phosphate isomerase, Gpi-2[sup 38/38], of mosquitofish (Gambusia holbrooki) has been identified as mercury-sensitive in an acute toxicity assay. Partially purified preparations of GPI-2 38/38 and GPI-2 100/100 were assayed to determine differences in maximum gluconeogenic reaction velocity at seven mercury (added as HgCl[sub 2]) concentrations, 15 to 960 nM Hg. Log-Probit analysis of the inhibition curves indicated that the log (IC50) (log[sub 10] of the Hg concentration causing a 50% reduction in reaction velocity) for GPI-2 100/100 initial uninhibited reaction velocity was greater than that of GPI-2 38/38. Although the mechanism of inhibition was not experimentally determined, under the assumption of noncompetitive interaction between Hg and GPI-2, the inhibitor dissociation constants (95% asymptotic C.I.) for GPI-2 100/100 and GPI-2 38/38 were estimated from the log (IC50) as 204 nM Hg (155---269 nM Hg) and 479 nM Hg (363-617 nM Hg), respectively. These results suggested that Hg susceptibility related to the Gpi-2[sup 38/38] genotype in acute toxicity assays was likely not due to enhanced Hg inhibition of GPI-2 38/38.
Advances in the analysis and design of adaptive optics

Opto-mechanical analysis and design techniques for development of adaptive optics are presented. Topics include actuator stroke limits, actuator failures, optimum placement of actuators, and optimum structural design.
A prospective study of diet, smoking, and lower urinary tract cancer.

The association of diet and smoking with bladder cancer was investigated in a cohort study conducted in Hawaii. The study included 7995 Japanese-American men who were born between 1900 and 1919, and were examined from 1965 to 1968. After 22 years of follow-up, 96 incident cases of bladder cancer were diagnosed. Current cigarette smokers had a 2.9-fold risk of bladder cancer, compared with nonsmokers. A direct dose-response relation was observed, based on pack-years of cigarette smoking. Consumption of fruit was inversely associated with the risk of bladder cancer (P = 0.038) The relative risk was 0.6 among subjects who had the most frequent (> 5 times/wk) intake of fruits compared to those with the least intake (≤ 1 time/wk). A weaker inverse association with milk intake was also observed (P = 0.07). Frequent consumption of fried vegetables, pickles, or coffee increased the risk of bladder cancer, but none of these foods showed a significant dose-response relationship. There was no association of other selected foods, alcohol, total calories, protein, fat, or carbohydrates with bladder cancer risk.
Schistosoma mansoni: neurotransmitters, longitudinal musculature and effects of electrical stimulation.

Abstract Longitudinal muscle shortening of adult male Schistosoma mansoni is produced by electrical stimulation. Responses are frequency and strength dependent. Neither 5-hydroxytryptamine (5-HT) antagonists nor dopamine interfere with the response. 5-HT does not enhance it. Carbachol (10−4M), eserine (10−6M), and metrifonate (10−5M) block the response but acetylcholine alone has no affect. Atropine (10−4M) partially counteracts the effects of carbachol. Hyperosmotic sucrose but not urea blocks the stimulation response. It is concluded that the response is nonneuronally conducted via a pathway involving gap junctions and that neurotransmitters probably act as modulators of motor activity rather than as initiators of it.
The relationship between pedometer-determined ambulatory activity and body composition variables

OBJECTIVE: To examine the relationship between pedometer-determined ambulatory activity (steps/day) and body composition variables body mass index (BMI) and percentage body fat). DESIGN: Secondary analysis of a cross-sectional objective activity monitoring study for up to 21 consecutive days. SUBJECTS: A total of 109 apparently healthy adults (eight African American males, 23 African-American females, 33 Caucasian males, 45 Caucasian females), age 44.9±15.8 y, BMI=26.9±5.1 kg/m2. MEASUREMENTS: Pedometer-assessed ambulatory activity (steps/day), height and weight, and percentage body fat by bioelectrical impedance. RESULTS: Analyzed as both a continuous and a categorical variable (determined using 25th and 75th percentiles for distribution for steps/day), ambulatory activity was consistently related to body composition variables. Steps/day was inversely correlated with BMI and percentage body fat (r=−0.30, and r=−0.27, respectively, both P<0.01). The consistency of the relationship was also evident when examined using accepted BMI cut-off points for normal-weight, overweight, and obese categories. CONCLUSIONS: Individuals in this small sample with values greater than approximately 9000 steps/day are more frequently classified as normal weight for height. Individuals with values less than approximately 5000 steps/day are more frequently classified as obese. These findings require further corroborative investigation but provide preliminary cutoff points for identifying individuals at risk who may benefit from appropriate physical activity intervention.
Community-physician education partnerships: one strategy to eliminate racial/ethnic health disparities. Commentary on "Teaching physicians-in-training to address racial disparities in health: a hospital-community partnership".

©2003 Association of Schools of Public Health Respectful and mutually beneficial educational partnerships between community members and physicians are an essential component of emerging national strategies to eliminate racial/ethnic health disparities. These partnerships often provide a combination of educational sessions, critical dialogue, and skill building in community practice settings for the purpose of physician training. Educational sessions in which community members teach by describing their lived experiences at the unique and complex interfaces of race/ethnicity, health, history, and the urgent conditions of contemporary daily life create a rich context for physicians to understand the meaning of health disparities for individuals and community groups. Community members are experts in describing and teaching the profound life consequences of health disparities as well as naming the skills, tools, and resources that must be cultivated and shared in order to eliminate health disparities affecting their particular community. Well-constructed teaching partnerships also offer formal settings for ongoing dialogue between the physician and community member participants so that misinformation can be carefully untangled and long-held erroneous beliefs about racial/ethnic groups or physician practices can be dismantled. Encouraged and sustained dialogue of this kind has the potential to change physicians’ knowledge base, behaviors, and practice patterns. In the best dialogue settings, physicians can also learn to acknowledge and honor the irreplaceable role of community members as equal partners in the difficult work of learning how to eliminate health disparities. Multilevel community-physician educational partnerships, in which physicians become both students of and partners with the community, offer the promise of community-physician problem solving. Partnerships like the one described by Jacobs et al.1 are examples that lift our spirits and sharpen our resolve that it is indeed possible to eliminate racial/ethnic health disparities in our lifetime.
Tenderizing spent fowl meat with calcium chloride. 3. Biochemical characteristics of tenderized breast meat

Biochemical characteristics of spent fowl meat injected with calcium chloride or sodium chloride were evaluated. Hot-boned breast fillets were injected to 10% (wt/wt) with 0.3 M CaCl2 or 0.6 M NaCl, tumbled, and aged 24 h. Tumbling was conducted at 20 C, -635 mm Hg, 20 rpm for 1 h. Hot-boned and cold-boned (24 h) fillets were used as controls. One fillet from each carcass was baked and sheared with an Allo-Kramer cell, whereas the other fillet was used for biochemical analysis. Shear values indicated that both CaCl2- and NaCl-treated samples had significantly (P 0.05) to cold-boned samples. The CaCl2 injection treatment significantly elevated (P 0.05) among all treatments, which indicated that CaCl2 or NaCl did not contribute to meat tenderness through degradative changes in collagen. Calpain data indicated that mu-calpain had disappeared by 24 h aging in all treatments. The m-calpain activity was significantly lower (P 0.05) to that of hot-boned controls. Sarcomeres of CaCl2-treated samples were significantly shorter (P 0.05) to those of hot-boned controls, and were shorter than those of NaCl-treated muscles. The sarcomere length and calpain data suggest that CaCl2 tenderized fillets by ionic strength and calcium-specific effects (possibly a proteolytic action), whereas the NaCl solution tenderized by ionic strength effect at a similar conductivity level to that of the CaCl2 solution.