cssi/SciSciGPT-SciSciNet huggingface dataset:
Evidence that disruption of apicoplast protein import in malaria parasites evades delayed-death growth inhibition

Malaria parasites ( Plasmodium spp.) contain a nonphotosynthetic plastid organelle called the apicoplast, which houses essential metabolic pathways and is required throughout the parasite life cycle. Hundreds of proteins are imported across 4 membranes into the apicoplast to support its function and biogenesis. The machinery that mediates this import process is distinct from proteins in the human host and may serve as ideal drug targets. However, a significant concern is whether inhibition of apicoplast protein import will result in a 9delayed-death9 phenotype that limits clinical use, as observed for inhibitors of apicoplast housekeeping pathways. To assess the growth inhibition kinetics of disrupting apicoplast protein import, we targeted a murine dihydrofolate reductase (mDHFR) domain, which is stabilized by the compound WR99210, to the apicoplast to enable inducible blocking of apicoplast-localized protein translocons. We show that stabilization of this apicoplast-targeted mDHFR disrupts parasite growth within a single lytic cycle in an apicoplast-specific manner. Consistent with inhibition of apicoplast protein import, stabilization of this fusion protein disrupted transit peptide processing of endogenous apicoplast proteins and caused defects in apicoplast biogenesis. These results indicate that disruption of apicoplast protein import avoids delayed-death growth inhibition and that target-based approaches to develop inhibitors of import machinery may yield viable next-generation antimalarials.
The search for my computer science

A journey spanning Nigeria, the United States, and Tanzania, is one woman's search for meaning and validation as a computer scientist.
“When you’re around, I can talk about everything”

In this chapter, we consider the complexity inherent in studies of cognition outside formal cognitive research and testing. These challenges urge us to consider the interrelationships across dimensions of cognition, especially in relation to distributed cognition (Hutchins, Cognition in the wild. Cambridge, MA: MIT Press, 1995), and to strengthen connections in at least two ways: between and across researchers working in disparate disciplines that touch those living with dementia, and between and across individuals participating in interactions involving those with dementia. The book ends with a call to embrace patience in life’s gray areas, as one lives with the demanding and nebulous questions at the intersection of language, dementia, and meaning making.
Introduction: Nomenclature and Classification

Nomenclature, classification, and diagnosis of vasculitis are difficult because of the broad spectrum of types and locations of vessels affected, multiple patterns of injury, diverse known etiologies and pathogenic mechanisms, absence of known etiologies and pathogenic mechanisms in some forms of vasculitis, and the myriad overlapping and nonspecific signs and symptoms caused by vasculitides. The goals of nomenclature, classification, and diagnostic systems are to enable effective communication among biomedical investigators and healthcare providers, guide clinical and basic research on well-defined cohorts (classes) of patients, and, most importantly, facilitate diagnosis and effective treatment of individual patients. This chapter reviews the historical basis for vasculitis nomenclature, classification, and diagnosis and the use of pathologic, clinical, and serologic data for classification and diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Physicians and scientists have made remarkable advances in the classification and diagnosis of vasculitides since the seminal observations in the 1800s; however, validated and widely applied classification criteria and diagnostic criteria that are sufficiently accurate and precise for clinical research and patient care, respectively, remain elusive. Even after well-validated criteria are established, they must be under constant scrutiny and adjusted as new knowledge emerges and new diagnostic modalities are introduced.
Crane operation planning in overlapping areas through dynamic supply selection

Abstract The planning of tower crane operations is a complex process that has significant impact on the time, cost, productivity, and safety of construction projects. This complexity pertains to the involvement of multiple tasks, cranes, and material supply locations, as well as their interactions with each other. Overlapping areas between cranes also lead to increased collision possibilities, resulting in additional crane operation complexity. To increase crane operation productivity while maintaining safety, proper linkage between tasks, cranes, and material supply locations is important. Past research has linked tasks to supply points based on minimized individual task operating time, such that a task is linked to a supply point that provides the minimum amount of time for task completion. This approach may not be as efficient as possible for construction sites with overlapping crane areas, as it may increase total project time although time for each individual task is at a minimum. To address this concern, this research develops a Java-based, agent-based modeling (ABM) simulation tool to investigate the effects of dynamic supply selection on crane efficiency. This ABM applies a dynamic supply selection system and tests numerous scenarios to ensure the most efficient linkage between tasks, cranes, and supply locations. To evaluate the capabilities of the developed method, it has been applied to a real-world construction project. The results of this case study indicate that effective crane operation planning, conducted through dynamic supply location selection, with respect to tasks and cranes, can have a significant impact on productivity and the total schedule time of crane tasks.
Equine-assisted psychotherapy among adolescents with ACEs: cultivating altercentrism, expressiveness, communication composure, and interaction management

Adverse childhood experiences (ACEs) can produce long-lasting effects for individuals. Mental health practitioners in clinical psychology and social work have utilized equine assisted psychotherapy (EAP) to treat trauma related to adverse experiences; however, few studies have centralized communication messages and processes in EAP. The current qualitative study included observations and interviews with 11 adolescents with ACEs and examined (a) equine communication as a mechanism for client awareness and emotion regulation, (b) the development of communication competencies for adolescents with ACEs, and (c) transference of communication competencies in other relational contexts. Adolescents cultivated altercentrism (e.g., ability to decode communication, to focus consciously on the other), communication composure (e.g., ability to deal with psychological stress, while engaging assertiveness), communication coordination (e.g., ability to effectively communicate, manage misunderstandings), and expressiveness (e.g., provide clarity and emotional control in one’s own communication). Finally, adolescents described how these communication competencies transferred to other relationships (e.g., family, peers, and teachers). Implications for understanding communication competence, the practitioner’s role in supporting communication skill development in EAP, and the unique role of equines in mitigating the negative effects of ACEs are discussed.
Figures and Tables

As the old adage goes, a picture is worth a thousand words. Given the page limitations of applications and the importance of making it easy for reviewers to understand your ideas, figures can be a powerful approach to transmit information. Again, the emphasis is on clarity and organization. It may take extra work for you to format your figures in a manner that is consistent and appealing to the eye, but in the end that effort pays off if the figures are crystal clear and professional in appearance.
Sleep duration and vascular inflammation using hybrid positron emission tomography/magnetic resonance imaging: results from the Multi-Ethnic Study of Atherosclerosis.

Study Objectives: Short sleep duration (SD) is associated with cardiovascular disease. We investigated the relationship between objective SD and subclinical atherosclerosis employing hybrid positro...
“There's No One as Irish as Barack O'Bama”: The Policy and Politics of American Multiracialism

For the first time in American history, the 2000 United States census allowed individuals to choose more than one race. That new policy sets up our exploration of whether and how multiracialism is entering Americans' understanding and practice of race. By analyzing briefly earlier cases of racial construction, we uncover three factors important to understanding if and how intensely a feedback effect for racial classification will be generated. Using this framework, we find that multiracialism has been institutionalized in the federal government, and is moving toward institutionalization in the private sector and other governmental units. In addition, the small proportion of Americans who now define themselves as multiracial is growing absolutely and relatively, and evidence suggests a continued rise. Increasing multiracial identification is made more likely by racial mixture's growing prominence in American society—demographically, culturally, economically, and psychologically. However, the politics side of the feedback loop is complicated by the fact that identification is not identity. Traditional racial or ethnic loyalties and understandings remain strong, including among potential multiracial identifiers. Therefore, if mixed-race identification is to evolve into a multiracial identity, it may not be at the expense of existing group consciousness. Instead, we expect mixed-race identity to be contextual, fluid, and additive, so that it can be layered onto rather than substituted for traditional monoracial commitments. If the multiracial movement successfully challenges the longstanding understanding and practice of “one drop of blood” racial groups, it has the potential to change much of the politics and policy of American race relations.
Detection and confirmation of zilpaterol in equine hair using liquid chromatography-mass spectrometry.

Zilpaterol is a β2 -adrenergic agonist and a repartitioning agent that has a high potential for abuse in equine performance athletes. Analysis of zilpaterol in hair is an alternative sampling matrix that extends detection time periods beyond those found in urine or blood samples. Our laboratory has been screening for zilpaterol in hair for many years and recently detected and confirmed its presence in official samples. Accordingly, a liquid chromatography-mass spectrometry method was developed and validated to detect and confirm zilpaterol in equine hair. Briefly, equine hair was decontaminated, cut, and pulverized prior to disruption and liquid-liquid extraction in basic conditions. Following extraction, the sample was introduced to an Agilent 1260 HPLC and zilpaterol was separated using a reverse phase gradient with a total run time of 12.5 min. Following chromatographic separation, zilpaterol and its corresponding stable isotope labeled internal standard were introduced via positive mode electrospray ionization to a Thermo Q-Exactive Plus mass spectrometer and spectra collected using parallel reaction monitoring. The methodology was validated using in-house criteria including characterization of accuracy, precision, recovery, linear range, matrix effects, limit of detection, and limit of quantitation, and the method was found to be fit-for-purpose to confirm the presence of zilpaterol in equine hair. This methodology has been used to detect and confirm the presence of zilpaterol from out-of-competition hair samples submitted by regional racing authorities.
A survival mediation model with Bayesian model averaging.

Determining the extent to which a patient is benefiting from cancer therapy is challenging. Criteria for quantifying the extent of “tumor response” observed within a few cycles of treatment have be...
CHAPTER 346 – Kidney

The kidney is a complex, highly sophisticated organ containing diverse cells types responsible for specialized functions, both in the renal vasculature and nephron segments. The structure of the kidney and the process of urine formation allow for cell-to-cell influences along single nephron segments that are distant in space. In addition, the proximity of parallel structures permits lateral communication between tubules, capillaries, and interstitial cells. These two kinds of cell-to-cell communication are central for functional integration at the single-nephron and whole-organ levels. Communication is mediated by paracrine and autocrine agents that act extracellularly or intracellularly by turning on signaling systems, thus eventually unifying homeostatic regulation of renal hemodynamics, glomerular filtration rate, tubule-transport processes, and urinary excretion. Endothelial cells regulate renal vascularresistance and reabsorption of salt and water by the renal tubules via a variety of messenger molecules, including nitric oxide, prostaglandins, EETs, 20-HETE, and endothelin. The vascular and epithelial cells regulate their own functions via the production of the autocrine agent 20-HETE. Tubule cells produce dopamine, purine nucleotides, nitric oxide, prostanoids, and endothelin. These agents act locally to regulate the vasculature and transepithelial transport of salt and water. Despite a rapidly growing understanding of cell-cell signaling in the kidney, the wide variety of autocrine and paracrine systems and their actions on multiple cell types are not completely understood. Interactions with hormones and neural control systems add to this complexity. Current research is largely reductionist. Integrative studies are also needed, in particular, to discern the relative importance, cross-talk, redundancy, and compensatory effects of the various systems under physiological and pathophysiological conditions.
Simulation of wafer scale diagnosis

Summary form only given. DWI (Diagnosis of Wafer Scale Integrated Circuits), is a DOS C/sup ++/ program whose purpose is to assess the practicality of system-level diagnosis on a wafer scale. On the manufacturing line, diagnosis offers a replacement for probe test. For in-the-field operation, diagnosis holds promise for increasing the accuracy whereby faulty elements are identified, at reduced cost. With all of these applications, diagnosis eliminates or greatly reduces the need of external test equipment. The increasing prevalence of monolithic and multichip wafer scale modules may accelerate the search for alternatives to probe and scan. DWI can help the designer answer architectural questions such as: 1) What is the effect of the element failure rate and distribution of failures? 2) What is the best diagnosis algorithm?.
Mouse brain phosphoserine phosphohydrolase and phosphotransferase.

Abstract Phosphoserine phosphatase has been partially purified from mouse brain. The preparation catalyzes the phosphohydrolysis of phosphoserine at an optimal pH of about 6.2. This hydrolysis is strongly inhibited by serine. The preparation also catalyzes an exchange reaction whereby the phosphoryl group of phosphoserine is transferred to serine at an optimal pH of about 7.5. Treatment with urea results in inhibition of the hydrolytic activity and enhancement of the transferase activity. Conversely, transferase activity is inhibited by sucrose while the hydrolase activity or its inhibition by serine is unaffected. These iindings are not compatible with a mechanism that equates serine's activity as an inhibitor of hydrolysis with serine's role as a substrate in phosphotransferase. It is suggested that these two activities may be separate phenomena.
The Church and the Usurers: Unprofitable Lending for the Modern Economy

Professor McCall explains in a scholarly yet accessible manner the core principles of the usury doctrine. Tracing its history from Biblical texts, through Aristotelian philosophy and Roman law, to the great scholastic synthesis, Professor McCall separates the unchanging principles from the changes in their applications to new economic realities. With debt, personal, business and government spiraling out of control and massive insolvencies of ancient nations like Greece, contemporary economic theory has offered little in response. Professor McCall contributes the wisdom of the centuries in a concise and readable study.
Longitudinal associations between MRI and cognitive changes in very early MS.

Abstract Objectives Cognitive dysfunction in multiple sclerosis (MS) has been primarily examined in patients with advanced disease. Our objective was to study the longitudinal associations between brain magnetic resonance imaging (MRI) metrics and neuropsychological outcomes in patients with early MS. Methods Relapsing MS patients within 12 months of onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow-up. MRI metrics included percent brain volume changes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). A neuropsychological battery was performed annually. Mixed model regression measured time trends and associations between imaging and neuropsychological outcomes, adjusting for sex, age and education level. Results Forty-three patients (mean age 36 years; 31 females) were enrolled within 7.5±4.9 months of disease onset. 11.6% of patients with baseline cognitive assessment met conservative criteria for cognitive impairment. Compared to placebo, riluzole had no significant effect on neuropsychological performance; thus, both groups were combined for the association analyses. Baseline T2LV predicted subsequent changes in PASAT (p=0.006) and SDMT (p=0.002) scores. Longitudinal changes of T2LV were associated with changes in CVLT-II (p Conclusion These findings suggest that cognitive impairment is relatively common in patients with very early MS. Baseline and longitudinal changes in the lesion load may be associated with some of the most frequently identified changes in cognitive function in MS.
Fetomaternal transfer of I131 gamma globulin in the rat

Abstract I 131 labeled globulin, in four different preparations, is shown to pass from injected fetuses into the maternal circulations of eleven rats. The route of transfer is considered to be transplacental. In conjunction with the possible production of fetal antibodies, a mechanism for the causation of disorders which occur in late pregnancy is suggested.
β-Cyano meso-unsubstituted porphyrins for intramolecular charge transfer

Abstract β-Cyano meso -unsubstituted porphyrin 10 , synthesized via a ‘3+1’ condensation using a bromotripyrrane, shows an effective charge transfer interaction across the porphyrin between electron-acceptor and -donor groups in β-positions.
Influence of Hormones on Enzyme Activity in Mouse Mammary Gland in Vitro

Abstract Organ cultures of the mouse mammary gland have been concerned largely with the hormonal induction of secretory responses in nonsecretory prelactating tissue taken at mid-pregnancy. The impetus for these in vitro studies derives from experimentation with endocrinectomized mice wherein prolactin and cortisol initiated secretion in mammary glands in which lobulo-alveolar growth had been initiated by ovarian hormones and prolactin (29). Lobulo-alveolar formation which normally precedes lactational development does not appear to be a strict requirement for cellular function inasmuch as milk protein synthesis can be hormonally-induced in vitro in embryonic (5) and prepubertal (47) mammary tissue devoid of alveoli. These latter findings indicate that lobulo-alveolar formation can be dissociated from secretory development but do not necessarily imply that the status of the mammary cells is not important in the normal sequence of events leading to secretory function. For example, mammary explants from late pregnancy are more sensitive to hormonal stimulation than those from midpregnancy, and explants from involuted glands are even less responsive than the latter (31, 34).
Comparison of Aerosol Sample Introduction Systems for a DCP

The results of a comparative study of the relative analytical performance of different nebulizer and spray-chamber designs with a direct-current plasma (DCP) are described. Concentric-glass, cross-flow, and Babington-type nebulizers were each evaluated with either a double-pass or an open spray-chamber geometry for the effect of each combination on the observed linear dynamic range and the magnitude of interferences arising from the presence of an easily ionizable element (sodium) and difficult-to-vaporize species (phosphate salts). The performance of each of these combinations was compared to that of the nebulizer/spray-chamber configuration provided by the manufacturer. For nearly all cases, the manufacturer's configuration provided, at worst, comparable signal intensities for all conditions investigated.
The Drexel Disk: hypertext-based instructional software as a tool for the exploration of a constrained knowledge space

In this paper, an example of multi-functional, transportable instructional software is described. The software provides the user with a constrained knowledge space and the necessary tool to explore it. Relying heavily on graphics and hypertext linkages, the software is easy to use; it is distributed throughout the university as part of a solution to the problems of training and supporting microcomputer users.
The Indirect Pathway of Allorecognition. The Occurrence of Self-Restricted T Cell Recognition of allo-MHC Peptides Early in Acute Renal Allograft Rejection and Its Inhibition by Conventional Immunosuppression

There is evidence that T cells can "directly" recognize intact allo-MHC molecules on the surface of allogeneic stimulator or target cells, and/or "indirectly" recognize processed allo-MHC peptides presented by self antigen-presenting cells (APCs). We and others have recently demonstrated that in vivo-primed rat CD4+ T cells recognize and proliferate to specific polymorphic amino acid sequences when presented as MHC allopeptides by self APCs. Studies on the mechanisms of indirect T cell recognition of alloantigen are now reported. First, we studied the immunogenicity of 4 synthetic polymorphic class II MHC allopeptides representing full-length sequences of the hypervariable domains of RT1.Du beta (DR or I-E-like) in several responder strains: LEW (RT1(l)), ACI (RT1a), BUF (RT1b), BN (RT1n), and control syngeneic WF (RT1u) strains. Immunogenicity of the individual 25mer allopeptides varied in the different responder strains, indicating that self-restricted T cell recognition of allo-MHC peptides is determined not only by polymorphisms, but also by the responder MHC genotype. Self-restricted CD4+ T cell recognition of processed allo-MHC peptides has been shown to occur during acute skin and cardiac allograft rejection, and there is evidence that this pathway may play an important role in initiating and amplifying the immune response to allografts. T cells from LEW animals primed in vivo by WF (RT1u) vascularized renal allografts were capable of proliferating to the RT1.Du beta peptides as early as 3 days postengraftment, when presented by self APCs. We then tested the effects of various immunosuppressive drugs on self-restricted primed T cell proliferative response to an immunogenic MHC allopeptide in vitro. Methylprednisolone, cyclosporine, and FK506 inhibited the proliferative response of RT1.Du beta 2-primed LEW T cells in a dose-dependent fashion. In addition, a single injection of cyclosporine (25 mg/kg i.m.) to LEW recipients of WF renal allografts on the day of transplantation completely abolished the proliferative response of in vivo-primed T cells to RT1.Du beta 2, indicating the susceptibility of the indirect pathway of allorecognition to conventional immunosuppressive drugs.
Meta-analysis of Cohen's kappa

Cohen’s κ is the most important and most widely accepted measure of inter-rater reliability when the outcome of interest is measured on a nominal scale. The estimates of Cohen’s κ usually vary from one study to another due to differences in study settings, test properties, rater characteristics and subject characteristics. This study proposes a formal statistical framework for meta-analysis of Cohen’s κ to describe the typical inter-rater reliability estimate across multiple studies, to quantify between-study variation and to evaluate the contribution of moderators to heterogeneity. To demonstrate the application of the proposed statistical framework, a meta-analysis of Cohen’s κ is conducted for pressure ulcer classification systems. Implications and directions for future research are discussed.
Global tectonics and metallogeny: Deep roots of some ore-controlling fracture zones. A possible relation to small-scale convective cells at the base of the lithosphere?

Abstract Criteria suggest that some of the ore-controlling fracture zones have deep roots, some extending into the upper mantle. The question is analyzed of whether a pattern of deep-seated fracture zones, extending to the base of a continental lithosphere, may be related to, or interact with, the small-scale convective cells (rolls) which originate [1,2] in the mantle beneath a moving lithospheric plate. The analysis follows a previous application of the same concept by others [3,4] who explained the origin of a chain of volcanoes by the movement of an oceanic lithospheric plate over a pattern of small-scale convective cells of the underlying mantle. The Canadian Shield is used to discuss the above question. A correlation has been found between: (1) the direction of two sets of long wavelength gravity anomalies detected by Stephenson and Beaumont, [8] in a study of the isostatic response of the Canadian Shield, and (2) the pattern of N-S and E-W trending trajectories of ore-controlling fracture zones, postulated by the author [5,6] in the southern part of the Canadian Shield. The Hudson Bay Paleolineament [7] correlates very well with the N-S set of gravity anomalies. The above correlation suggests that the ore-controlling lineaments and the long wavelength anomalies of the Canadian Shield are related. If the gravity anomalies reflect, as Stephenson and Beaumont [8] tentatively suggest, a pattern of convective cells beneath the base of the lithosphere, then the volcanic activity and metallogenesis may be related to the boundaries and corners of the cells. The author suggests that the convective cells could, in this case, originate by melting of the mantle material proceeding preferentially along the intersecting deep-seated fracture zones. The pattern of deep-seated fracture zones, compiled for the western United States [9] also shows a relationship of major ore deposits and ore clusters to the corners of rectangular blocks, defined by mutual intersection of the E-W and N-S fracture zones. In this case, the size of the blocks, measured in an E-W direction, is about 530 km, and in a N-S direction about 600 km. These figures are significantly close to the distance from the seismic discontinuity at a depth of 650 km, which is considered by others [2,4] as the lower boundary of the small-scale convection.
Determination of the gas-phase acidities of cysteine-polyalanine peptides using the extended kinetic method

We determined the gas-phase acidities of two cysteine-polyalanine peptides, HSCA3 and HSCA4, using a triple-quadrupole mass spectrometer through application of the extended kinetic method with full entropy analysis. Five halogenated carboxylic acids were used as the reference acids. The negatively charged proton-bound dimers of the deprotonated peptides with the conjugate bases of the reference acids were generated by electrospray ionization. Collision-induced dissociation (CID) experiments were carried out at three collision energies. The enthalpies of deprotonation (ΔacidH) of the peptides were derived according to the linear relationship between the logarithms of the CID product ion branching ratios and the differences of the gas-phase acidities. The values were determined to be ΔacidH(HSCA3)=317.3 ± 2.4 kcal/mol and ΔacidH (HSCA4)=316.2±3.9 kcal/mol. Large entropy effects (Δ(ΔS)=13–16 cal/mol K) were observed for these systems. Combining the enthalpies of deprotonation with the entropy term yielded the apparent gas-phase acidities (ΔacidGapp) of 322.1±2.4 kcal/mol (HSCA3) and 320.1±3.9 kcal/mol (HSCA4), in agreement with the results obtained from the CID-bracketing experiments. Compared with that in the isolated cysteine residue, the thiol group in HSCA3,4 has a stronger gas-phase acidity by about 20 kcal/mol. This increased acidity is likely due to the stabilization of the negatively charged thiolate group through internal solvation.
The Preaching Power of Cardinal John Henry Newman

AbstractCardinal John Henry Newman is remembered as one of the greatest preachers of the 19th century. His influence is unrivalled as he drew enormous crowds to hear his Sunday afternoon sermons at St Mary’s at Oxford. Yet many historical accounts of his preaching style reveal what may be labelled as serious defects by modern standards. Eye witnesses report him as having little biblical exegesis, reading from a manuscript with his eyes down, speaking quickly in a monotone voice broken up by long pauses and occasionally not even being loud enough to reach everyone in the room. The question raised, therefore, is: what made John Henry Newman such a great preacher? The comments of his listeners and Newman’s own reflections on preaching reveals that one of the chief characteristics that granted Newman such power from the pulpit was not his ability to exegete and exposit a biblical text, but rather his ability to exegete and exposit his audience. Modern preachers can learn from Newman’s example the ability to e...
Airway epithelium modulates the reactivity of guinea-pig respiratory smooth muscle☆

Abstract The influence of the epithelium on the reactivity of guinea-pig tracheal smooth muscle in vitro was investigated. Mechanical removal of the epithelium produced contrasting effects on methacholine-, histamine- and K + -induced contractions of tracheal strips. Epithelium removal resulted in 2.1-fold shifts to the left of histamine and methacholine concentration-response curves, and an increase in the maximum response to histamine; the maximum response to methacholine was unaffected. Epithelium removal had little effect on the sensitivity, but decreased the maximum response to K + . The results suggest that inhibitory and excitatory factor(s) are released from epithelial cells, and that these factors modulate the reactivity of the smooth muscle. Indomethacin (1 μM) produced in epithelium-containing preparations qualitatively identical effects on the sensitivity to methacholine and on the maximum response to histamine as removal of the epithelium. However, indomethacin was without efect on the sensitivity to histamine in the presence or absence of the epithelium. Alterations in the production or release of epithelial cell-derived factors may contribute to the airway hyperreactivity observed in respiratory disorders.
ACUTE INJURIES AND SPECIFIC PROBLEMS IN ADULT ATHLETES

Special considerations need to be given to specific groups of adult athletes. The most common problems and needs of female and older athletes are discussed in the first section of this article. The second section reviews the diagnosis and management of certain acute injuries most frequently encountered in adult athletes. The last section discusses the differentiation between tarsal tunnel syndrome and plantar fasciitis, chronic compartmental pressure syndrome and medial tibial stress syndrome ("shin splints"), and pelvic stress fractures and osteitis pubis, some commonly encountered difficult diagnoses.
Comparison of Narrow Bipolar Events with Ordinary Lightning as Proxies for the Microwave-Radiometry Ice-Scattering Signature

Abstract The narrow bipolar event (NBE) is a unique lightning discharge that has a short (∼10 μs) overall duration, lacks a prior leader phase, and produces too little light output to be visible by optical lightning detectors on satellites. NBEs thus have basic differences from ordinary lightning discharges, which occur in flashes lasting up to a fraction of a second, carry significant current in a “stroke” only after a leader stage that prepares the conductive channel, and produce copious light that is recordable from space. Thus, the authors are motivated to determine whether the meteorological setting of NBEs differs from, or is similar to, that of ordinary lightning. A previous paper started this project of comparing NBEs with ordinary lightning by comparing the placement of either type of lightning within spatial structures of cloud depth, as revealed by infrared cloud-top temperature. That previous study employed lightning data from the Los Alamos Sferic Array (LASA) in Florida. The present paper ex...
Purification and primary structure of galanin from the alligator stomach.

Galanin-like immunoreactivity (6 pmol/g tissue) was detected by radioimmunoassay in an extract of the stomach of the alligator, Alligator mississipiensis, but the peptide was present only in low concentration (<0.5 pmol/g) in extracts of the brain and small intestine. Alligator galanin comprises 29 amino acid residues and contains an α-amidated C-terminal residue. Residues 1–22 of alligator galanin are identical to the corresponding sequence in pig/sheep/rat galanins, demonstrating that strong evolutionary pressure has acted to conserve the receptor-binding domain of the peptide. Unexpectedly, in view of the close phylogenetic relationship between crocodilians and birds, alligator galanin is structurally more similar to sheep galanin (three amino acid substitutions) than to chicken galanin (four amino acid substitutions).
The categorical framework of object-oriented concurrent systems

Abstract Category Theory is introduced as a mathematical model for an object-oriented concurrent system which is viewed as a collection of objects and processes. An object can be represented as an algebra, whereas a process as a subalgebra.
Reflections on the early days of THz spectroscopy

Early struggles in the development of THz spectroscopy are reviewed. The field, covering an important spectral region for material characterization, suffered badly from poor lightsources and detectors in the old days, but blossomed rapidly after the arrival of femtosecond lasers. It provides another example how advances of laser technology revolutionize a field.
The Glucocorticoid Receptor Resource

The glucocorticoid receptor resource focuses on the structure-function relationships of the glucocorticoid receptor. As well as links to sequence and bibliographic databases via the World Wide Web, the database contains sequence comparisons of receptors from different species and source information for glucocorticoid receptor clones, probes, cell lines and antibodies. The resource allows the electronic publication of essays, unpublished data and reviews on steroid receptors. These publications will not be reviewed or edited and should allow the rapid dissemination of information to the scientific community. The resource can be reached at: http://biochem1.basic- sci.georgetown.edu/grr/grr.html.
Benefits and Costs of a Physician to a Community

TEEPLY RISING medical costs and the inaccessibility of health care to residents in the rural areas are causes of growing concern in this country. The Comprehensive Health Planning Act of 1966 and the Partnership for Health Amendments of 1967 reflect this public concern about the present allocation of health care resources. These acts establish a mechanism for comprehensive areawide and statewide planning that can identify health problems and establish priorities in the allocation of resources. Both a general understanding and specific estimates of the basic behavior relations of the
Leukocytes navigate by compass: roles of PI3Kγ and its lipid products

Morphologic polarity is necessary for the motility of mammalian cells. In leukocytes responding to a chemoattractant, this polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). Moreover, in neutrophils, lipid products of PI3Ks appear to regulate activation of Rho GTPases, are required for cell motility and accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells. By spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles not only in establishing leukocyte polarity but also as compass molecules that tell the cell where to crawl.
Processes active in mafic magma chambers: The example of Kilauea Iki Lava Lake, Hawaii

Abstract Kilauea Iki lava lake formed in 1959 as a closed chamber of 40 million m 3 of picritic magma. Repeated drilling and sampling of the lake allows recognition of processes of magmatic differentiation, and places time restrictions on the periods when they operated. This paper focuses on evidence for the occurrence of lateral convection in the olivine-depleted layer, and constraints on the timing of this process, as documented by chemical, petrographic and thermal data on drill core from the lake. Lateral convection appears to have occurred in two distinct layers within the most olivine-poor part of the lake, created a slightly olivine-enriched septum in the center of the olivine-depleted section. A critical marker for this process is the occurrence of loose clusters of augite microphenocrysts, which are confined to the upper half of the olivine-poor zone. This process, which took place between late 1962 and mid-1964, is inferred to be double-diffusive convection. Both this convection and a process of buoyant upwelling of minimum-density liquid from deep within the lake (Helz, R.T., Kirschenbaum H. and Marinenko, J.W., 1989. Diapiric melt transfer: a quick, efficient process of igneous differentiation: Geological Society of America Bulletin, v. 101, 578–594) result from the fact that melt density in Kilauea Iki compositions decreases as olivine and augite crystallize, above the incoming of plagioclase. The resulting density vs. depth profile creates (1) a region of gravitationally stable melt at the top of the chamber (the locus of double-diffusive convection) and (2) a region of gravitationally unstable melt at the base of the melt column (the source of upwelling minimum-density melt, Helz, R.T., Kirschenbaum H. and Marinenko, J.W., 1989. Diapiric melt transfer: a quick, efficient process of igneous differentiation: Geological Society of America Bulletin, v. 101, 578–594). By contrast the variation of melt density with temperature for the 1965 Makaopuhi lava lake does not show a decrease in density as temperature decreases, so neither process should have occurred in that lava lake. Because many mafic magmas crystallize significant olivine and/or pyroxene before they begin to crystallize plagioclase, the density relations observed for Kilauea Iki, and the processes that result from them, may be relevant to crystallization in other mafic magma chambers. The results for the 1965 Makaopuhi lava lake emphasize the role of bulk composition as a critical control on magmatic processes.
History of desorption induced by electronic transitions

Abstract Desorption induced by electronic transitions (DIET) encompasses electron- and photon-stimulated desorption (ESD and PSD) of atoms, molecules and ions from surfaces. In this paper, we focus on the key experimental and theoretical developments that have led to a fundamental understanding of DIET processes. We emphasize the effects of ionizing radiation, i.e., electrons and photons with energies ≳ 10 eV. The first DIET studies were occasioned mainly by the observation of anomalous peaks in mass spectrometers and spurious signals in ionization gauges. These observations were followed in the early 1960's by systematic studies of Redhead, and Menzel and Gomer, who independently proposed a Franck-Condon excitation model for electron-stimulated desorption of ions and neutrals from surfaces. In the years after this seminal work, ESD and PSD developed as fields of active interest to surface scientists. In addition to providing insights into the fundamental mechanisms linking atomic motion and electronic energy dissipation at surfaces, DIET investigations are continuing to impact upon radiation damage processes in areas as diverse as X-ray optics, semiconductor electronics, surface analysis and synthesis of molecules in interplanetary space.
Favorable results of implantable cardioverter-defibrillator implantation in patients older than 70 years.

Abstract Background . The clinical results of implantable cardioverter-defibrillator (ICD) implantation in the elderly have received limited documentation. As the longevity of the U.S. population has increased, so has the need for ICD implantation in the elderly. We evaluated the efficacy and outcome of ICD implantation in elderly patients (>70 years) compared with younger patients. Methods . The case records of all consecutive patients who underwent ICD implantation at our institution between 1986 and 1994 were reviewed. Of a total of 238 patients, 78 patients were 70 years of age or older and 160 patients were younger than 70 years of age. Results . The mean age of the younger group was 58 years and that of the elderly group was 74 years. There were no statistical differences in the presence of coronary artery disease, left ventricular systolic function, the inducibility of arrhythmias, or the history of sudden cardiac death. The hospital morbidity rate was similar in both groups (6.9% in the younger group and 7.7% in the elderly group; p = not significant). The operative mortality rate was 1.9% for the younger group and 1.3% for the elderly group ( p = not significant). At a mean follow-up of 33 ± 26 months, Kaplan-Meier survival curves demonstrated similar survival rates, with 93%, 82%, and 65% of the patients alive at 1, 3, and 6 years, respectively. Conclusions . Implantable cardioverter-defibrillator implantation was equally effective in the treatment of patients older than 70 years as in younger patients. No differences in theoretic survival or morbidity were observed.
Second-order Z-dependent theory of many-electron atoms

Abstract A quantitative description of complex term spectra requires accurate knowledge of the three leading coefficients in the Z expansions E = E0Z2 + E1Z + E2 + E3Z−1 + … of term energies. The screening approximation (described in a previous paper) yields exact values for E0 and E1 but only estimates of the remaining expansion coefficients. The present paper is concerned with the coefficient E2, which may be split up into two physically and mathematically distinct components, E2′ and E2″. The intermediate states that figure in the perturbation formulae for E2′ and E2″ differ from the initial state in one and two principal quantum numbers respectively. The Hartree-Fock and extended Hartree-Fock (Section II) approximations to E2 prove to be successive approximations to the component E2′. E2HF, E2EHF and E2′ can all be readily evaluated directly from their perturbation formulae. Examples of such calculations are given and the results are compared with the results of conventional calculations of the same quantities. The component E2″ can be expressed as a linear combination of values of E2″ for two-electron states in a manner first described, schematically, by Bacher and Goudsmit in 1934 (19). For two-electron states, the coefficient E2 can be evaluated by existing techniques, and from E2 one easily obtains E2″. Using published variational calculations of E2 for the two-electron states 1s 2 1 S , 1s2s 1 S and 1s2s 3 S , we evaluate E2″ for the three-electron state 1s 2 2s 2 S . The properties of the coefficient E2, together with considerations based on the screening approximation, enable one to understand why, in low-lying configurations, term-energy patterns appropriate to high degrees of ionization usually persist down to quite low degrees of ionization. First-order calculations of the matrix elements of one-electron operators are shown to correspond in complexity, not to complete second-order energy calculations as one might expect on general perturbation-theoretic grounds, but to calculations of E2EHF. They can either be based on perturbation expansions which involve single generalized sums of products of hydrogenic radial integrals, or they can be made to depend on the solution of ordinary, inhomogeneous, second-order differential equations.
Removal of High-Molecular-Weight DNA by Carboxylated Magnetic Beads Enhances the Detection of Mutated K-ras DNA in Urine

We have previously demonstrated that mutated DNA derived from the circulation can be detected in urine and predominantly exists as DNA fragments < 1 kb. To preferentially isolate the trans-renal DNA from urine, we developed a method using carboxylated beads to separate high-MW (1 kb or larger) from low-MW DNA in urine. A primer set for 18s rRNA (generating a PCR product of 872 bp) was designed and optimized for real-time PCR quantification of high-MW DNA templates. To evaluate the method, urine samples from 5 volunteers with no known diseases and 36 patients with various colorectal diseases were collected and tested. It was found that the average removal efficiency of high-MW DNA from total urine DNA using carboxylated beads is 92.72% ± 1.42%. Furthermore, compared with using total urine DNA, our method provides a greater ability to detect mutated K-ras in the urine of colorectal cancer patients. The concurrence of K-ras mutations detected in disease tissue and the corresponding urine specimen is significantly higher (P = 0.0015) when the samples were enriched in low-MW DNA.
Preparation of Well-Defined, Metathetically Active Oxo Alkylidene Complexes of Tungsten

The reaction between W(CH-t-Bu)(O)(PMe3)2Cl2 and 2 equiv of KO-2,6-Ph2C6H3 yields yellow crystalline syn-W(CH-t-Bu)(O)(OAr)2(PMe3) (1a; Ar = 2,6-Ph2C6H3) in which the PMe3 is bound to tungsten on the NMR time scale. An analogous PPh2Me complex, syn-W(CH-t-Bu)(O)(OAr)2(PPh2Me) (1b), can be prepared. Both 1a and 1b react readily with 2,3-dicarbomethoxynorbornadiene (2a) and 2,3-bis(trifluoromethyl)norbornadiene (2b) in dichloromethane or toluene to give polymers that are >95% cis and >95% isotactic.
Computation of External Aerodynamics for a Canard Rotor/Wing Aircraft

The aerodynamic loads on a Canard Rotor/Wing vehicle are investigated using inviscid numerical simulations in order to understand the flight characteristics of the vehicle during conversion from rotor craft to fixed-wing flight. A series of numerical simulations at seven azimuthal rotor indices are presented covering a quarter turn of the rotor With symmetry arguments, these simulations produce 25 data points for a complete rotation. A Cartesian mesh approach is used to compute the flow field about a configuration with faired-over engine inlet and exhaust that matches the wind tunnel geometry. These simulations were performed using meshes with approximately nine Million Cartesian cells. To better understand the aerodynamic effects of the rotor hub on the configuration, the same set of simulations were repeated for a hub-less geometry. Overall loads for both configurations are similar but are due to somewhat different aerodynamic mechanisms.
Particle migrations in laminar mixing of a suspension with a clean fluid

Die laminare Mischung von zwei Flussigkeitsstromen wird untersucht, von denen der eine Suspensionsteilchen mitfuhrt, wahrend der andere ursprunglich rein ist. Berucksichtigt wird der Schlupf, sowie die in der Scherstromung auftretende Querkraft auf die Teilchen. Storungslosungen werden fur den Anfang der Mischzone, sowie fur die weit stromabwarts liegenden Gebiete angegeben; diese beschreiben das Geschwindigkeitsfeld beider Phasen, den Phasenschlupf, sowie die Teilchenkonzentration.