cssi/SciSciGPT-SciSciNet huggingface dataset:
In vitro inhibition of mouse hepatic mixed-function oxidase enzymes by helenalin and alantolactone

The sesquiterpene lactones (STL) helenalin and alantolactone were effective in vitro inhibitors of the mouse hepatic microsomal mixed-function oxidase (MFO) enzymes, aminopyrine demethylase (APD), aniline hydroxylase (ANH) and 7-ethoxyresorufin deethylase (ERD). Helenalin and alantolactone concentrations of 0.5 mM produced a 50-60% inhibition of APD and ERD, and a 20-30% inhibition of ANH. An increase in substrate (aminopyrine) concentration from 0.5 to 25 mM decreased STL inhibition of APD by 12-32%. APD was also inhibited at low aminopyrine concentrations (0.5 mM) by the helenalin derivative 2,3,11,13-tetrahydrohelenalin (tetrahydrohelenalin). The STL produced type I binding spectra with oxidized microsomes; Ks values for helenalin and alantolactone were 161 and 9 microM respectively. These results suggest that STL inhibition of the MFO system results, in part, from STL binding to the substrate-binding site of cytochrome P-450. It has been reported that the irreversible alkylation of protein cysteinyl residues is responsible for STL inhibition of several different enzymes, and second-order rate constants for the reaction of helenalin and alantolactone with glutathione were 25.1 and 1.80 mM-1.hr-1 respectively. Tetrahydrohelenalin did not react with glutathione. However, the subsequent addition of 3.0 mM thiols, i.e. L-cysteine, N-acetylcysteine or glutathione, to STL-treated (0.5 mM) microsomes reversed helenalin and alantolactone inhibition of APD and ERD by 50-80%. The ability of thiols to reverse STL inhibition of APD was decreased 20-43% by the coincubation of STL and microsomes with an NADPH-generating system. In addition, established effects of sulfhydryl-reactive compounds on the MFO system, i.e. inhibition of NADPH-cytochrome c reductase and conversion of cytochrome P-450 to cytochrome P-420, were not observed after addition of helenalin (1.0 mM) or alantolactone (0.5 mM) to mouse hepatic microsomes. These results suggest that STL inhibition of MFO enzymes may not be dependent upon the reactivity of the STL towards sulfhydryl groups. Instead, we suggest that STL binding to the substrate-binding site of cytochrome P-450 and subsequent metabolism of the STL may contribute to inhibition of the MFO system.
Characterization of a Lipopolysaccharide-Targeted Monoclonal Antibody and Its Variable Fragments as Candidates for Prophylaxis against the Obligate Intracellular Bacterial Pathogen Coxiella burnetii

Our previous study demonstrated that treatment of Coxiella burnetii with the phase I lipopolysaccharide (PI-LPS)-targeted monoclonal antibody (MAb) 1E4 significantly inhibited C. burnetii infection in mice, suggesting that 1E4 is a protective MAb. To determine whether passive transfer of antibodies (Abs) can provide protection against C. burnetii natural infection, we examined if passive transfer of 1E4 would protect SCID mice against C. burnetii aerosol infection. The results indicated that 1E4 conferred significant protection against aerosolized C. burnetii, suggesting that 1E4 may be useful for preventing C. burnetii natural infection. To further understand the mechanisms of 1E4-mediated protection and to test the possibility of using humanized 1E4 to prevent C. burnetii infection, we examined whether the Fab fragment of 1E4 (Fab1E4), a recombinant murine single-chain variable fragment (muscFv1E4), and a humanized single-chain variable fragment (huscFv1E4) retained the ability of 1E4 to inhibit C. burnetii infection. The results indicated that Fab1E4, muscFv1E4, and huscFv1E4 were able to inhibit C. burnetii infection in mice but that their ability to inhibit C. burnetii infection was lower than that of 1E4. In addition, treatment of C. burnetii with Fab1E4, muscFv1E4, or huscFv1E4 can block C. burnetii infection of macrophages. Interestingly, treatment of C. burnetii with huscFv1E4 can significantly reduce C. burnetii infectivity in human macrophages. This report provides the first evidence to demonstrate that the humanized variable fragments of an LPS-specific MAb can neutralize C. burnetii infection and appears to be a promising step toward the potential use of a humanized MAb as emergency prophylaxis against C. burnetii exposure.
Kupffer cell tumor necrosis factor-α production is suppressed during liver regeneration

Abstract Mammalian liver regeneration following resection invokes intrinsic hepatic responses which result in rapid tissue repair. The role of soluble immune cytokines in this phenomenon is not known. The capacity of Kupffer cells (KC) from regenerating liver to produce the potent cytokine TNF-α was evaluated. Twenty-four hours after 70% partial hepatectomy (PHx) or sham operation, Kupffer cells were harvested from collagenase-digested Wistar-Furth rat livers and purified (>95% by phagocytosis) by adherence. Following overnight culture with or without the cyclooxygenase inhibitor indomethacin (10 μM), 5 × 105 KC were repleted with fresh media with or without 2.5 μg/ml lipopolysaccharide (LPS). Supernatant TNF-α activities (units/ml) were measured using the L929 fibroblast lysis assay. With LPS, sham KC TNF-α levels were significantly higher (P
Towards a service-based middleware layer for runtime environments

Natively compiled, binary-code application programs are typically thought of as executing on the "raw" operating system. However, they do in fact utilize a bare-bones middleware layer---the dynamic linker. This paper presents a service-based view of an expanded run-time environment in which the current dynamic linker is only a core service, and other middleware-type services are available to the application and its components (shared libraries). This paper then describes a prototype implementation of such an environment, called SBRT, or Service-Based Run-Time. SBRT also contains a unified event-based interface that allows for customized middleware services by means of an extension mechanism.
Developmental transformation of dendritic arbors in mouse whisker thalamus

Neurons in slices though the somatosensory thalamus of postnatal day 6 and adult mice were injected with Lucifer yellow. Dendritic arbors on postnatal day 6 are confined to single barreloids (single whisker representations); in adults they are seven times longer, extending beyond their barreloid to adjacent barreloids. The postnatal transformation of dendritic arbors by total process growth and extension to adjacent barreloids suggests a developmental change in the role of these cells from instructing whisker pattern formation to integrating sensory information from more than one whisker.
Carrying the Cross, Caring for Kin: The Everyday Life of Charismatic Christianity in Remote Aboriginal Australia

In this paper, I address the important yet under-examined role of charismatic Protestant Christianity in the reconfiguring of personhood and social relations in the remote Yolngu settlement of Galiwin'ku. I focus in particular on the ways in which this form of Christianity, locally articulated, brings together indigenous concepts of personhood with those introduced by the market, the state, and evangelism to produce what I refer to as Christian individuality and Christian relatedness. These dialectical tendencies in postcolonial settlement life call attention to the ways Yolngu converts use their Christian practices both to continue kin-based moralities in the present and to engage (if selectively) modern individualism. This paper addresses post-colonial conditions where demands of state institutions and modern governance interact with changing ideas of personhood and sociality. It contributes to the growing anthropological literature on Pentecostal and charismatic Christianity.
ZigBee-based wireless multi-sensor system for physical activity assessment

Physical activity (PA) is important for assessing human exposure to the environment. This paper presents a ZigBee-based Wireless wearable multi-sensor Integrated Measurement System (WIMS) for in-situ PA measurement. Two accelerometers, a piezoelectric displacement sensor, and an ultraviolet (UV) sensor have been used for the physical activity assessment. Detailed analysis was performed for the hardware design and embedded program control, enabling efficient data sampling and transmission, compact design, and extended battery life to meet requirements for PA assessment under free-living conditions. Preliminary testing of the WIMS has demonstrated the functionality of the design, while performance comparison of the WIMS with a wired version on an electromagnetic shaker has demonstrated the signal validity.
Histiotypic electrophysiological responses of cultured neuronal networks to ethanol.

Abstract Embryonic murine neuronal networks cultured on substrate-integrated microelectrode arrays were used to quantify acute electrophysiological effects of ethanol by using extracellular, multichannel recording of action potentials. Spontaneously active frontal cortex cultures showed repeatable, concentration-dependent sensitivities to ethanol, with initial inhibition at 20 mM and a spike rate 50% effective concentration (EC 50 ) of 48.8±5.4 mM. Ethanol concentrations of greater than 100 mM led to cessation of activity. The ethanol inhibitions up to the maximum tested 160 mM were reversible. Although ethanol did not change the shape of action potentials, unit-specific spike pattern effects were found. At 40 mM, ethanol decreased neuronal firing in 71%, increased firing in 20%, and generated no effect in 9% of all units observed (14 cultures, 200 discriminated units). The effects of combined application of ethanol and fluoxetine were additive. Excellent agreement with findings obtained from experimental studies with animals validates the use of these in vitro systems for alcohol research.
Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies.

In patients with multiple sclerosis, investigation of a treatment effect on disease progression in clinical trials and observational studies often uses sustained progression on the expanded disability status scale (EDSS) as an outcome. It is not clear whether this outcome is the most powerful to detect a treatment effect on clinical disease progression. Assessment of EDSS modeling choice on the detection of treatment effect was of interest. This assessment was separately conducted under three potential treatment effects: treatment reducing the chance of higher future EDSS, treatment increasing the chance of lower future EDSS, and treatment leading to both effects. To assess the effect of modeling choice, nine modeling strategies were applied to the data to determine the most powerful approach. EDSS measurements were simulated at 6 month intervals for 24 months. Each patient’s initial EDSS value ranged between 0 and 3, and probabilities of transitioning from one EDSS state to another were based on the empirical probabilities of transition obtained from available clinical data. Modeling approaches based on sustained progression had less power than approaches which modeled the EDSS score directly, regardless of treatment effect. This difference was especially pronounced when the treatment effect corresponded to an increase in the probability of improvement. Sustained progression on the EDSS is a less powerful outcome measure for clinical progression than approaches based on the actual EDSS values.
SITE-DIRECTED MUTAGENESIS OF THE YEAST V-ATPASE B SUBUNIT (VMA2P)

The B subunit of the vacuolar (H+)-ATPase (V-ATPase) has previously been shown to participate in nucleotide binding and to possess significant sequence homology with the alpha subunit of the mitochondrial F-ATPase, which forms the major portion of the noncatalytic nucleotide binding sites and contributes several residues to the catalytic sites of this complex. Based upon the recent x-ray structure of the mitochondrial F1 ATPase (Abrahams, J.P., Leslie, A.G., Lutter, R., and Walker, J.E. (1994) Nature 370,621-628), site-directed mutagenesis of the yeast VMA2 gene has been carried out in a strain containing a deletion of this gene. VMA2 encodes the yeast V-ATPase B subunit (Vma2p). Mutations at two residues postulated to be contributed by Vma2p to the catalytic site (R381S and Y352S) resulted in a complete loss of ATPase activity and proton transport, with the former having a partial effect on V-ATPase assembly. Interestingly, substitution of Phe for Tyr-352 had only minor effects on activity (15-30% inhibition), suggesting the requirement for an aromatic ring at this position. Alteration of Tyr-370, which is postulated to be near the adenine binding pocket at the noncatalytic sites, to Arg, Phe, or Ser caused a 30-50% inhibition of proton transport and ATPase activity, suggesting that an aromatic ring is not essential at this position. Finally, mutagenesis of residues in the region corresponding to the P-loop of the alpha subunit (H180K, H180G, H180D, N181V) also inhibited proton transport and ATPase activity by approximately 30-50%. None of the mutations in either the putative adenine binding pocket nor the P-loop region had any effect on the ability of Vma2p to correctly fold nor on the V-ATPase to correctly assemble. The significance of these results for the structure and function of the nucleotide binding sites on the B subunit is discussed.
A Man with a Prosthetic Aortic Valve and Subacute Calf Pain

Diagnosis: Cardiobacterium hominis prosthetic valve endocarditis. C. hominis is one of the fastidious gram-negative bacteria that belong to the HACEK group of organisms (Haemophilus parainfluenzae, Haemophilus aphrophilus, Haemophilus paraphrophilus, Actinobacillus actinomycetemcomitans, C. hominis, Eikenella corrodens, and Kingella kingae). Tucker et al. [1] first reported it as a cause of endocarditis in 1962. The HACEK group are part of the normal oropharyngeal flora. Poor dentition and/ or having undergone dental work within the past 6 months have been described as sources of infection [2]. HACEK organisms cause -3% of cases of infective endocarditis [3]. One study found that it takes, on average, 3.4 days (range, 1-10 days) to grow these organisms with automated blood culture systems [3]. On Gram stain, C. hominis appears as teardropand dumbbell-shaped gram-negative rods. Figure 1 demonstrates the filamentous form of this organism. Classically, one can see a rosette shape on the Gram stain. The other gram-negative HACEK organisms have their own characteristics on Gram stain. Both A. actinomycetemcomitans and Haemophilus species are small coccobacillary rods, but, with the latter, one can occasionally see filamentous forms. E. corrodens typically appears as slender straight rods with round ends. K. kingae appears as short straight rods with square ends that form pairs and chains [4]. Biochemical testing of C. hominis usually reveals it to be oxidase positive, indole positive, and catalase negative; E corrodens and K. kingae are oxidase positive, whereas Haemophilus species and A. actinomycetemcomitans are oxidase negative. A. actinomycetemcomitans is the only catalase-positive organism in the HACEK group [4].
The Ignition Behavior of Various Amines With White Fuming Nitric Acid

Spontaneous ignitibil ity depends on synergetic behavior of several reactions, each of which exerts its greatest independent influence at a different t ime during the ignit ion period. The m o s t important of these reactions are a l iquid phase neutral izat ion reaction for al iphatic amines , a l iquid phase ni trat ion reaction for aromatic amines , and a slower, rate determining oxidation reaction which follows the others. Mixing which is too rapid can quench ignit ion if the mixture ratios, favoring the various reactions leading to ignit ion, are too widely separated.
Responsible and irresponsible liberalism: Dostoevsky's stavrogin

Genuine liberalism inspires suicidal boredom or murderous rage in those unable to endure it. That is the experience of Stravrogin in Dostoevsky's « Possessed ». He realises that the liberalism's liberation severs all ties with the moralities determining good and evil in mankind's herds. By nature there is only the individual free of all moral-political obligations
Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with haemophilia and high-responding inhibitors.

The development of inhibitors to therapeutic factor concentrates in children with haemophilia A or B is a troublesome complication of factor replacement therapy. Immune tolerance protocols have been d
A benzodiazepine used in the treatment of insomnia phase-shifts the mammalian circadian clock

Between 5 and 20% of the adult population in Western countries suffer from insufficient and/or unsatisfying sleep, often associated with certain psychiatric disorders or with certain types of professional activities (for example, shift workers) and travel schedules (for example, jet lag). The benzodiazepines are at present the drug treatment of choice for the management of anxiety and stress-related conditions as well as insomnia. Benzodiazepines are thought to act by potentiating the action of the neurotransmitter gamma-aminobutyric acid (GABA), a widely distributed transmitter in the central nervous system. The circadian system has a key role in the regulation of the sleep-wake cycle, and at least some forms of insomnia may be the result of a disorder of the circadian sleep-wake rhythm. Similarly, at least some forms of depression may also involve disruption of normal circadian rhythmicity. A central pacemaker for the generation of many circadian rhythms in mammals, including the sleep-wake cycle, appears to be located in the suprachiasmatic nucleus, and recent research indicates that both cell bodies and axons containing GABA are present within the bilaterally paired suprachiasmatic nuclei. These findings raise the possibility that the benzodiazepines, commonly prescribed for sleep and mental disorders, may have an effect on the central circadian pacemaker. Here we report that the acute administration of triazolam, a short-acting benzodiazepine commonly prescribed for the treatment of insomnia, induces a phase-shift in the circadian rhythm of locomotor activity in golden hamsters. This suggests a role for GABA-containing neurones in the mammalian circadian system.
WC1+ γδ T cell memory population is induced by killed bacterial vaccine

Limited studies have addressed the ability of γδ T cells to become memory populations. We previously demonstrated that WC1.1+ γδ T cells from ruminants vaccinated with killed Leptospira borgpetersenii proliferate and produce IFN-γ in recall responses. Here we show that this response is dependent upon antigen-responsive CD4 T cells, at least across transwell membranes; this requirement cannot be replaced by IL-2. The response was also dependent upon in vivo priming, since γδ T cells from leptospira vaccine-naive animals did not respond to antigen even when co-cultured across membranes from antigen-responsive PBMC. γδ T cells were the major antigen-responding T cell population for the first 4 wks following vaccination and replicated more rapidly than CD4 T cells. Primed WC1+ γδ T cells circulated as CD62Lhi/CD45ROint/CD44lo, characteristics of TCM cells. When stimulated with antigen, they decreased CD62L, increased CD44 and CD25, and had no change in CD45RO expression. These changes paralleled those of the leptospira antigen-responsive CD4 T cells but differed from those of γδ T cells proliferating to mitogen stimulation. This system for in vivo γδ T cell priming is unique, since it relies on a killed antigen to induce memory and may be pertinent to designing vaccines that require type 1 pro-inflammatory cytokines.
Inquiry as a Tool for Professional Development School Improvement: Four Illustrations.

Abstract Given the increasing pressures of high-stakes accountability associated with state mandates and No Child Left Behind (U.S. Department of Education, 2002), linking teacher preparation within professional development schools to the goal of school improvement has become essential. This article illustrates the University of Florida's efforts to understand the ways that prospective teacher education can be linked to individual school improvement efforts. It explains how teacher educators and their school-based partners collaboratively craft their professional development school work with prospective and practicing teachers to target school improvement and teacher learning. Four models for engaging in inquiry-oriented school improvement are illustrated and the factors that underlie their design are outlined. The four models illustrate the ways that inquiry-oriented professional development school work contributes to individual school improvement efforts while cultivating in its participants an inquiry ...
Surveillance and Monitoring of White-Tailed Deer for Chronic Wasting Disease in the Northeastern United States

Abstract Chronic wasting disease (CWD) is a prion disease that affects both wild and captive cervid populations. In the past 45 y, CWD has spread from northern Colorado to all bordering states, as well as the midwestern United States (Midwest) and northeastern United States (Northeast), Canada, and South Korea. Because CWD is a relatively new issue for wildlife management agencies in the Northeast, we surveyed a representative (e.g., cervid biologist, wildlife veterinarian) from 14 states to gain a better understanding of state-specific surveillance measures. Between 2002 and 2012, New York (37,093) and Pennsylvania (35,324) tested the greatest number of harvested white-tailed deer Odocoileus virginianus in the Northeast. Additionally, the 14 states surveyed have tested 121,730 harvested deer, or approximately 15,216/y, since CWD was first detected in 2005. The most common tissues used by agencies in the Northeast for testing were retropharyngeal lymph nodes, which have been determined to be the most reli...
Limit cycles in a disease transmission model

We show that certain disease transmission systems have stable limit cycles through Hopf bifurcation. Two-parameter families of systems with stable limit cycles are described.
An important constraint on tropical cloud ‐ climate feedback

[1] Tropical convective anvil clouds detrain preferentially near 200 hPa. It is argued here that this occurs because clear-sky radiative cooling decreases rapidly near 200 hPa. This rapid decline of clear-sky longwave cooling occurs because radiative emission from water vapor becomes inefficient above 200 hPa. The emission from water vapor becomes less important than the emission from CO2 because the saturation vapor pressure is so very low at the temperatures above 200 hPa. This suggests that the temperature at the detrainment level, and consequently the emission temperature of tropical anvil clouds, will remain constant during climate change. This constraint has very important implications for the potential role of tropical convective clouds in climate feedback, since it means that the emission temperatures of tropical anvil clouds and upper tropospheric water vapor are essentially independent of the surface temperature, so long as the tropopause is colder than the temperature where emission from water vapor becomes relatively small.
Preliminary list of the lepidopterous insects in the Arizona State University Hasbrouck Insect Collection

The Arizona State University Hasbrouck Insect Collection (ASUHIC) is one of the vital Southwest Arthropod collections in America North of Mexico, providing important biological information. The principal objective of the Catalog is to give a complete list of the lepidopterous insects held in the ASUHIC. Furthermore, it will be an online catalog of the Lepidoptera of Arizona. The preliminary Lepidoptera checklist is presented, consisting of 1983 species and 175 subspecies of 55 families in approximately 60,000 holdings at the ASUHIC. This article follows the recent classification and nomenclature (Hodges RW. 1983. Check list of the Lepidoptera of America north of Mexico. London, UK: E.W. Classey Ltd. and the Wedge Entomological Research Foundation; Moth Photographers Group (MPG). 2014. http://mothphotographersgroup.msstate.edu/MainMenu.shtml).
Psychopharmacology and Social Work Practice: Introduction:

This article provides an overview of the medication issues and concerns that social workers will encounter in practice Special emphasis is placed on the role of the social worker in regard to new trends in the field. Knowledge regarding medication use and misuse is highlighted. The intent is to provide social work professionals with a basic knowledge of medication-prescribing considerations to assist with assuming a client broker and advocate stance for the clients served.
Repression of the soma-specific transcriptome by Polycomb-repressive complex 2 promotes male germ cell development

Polycomb-repressive complex 2 (PRC2) catalyzes the methylation of histone H3 Lys27 (H3K27) and functions as a critical epigenetic regulator of both stem cell pluripotency and somatic differentiation, but its role in male germ cell development is unknown. Using conditional mutagenesis to remove the core PRC2 subunits EED and SUZ12 during male germ cell development, we identified a requirement for PRC2 in both mitotic and meiotic germ cells. We observed a paucity of mutant spermatogonial stem cells (SSCs), which appears independent of repression of the known cell cycle inhibitors Ink4a/Ink4b/Arf. Moreover, mutant spermatocytes exhibited ectopic expression of somatic lamins and an abnormal distribution of SUN1 proteins on the nuclear envelope. These defects were coincident with abnormal chromosome dynamics, affecting homologous chromosome pairing and synapsis. We observed acquisition of H3K27me3 on stage-specific genes during meiotic progression, indicating a requirement for PRC2 in regulating the meiotic transcriptional program. Together, these data demonstrate that transcriptional repression of soma-specific genes by PRC2 facilitates homeostasis and differentiation during mammalian spermatogenesis.
Response to “Measuring consumer response to food products”. Sensory tests that predict consumer acceptance

Abstract As noted by Garber, Hyatt, and Starr (2002) , favorable sensory and taste ratings do not directly translate into the purchase, consumption, or market success of a product. Indeed, there is often a sizable gap between such tests and market success. Segmentation differences, consumer suggestibility, and measurement relevance all limit the value of sensory tests to brand managers and marketers. These limitations unfortunately compromise the value that sensory researchers could have to a firm and to a product's ultimate market success. Yet there is no reason sensory measurement methods and analysis can not be modified to more directly help predict the factors that will influence the purchase, consumption, and market success of a product.
Intrarater and interrater reliability of the Eaton classification of basal joint arthritis.

Abstract The Eaton classification is a radiographic rating used to define the severity of basal joint arthritis. Despite widespread use, the intrarater and interrater reliability has never been determined. Seven men and 33 women, mean age 60 years (range, 31–88 y) were clinically diagnosed with basal joint arthritis. Forty radiographs of these patients' basal joints (21 right and 19 left) were staged according to Eaton, stages I through IV. Three hand surgeons with a Certificate of Added Qualification and 3 orthopedic surgical residents reviewed the films on 2 separate occasions at least 1 week apart. The results of intrarater and interrater reliability were assessed by using κ statistical analysis, with results classified as poor (0–.50), moderate (.51–.75), or excellent (>.75). The overall mean intrarater and interrater reliability was moderate,.657 and.529, respectively. The hand surgeons' intrarater reliability (.666) was slightly better than the residents (.648). There was a greater difference in the mean interrater reliabilities among the hand surgeons (.601) than the orthopedic residents (.487). These results are similar to those found when other orthopedic radiographic classifications have been evaluated for interrater and intrarater reliability. (J Hand Surg 2002;27A:882–885. Copyright © 2002 by the American Society for Surgery of the Hand.)
Improving Training in Laboratory Medicine

In this issue of Clinical Chemistry , we publish a proposal for curriculum content of residency training in laboratory medicine and for evaluation of resident competency (1). The proposal was developed by the Academy of Clinical Laboratory Physicians and Scientists (ACLPS) and covers residency training in all areas of laboratory medicine. Why have we chosen to publish this curriculum? Why did we publish the entire document, rather than just the portion related to clinical chemistry? Why is the curriculum important to the readers of Clinical Chemistry —particularly PhD and MD laboratory directors? In a broad sense, the first reason for publishing the document is that it represents a comprehensive, well-written template for curriculum content for training of residents in laboratory medicine. Because Clinical Chemistry is a leading journal in laboratory medicine, we know that many of those individuals who are responsible for training pathology residents are among our readers and are members of AACC, which publishes the journal. Now is an important time to address the curriculum of residency programs. As the authors of the curriculum document clearly state in their introduction, the field of laboratory medicine and training in pathology have changed dramatically since the last consensus recommendations were published in 1995 (2). At that time, routine molecular diagnostics was just beginning, the clinical use of pharmacogenomics was only being hinted at, “proteomics” consisted of 2-dimensional gels and serum protein electrophoresis, point-of-care testing was primarily portable glucose meters, and electronic medical records existed only in the VA system. Simultaneous to this explosion of knowledge and technology, the length of residency training in pathology was decreased by 1 year for both combined anatomic pathology/clinical …
Solid-state bootstrap sweep generator

An analysis of the bootstrap-integrator sweep circuit is presented which is applicable to circuits using both field-effect and bipolar transistors. Sources of error are investigated, and it is shown that ramp rates ranging from 0 1 V/s to 10 MV/s may be generated with high accuracy.
Pathway selection to the axon depends on multiple targeting signals in NgCAM

Similar to most differentiated cells, both neurons and epithelial cells elaborate distinct plasma membrane domains that contain different membrane proteins. We have previously shown that the axonal cell-adhesion molecule L1/NgCAM accumulates on the axonal surface by an indirect transcytotic pathway via somatodendritic endosomes. MDCK epithelial cells similarly traffic NgCAM to the apical surface by transcytosis. In this study, we map the signals in NgCAM required for routing via the multi-step transcytotic pathway. We identify both a previously mapped tyrosine-based signal as a sufficient somatodendritic targeting signal, as well as a novel axonal targeting signal in the cytoplasmic tail of NgCAM. The axonal signal is glycine and serine rich, but only the glycine residues are required for activity. The somatodendritic signal is cis-dominant and needs to be inactivated in order for the axonal signal to be executed. Additionally, we show that the axonal cytoplasmic signal promotes apical targeting in MDCK cells. Transcytosis of NgCAM to the axon thus requires the sequential regulated execution of multiple targeting signals.
Transport profiles in the conducting airways of the human lung

Transport in the conducting region of the human airways affects many diagnostic and therapeutic procedures. In this work, convective mass transport is characterized by a transport profile that is used to (1) investigate the significance of simple streaming and augmented dispersion mechanisms, and (2) understand steady streaming in the human airways. Laser-induced fluorescence experiments and numerical simulations were performed to assess transport profiles on inspiration and expiration for a range of Reynolds numbers at various locations in a three-generation model of the conducting region of the lung. The shape of the transport profile was found to be largely independent of generation, branch, flow direction, and Reynolds number. Simple streaming was relatively more important to convective dispersion than augmented dispersion. An alternative explanation for steady streaming, based on geometric asymmetries associated with a bifurcation network, is presented.
Processing of Boron-Nitrogen Preceramic Polymers

A number of new oligomeric and polymeric reagents rich in boron and nitrogen have recently been derived by several research groups. These reagents offer potential for the formation of boron nitride (BN) as controlled morphology powders as well as nonpowder forms. Specifically, it has been found that a family of “3-point” and “2-point” poly(borazinylamine) reagents may be processed by techniques used in organic polymer chemistry, with subsequent formation of BN ceramic fibers, coatings, xerogels, aerogels, and aerosols.
Situational Obstacles to Adherence for Adolescents with Diabetes

Twenty adolescents with insulin -dependent diabetes mellitus were interviewed to obtain samples of problem situations that create obstacles to dietary adherence. The resulting 57 situations were analyzed using a reliable coding system to determine the presence or absence of 28 stimulus features. A hierarchical cluster analysis was used to identify 10 relatively homogeneous categories of obstacles to dietary adherence: being tempted to stop trying; negative emotional eating; facing forbidden foods; peer interpersonal conflict; competing priorities; eating at school; social events and holidays; food cravings; snacking when home, alone, or bored; and social pressure to eat. Diabetes educators should consider an individual's ability to cope with this array of obstacles to adherence when individualizing treatment. Dietary intervention then can be personalized to address specific situational obstacles.
Barriers to Cross-Systems Collaboration in Child Welfare, Education, and the Courts: Supporting Educational Well-being of Youth in Care Through Systems Change

Cross-systems collaboration between child welfare, education, and the courts benefits when challenges and priorities are identified early. We measured perceptions of educational stability in foster youth with a statewide survey of 1,603 professionals in education, child welfare, and the courts. Results reveal commonalities among perceived challenges to collaboration across systems (e.g., multiple foster care placements; school changes) and differences in perceived importance or significance of a given issue by professional group. Results guided collaborative work in Kansas and may assist other states seeking strategies that inform cross-systems collaboration to improve educational well-being for youth in foster care.
Receptor-mediated signal transduction pathways and the regulation of pancreatic acinar cell function.

Purpose of reviewRecent studies on pancreatic acinar cell function have led to a more detailed understanding of the signal transduction mechanisms regulating digestive enzyme synthesis and secretion as well as pancreatic growth. This review identifies and puts into context these recent studies, whic
A kinetic analysis of the action of the insect prothoracicotropic hormone.

Abstract A modified in vitro assay was used to assess the kinetics of activation and the decay of activation of the prothoracic glands (PG) by the prothoracicotropic hormone (PTTH) in Manduca sexta. Time-courses of ecdysone synthesis by PTTH-activated day 3 larval and day 0 pupal PG were comparable both quantitatively and temporally, but dose-responses of PTTH activation revealed that larval glands were 1.8 times more sensitive to the neurohormone. The exposure time necessary for maximal activation of the PG by PTTH was the same for both glands, with half-maximal activation in ~ 0.5 min. Once PTTH was removed the rate of ecdysone synthesis by larval and pupal PG remained constant for about 2 h, after which the activated response for both glands decayed rapidly, reaching the unactivated basal synthesis rate within 45 min. These kinetics data suggest that PG activation by PTTH in vitro occurs in a manner indicative of activation in situ and, thus, that this in vitro system is suitable for probing the molecular mechanism by which PTTH activates the PG.
Knowledge Discovery in Academic Drug Discovery Programs: Opportunities and Challenges

In United State several universities and research institutes including the national health institute (NIH) recently started programs aiming for drug discovery. With the initiatives, huge volumes of data have been collected and shared with public free of charge. Those initiatives provide an unprecedented opportunity for data miner and machine learner to study knowledge discovery problems associated with drug design. In this tutorial, the presenter will review the knowledge discovery and management needs in the drug discovery process. Latest methodology development, primarily those from data mining, machine learning, and statistical learning will be discussed.
Impact of pleurotomy, continuous positive airway pressure, and fluid balance during cardiopulmonary bypass on lung mechanics and oxygenation.

Objective: To determine effects of surgical pleurotomy, continuous positive airway pressure, and fluid balance during cardiopulmonary bypass (CPB) on lung mechanical properties and indices of oxygenation. Design: Prospective, descriptive, and interventional study. Setting: Cardiothoracic service at a major university referral center. Participants: Eighteen anesthetized-paralyzed patients undergoing elective coronary artery bypass grafting requiring CPB. Interventions: During CPB, continuous positive airway pressure (CPAP) was applied to nine patients; in nine others, no CPAP was applied. Measurements and Main Results: From measurements of airway and esophageal pressures and flow, lung resistance and elastance were determined before sternotomy and after sternal reapproximation. Measurements were made during forced ventilation over a physiologic range of tidal volumes and frequencies, and frequency and volume dependences of lung resistance and elastance were additionally identified. In all patients, lung resistance and elastance increased after CPB, consistent with models of pulmonary edema. Multiple regression analysis showed that these increases were relatively less in patients with intact pleurae ( p p p p p Conclusions: These findings suggest that pleurotomy before CPB and positive fluid balance during CPB enhance postbypass pulmonary edema and/or atelectasis, as demonstrated by acute changes in respiratory mechanics and indices of oxygenation. Low levels of CPAP applied during CPB did not significantly change either mechanical properties or oxygenation.
Microwave-assisted extraction of lime pectin $

Pectin was extracted from lime flavedo, albedo and pulp by employing microwave-assisted extraction (MAE) under pressure. Heating times ranged from 1 to 10 min. Optimal time of heating was 3 min. Molar mass, viscosity, radius of gyration and hydrated radius were found to decrease with heating time. At 3 min heating time, depending on the lime fraction which was extracted, weight average molar mass ranged from about 310,000 to 515,000 Da, and weight average intrinsic viscosities ranged from about 9.5 to 13 dL/g. Pectins dissolved in 0.05 sodium nitrate were characterized by HPSEC with online light scattering, dynamic light scattering and viscosity detection. Molar mass polydispersity passed through maximum at 4 min. Molecules of pectin became less compact with increasing heating time. The results obtained here are consistent with previous evidence that extracted pectins may exist in solution as networks, partially formed networks, i.e. branched molecules or linear molecules depending on extraction conditions and the solvent in which they are dissolved.
Bearing strength of commingled boron/glass fiber reinforced aluminum laminates

Abstract The bearing properties of recently developed hybrid fiber/metal laminates, or COmmingled Boron/glass fiber Reinforced Aluminum laminates (COBRA), are investigated in this study. The bolt-type bearing tests on GLass REinforced aluminum laminates (GLARE), non-commingled hybrid boron/glass/aluminum fiber/metal laminates (HFML) and COBRA were carried out as a function of e / D ratio, metal volume fraction, fiber volume fraction, and fiber orientation. Experimental results show that with the same joint geometry and metal volume fraction, the commingling of boron fibers improves the bearing strength of fiber/metal laminates. Observations show the boron/glass fiber prepreg, transverse to the loading direction, results in a bearing mechanism that effectively increases the bearing strength. The bearing strength of COBRA with longitudinal fibers is lower than that with transverse fibers due to the fact that shearout failure takes place before maximum bearing strength is reached. The experimental results show that, with only either transverse fiber orientation or longitudinal fiber orientation, COBRA with 18% boron fiber volume fraction possesses a higher bearing strength when compared to HFML with 6% boron fiber volume fraction. In addition to the properties in COBRA with parallel-plies commingled prepreg, the bearing properties of various COBRA with [0°/90°] and [0°/90°/90°/0°] cross-ply commingled prepregs are also discussed.
Inflammatory changes in gingival collagen in the alloxan-diabetic rat.

Chronic inflammation was induced by repeatedly injecting ferritin-antiferritin (AgAb) complex into gingiva of normal, untreated and insulin-treated alloxan diabetic rats. Blood glucose levels, the urinary excretion of hydroxyproline, and the salt-soluble, acid-soluble and insoluble collagen levels in gingiva were measured in all groups of rats. Additionally, the gingival tissues were examined by light and electron microscopy. Injection of AgAb into the gingiva of normal rats produced typical chronic inflammatory cell infiltrates, fibroblasts containing profiles of intracellular collagen, disruption of extracellular collagen fibrils and a reduction in collagen concentration primarily affecting the insoluble fraction. The inflamed gingiva of the diabetic rats demonstrated similar changes histologically except that the macrophages were more congested with phagocytosed material and the fibroblasts appeared smaller and less well developed. Unlike the normal rats, the collagen content of the diabetic gingiva was not reduced by inflammation. This loss of the inflammatory effect on gingival collagen content during experimental diabetes was explained by three possibilities: (1) that diabetic fibroblasts had a decreased ability to effect collagen remodeling during inflammation, (11) that the inflammatory cells responsible for gingival collagen loss were less active in diabetes, and (111) that diabetic gingival collagen, because it was more highly crosslinked than normal, resisted the degradative enzymes produced in increased amounts during the inflammatory process.
Structural Studies on Casein Micelles of Human Milk: Dissociation of β-Casein of Different Phosphorylation Levels Induced by Cooling and Ethylenediaminetetraacetate

Abstract Information on the structure of human casein micelles has been obtained from dissociation of β -casein (CN). Two approaches were used: cooling at 4°C and addition of EDTA. An initial loss of about 80% of the protein optical density occurred upon cooling to 4°C. Dissociation was time dependent, and at ≥24h about 10% remained. However, mean size and voluminosity of micelles increased, as indicated by laser light scattering and viscosity measurements. This process was reversible, and 95% of the protein reentered the micelles upon incubation for 3h at 37°C. Upon cooling, amounts of nonphosphorylated β -CN increased, and singly phosphorylated β -CN levels were almost constant relative to the total β -CN in micelles. Upon addition of EDTA (0 to 5m M ), the forms with three to five phosphates were the major dissociating constituents; EDTA that was added by dialysis produced similar results but at lower concentrations. These data suggest that, in the absence of significant amounts of α s1 -CN, nonphosphorylated and singly phosphorylated human β -CN may form a framework, as proposed for α s1 -CN for bovine milk, along with the colloidal calcium phosphate for the development of the final micelle structure by addition of the more highly phosphorylated forms. The results also indicate that human casein micelles have a less rigid structure than those of other species.
Lunar Dust and Terrestrial Ice Nucleus Concentration

BIGG1 demonstrated a relation between summer ice nucleus concentration and lunar phase. If one assumes that increase of ice nuclei causes increase in precipitation, relations between precipitation and lunar phase can be accounted for. The effect is global and it occurs in lower latitudes with a delay of a few days. When Bigg's curves are reduced to 34° S. latitude, they show two equal maxima of ice nuclei concentration, the first occurring 6 days, the second 18 days after new Moon. The maxima are 12 days apart (synodic month = 29.53 days).
Facilitating adaptation to global climate change: perspectives from experts and decision makers serving the Florida Keys

Slivers of land amidst the world’s third largest barrier reef, the Florida Keys provide unique insights on the emerging challenges associated with adaptation to global climate change. While political will and public awareness are gradually shifting on the imposing risks, analysis of survey responses from experts and decision makers serving the Florida Keys (federal, state and local personnel) reveals insufficient resources, limited direction and leadership, and lack of institutional frameworks to facilitate the adaptation process. Against this backdrop, we investigate experts and decision makers’ interest in an array of adaptation measures including their willingness to support a proposed ‘Community Adaptation Fund’ (CAF) to mobilize resources and lay the foundation for adaptation initiatives in the Florida Keys. We also explore potential funding sources for establishing the proposed CAF, and test the feasibility of a diverse set of financing mechanisms. We discuss implications of our findings in the context of enhancing adaptive capacity in the Florida Keys and beyond.
Evidence of a Low Stromal Mg Concentration in Intact Chloroplasts in the Dark: I. STUDIES WITH THE IONOPHORE A23187.

The loss of Mg2+ upon the addition of the ionophore A23187 in the dark was prevented by less than 0.1 millimolar MgCl2 with intact chloroplasts suspended in a sorbitol medium, but required 1 to 3 millimolar MgCl2 if the chloroplasts were in a K+ -gluconate medium. Measurements of stromal pH in the dark indicated that, in the K+ -gluconate medium, the stromal pH is nearly the same as that of the medium, whereas in the sorbitol medium it is much more acidic as reported previously. These observations suggest that the free Mg2+ concentration in the stroma in the dark is between 1 and 3 millimolar. Other experiments on the inihibition by A23187 of CO2 fixation in the light and in a system capable of catalyzing CO2 fixation in the dark, and on the Mg2+ binding properties of thylakoid membranes, are consistent with this conclusion. The results provide further support for the hypothesis that light-induced Mg2+ concentration changes occur in the stroma that are important in the light-dark regulation of CO2 fixation.