cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of a cell culture model for the study of adenosine deaminase- and purine nucleoside phosphorylase-deficient immunologic disease

The absence of erythrocytic adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) has been associated with severe immunodeficiency disease in children. We have developed a cell culture model to study the possible relationships between purine salvage enzymes and immunologic function using an established T cell lymphosarcoma (S49) and a potent inhibitor of ADA, erythro-9(2-hydroxy-3-nonyl) adenine (EHNA). Wild-type S49 cells are killed by dexamethasone or dbc AMP, and adenosine (5 muM) in the presence of an ADA inhibitor (6 muM EHNA) also prevents the growth of and kills these S49 cells. It has been proposed that adenosine is toxic to lymphoid cells by virtue of its ability to increase the intracellular concentrations of cyclic AMP. We examined the sensitivity of three mutants of S49 cells, with distinctive defects in some component of cyclic AMP metabolism or action, to killing by adenosine and EHNA. All three mutants are resistant to killing by isoproterenol or cholera toxin and two are resistant to dbc AMP itself, but all are sensitive to killing by adenosine and EHNA. Similarly, two dexamethasone-resistant S49 mutants are as sensitive to adenosine and EHNA as are the wildtype cells. We have also simulated the purine nucleoside phosphorylase deficiency in S49 cells by adding inosine and adenosine to the growth medium. In the presence of EHNA or inosine, the toxic effects of adenosine can be partially reversed by addition of (10-20 muM) uridine, an observation suggesting that adenosine is toxic as the result of its inducing pyrimidine starvation.
Testicular cancer incidence trends in the USA (1975–2004): plateau or shifting racial paradigm?

Summary Objective It has been reported that the incidence of testicular cancer has plateaued in some parts of the USA, especially among non-Hispanic Whites in Los Angeles. Temporal trends analysis was conducted over three decades to assess the evidence for such a plateau, and to examine whether the incidence of testicular cancer remains stable across racial/ethnic groups. This study also investigated the influence of age at diagnosis on the incidence of testicular cancer. Study design Population-based temporal trends analysis. Methods Using the Surveillance Epidemiology and End Results (SEER), 16,580 newly diagnosed cases of testicular cancer in males aged 15–49 years were identified between 1975 and 2004. Incidence rates were examined by calculating the age-adjusted rates and their 95% confidence interval (CI) for age at diagnosis, SEER areas and race for the year of diagnosis. The percentage change and annual percentage change were examined for trends. Results The incidence of testicular cancer is continuing to increase among US males, despite the plateau of the 1990s. Between 1975 and 2004, the age-adjusted incidence rate for males aged 15–49 years increased from 2.9 (1975) to 5.1 (2004) per 100,000. The trends indicated a percentage change of 71.9% and a statistically significant annual percentage change of 1.6% (95%CI 1.3–2.0; P Conclusions Overall, the incidence of testicular cancer continues to plateau in the USA, while racial variance persists. Black males demonstrate the greatest increase in annual percentage change. Further studies are needed to examine the recent increase among Black males and the potential determinants.
Preferential repair of damage in actively transcribed DNA sequences in vivo.

My colleagues and I have discovered intragenomic heterogeneity in DNA repair in mammalian cells. Consequences of unrepaired DNA damage depend upon the precise location of the damage with respect to...
Common phrases and minimum-space text storage

A method for saving storage space for text strings, such as compiler diagnostic messages, is described. The method relies on hand selection of a set of text strings which are common to one or more messages. These phrases are then stored only once. The storage technique gives rise to a mathematical optimization problem: determine how each message should use the available phrases to minimize its storage requirement. This problem is nontrivial when phrases which overlap exist. However, a dynamic programming algorithm is presented which solves the problem in time which grows linearly with the number of characters in the text. Algorithm 444 applies to this paper.
Raising the Bar: The Curative Potential of Human Cancer Immunotherapy

Immunotherapy with interleukin-2 can cure 5 to 10% of patients with metastatic melanoma and renal cancer. Recent adoptive cell transfer (ACT) immunotherapies have improved cure rates in metastatic melanoma to 20 to 40%. Genetic engineering of T cells to express conventional alpha/beta T cell receptors or antibody-based chimeric antigen receptors provides an opportunity to extend ACT to patients with common epithelial cancers.
Tensile Characterization of Porcine Temporomandibular Joint Disc Attachments

The frequency and impact of temporomandibular joint (TMJ) disorders necessitate research in characterizing the joint’s function. The 6 discal attachments have not yet been systematically characterized under tension. Understanding their role in joint function may guide our study of TMJ pathologies, including disc displacement. In the present study, a porcine model was used to characterize the attachments in tension anteroposteriorly and mediolaterally, based on previously identified similarities in the porcine and human masticatory behaviors and discal properties. Tensile stiffness, strength, toughness, and maximum strain were quantified. Collagen alignment was characterized via polarized light and scanning electron microscopy. Anisotropy was demonstrated in all attachments, with the exception of the anterior inferior attachment. Anteroposteriorly, the lateral attachment was stiffest (8.3 MPa) and the anterior superior was least stiff (1.4 MPa). Mediolaterally, the posterior superior attachment was stiffest (16.3 MPa) and the medial was least stiff (1.4 MPa). The greatest strain was observed in the lateral attachment in the mediolateral direction and the posterior superior attachment in the anteroposterior direction. With greatest strains in the most commonly observed directions of disc displacement, it is suggested that compromise in the posterior and lateral attachments contributes to partial lateral and anterior disc displacement.
RegB Kinase Activity Is Controlled in Part by Monitoring the Ratio of Oxidized to Reduced Ubiquinones in the Ubiquinone Pool

ABSTRACT RegB is a membrane-spanning sensor kinase responsible for redox regulation of a wide variety of metabolic processes in numerous proteobacterial species. Here we show that full-length RegB purified from Escherichia coli membranes contains bound ubiquinone. Four conserved residues in the membrane-spanning domain of RegB are shown to have important roles in ubiquinone binding in vitro and redox sensing in vivo . Isothermal titration calorimetry measurements, coupled with kinase assays under oxidizing and reducing conditions, indicate that RegB weakly binds both oxidized ubiquinone and reduced ubiquinone (ubiquinol) with nearly equal affinity and that oxidized ubiquinone inhibits kinase activity without promoting a redox reaction. We propose a model in which ubiquinone/ubiquinol bound to RegB readily equilibrates with ubiquinones/ubiquinols in the membrane, allowing the kinase activity to be tuned by the redox state of the ubiquinone pool. This noncatalytic role of ubiquinone in controlling RegB activity is distinct from that of other known ubiquinone-binding proteins, which use ubiquinone as an electron donor or acceptor. IMPORTANCE Two-component signaling systems are comprised of a sensor kinase and a cognate response regulator that together control many cellular processes in response to a change in environmental conditions. Many sensor kinases are components of the cell membrane, with a domain that senses a specific environmental stimulus to control the activity of a cytosolic kinase domain. The broadly disseminated RegB/RegA two-component system regulates many energy-related processes in response to changes in the cellular redox state. In this study, the membrane-spanning sensor kinase RegB is shown to regulate its activity by interacting with the ubiquinone pool in a manner that involves novel noncatalytic equilibrium binding of ubiquinone.
B/sup +/-tree indexes with hybrid row identifiers in Oracle8i

Most commercial database systems support B/sup +/-tree indexes using either: physical row identifiers, for example, DB2; or logical row identifiers, for example, NonStop SQL. Physical row identifiers provide fast access to data. However, unlike logical row identifiers, they need to be updated whenever the row moves. This paper describes an alternate approach where hybrid row identifiers are used. A hybrid row identifier consists of two components: a logical component, namely, the primary key of the base table row; and a physical component, namely, the database block address (DBA) of the row. By treating the DBA as a guess regarding where the row may be found, performance comparable to physical B/sup +/-tree indexes is attained for valid guess-DBAs. This scheme retains the logical index advantage of avoiding an immediate index update when the base table row moves. Instead, an online utility can be used to lazily fix the invalid guess-DBAs. This scheme has been used to implement B/sup +/-tree indexes for Oracle8i index-organized tables (primary B/sup +/-tree like structure) which encounter both row movement and table reorganization.
False preferred event analysis for the energy-subtraction Compton scatter camera

For the energy-subtraction Compton scatter camera (ESCSC) for medical imaging, a critical requirement is the efficient selection of true preferred events, which will directly affect image contrast. To be able to distinguish preferred events, a set of selection criteria, based on different physical restrictions for different scenarios, is used. However, due to finite energy and timing resolution of the detector systems, some false preferred events (FPEs) will pass all of the criteria. In this study, we attempt to identify major sources of FPEs and their fraction among preferred events. Results from this analysis would be useful in designing the ESCSC as well as other Compton cameras. In addition, these results can be used in development of a weighting scheme indicative of the likelihood that an event that passes all of the criteria is actually a preferred event. This extension is purely analytical and based on the solution of the photon transport problem prescribed by the ESCSC. Two major contributors to FPEs, source volume scatters and chance coincidences, are identified. For a potential ESCSC geometry, the fractions of FPEs are calculated for various system energy and timing resolutions. Recommendations for optimal source energy and preferred event weighting function are provided.
Characterization of the 9-cis-epoxycarotenoid dioxygenase gene family and the regulation of abscisic acid biosynthesis in avocado.

Avocado (Persea americana Mill. cv Lula) is a climacteric fruit that exhibits a rise in ethylene as the fruit ripens. This rise in ethylene is followed by an increase in abscisic acid (ABA), with the highest level occurring just after the peak in ethylene production. ABA is synthesized from the cleavage of carotenoid precursors. The cleavage of carotenoid precursors produces xanthoxin, which can subsequently be converted into ABA via ABA-aldehyde. Indirect evidence indicates that the cleavage reaction, catalyzed by 9-cis-epoxycarotenoid dioxygenase (NCED), is the regulatory step in ABA synthesis. Three genes encoding NCED cleavage-like enzymes were cloned from avocado fruit. Two genes, PaNCED1 and PaNCED3, were strongly induced as the fruit ripened. The other gene, PaNCED2, was constitutively expressed during fruit ripening, as well as in leaves. This gene lacks a predicted chloroplast transit peptide. It is therefore unlikely to be involved in ABA biosynthesis. PaNCED1 was induced by water stress, but expression of PaNCED3 was not detectable in dehydrated leaves. Recombinant PaNCED1 and PaNCED3 were capable of in vitro cleavage of 9-cis-xanthophylls into xanthoxin and C25-apocarotenoids, but PaNCED2 was not. Taken together, the results indicate that ABA biosynthesis in avocado is regulated at the level of carotenoid cleavage. Fruit ripening involves a complex series of biochemical events in which the tissue undergoes programmed changes in texture, aroma, coloration, flavor, and firmness (Brady, 1987). Climacteric species, such as avocado (Persea americana Mill. cv Lula), are characterized by the autocatalytic production of the ripening hormone ethylene and a ripening-related transient burst in CO2 evolution (Biale and Young, 1981). In avocado the increase in ethylene production is followed by an increase in abscisic acid (ABA) levels (Adato et al., 1976). Although ethylene induces the synthesis of many genes involved in fruit ripening (Brady, 1987), it is not known whether the rise in ethylene is related to the increase in ABA in avocado. Further, the role that ABA plays in the ripening process is also unknown. Ripening avocado fruit produces high levels of ABA and thus provides an ideal system in which to study the regulation of ABA biosynthesis.
Convection and flow in porous media. Part 2. Visualization by shadowgraph

We present results for pattern formation at the onset of convection in fluid-saturated porous media obtained by a novel variation on the shadowgraphic technique (modified shadowgraphic technique). Both ordered and disordered media are used, each exhibiting distinct behaviour. Ordered porous media are constructed from grids of overlapping bars. Convective onset in this type of medium is characterized by a sharp, well-defined bifurcation to straight parallel rolls. The orientation of the convection rolls is determined by the number of bar layers, N b ; odd N b leads to rolls with axes perpendicular to the direction of the top and bottom bars, and even N b to rolls at 45° to the bars. Disordered porous layers are produced by stacking randomly drilled disks separated by spacers. In this system, we observe a rounded bifurcation to convection with localized convection near convective onset. More specifically, the flow patterns take on one of several different three-dimensional cellular structures after each cycling through convective onset. These observations may be described by two different mechanisms: random spatial fluctuations in the Rayleigh number (Zimmermann et al. 1993), and/or spatial variation in the thermal conductivity on the length scale of the convection wavelength (Braester & Vadasz 1993).
Suppression of Endocytosis in Neutrophils by Influenza A Virus in Vitro

The effect of influenza A virus on the endocytic pathway in polymorphonuclear leukocytes (PMNLs) and the relationship of altered endocytic activity to virus-induced inhibition of other PMNL functions were examined with virus that caused decreased phagosomelysosome fusion and bacterial killing (depressing virus [DV]) and virus that did not (non-DV). Binding of both viruses to PMNL surface receptors was similar, but uptake of DV into PMNLs was decreased compared with that of non-DV. Both viruses were associated with the PMNL plasma membrane and were in endosomes. DV caused less stimulation of pinocytosis than did non-DV. The rate of exocytosis of fluoresceinated-dextran (FL-dextran) from cells stimulated with DV was significantly less than for non-DV. When PMNLs were pretreated with buffer, DV, or non-DV and then exposed to FL-dextran and N-formylmethionylleucylphenylalanine, the pinocytosis of FL-dextran was significantly less in cells pretreated with DV as compared with non-DV or buffer.
Gender Differences in First Impressions of Web Pages: The Role of Attractiveness, Complexity, and Brightness on Perceived Design Quality:

First impressions of a web page are important since users can form a lasting impression of a site in as little as 50ms (Lindgaard et al, 2006; Lindgaard et al, 2011). This study examined gender differences of initial impressions of 50 e-commerce web pages. Participants rated each page on five attributes: masculinity/femininity, brightness, attractiveness, complexity, and design quality. Results from a multiple linear regression showed that user perceptions of attractiveness and complexity were predictive of whether a web page was rated as well-designed. When examined by gender, it was found that this same finding was true of females but not for males, who did not report the same relationship between complexity and design quality. Sample pages which resulted in gender rating differences are discussed.
Risk-Efficient Sequential Estimation of the Number of Multinomial Cells

We consider risk-efficient sequential estimation under squared error loss of the number of classes which are equally probable to occur in a given multinomial population. It is assumed that the sampling cost per observation is constant. Large-sample properties of the sequential estimator are studied. Finally, Monte Carlo simulation is carried out in order to investigate its finite sample behavior. The proposed sequential procedure performs better (in the sense of reducing average stopping time and risk) than the one based on the estimator K n , the number of distinct cells observed in a sample of size n.
Immunobiology and pathogenesis of viral hepatitis.

AbstractAmong the many viruses that are known to infect the human liver, hepatitis B virus (HBV) and hepatitis C virus (HCV) are unique because of their prodigious capacity to cause persistent infection, cirrhosis, and liver cancer. HBV and HCV are noncytopathic viruses and, thus, immunologically mediated events play an important role in the pathogenesis and outcome of these infections. The adaptive immune response mediates virtually all of the liver disease associated with viral hepatitis. However, it is becoming increasingly clear that antigen-nonspecific inflammatory cells exacerbate cytotoxic T lymphocyte (CTL)-induced immunopathology and that platelets enhance the accumulation of CTLs in the liver. Chronic hepatitis is characterized by an inefficient T cell response unable to completely clear HBV or HCV from the liver, which consequently sustains continuous cycles of low-level cell destruction. Over long periods of time, recurrent immune-mediated liver damage contributes to the development of cirrhos...
Balancing Performance and Reliability in the Memory Hierarchy

Cosmic-ray induced soft errors in cache memories are becoming a major threat to the reliability of microprocessor-based systems. In this paper, we present a new method to accurately estimate the reliability of cache memories. We have measured the MTTF (mean-time-to-failure) of unprotected first-level (L1) caches for twenty programs taken from SPEC2000 benchmark suite. Our results show that a 16 KB first-level cache possesses a MTTF of at least 400 years (for a raw error rate of 0.002 FIT/bit.) However, this MTTF is significantly reduced for higher error rates and larger cache sizes. Our results show that for selected programs, a 64 KB first-level cache is more than 10 times as vulnerable to soft errors versus a 16 KB cache memory. Our work also illustrates that the reliability of cache memories is highly application-dependent. Finally, we present three different techniques to reduce the susceptibility of first-level caches to soft errors by two orders of magnitude. Our analysis shows how to achieve a balance between performance and reliability
Beauty and Body Image Concerns Among African American College Women

The current study examined body image concerns among African American women. In recent years, there has been an attempt to include ethnic minority samples in body image studies (e.g., Grabe & Hyde, 2006; Hrabosky & Grilo, 2007; Lovejoy, 2001) but few specifically examine unique issues pertaining to beauty and body image for African American college age women. A total of 31 African American women participated in one of five focus groups on the campus of a large Southwestern University to examine beauty and body image. Data were analyzed using a thematic approach and several themes were identified. The majority of themes pertained to issues related to hair, skin tone, body type, and message sources. Themes included: sacrifice, ignorance/racial microaggressions, and validation and invalidation by others, thick/toned/curvy as optimal, hypersexualization, and being thin is for White women. Findings of the current study suggest a reconceptualization of body image for African American women where relevant characteristics such as hair and skin tone are given more priority over traditional body image concerns often associated with European American women.
IntegromeDB: an integrated system and biological search engine.

With the growth of biological data in volume and heterogeneity, web search engines become key tools for researchers. However, general-purpose search engines are not specialized for the search of biological data. Here, we present an approach at developing a biological web search engine based on the Semantic Web technologies and demonstrate its implementation for retrieving gene- and protein-centered knowledge. The engine is available at http://www.integromedb.org . The IntegromeDB search engine allows scanning data on gene regulation, gene expression, protein-protein interactions, pathways, metagenomics, mutations, diseases, and other gene- and protein-related data that are automatically retrieved from publicly available databases and web pages using biological ontologies. To perfect the resource design and usability, we welcome and encourage community feedback.
Patient Education Reimbursement: An Experiment in Maine

With increasing emphasis being placed on controlling health care costs the Maine Department of Human Services decided in 1977 to undertake a three year experimental effort designed to demonstrate the potential of patient education for reducing medical care costs. Focusing on rural ambulatory care the program established formal patient education in health centers across the state. This article will cover the scope and sequence of events during the first two years with particular emphasis on the problems encountered in program planning and implementation. It will discuss some problems of rural development and includes recommendations for the reimbursement of patient education for third party programs.
Social support among persons with multiple sclerosis

The source and magnitude of perceived social support functions and structure were examined in relation to illness duration, gender, and presence or absence of spouses among 200 persons with multiple sclerosis. The associations between social support variables and a health index, ADL level of functioning, also were examined. Significant gender differences were shown for perceived availability of affect, affirmation, and aid functions. A significant change in the network property, average frequency of relationships, occurred over the chronic illness trajectory. Low to moderate correlations were observed between a number of activities of daily living and both perceived social support functions and network size, particularly for women. Implications for professional staff who provide health services for persons with MS are presented. Further study regarding lower levels of perceived social support in women than men and low levels of informational support in both men and women is suggested.
Bayesian Modeling of Haplotype Effects in Multiparent Populations

A general Bayesian model, Diploffect, is described for estimating the effects of founder haplotypes at quantitative trait loci (QTL) detected in multiparental genetic populations; such populations include the Collaborative Cross (CC), Heterogeneous Socks (HS), and many others for which local genetic variation is well described by an underlying, usually probabilistically inferred, haplotype mosaic. Our aim is to provide a framework for coherent estimation of haplotype and diplotype (haplotype pair) effects that takes into account the following: uncertainty in haplotype composition for each individual; uncertainty arising from small sample sizes and infrequently observed haplotype combinations; possible effects of dominance (for noninbred subjects); genetic background; and that provides a means to incorporate data that may be incomplete or has a hierarchical structure. Using the results of a probabilistic haplotype reconstruction as prior information, we obtain posterior distributions at the QTL for both haplotype effects and haplotype composition. Two alternative computational approaches are supplied: a Markov chain Monte Carlo sampler and a procedure based on importance sampling of integrated nested Laplace approximations. Using simulations of QTL in the incipient CC (pre-CC) and Northport HS populations, we compare the accuracy of Diploffect, approximations to it, and more commonly used approaches based on Haley-Knott regression, describing trade-offs between these methods. We also estimate effects for three QTL previously identified in those populations, obtaining posterior intervals that describe how the phenotype might be affected by diplotype substitutions at the modeled locus.
Activation of the PI3K Pathway in Cancer Through Inhibition of PTEN by Exchange Factor P-REX2a

PTEN (phosphatase and tensin homolog on chromosome 10) is a tumor suppressor whose cellular regulation remains incompletely understood. We identified phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) as a PTEN-interacting protein. P-REX2a mRNA was more abundant in human cancer cells and significantly increased in tumors with wild-type PTEN that expressed an activated mutant of PIK3CA encoding the p110 subunit of phosphoinositide 3-kinase subunit α (PI3Kα). P-REX2a inhibited PTEN lipid phosphatase activity and stimulated the PI3K pathway only in the presence of PTEN. P-REX2a stimulated cell growth and cooperated with a PIK3CA mutant to promote growth factor–independent proliferation and transformation. Depletion of P-REX2a reduced amounts of phosphorylated AKT and growth in human cell lines with intact PTEN. Thus, P-REX2a is a component of the PI3K pathway that can antagonize PTEN in cancer cells.
Antigenic evaluation of a recombinant baculovirus-expressed Sarcocystis neurona SAG1 antigen.

Sarcocystis neurona is the primary parasite associated with equine protozoal myeloencephalitis (EPM). This is a commonly diagnosed neurological disorder in the Americas that infects the central nervous system of horses. Current serologic assays utilize culture-derived parasites as antigen. This method requires large numbers of parasites to be grown in culture, which is labor intensive and time consuming. Also, a culture-derived whole-parasite preparation contains conserved antigens that could cross-react with antibodies against other Sarcocystis species and members of Sarcocystidae such as Neospora spp., Hammondia spp., and Toxoplasma gondii. Therefore, there is a need to develop an improved method for the detection of S. neurona–specific antibodies. The sera of infected horses react strongly to surface antigen 1 (SnSAG1), an ∼29-kDa protein, in immunoblot analysis, suggesting that it is an immunodominant antigen. The SnSAG1 gene of S. neurona was cloned, and recombinant S. neurona SAG1 protein (rSnSAG1-B...
Group Work: How to Use Groups Effectively

Many students cringe and groan when told that they will need to work in a group. However, group work has been found to be good for students and good for teachers. Employers want college graduates to have developed teamwork skills. Additionally, students who participate in collaborative learning get better grades, are more satisfied with their education, and are more likely to remain in college. This paper will discuss the use of group work in higher education.
The interplay of long non-coding RNAs and MYC in cancer

Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are changing how researchers view eukaryotic gene regulation. Once considered to be non-functional products of low-level aberrant transcription from non-coding regions of the genome, lncRNAs are now viewed as important epigenetic regulators and several lncRNAs have now been demonstrated to be critical players in the development and/or maintenance of cancer. Similarly, the emerging variety of interactions between lncRNAs and MYC, a well-known oncogenic transcription factor linked to most types of cancer, have caught the attention of many biomedical researchers. Investigations exploring the dynamic interactions between lncRNAs and MYC, referred to as the lncRNA-MYC network, have proven to be especially complex. Genome-wide studies have shown that MYC transcriptionally regulates many lncRNA genes. Conversely, recent reports identified lncRNAs that regulate MYC expression both at the transcriptional and post-transcriptional levels. These findings are of particular interest because they suggest roles of lncRNAs as regulators of MYC oncogenic functions and the possibility that targeting lncRNAs could represent a novel avenue to cancer treatment. Here, we briefly review the current understanding of how lncRNAs regulate chromatin structure and gene transcription, and then focus on the new developments in the emerging field exploring the lncRNA-MYC network in cancer.
Formation and metabolism of bile acids in extrahepatic biliary atresia.

Abstract Cholesterol-4- 14 C, cholic acid-24- 14 C, and chenodeoxycholic acid-24- 14 C were administered to infants with extrahepatic biliary atresia, and excretion of isotope in urine and feces was followed. Fifteen per cent of the administered cholesterol was eliminated in a 17 day period. Twenty-four to 48 per cent of daily excreted isotope was recovered from feces as neutral steroids, mainly cholesterol. The isotope in urine consisted of labeled bile acids, mainly cholic and chenodeoxycholic acid. A minor part of the urinary isotope consisted of a complex mixture of different bile acids. After administration of cholic acid-24- 14 C, 55 to 77 per cent of the isotope was excreted in urine in a 4 day period. Chenodeoxycholic acid-24- 14 C was excreted very slowly and only 15 to 17 per cent of the isotope was excreted in a 4 day period. Less than 3 per cent of the administered isotope was excreted in feces. Cholic acid was found to be a metabolic end product, whereas 4 to 7 per cent of chenodeoxycholic acid was transformed prior to urinary excretion.
Immobilization of cellulase on a silica gel substrate modified using a 3-APTES self-assembled monolayer

Cellulase was immobilized onto silica gel surfaces pretreated with (3-aminopropyl) triethoxy-silane (3-APTES), and glutaraldehyde (GA) was used as a cross-linker. A carboxymethyl cellulose sodium salt (CMC) solution was used for activity experiments. Protein assay was performed to determine the mass immobilized and compare with free enzyme. Cellulase was successfully demonstrated to be immobilized on the modified silica gel surface, and no detectable amount of enzyme was stripped off during the hydrolysis of the CMC solution. The specific activity of the immobilized cellulase is 7 ± 2 % compared to the similar amount of free cellulase. Significant activity over multiple reuses was observed. The seventh batch achieved 82 % activity of the initial batch, and the fifteenth batch retained 31 %. It was observed that the immobilized cellulase retained 48 % of its initial activity after 4 days, and 22 % even after 14 days.
Abstract 684: Principal Component Analysis Identifies Lipoprotein Subfractions Associated with Coronary Artery Calcification in a Young High Cardiometabolic Risk Population: The Baptist Employee Healthy Heart Study

Introduction: There is limited evidence relating lipoprotein subfractions or their composite measures to subclinical markers of atherosclerosis. In this study, we tested whether combinations of lipoprotein subfractions independently predict the presence of Coronary Artery Calcification (CAC) among presumably healthy people with high cardiovascular disease (CVD) risk. Methods: Cardio IQ™ Ion Mobility lipoprotein fractionation was measured at baseline in 172 high CVD risk participants of the Baptist Employee Healthy Heart Study (BEHHS). Principal component analysis was used to check for eventual components of CVD risk. Using bootstrap techniques, we created 1000 data sets of size 5000 and analyzed results of logistic regression. Results: Three principal components (PC) accounted for 88% variability. PC1 represented an increase in all lipoprotein measures; PC2 a decrease in HDL, large and medium LDL with an increase in VLDL and small and very small LDL; PC3 an increase in HDL, and a decrease in LDL subfracti...
Abstract 15685: Copper Transport Protein Antioxidant-1 Mediates Vascular Remodeling via Promoting Macrophage Infiltration and Copper- and Rac1-dependent Vascular Migration

Vascular smooth muscle cell (VSMC) migration and inflammation are critically important in neointimal formation following vascular injury and atherosclerosis lesion formation. Copper (Cu) chelator inhibits neointimal formation with unknown mechanism. We previously demonstrated that Cu chaperone antioxidant-1 (Atox1) is involved in Cu-induced cell growth and that Cu transporter ATP7A, which obtains Cu from Atox1, is involved in VSMC migration. However, the role of Atox1 in neointimal formation after injury is unknown. In vivo, Atox1 is ubiquitously expressed in VSMCs and endothelial cells of noninjured vessels in wild type (WT) mice. Following wire injury, Atox1 expression is upregulated in injured vessels, and its expression is colocalized with ATP7A (+) cells, mainly in CD45 (+) inflammatory cells at day 3 and 7, and in neointimal α-smooth muscle actin (α-SMA) (+) VSMCs at day 14. Atox1 KO mice show significant inhibition of neointimal formation (I/M ratio: 53%) and fibrosis (34%) at day 21 compared to WT mice, which is associated with decreased α-SMA (+) cells infiltration within neointima at day 14. Mechanistically, in cultured VSMC, siRNAs for Atox1 or ATP7A inhibit VSMC migration induced by platelet-derived growth factor (PDGF) (77% and 70%) or wound scratch (63% and 60%). PDGF promotes Atox1 binding to ATP7A within 5 min via Cu-dependent manner, which in turn recruits Rac1 to the Atox1/ATP7A complex. Functional significance of this complex is demonstrated that Atox1 siRNA inhibits PDGF-induced ATP7A and Rac1 translocation to the leading edge, thereby inhibiting Cu- and Rac1-dependent lamellipodia formation. Furthermore, Atox1 KO mice show decreased perivascular macrophage infiltration at day 7 and 14 (56% and 57%). This result is further confirmed that thioglycollate-induced peritoneal macrophage recruitment is reduced in Atox1 KO mice (62%), suggesting that Atox1 also mediates macrophage recruitment in inflammatory conditions. In summary, Atox1 is involved in neointimal formation after vascular injury, through promoting VSMC migration and inflammation in injured vessels. Our results will provide new insight into Atox1 as a potential therapeutic target for the crucial events in inflammation and VSMC migration-related vascular diseases.
The Archaeology of Ritual: The Sanctuary of Pan at Banias/Caesarea Philippi

From the third century B. C. through the fifth century A. D. a sanctuary to the Greek god Pan existed at the mouth of the Jordan River. At its founding, the sanctuary served as a rural shrine for t...
Infant Colic Is Associated with Maternal Migraine (S36.005)

Objective: To determine whether maternal migraine is associated with an increased prevalence of infant colic. Background Childhood periodic syndromes are thought to be early life expressions of the genetic tendency for migraine. Infant colic, i.e. excessive crying in an otherwise healthy infant, may be another such example of an early manifestation of a migraine genetic tendency. Design/Methods: This is a cross-sectional study of infant colic and parental migraine history in general pediatric clinics in San Francisco. To minimize recall bias, mothers were surveyed at their infants9 two-month-old well-child visit, as this is the age when infant colic is most prevalent. Colic was ascertained via parental report using modified Wessel9s colic criteria. Migraine history was obtained by having a physician diagnosis of migraine or a positive screen on IDMigraine. The primary outcome measure was difference in colic prevalence in infants with and without a maternal history of migraine. The Chi-squared test was used to compare differences between groups. Results: One-hundred and sixty-five surveys were collected; data from 154 infant-mother pairs were analyzed. Infants with a maternal history of migraine were 2.6 times as likely to have colic than infants without a maternal history of migraine (28.6% vs. 11.1%, prevalence ratio 2.6 (1.2-5.5); p=0.02). There was no difference in the accuracy with which migraineur mothers perceived their infants9 colic status compared to non-migraineur mothers. Data on paternal history of migraine was available for ninety-three of the infants. Infants with a paternal history of migraine had a trend toward higher prevalence of colic (22.2% vs. 9.5%, prevalence ratio 2.3 (0.6-9.4), p=0.24). Conclusions: Maternal migraine is associated with increased risk of infant colic. As migraine has a strong genetic underpinning, this association suggests that infant colic may be an early life manifestation of migraine. Disclosure: Dr. Gelfand has received personal compensation in an editorial capacity for Journal Watch Neurology. Dr. Thomas has nothing to disclose. Dr. Goadsby has received personal compensation for activities with Allergan, Inc., Amgen Inc, Colucid, MAP Pharmaceuticals, MSD, Neuralieve, Neuraxon, ATI, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Scientific, Coherex, Eli Lilly & Company, Medtronic, Inc., Linde, Bristol-Myers Squibb Company, Pfizer Inc, and Air Products. Dr. Goadsby has received research support from GlaxoSmithKline, Inc., Amgen Inc, MSD, Neuralieve, and Boston Scientific.
The Lived Experiences of LGBTQQIAA Advocates in Education

Lesbian, gay, bisexual, transgender, queer, questioning, intersex, asexual, and ally (LGBTQQIAA) students are not commonly discussed in teacher education programs. Issues related to LGBTQQIAA learners need to be addressed in schools and in teacher education programs. Extant research shows that LGBTQQIAA students often face hostile school climates, with few resources and little support, which can lead to higher levels of absence and truancy, lower levels of academic achievement, and numerous negative health outcomes. This article uses autoethnographic methods to examine the experiences of an activist group working with preservice teachers, teacher educators, and other social justice advocates on a long-term service project for undergraduate teacher candidates aimed at increasing recognition of and giving voice to K—12 LGBTQQIAA students' experiences. Issues related to agency and resistance are addressed, and implications for teacher preparation programs are discussed.
LFA1 Mediated Attachment of Primary Human Monocytes to Activated Brain Microvascular Endothelial Cells Is Regulated by SDF-1α through the SRC Family Kinase Lyn; Potential Involvement of This Signaling Pathway in HIV-Associated Dementia.

Infiltration of activated monocytes into the brain of HIV-infected patients is a prerequisite for the development of HIV-associated dementia (HAD). The chemokine stromal derived factor-1α (SDF-1α) is expressed at increased levels in the central nervous system (CNS) of HAD patients and elicits chemotaxis and other cellular effects through its receptor CXCR4. In this project, we investigated the intracellular signaling pathway by which SDF-1α mediates the movement and attachment of monocytes to brain microvascular endothelia, and which may contribute to their infiltration into the CNS in HAD. We demonstrated that SDF-1α stimulates migration of primary human monocytes through its receptor CXCR4, and decreases monocyte adherence to surfaces coated with ICAM-1. SDF-1α also decreases monocyte adherence to brain microvascular endothelial cells (BMVEC) activated with the pro-inflammatory cytokines TNF-α or IL-1β, or with recombinant HIV-1 envelope glycoprotein (gp120), which increase endothelial cells expression of ICAM-1. The decreased monocyte adherence was linked to down regulation of the activation-dependent epitope of the β2 integrin LFA-1 which is a ligand for ICAM-1. We then demonstrated that the Src family kinase Lyn is a central modulator of migration and LFA-1-mediated adhesion of SDF-1α-stimulated primary monocytes. Using siRNA knockdown we achieved 80% down regulation of Lyn kinase in human monocytes. Lyn down regulation decreased SDF-1α-mediated migration and prevented its inhibition of monocyte attachment to ICAM-1 coated surfaces and activated BMVEC. These data indicate that in SDF-1α-stimulated primary human monocytes Lyn is a positive regulator of cell migration, and a negative regulator of cell adhesion to BMVEC by inhibiting the ICAM-1 binding activity of the LFA-1 integrin. Thus, CXCR4-triggered inside-out integrin signaling, through Lyn, inhibits adherence and stimulates movement of monocytes towards SDF-1α gradient on BMVEC monolayers. These results provide new insight into the intracellular signaling cascade that controls primary human monocytes movement and attachment at the blood brain barrier.
Induction therapy in renal transplant recipients: how convincing is the current evidence?

The goal of organ transplantation is to provide durable organ function while minimizing risks such as infection and cancer. Induction therapy in renal transplantation provides improved short- and long-term graft outcomes compared with placebo. Three agents are currently available and widely used in the US; rabbit anti-thymocyte globulin (rATG), basiliximab and alemtuzumab. These agents are all clinically effective in transplantation. In patients at high risk of rejection, graft outcomes are improved with the use of depleting agents, such as rATG or alemtuzumab, rather than basiliximab. Depleting agents are associated with more complications, such as infection and malignancy. The risk-benefit analysis for low-risk patients indicates that basiliximab may be the preferred agent in this population. Use of induction therapy, particularly with rATG, may not only allow for but also mandate reduction of maintenance immunosuppression.
The basic attractor and the remainder of homo- and heteroclinic orbits

Abstract In this paper, we discuss some issues in the dynamical systems theory of dissipative nonlinear partial differential equations (PDEs), on a bounded domain. A decomposition theorem says that attractors of PDEs can be decomposed into a basic attractor (a core) that attracts sets of positive measure, it attracts a prevalent set in phase space, and a remainder whose basin, up to sets that are attracted to the basic attractor, is shy, or of zero (infinite-dimensional) measure. If the basic attractor is low-dimensional and the remainder high-dimensional, then the dynamics can still be analyzed up to transients that are exponentially decaying toward the attractor in time. We focus on (ODE) examples of homo- and heteroclinic connections and show that generically these connections lie in the remainder but there exist exceptional cases where they lie in the basic attractor.
Vision-Based Apple Counting and Yield Estimation

We present a novel method for yield estimation in apple orchards. Our method takes segmented and registered images of apple clusters as input. It outputs number and location of individual apples in each cluster. Our primary technical contributions are a representation based on a mixture of Gaussians, and a novel selection criterion to choose the number of components in the mixture. The method is experimentally verified on four different datasets using images acquired by a vision platform mounted on an aerial robot, a ground vehicle and a hand-held device. The accuracy of the counting algorithm itself is \(91\%\). It achieves 81–85% accuracy coupled with segmentation and registration which is significantly higher than existing image based methods.
Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation.

BACKGROUND As systemic therapy has improved for locally advanced pancreatic cancer (LAPC), efforts to improve local control with optimal radiotherapy may be critical. Although conventionally fractionated radiation therapy (CFRT) has more recently shown a limited role in LAPC, stereotactic body radiation therapy (SBRT) is an emerging approach with promising results. With no studies to date comparing SBRT with CFRT for LAPC, this study used the National Cancer Data Base (NCDB) to evaluate these 2 modalities. METHODS With the NCDB, patients with American Joint Committee on Cancer cT2-4/N0-1/M0 adenocarcinoma of the pancreas diagnosed from 2004 to 2013 were analyzed. Radiation therapy delivered at ≤2 Gy was deemed CFRT, and radiation therapy delivered at ≥4 Gy per fraction was considered SBRT. Kaplan-Meier analysis, log-rank testing, and multivariate Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching was used. RESULTS Among 8450 patients, 7819 (92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. Receipt of SBRT was associated with superior OS in the multivariate analysis (hazard ratio, 0.84; 95% confidence interval, 0.75-0.93; P < .001). With propensity score matching, 988 patients in all were matched, with 494 patients in each cohort. Within the propensity-matched cohorts, the median OS (13.9 vs 11.6 months) and the 2-year OS rate (21.7% vs 16.5%) were significantly higher with SBRT versus CFRT (P = .0014). CONCLUSIONS In this retrospective review using a large national database, SBRT was associated with superior OS in comparison with CFRT for LAPC, and these findings remained significant in a propensity-matched analysis. Further prospective studies investigating these hypothesis-generating results are warranted. Cancer 2017;123:3486-93. © 2017 American Cancer Society.
Investigation of pyrophosphate versus ATP substrate selection in the Entamoeba histolytica acetate kinase.

Acetate kinase (ACK; E.C. 2.7.2.1), which catalyzes the interconversion of acetate and acetyl phosphate, is nearly ubiquitous in bacteria but is present only in one genus of archaea and certain eukaryotic microbes. All ACKs utilize ATP/ADP as the phosphoryl donor/acceptor in the respective directions of the reaction (acetate + ATP [Formula: see text] acetyl phosphate + ADP), with the exception of the Entamoeba histolytica ACK (EhACK) which uses pyrophosphate (PPi)/inorganic phosphate (Pi) (acetyl phosphate + Pi [Formula: see text] acetate + PPi). Structural analysis and modeling of EhACK indicated steric hindrance by active site residues constricts entry to the adenosine pocket as compared to ATP-utilizing Methanosarcina thermophila ACK (MtACK). Reciprocal alterations were made to enlarge the adenosine pocket of EhACK and reduce that of MtACK. The EhACK variants showed a step-wise increase in ADP and ATP binding but were still unable to use these as substrates, and enzymatic activity with Pi/PPi was negatively impacted. Consistent with this, ATP utilization by MtACK variants was negatively affected but the alterations were not sufficient to convert this enzyme to Pi/PPi utilization. Our results suggest that controlling access to the adenosine pocket can contribute to substrate specificity but is not the sole determinant.