cssi/SciSciGPT-SciSciNet huggingface dataset:
The Spliceosomal Component Sf3b1 Is Essential for Hematopoietic Differentiation

Myelodysplastic syndrome (MDS) is a disorder arising from hematopoietic stem and progenitor cell (HSPC) dysfunction resulting in ineffective hematopoiesis. A multitude of recurrent somatic mutations in spliceosomal components were recently identified in MDS that likely contribute to the pathogenesis of the disease. The lack of in vivo models to study cell-type specific effects of spliceosomal mutations limits our understanding of why such mutations lead to hematopoietic abnormalities. Using a zebrafish with a loss-of-function mutation in sf3b1 ( sf3b1 hi3394 ), an essential member of the spliceosome, we demonstrate hematopoietic cell differentiation and hematopoietic stem and progenitor cell (HSPC) specification are processes sensitive to spliceosomal malfunction. Primitive erythropoiesis initiates normally in sf3b1 mutants as evidenced by expression of scl in the posterior lateral plate mesoderm at 14 hours post fertilization (hpf) as well as gata1 and beta-globin at 24 hpf. Flow cytometry quantification of gata1:gfp positive erythrocytes showed sf3b1 mutants have 25% more cells at 24 hpf, but greater than 3-fold fewer cells at 36 and 48 hpf, time points when wild type erythroblasts are expanding and differentiating. At 48 hpf, we also observed decreased levels of o-dianisidine positive erythrocytes, low numbers of morphologically mature erythroblasts, and higher levels of immature erythroblasts in sf3b1 mutants. Similarly, we observed normal initiation of primitive myelopoiesis marked by stem cell leukemia (scl) expression in the anterior lateral plate mesoderm at 14 hpf, but diminished expression of more differentiated markers, l-plastin and myeloperoxidase at 24 and 28 hpf in sf3b1 mutants. Quantification of lysozyme C:dsred positivemyeloid cells using flow cytometry also showed 24-fold fewer mature myeloid cells in sf3b1 mutants at 36 hpf. Our data on primitive erythropoiesis and myelopoiesis indicate sf3b1 is required for hematopoietic cell differentiation. Additionally, sf3b1 mutants have diminished expression of the definitive HSPC marker runx1 within the aorta at 28 hpf. In contrast, we observed normal expression of the pan-endothelial marker kinase insert domain receptor-like (kdrl) and aorta-specific markers notch1b and notch3 at 24 hpf. Flow cytometry quantification of kdrl:gfp endothelial cells at 24 hpf shows no difference in the frequency of endothelial cells in sf3b1 mutants. Moreover, we observed fewer cmyb:gfp; kdrl:dsred double positive HSPCs along the dorsal aorta. The data suggest that decreased HSPC formation in sf3b1 mutants is due to a failure in hemogenic induction. From these studies, we show sf3b1 is required at specific stages of hematopoietic cell development. These results provide novel insight into the role of splicing in blood cell development, and can afford a deeper understanding of the mechanism of splicing regulation on the origins of MDS. Disclosures No relevant conflicts of interest to declare.
Abuse-related effects of subtype-selective GABAA receptor positive allosteric modulators in an assay of intracranial self-stimulation in rats.

GABAA positive allosteric modulators (GABAA PAMs), such as diazepam and zolpidem, are used clinically for anxiety and insomnia, but abuse liability is a concern. Novel GABAA PAMS may have lower abuse liability while retaining clinical utility. The present study compared abuse-related effects of the non-selective GABAA PAM diazepam, the α1-selective GABAA PAM zolpidem, and three novel GABAA PAMs (JY-XHe-053, XHe-II-053, and HZ-166) using intracranial self-stimulation (ICSS) in rats. These novel compounds have relatively low efficacy at α1-, α2-, and α3-containing GABAA receptors, putative in vivo selectivity at α2/α3-containing GABAA receptors, and produce anxiolytic-like effects with limited sedation in non-human primates. Adult, male Sprague-Dawley rats (n = 17) were each implanted with a bipolar electrode in the medial forebrain bundle and trained to respond under a fixed-ratio 1 schedule of reinforcement for electrical brain stimulation. The potency and time course of effects were compared for diazepam (0.1–10 mg/kg), zolpidem (0.032–3.2 mg/kg), and the three novel compounds (JY-XHe-053, XHe-II-053, and HZ-166; all 3.2–32 mg/kg). Zolpidem and diazepam produced transient facilitation of ICSS at small doses and more sustained rate-decreasing effects at larger doses. JY-XHe-053 and HZ-166 produced weak and inconsistent ICSS facilitation, whereas XHe-II-053 had no effect on ICSS. These results support a key role for α1-containing GABAA receptors in mediating GABAA PAM-induced ICSS facilitation. These results are concordant with drug self-administration studies in monkeys in suggesting that GABAA PAMs with low α1 efficacy and putative α2/α3 selectivity have lower abuse liability than high-efficacy non-selective or α1-selective GABAA PAMs.
Opioid-induced respiratory depression: the role of genetics

ABSTRACTIntroduction: Opioids are commonly used for treatment of many types of pain, including postoperative chronic and cancer pain. Respiratory depression is a potentially fatal adverse effect of...
Nonuniform Composition Profiles in Amorphous Multimetal Oxide Thin Films Deposited from Aqueous Solution

Metal oxide thin films are ubiquitous in technological applications. Often, multiple metal components are used to achieve desired film properties for specific functions. Solution deposition offers an attractive route for producing these multimetal oxides because it allows for careful control of film composition through the manipulation of precursor stoichiometry. Although it has been generally assumed that homogeneous precursor solutions yield homogeneous thin films, we recently reported evidence of nonuniform electron density profiles in aqueous-deposited films. Herein, we show that nonuniform electron densities in lanthanum zirconium oxide (LZO) thin films are the result of inhomogeneous distributions of metal components. Specifically, La aggregates at the film surface, whereas Zr is relatively evenly distributed throughout single-layer films. This inhomogeneous metal distribution persists in stacked multilayer films, resulting in La-rich interfaces between the sequentially deposited layers. Testing of ...
Point-of-Care Testing in Community Pharmacies: Keys to Success From Pennsylvania Pharmacists.

BackgroundClinical Laboratory Improvement Amendments (CLIA)-waived tests allow for quick, accurate, and noninvasive laboratory testing. Community pharmacists utilize CLIA-waived tests to provide cl...
Robust programs with filtered iterators

We present a new language construct, filtered iterators, for robust input processing. Filtered iterators are designed to eliminate many common input processing errors while enabling robust continued execution. The design is inspired by (1) observed common input processing errors and (2) successful strategies implemented by human developers fixing input processing errors. Filtered iterators decompose inputs into input units and atomically and automatically discard units that trigger errors. Statistically significant results from a developer study demonstrate the effectiveness of filtered iterators in enabling developers to produce robust input processing code without common input processing defects.
Targeting the Wnt5a-β-catenin pathway in the melanoma microenvironment to augment checkpoint inhibitor immunotherapy.

3054 Background: While checkpoint inhibitor immunotherapy has demonstrated recent success in patients with advanced melanoma, a significant fraction of these patients continue to fail therapy. The ...
Effects of porosity and strain rate on the uniaxial compressive response of ice-templated sintered macroporous alumina

Abstract We investigated and thoroughly analyzed compressive response of ice-templated ceramics in quasistatic and dynamic regimes of strain rate. In the high pore volume regime, sintered scaffolds exhibited highly lamellar pore morphology and pore architecture transitioned to dendritic with the decreasing pore volume. Mechanical property measurements in the quasistatic regime of strain rate revealed that with increasing density, compressive response transitioned from a damageable, cellular-like failure to a brittle-like failure. We rationalized the measured results in terms of the propensity of the lamella walls to undergo buckling. Our conjecture is that in the high pore volume regime, lamella walls of the scaffolds are prone to buckling-induced elastic instability, which leads to a compressive response that manifests a gradual decrease of stress beyond peak stress. In contrast, we suggest that in the low pore volume regime thick lamella walls and extensive transverse bridging exhibit marked resistance to buckling-induced instability and scaffolds undergo a global failure, which is manifested in the measured quasistatic compressive response as a sharp drop of stress beyond peak stress. Dynamic compressive response of the scaffolds exhibited measurable differences relative to the quasistatic compressive response. Scaffolds exhibited a relatively gradual decrease of dynamic compressive stress beyond peak stress, and an overall improvement of compressive response and energy absorption capacity was measured under the dynamic loading conditions. We rationalized the measured differences in between the strain rate regimes in terms of the micro-inertia and other effects. This study is of critical significance for applications of ice-templated structures in dynamic environments.
Urban(izing) University Strategic Planning: An Analysis of London and New York City:

While there is a growing recognition of the mutually beneficial relationships universities and cities can forge around local and regional development, urban and academic leaders have often struggle...
Inkjet Printing for Biomimetic and Biomedical Materials

Growth of biological tissues often occurs by a layer of cells building new tissue layer-by-layer. Each new layer is the result of the reaction between a series of reagents and catalysts expressed by the cell layer. The nozzles of inkjet printheads have dimensions similar to those of cells and so it is possible to imagine a versatile inkjet printer also building tissues by depositing a series of drops of various reagents. This paper describes preliminary tests of this approach, the use of inkjet printing to form lines and layers of polymers, reaction between successive drops to produce layers of gels about 100nm thick, addition of enzymes into these gels and there use to produce mineralized structures.
Increased Adipose Tissue Insulin Resistance in Metabolic Syndrome: Relationship to Circulating Adipokines

Abstract Background: Although hepatic insulin resistance has been documented in patients with metabolic syndrome using homeostasis model assessment of insulin resistance (HOMA-IR) as a measure, there is scanty data on adipose insulin resistance (Adipo-IR) and its relationship with the dysregulation of adipokines in metabolic syndrome. Thus, we examined whether Adipo-IR is increased in metabolic syndrome as well as its correlation with circulating adipokines. Methods: In 42 individuals including controls and participants with metabolic syndrome, we measured fasting plasma insulin and free fatty acids (FFA). Adipo-IR was calculated as the product of FFA×insulin. We examined the association between Adipo-IR, metabolic syndrome variables, and circulating adipokines, including leptin, adiponectin, chemerin, omentin-1, and retinol-binding protein-4. Results: Adipo-IR was higher in metabolic syndrome (n=19; median 68.7 mmol/L·pmol/L; 25th–75th percentile, 50.0–104.7) compared to controls (n=23; 22.9 mmol/L·pmol/...
Classical Retrieval Models

This chapter provides a detailed treatment of classical information retrieval models. A distinction is made between bag of words models and those models that go beyond the bag of words assumption. The bag of words models covered include the binary independence retrieval model, the 2-Poisson model, the BM25 model, unigram language models, and several other bag of words models. The models covered that go beyond the bag of words assumption include n-gram language models, the Indri inference network model, as well as several other previously proposed models. The chapter concludes with a discussion of the current state-of-the-art retrieval models, including their pros and cons.
Calcium release channel of sarcoplasmic reticulum: an important target for doxorubicin-mediated cardiotoxicity.

Sarcoplasmic reticulum (SR) of cardiac muscle makes essential contributions to excitation-contraction (E-C) coupling by regulating the free calcium (Ca2+) levels in the myoplasm. The ryanodine receptor constitutes the ligand-gated Ca2+ channel localized at junctional regions of SR through which Ca2+ is released in response to the action potential at the T tubule membrane. The ryanodine receptor complex appears to be co-associated with the voltage-dependent Ca2+ channels of the sarcolemma at the triad junction and the interaction of these proteins is critical to the process of E-C coupling. The role of triadic receptors in the etiology of drug-induced cardiomyopathy is explored. Doxorubicin and its anthraquinone (AQ) congeners are clinically valuable chemotherapeutic agents effective against a broad spectrum of human cancers. The repetitive doses of AQ required for control of malignancies coincides with induction of a progressive and irreversible cardiomyopathy which results in arrhythmias, tachycardia, declining ventricular output, and eventually congestive heart failure. Greater than 65% of patients receiving the maximal acceptable cumulative dosages of doxorubicin develop debilitating ventricular dysfunction. The etiology of AQ cardiomyopathy is unknown, but like genetic dilated cardiomyopathy, the drug-induced disease exhibits a similar progression of abnormal diastolic filling and impaired rates of ventricular relaxation.
Post-Deposition Annealing Effects on Ferromagnetic CoFeB Thin Films

We investigate the role of annealing Co40Fe40B20 at different temperatures and how it affects the crystallinity and the ferromagnetic resonance (FMR) behavior. The onset of crystallization was shown to occur after annealing in nitrogen at 370 °C for 1 h. The crystallization peak of the post-annealed Co40Fe40B20 was matched to the analysis of (110) Co7Fe3, due to secondary phase segregation. Magnetic force microscopy images show a pattern of magnetization ripples in the magnetic phase images for samples upto 250 °C. The grain size of the Co7Fe3 (110) was shown to increase from 20 to 56 nm when annealed above 370 °C to 600 °C. The segregated Co7Fe3 causes scattering of the FMR linewidth, which shifts the resonance peak location, broadens peak-to-peak linewidth, and causes an additional resonance peak to appear close to the uniform resonance of the amorphous phase. Annealing above 500 °C leads to a complete phase change to Co7Fe3, which changes the FMR spectra back to a single resonance peak, shifted to lower fields with broader peak-to-peak linewidth of ~71.2 (kA/m).
Medialization laryngoplasty/arytenoid adduction: U.S. outcomes, discharge status, and utilization trends.

OBJECTIVES/HYPOTHESIS To evaluate trends, outcomes, and healthcare utilization following medialization laryngoplasty (ML) with or without arytenoid adduction (AA) over 10 years. STUDY DESIGN Retrospective observational study. METHODS Using OptumLabs Data Warehouse, trends, outcomes, and healthcare utilization from 2006 to 2015 were examined with a focus on discharge type (same day or not). Predictors of postoperative emergency department (ED) use and hospitalization were determined by multivariable logistic regression. RESULTS Overall rate of ML was 1.09 per 100 thousand enrollees per year. Of these, 7.8% ML were combined with an AA. Outpatient same-day discharge represented 62.0% (1,142 of 1,843) of total patients, steadily increasing over the 10-year period (P < 0.01). There was a 5.9% revision ML rate and 1.0% rate of tracheotomy within 1 day of ML. A total of 5.6% visited an ED, and 5.4% were admitted to a hospital following initial discharge within 30 days. Same-day discharge was found to be a predictor of hospitalization within 30 days after ML (odds ratio [OR] 1.74, P = 0.0452), along with Elixhauser comorbidity index of 4 + (OR 5.74, P = 0.0001). Pulmonary embolism, pulmonary hypertension, and weight loss were top predictors of ED visit or hospitalization. CONCLUSION To our knowledge, this is the first search evaluating national claims data for ML with or without AA. Overall rate of ML is low, and same-day discharge has become more common over a 10-year period, with an associated higher 30-day hospital admission risk. Correct patient selection criteria for disposition status cannot be fully determined based on current data, but a high Elixhauser comorbidity index clearly carries increased risk for hospitalization after initial discharge. LEVEL OF EVIDENCE 4 Laryngoscope, 129:952-960, 2019.
How to Evolve the Response to the Global HIV Epidemic With New Metrics and Targets Based on Pre-Treatment CD4 Counts.

Early diagnosis and treatment of HIV following seroconversion improves individual and population health. Using published data on pre-treatment CD4 cell counts, we benchmarked the level of immunodeficiency at HIV diagnosis and ART initiation in the “real world” against those of the treatment and control arms of landmark controlled trials that successfully reduced HIV-related deaths (INSIGHT/START) and onward HIV transmission (HPTN 052). The median CD4 count in the treatment vs. control arms of the INSIGHT/START trial and HPTN 052 were 650 vs. 408 cells/μL and 442 vs. 221 cells/μL, respectively. In the real world, recent global estimates of the median CD4 count at start of ART range from 234 to 350 cells/μL, and only 25% of those initiating ART do so early (i.e., with CD4 > 500 cells/μL). Recent global data on trends in the median CD4 count at diagnosis and ART initiation are not encouraging. We identify a critical need for new targets and metrics for persons newly diagnosed with HIV, newly enrolling in HIV care, and newly initiating ART, based on pre-treatment CD4 counts, to help increase the focus of implementation efforts on achieving earlier diagnosis, linkage to care, and ART initiation.
The Use of Tick Salivary Proteins as Novel Therapeutics

The last three decades of research into tick salivary components has revealed several proteins with important pharmacological and immunological activities. Two primary interests have driven research into tick salivary secretions: the search for suitable pathogen transmission blocking or “anti-tick” vaccine candidates and the search for novel therapeutics derived from tick salivary components. Intensive basic research in the field of tick salivary gland transcriptomics and proteomics has identified several major protein families that play important roles in tick feeding and overcoming vertebrate anti-tick responses. Moreover, these families contain members with unrealized therapeutic potential. Here we review the major tick salivary protein families exploitable in medical applications such as immunomodulation, inhibition of hemostasis, and inflammation. Moreover, we discuss the potential, opportunities, and challenges in searching for novel tick-derived drugs.
Bandwagon effects in social television: How audience metrics related to size and opinion affect the enjoyment of digital media

Abstract In this era of social television, we see not only the content of online videos but also how many other viewers are viewing them and how they are reacting to them. Do these metrics about audience size and opinion affect our own reactions? And, does it matter where these viewers are geographically located? We investigated these questions by first proposing a typology of audience cues based on size, opinion, and identity, and then testing the effects of each of these cues through a 2 (frequency metric: high number of viewers vs. low number) x 3 (evaluative metric: positive comments vs. negative comments vs. no comment control) x 2 (distance metric: low distance vs. high distance) between-subjects experiment (N = 410). We discovered that view counters and comments affect media enjoyment through perceptions of audience size and collective opinion respectively. Theoretical and practical implications are discussed.
Inpatient Mortality of Patients with Multiple Myeloma on Dialysis Undergoing Autologous Stem Cell Transplantation: Analysis of the National Inpatient Sample

Introduction Renal impairment is a common problem in patients with multiple myeloma (MM), and approximately 2-3% of patients develop renal impairment requiring dialysis. Autologous stem cell transplantation (ASCT) is a mainstay of treatment for eligible patients. Although dialysis is not a contraindication to ASCT, further data on the safety of ASCT for these patients is needed, especially for patients on peritoneal dialysis (PD) for which there is limited data available. Methods The National Inpatient Sample (NIS) is a database that provides information on all inpatient hospitalizations in the United States (US), including primary and secondary diagnoses, procedures, length of stay, and disposition. Approximately 20% of admissions are tracked, and weighted estimates are provided regarding the total number of hospitalizations in the US. Using this database, we were able to track hospital admissions for MM patients who underwent ASCT. We reviewed data from 2002 to 2014, using ICD 9 coding. Results During the years 2002-2014, the total weighted estimate of inpatient admissions for ASCT among MM patients was 47,253 (unweighted N=10,231). However, a weighted total of only 45 patients with MM received PD during their hospital stay for ASCT in theUS, as opposed to 1709 patients with MM who received HD during their hospital stay for ASCT. The inpatient mortality rate was numerically higher for patients receiving hemodialysis (HD) compared to PD during their hospital stay for ASCT (20.5% for patients receiving peritoneal dialysis versus 13.8% for patients receiving HD), but this difference was not statistically significant (p=0.58). However, inpatient mortality overall for patients with MM undergoing ASCT not on dialysis was only 1.1%, indicating a markedly increased risk of inpatient mortality for patients with MM on dialysis undergoing ASCT (p The length of stay was comparable between patients receiving HD vs PD (28.7 days for HD vs 26.7 for PD, p=0.69). The length of stay for patients not on dialysis was 17.9 days (p Conclusion Patients with MM requiring either PD or HD undergoing inpatient ASCT are at a significantly increased risk of inpatient mortality. Collaborative efforts are needed to help determine best practices for these patient populations, especially as pertains to patients on PD.
Preference, Choice, and Self-Determination in the Healthcare Context

Persons with disabilities often experience fewer opportunities to exercise choice and control in their lives than members of the general population. As a result, the services and supports they receive are often not the ones that provide them with the opportunity to lead a high quality of life. One area in which members of this group have historically been denied the opportunity to have their preferences and choices respected is within the healthcare system. In this chapter, taking an ecological approach, we review some of the critical characteristics of healthcare systems associated with health disparities that make it challenging for persons with disabilities to exercise desired levels of choice and control within this context. These range from systemic factors including healthcare financing and the inadequacies of healthcare provider training to the lack of knowledge and attitudes/beliefs medical personnel often have about individuals with disabilities. In looking for solutions to the current state of affairs, we focus on changes to the system and “how” we provide healthcare to persons with disabilities who present a diverse set of needs for services and supports. These include the development of competencies for healthcare professionals working with individuals with disabilities, patient-centered medical homes, approaches to shared and supported decision-making, and healthcare coordination and navigation.
Effects of an 8-Week Judo Program on Behaviors in Children with Autism Spectrum Disorder: A Mixed-Methods Approach

Prior studies suggest that a combination of physical activity and mind–body exercises, often seen in martial arts, may attenuate negative behaviors in youth with Autism Spectrum Disorder (ASD). Therefore, the aim of this study was to examine the effects of an 8-week judo program on behavioral factors in children with ASD, using a mixed-methods approach. A total of 25 children (ages 8–17), diagnosed with ASD, participated in an 8-week judo program (1 × week). Parents of participants were given the Aberrant Behavior Checklist (ABC) to compare the severity of ASD-related behavior at baseline and at the end of the program. A subset of parents (n = 9) participated in semi-structured interviews that focused on their child’s behaviors during the judo program. Non-parametric paired t-tests were conducted to compare differences in the ABC scores from at baseline and at the end of the program. Interviews were coded independently by two trained researchers and categorized into behavioral themes. Participants attended an average of 7.04 ± 1.06 classes (out of 8 sessions). There were no significant changes in ABC scores, however, parent interviews revealed that 78% of parents observed improvements in both social skills and self-esteem as a result of the judo program. Despite no significant differences in ABC scores pre and post-judo, data from parent interviews indicate improvements in self-esteem and social skills. Future studies should further examine the effects of judo in a larger sample of youth with ASD, and include control conditions (e.g. no-exercise group) for comparison purposes.
Postpartum glucose screening among women with gestational diabetes.

Abstract Objective (1) Determine the rate of completion of glucose screening for diabetes in the postpartum period for women who had gestational diabetes mellitus, and (2) compare the rates of follow up glucose screening among women who had A1GDM or A2GDM 4-12 weeks postoartum. Design A retrospective comparative study. Setting An academic hospital in an urban community. Participants One hundred and seventy-five women with gestational diabetes who gave birth between January 2012 and September 2015. Methods The electronic medical record was reviewed to confirm diagnosis of gestational diabetes at 24–28 weeks and completion of 4–12 weeks postpartum glucose screening. All consecutive women meeting eligibility criteria were included. Results The rate of postpartum glucose screening was 38.9%. There were 22 (31.0%) women with A1GDM and 46 (44.2%) women with A2GDM who had postpartum glucose screening (χ2 = 3.12, p = 0.08). Conclusions The type of GDM, did not affect the rate of follow-up for postpartum glucose screening. Strategies need to be developed to improve postpartum screening rates in women with gestational diabetes.
Patterns of sex hormone receptor expression in stimulated endometrium from oocyte donors.

In patients with high serum E2 embryo transfer is often postponed, as high E2 levels adversely affect embryo transfer outcome. We aimed to determine if stratified serum oestradiol (E2) and progeste...
Is Ciprofloxacin a Substrate of P‐glycoprotein?

INTRODUCTION: Studies using MDCKII and LLC-PK1 cells transfected with MDR1 cDNA indicate that ciprofloxacin is not a substrate of P-glycoprotein. However, our data has shown that transport studies done using different P-gp overexpressing cell lines (MDCKI-MDR1, MDCKII-MDR1 and L-MDR1), could lead to contradictory conclusion on whether a compound is a substrate of P-gp. The aim of our study was to determine if ciprofloxacin is indeed not a P-glycoprotein substrate using MDCKI cells transfected with human MDR1 cDNA. METHODS: Semi-quantitative RT-PCR was used to determine the mRNA level of MDR1 while Western blot was performed to determine the protein expression level of P-gp, MRP1 and MRP2 in various cells. Ciprofloxacin bidirectional transport studies were performed in MDCKI, MDCKI-MDR1, MDCKII, MDCKII-MDR1, MDCKII-MRP2, LLC-PK1, L-MRP1 and L-MDR1 cells. RESULTS: Ciprofloxacin showed net secretion in MDCKI-MDR1 but net absorption in MDCKI cells. Various P-gp inhibitors decreased the B to A and increased the A to B transport of ciprofloxacin in MDCKI-MDR1 cells while having no effect in MDCKI cells. The B to A transport of ciprofloxacin in MDCKI-MDR1 cells was not affected by non-P-gp inhibitors. In the presence of indomethacin, ciprofloxacin showed net secretion instead of net absorption in MDCKI cells while in the presence of probenecid and sulfinpyrazone, there was no net secretion and absorption. There was no difference in ciprofloxacin transport between MDCKII and MDCKII-MDR1, LLC-PK1 and L-MDR1, LLC-PK1 and L-MRP1 and MDCKII and MDCKII-MRP2. CONCLUSIONS: Transport data in MDCKI and MDCKI-MDR1 cells indicate that ciprofloxacin is a substrate of P-gp but data from MDCKII, MDCKII-MDR1, LLC-PK1 and L-MDR1 cells indicate that ciprofloxacin is not a substrate of P-gp. Vinblastine, a well-known P-gp substrate, also did not show differences between LLC-PK1 and L-MDR1 cells. Further studies need to be performed to characterize these P-gp overexpressing cell lines and the transport of ciprofloxacin.
Label space: a multi-object shape representation

Two key aspects of coupled multi-object shape analysis are the choice of representation and subsequent registration to align the sample set. Current techniques for such analysis tend to trade off performance between the two tasks, performing well for one task but developing problems when used for the other. This article proposes Ln label space, a representation that is both flexible and well suited for both tasks. We propose to map object labels to vertices of a regular simplex, e.g. the unit interval for two labels, a triangle for three labels, a tetrahedron for four labels, etc. This forms a linear space with the property that all labels are equally separated. On examination, this representation has several desirable properties: algebraic operations may be done directly, label uncertainty is expressed as a weighted mixture of labels, interpolation is unbiased toward any label or the background, and registration may be performed directly. To demonstrate these properties, we describe variational registration directly in this space. Many registration methods fix one of the maps and align the rest of the set to this fixed map. To remove the bias induced by arbitrary selection of the fixed map, we align a set of label maps to their intrinsic mean map.
Displacement analysis of the interior walls of a pipe using panoramic holointerferometry

Standard phase-displacement equations, used for both double exposure and real time holo-interferometry, are combined with the geometrical mapping and optical characteristics of panoramic annular lenses to accurately measure surface displacement on the interior wall of a pipe. In this approach, one panoramic annular lens is used to illuminate the surface with coherent light, and the resulting intensity distribution is holographically recorded through a second panoramic annular lens. Interference fringes are obtained in real-time by comparing holograms recorded before and after the pipe is displaced. The annular images and the holographic fringes are acquired and stored digitally in a computer system. Image transformation algorithms are applied to remove optical distortions in the holographic pattern and fringe loci are compared to those predicted on the basis of theory.
Bone and Teeth, Properties of

Bone has a variety of functions in the body of which some of the most important are structural in nature: protection of vulnerable body parts, support of the body, and to provide muscle attachments. A knowledge of the mechanical and adaptive properties of bone is useful in the design and use of prostheses that replace a bone or a portion of a bone. Mechanical properties of bone are also of interest in trauma biomechanics and in efforts to prevent injury to the body. As for teeth, they also are replaced by artificial materials which are called upon to perform the mechanical functions of the original tooth. This article contains a survey of known properties of bone and teeth and their components collagen and apatite, with an emphasis on bone and its mechanical properties. Keywords: collagen; apatite; biomechanics; bone; adaptive properties; electrical properties
Abstract P259: Genome-Wide DNA Methylation and Subclinical Cardiovascular Disease in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Coronary artery calcification (CAC) and carotid intima-media thickness (CIMT), established measures of subclinical atherosclerosis, that have been demonstrated to improve prediction of coronary artery disease (CAD) risk beyond classical risk factors (CRFs). This study examined the epigenetic mechanisms underlying the appearance of CAC and increased CIMT, which have not been previously explored. Methods: We conducted an epigenome-wide association study (EWAS) in 46 non-smoking and non-diabetic white subjects randomly selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CAC and CIMT were measured by computed tomography (CT) and catotid artery ultrasound at examination year (Y) 20. The Illumina HumanMethylation450 BeadChip was used to measure DNA methylation in white blood cells collected at Y15. We dropped one sample with >1% of the CpG sites having a detection p-value >0.05 and then exclude ~160k CpG probes due to their ambiguously mapping to the genome or with the presence of common SNPs, etc. Both background adjustment and normalization were performed separately for Infinium I and II probes, and new values were calculated and then transformed into M-values. After correction for potential chip effect, we examined the associations between these pre-processed methylation levels at each CpG site with CAC and CIMT using multiple logistic and linear regression models, respectively. Pathway analysis was performed to explore the gene sets that were significantly associated with CAC and CIMT. Results: Several CpG sites in multiple genes were significantly associated with CAC or CIMT. Some of these genes play roles in the regulation of vascular function, such as ion binding and transport ( HRH1 , LRP1B , KCNJ9 , TRIM40 , ADAMTS3 for CAC and BRSK2 , ZNF428 , TROVE2 , C1orf86 for CIMT) and metabolic processes ( LEPR for CAC and NUP50 for CIMT). Pathway analyses revealed several common canonical pathways for CAC and CIMT including, calcium signaling, axon guidance, and focal adhesion etc., which are relevant to the occurrence of these two subclinical CADs. The statistical significance of identified CpG sties for either CAC or CIMT did not remain after correction for multiple testing, possibly due to the small sample size. Conclusion: Our preliminary findings suggest that methylomic mechanisms may play a role in the development of CAC and CIMT, and subsequently the etiology of CAD. Future replication studies in larger longitudinally studies are needed.
Quantitative Analysis of MR Imaging to Assess Treatment Response for Patients with Multiple Myeloma by Using Dynamic Intensity Entropy Transformation: A Preliminary Study.

Our study demonstrated feasibility by using the newly developed three-dimensional dynamic intensity entropy transformation method to quantify bone marrow changes in MR imaging and to assess treatment response of patients with multiple myeloma after bone marrow transplantation.
Expression of the aryl hydrocarbon receptor/transcription factor (AhR) and AhR-regulated CYP1

Exposure to ubiquitous environmental chemicals, such as polycyclic aromatic hydrocarbons (PAH), may contribute to human breast cancer. In animals, PAH induce tumors in part by activating the aryl hydrocarbon receptor (AhR)/transcription factor. Historically, investigations into AhR-regulated carcinogenesis have focused on AhR-dependent transcriptional regulation of cytochrome P450 (CYP) enzymes which oxidize PAH to mutagenic intermediates. However, recent studies suggest that the AhR directly regulates cell growth. Given the postulated role of the AhR in carcinogenesis, we predicted that: (1) tissue predisposed to PAH tumorigenesis would express the AhR and (2) aberrant AhR and/or AhR-regulated gene expression would accompany malignant transformation. To test these hypotheses, AhR and CYP1 protein and/or mRNA levels were evaluated in rat mammary tumors induced with 7, 12-dimethylbenz[a]anthracene (DMBA), a prototypic PAH and AhR ligand. Results indicate modest AhR expression in normal mammary myoepithelial and ductal epithelial cells. In contrast, high AhR levels were detected in DMBA-induced tumors. Nuclear AhR localization in tumors suggested constitutive AhR activation. In situ hybridization and quantitative RT-PCR assays indicated high AhR mRNA levels in neoplastic epithelial cells. While both AhR-regulated CYP1A1 and CYP1B1 mRNAs were induced in breast tissue within 6 h of DMBA gavage, only CYP1B1 mRNA remained elevated in tumors. These results: (1) help explain targeting of breast tissue by carcinogenic PAH, (2) imply that AhR and CYP1B1 hyper-expression represent molecular biomarkers for, at least, PAH-induced mammary cell transformation, and (3) suggest mechanisms through which the AhR may contribute to carcinogenesis well after exogenous AhR ligands have been eliminated.
Intimate Distance: the Dislocation of Nature in Modernity

the methods of literary analysis in an effort to understand both canonical texts and current sociopolitical events. This analysis focuses less on the meaning of terms than on the role they play; it involves a "shift from historical definition to the problematics of reading" (de Man 1979: ix). This new theory is especially helpful in discussing some of the central, and essentially contested, concepts in political theory. It helps us to understand these terms, not as unified markers, but in terms of the role they play in a given writer's thought or in the dynamics of a political culture. One of these key terms is "nature." Nature has had many meanings in political theory, and the unity and stability of those meanings has varied over time. A central feature of modernity is the shifting, problematic relation between nature and culture. In Ernesto Laclau's terms, nature has been "dislocated" insofar as its identity or meaning "depends on an outside which both denies that identity and provides its condition of possibility at the same time" (Laclau 1990: 39). Dislocation describes a situation of inescapable ambiguity. The opposition to "culture" provides the bedrock meaning of "nature" in the West, but this opposition has become fraught with tension. Since the eighteenth century, the "outside" of culture has given meaning to nature, but it has also increasingly been used to deny the identity of nature as something distinct from culture. This dislocation of nature is directly relevant to arguments about and within current social movements. They are relevant because nature underlies several crucial nodes of political argument: ideas of justice, of the desirability of change, of freedom and the limits of human action, of the source and possibility of knowledge, all involve differing senses and aspects of nature. The destabilization of nature is the open-
On the type of linkage binding fatty acids present in brain white matter proteolipid apoprotein

Summary Fatty acids (FA) which constitute about 2.5% by weight of exhaustively delipidated proteolipid apoprotein (PLA) have been shown to be bound mainly, if not exclusively, by ester linkages. Indeed, they are progressively released by mild alkaline hydrolysis, and reduction of PLA with NABH 4 yields corresponding fatty alcohols. The FA are not constituents of residual contaminating known lipids except possibly in a very small proportion.
Parametric duality models for discrete minmax fractional programming problems containing generalized (θ,η,ρ)-V-invex functions and arbitrary norms

The purpose of this paper is to construct several parametric duality models and prove appropriate duality results under various generalized (θ, η, ρ)-V-invexity assumptions for a discrete minmax fractional programming problem involving arbitrary norms.
Assessing Professional Collaboration in Schools: Knowing What Works

Teacher collaboration has become an legitimate service delivery option for students with disabilities and students at risk for learning and/or behavior problems. Notwithstanding its growing popularity, there is little empirical research on the fidelity of implementation of intervention plans that stem from professional collaboration. The modest body of available research focuses more on process than outcomes. Accordingly, the authors draw on the literature to propose a multidimensional model for school personnel to evaluate the actual impact of collaboration.
Modeling of Contaminant Transport Resulting from Dissolution of Nonaqueous Phase Liquid Pools in Saturated Porous Media

A mathematical model for transient contaminant transport resulting from the dissolution of a single component nonaqueous phase liquid (NAPL) pool in two-dimensional, saturated, homogeneous porous media was developed. An analytical solution was derived for a semi-infinite medium under local equilibrium conditions accounting for solvent decay. The solution was obtained by taking Laplace transforms to the equations with respect to time and Fourier transforms with respect to the longitudinal spatial coordinate. The analytical solution is given in terms of a single integral which is easily determined by numerical integration techniques. The model is applicable to both denser and lighter than water NAPL pools. The model successfully simulated responses of a 1,1,2-trichloroethane (TCA) pool at the bottom of a two-dimensional porous medium under controlled laboratory conditions.
TagOrbitals: a tag index visualization

With the rise of web-based tagging systems, it has become important to help users search and browse the index of tags that are being created. One promising approach is visualization, but existing techniques rely on hard-to-interpret network diagrams or focus only on a small subset of a collection. This sketch introduces TagOrbitals, a technique that can display an entire index at once, while simultaneously showing details of individual tags and items.
Borohydride anion exchange resin stabilization of flash-lamp-pumped coumarin dye lasers

Abstract The operation of flash-lamp-pumped Coumarin 460 and 480 dye laser with ethanol solvent produced acetaldehyde; its production paralleled the increase in the optical density of the dye solution at the dye lasing wavelength and the decrease in the output intensity of the dye laser. The yield of acetaldehyde was shown to be higher with higher light intensity and with the presence of molecular oxygen. Acetaldehyde formation was further enhanced by simultaneous excitation of the singlet-singlet and triplet-triplet absorption bands of Coumarin 460. The formation of acetaldehyde and other material which interferes with stimulated emission is discussed in terms of upper triplet state energy transfer from the dye to the solvent. The concentrations of acetaldehyde and material absorbing at the lasing wavelength of the dye were controlled in real time by introducing a cartridge containing a borohydride anion exchange resin in the dye steam to reduce carbonyl functional groups to less absorbing alcohol functional groups as they were formed photochemically. The presence of the resin increased the initial output power of the dye laser and substantially improved its output stability.
Archimedean and continuity

Abstract Let ≽ be a complete and transitive binary relation on the set of all lotteries on finite sets of prizes. Then ≽ is mixture continuous if and only if it satisfies the Archimedean axiom and a condition called local mixture dominance.
Surrogate end points for long-term outcomes in chronic myeloid leukemia

AbstractThe natural history of the chronic phase (CP) of chronic myeloid leukemia (CML) and the high response rates achieved with BCR–ABL inhibitor therapy necessitate long-term evaluation of survival-based outcome measures. Prior to the availability of long-term BCR–ABL inhibitor data, short-term surrogate end points predictive of longer-term outcomes have been identified using data from clinical trials of patients with CML-CP treated with interferon-α-based therapy and approved BCR–ABL inhibitors. In patients with newly diagnosed CML-CP treated with imatinib, achieving a complete cytogenetic response (CCyR) by 12 months has been associated with more favorable outcomes, and both CCyR and major cytogenetic response have been used as surrogate end points for regulatory approval. Following approval of second-generation BCR–ABL inhibitors in the first-line setting (nilotinib, dasatinib), which have significantly faster and deeper response rates than imatinib, molecular-based surrogate markers at earlier time...
Shell model calculations using modified Sussex matrix elements for A<=4

The /sup 3/S/sub 1/ and /sup 3/S/sub 1hyphen/ /sup 3/D/sub 1/ Sussex matrix elements are modified by the addition of the matrix elements of a potential whose radial form is that of a momentum-dependent delta function. The strength parameters of the potential are found by fitting to the binding energy and quadrupole moment of the deuteron. Shell model calculations in a 4h..omega.. model space using the modified matrix elements and a size parameter of 1.5 fm give binding energies of 7.55, 6.79, and 27.77 MeV for /sup 3/H, /sup 3/He, and /sup 4/He, respectively. The energies of the negative parity states in /sup 4/He are also calculated using the modified matrix elements in a 5h..omega.. model space. It is found that their calculated absolute energies are much improved as compared to calculations using the unmodified matrix elements. The relative energies of these states are not significantly changed by the modifications, as expected.
MINIMAL F2-FLOWS

Let a be an ergodic endomorphism of the /--dimensional torus and IT a semigroup generated by two affine transformations lying above a. We show that the flow defined by n admits minimal sets of positive Hausdorff dimension and we give necessary and sufficient conditions for this flow to be minimal.
A Biopsychosocial Model of Hypersexual Disorder/Sexual Addiction

Since 1977, when Dr. George Engel authored, “The Need for A New Medical Model: A Challenge for Biomedicine,” (Engel, 1977) the biopsychosocial model has advanced our understanding of diseases and t...
Short-term inhalation of cadmium oxide nanoparticles alters pulmonary dynamics associated with lung injury, inflammation, and repair in a mouse model.

AbstractContext: Cadmium oxide nanoparticles (CdO NPs) are employed in optoelectronic devices and as a starting material for generating quantum dots as well as for medical imaging and targeting of pharmaceutical agents to disease sites. However, there are lack of data concerning short- and long-term effects of CdO NPs on the lungs.Objective: To determine the effects of inhaled CdO NPs at an occupationally relevant concentration on pulmonary injury and repair, and on systemic immunity in adult male mice.Methods: Mice were exposed to 240 μg CdO NPs/m3 for seven days (3 h/d) and lavage levels of pulmonary injury/inflammatory markers, bacterial uptake by circulating phagocytes, and lung histology examined either one or seven days following the final exposure.Results: Levels of total protein, lactate dehydrogenase activity, cytokine markers of inflammation (i.e. interleukin-1β, tumor necrosis factor-α, and interferon-γ), tissue remodeling matrix metalloproteinases (MMP)-2 and -9 activity, and phagocytic activi...