cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract A02: Integrative analysis identifies differential miRNA expression in HPV-positive head and neck squamous cell carcinoma including mir-9 overexpression and corresponding downregulation of the target YAP1

Background: HPV-positive (HPV+) head and neck squamous cell cancer (HNSCC) differs significantly from HPV-negative (HPV-) in terms of biology, response to treatment, and clinical outcome. The molecular mechanisms underlying these differences and the potential contribution of microRNA (miRNA) in regulating the behavior of HPV- disease are not well understood. Methods: We conducted an integrated analysis of miRNA expression as well as protein and mRNA expression from HPV+ and HPV - HNSCC to identify candidate genes and proteins that might be regulated by miRs. We first compared miRs in HPV+ (n=36) versus HPV- (n=243) cancers from The Cancer Genome Atlas (TCGA) to identify miRs that were differentially expressed between these groups (by t-test, p≤0.05, fold change≥2.8). Using TargetScan and the mirWalk systems, we then predicted potential targets for these miRs. Next, differences in the expression of predicted targets were evaluated by comparing levels of proteins (assessed using reverse phase proteomic arrays (RPPA)) and mRNA levels (by RNASeq) between HPV+ and HPV- tumors. Results: We identified eight miRs that differed significantly between HPV+ versus HPV- HNSCC tumors. Among these miRs, mir-9, mir-20b, mir-363, and mir-106a were higher in HPV+ tumors, while mir-767, mir-105, mir-1269, and mir-206 were present at lower levels. Predicted target genes of these miRs that were confirmed to be differentially expressed at the mRNA or protein level include YAP1, a known effector of the Hippo pathway and predicted target gene for mir-9. Specifically, HPV+ tumors demonstrated lower YAP1 mRNA expression (p=3.48E-05, fold change=-1.6) as well as lower levels of phosphorylated YAP 1 protein (p=.0015. fold change=-1.7). Other potential candidates identified include EEF2 (mir-106a target) and phosophorylated PDK1 (mir-363 target), which both exhibited lower protein levels in HPV+ cancer. Conclusions: Our analysis identified eight miRs that differed significantly between HPV + and HPV- cancers. Through an integrative analysis, we identified the YAP1 pathway as a potential target for mir-9 , a miR that has previously been found to be elevated in other cancers, including non-small cell lung cancer. These data suggest that miRs may contribute to differences between HPV+ and HPV- HNSCCs. Further investigations on the role of miRs in the pathogenesis of HPV+ and HPV- OSCCs are ongoing. Citation Format: Claudia Isabel Heymach, Lixia Diao, Pan Tong, Patrick Kwok Shing Ng, Gordon B. Mills, Jing Wang, Lauren Byers. Integrative analysis identifies differential miRNA expression in HPV-positive head and neck squamous cell carcinoma including mir-9 overexpression and corresponding downregulation of the target YAP1. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A02.
Photovoltaic Material Characterization With Steady State and Transient Photoluminescence

In this study, we develop an approach to characterize the surface and bulk properties for thin films of photovoltaic materials by combining two experimental photoluminescence (PL) techniques with one multiphysics simulation. This contactless, in-line characterization technique allows reliable extraction of key lifetime parameters. In this study, we first discuss the strengths and weaknesses of both steady-state and transient PL techniques (specifically, steady-state PL excitation spectroscopy and time-resolved PL) and show that combining them with numerical simulation can be used to extract surface and bulk lifetimes self consistently. The method is applied to InP thin films grown with a novel vapor-liquid-solid method. The InP thin film tested is found to have a bulk Shockley-Read-Hall (SRH) lifetime of 12 ns and a front surface recombination velocity of 5×10 4 cm/s.
Morphological control of diamond thin films: its influence on friction and wear

Microwave plasma enhanced chemical vapor deposition was used to grow diamond films with different morphologies and surface roughnesses. With the proper choice of deposition parameters (111) faceted, octahedral, flat (100) and microcrystalline diamond films were obtained. Scanning electron microscopy, atomic force microscopy and stylus profilometry were used to assess the surface topography for each type of film. Raman spectroscopy and x-ray diffraction were also used to determine the purity of the diamond phase and growth orientation of the films, respectively. Single pass friction and wear tests were conducted on each film in order to determine the effect of surface morphology on the coefficient of friction and wear of the counterface materials and/or diamond films. Counterface materials included alumina, tungsten carbide, zirconia, and the (100) face of a synthetic diamond single crystal. Results showed a decrease in the coefficient of friction as the film roughness decreased. Specific wear of the non-diamond counterface materials showed a marked decrease for the flatter and smoother diamond surfaces. For diamond on diamond, the coefficient of friction also decreased as film topography became smoother. Wear of the diamond films occurred by fracture or shearing of asperity tips which was most severe for the rougher films. Control of diamond morphology is shown to be of paramount importance in tribological applications in order to reduce abrasive wear, material transfer, and diamond film fracturing.
STUDIES OF LINKAGE IN POPULATIONS. VII. TEMPORAL VARIATION AND X-CHROMOSOMAL LINKAGE DISEQUILIBRIUMS.

A fundamental tenet of modern evolutionary thought is that mechanisms must exist to promote the development of systems of interacting non-allelic genes, since few if any significant adaptations involve single gene effects. The preceding paper (Levitan, 1973) has demonstrated that the gene arrangements on the two arms of the X-chromosome of Drosophila robusta Sturtevant provide evidence for one such interaction system, inasmuch as the frequencies of certain combinations of these linked arrangements often exhibit cyclic seasonal variation not attributable to one or another of the constituent arrangements. The writer has shown earlier (Levitan, 1955, 1958a, 1961a, 1961b, 1964) that in several localities another manifestation of such an adaptive interaction system is the presence of linkage disequilibrium. A linkage disequilibrium or association exists when, contrary to theoretical expectations in the absence of selection (Robbins, 1916; Geiringer, 1944, 1948), certain combinations of linked genes or gene arrangements are significantly in excess of random proportions, other combinations deficient. A number of writers have since developed theoretical models outlining the conditions of recombination and selection for epistatic interaction that would be conducive to such disequilibriums (see Bodmer and Parsons (1962), Feldman and Crow (1970), and Sved (1971) for references to the work of Felsenstein, Karlin, Kimura, Lewontin, and others). The previously reported linkage disequilibriums were based on the frequencies of the arrangement combinations over a period of several years. They did not take into account the possibility that the "total" data were seasonally heterogeneous, as proved to be the case. This paper reanalyzes these data, and presents results from several additional localities, to determine whether the concept of linkage disequilibriums remains valid in the light of the variations in the component samples. It also examines the possibility that the seasonal samples themselves evidence disequilibriums and, if so, whether their nature are attributable to the fluctuations in the linkage combinations described by Levitan (1973). It turns out that the populations studied for temporal variation contain three different X-chromosomal disequilibrium (linkage association) systems. The data for each system will be discussed separately. Methods and notation are described in Levitan (1973).
Collagenous colitis treated successfully with bismuth subsalicylate.

Collagenous colitis is a relatively recently described well-recognized entity. Considered a unique variety of idiopathic inflammatory bowel disease, it was initially grouped along with lymphocytic colitis and called microscopic colitis. Its distinctive histological characteristics include a thickened subepithelial collagen band, evidence for chronic inflammation in the lamina propria, and increased intraepithelial lymphocytes. Multiple therapeutic approaches have been attempted including mesalamine compounds and corticosteroids with variable responses, usually requiring either maintenance therapy or repeated courses to maintain a state of remission. We describe a case of collagenous colitis treated with a short course of open-label bismuth subsalicylate (PeptoBismol) with prompt resolution of symptoms and histological abnormalities, and a prolonged clinical remission.
Selective culture of bovine retinal vascular endothelial cell and pericytes

Objective To establish simple methods for selective culture of bovine retinal endothelial cell and pericytes.Methods Cell weeding or seperation were used ,in addition,culture dishes were coated with different matrix components and supplements benefit to cell growth were added into culture media.Results Relative pure bovine retinal vascular endothelial cells and pericytes were obtained selectively (purity95%)and could be passaged serially.Passaged pericytes showed higyly irregular peripheries and more silky structure in cells, and positive staining for a monoclonal antibody α smooth muscle actin.Retinal endothelial cells showed ‘stone’ type when confluent,and positive staining for factor Ⅷ antibody.Conclusion The suitable condition for endothelial cell were use of gelatin coat culture dishes, and adding of heparin,endothelial growth factor and highly fetal serum into culture media. The suitable condition for pericytes are adding 20 g·L -1 fetal serum into DMEM. Percoll can also be used to selective culture of endothelial cells and pericytes.
Effect of posture on intraocular pressure in normal and glaucoma patients

Objective To study the effect of posture on intraocular pressure(IOP) in normal and glaucoma patients. Methods Twelve glaucoma patients(24 eyes) at the mean age of 27.5±7.0 years admitted to our hospital from November 2012 to January 2013 served as a glaucoma and 22 normal volunteers(44 eyes) at the mean age of 25.7±4.3 years served as control group in this study. Their IOP at sitting position and horizontal position was measured with a rebound ophthalmotonometer. Their IOP at horizontal position was measured at 5, 10, 15, 20, 25 and 30 min, respectively. Results The average IOP was 16.875±9.441 mmHg(1 mmHg=0.133 kPa) and 17.409±2.576 mmHg, respectively in glaucoma group and control group at horizontal position. The average IOP was 24.500± 9.200 mmHg, 24.083±9.453 mmHg, 25.333±8.004 mmHg, 25.417±7.902 mmHg, 25.167±9.796 mmHg, 22.417±9.681 mmHg respectively and 24.136±3.550 mmHg, 23.273±2.815 mmHg, 22.682±3.772 mmHg, 21.727±3.718 mmHg,18.955±3.415 mmHg, 18.091±3.407 mmHg respectively in glaucoma group and control group at 5, 10, 15, 20, 25 and 30 min. The IOP reached its peak in glaucoma group at horizontal position at 20 minutes and was significantly higher than in control group(P0.05), and then gradually decreased. Conclusion The IOP is higher in normal and glaucoma patients at horizontal position than at sitting position. The IOP increases at first and then decreases in the two groups at horizontal position.
Drug Resistance of Non-tuberculosis Mycobacteria in Sichuan Province

Objective To investigate the epidemiology and drug resistance characteristics of non-tuberculosis mycobacterium(NTM),and thus to provide scientific basis for prevention and control strategies for NTM caused pulmonary diseases.Methods NTM identification and antimicrobial susceptibility test were performed on mycobacterium strains collected from 2002 to 2011.Epidemiological analysis was applied to identify NTM infected cases.Results Totally 251 strains of NTM were identified from 2 356 mycobacteria strains(10.65%),and 245 of which(97.60%) were resistant to common anti-tuberculosis drugs such as isoniazid,sodiumaminosalicylate,ethambutol,rifampicin and streptomycin.Most strains showed multi-resistance to anti-tuberculosis agents.Conclusion The morbidity of NTM infection shows a rising trend,and isolated strains have great resistance to antituberculotic substance.More effective diagnosis approach and new drugs for NTM caused pulmonary disease are imperative.
Damage in total knee replacements from mechanical overload.

The mechanical loads acting across the knee joint following total knee replacements (TKR) during activities of daily living have recently been measured using instrumented TKRs. Using a series of postmortem retrieved TKR constructs we investigated whether these mechanical loads could result in damage to the implant bone interface or supporting bone in the tibia. Eighteen cemented en bloc tibial components (0 to 22 years in service) were loaded under axial compression in increments from 1 to 10 times body weight and digital image correlation was used to measure bone strain and interface micromotion during loading and unloading. Failure was considered to occur when micromotion exceeded 150µm or compressive bone strain exceeded 7300μe. The results show that all retrieved specimens had sufficient bone strength to support most activities of daily living, but ~40% would be at risk under larger physiologic loads that might occur secondary to a higher impacts such as jogging or a stumble. The tray-bone micromotion (regression model R(2)=0.48, p=0.025) was greater for donors with lower age at implantation (p=0.0092). Proximal bone strain (model R(2)=0.46, p=0.03) was greater for donors with longer time in service (p=0.021). Distal bone strain (model R(2)=0.58, p=0.005) was greater for donors with more time in service (p=0.0054) and lower peri-implant BMD (p=0.049). High mechanical overload of a single or repetitive nature may be an initiating factor in aseptic loosening of total joint arthroplasties and should be avoided in order to prolong the life of the implant.
Aortic nerve-activated cardioinhibitory neurons and interneurons

Unit activity evoked by electrical stimulation of the aortic and vagus nerves was recorded in the dorsal motor nucleus and nucleus solitarius of unanesthetized rabbits. Cardioinhibitory cells which showed antidromic activation to stimulation of the vagus nerve and synaptic activation to stimulation of the aortic nerve were localized in lateral dorsal motor nucleus 0.5-0.8 mm anterior of the obex. Additionally, units were found that appeared to be interneurons in the medullary pathway subserving baroreceptor reflex effects on cardioinhibitory neurons. These cells were activated by aortic, and usually vagus, nerve stimulation, appeared to be polysynaptically activated, and were located in medial nucleus solitarius rostral to the obex. Neurons reflecting a cardiac rhythm but not activated by aortic nerve stimulation were also observed.
Probing Structural Dynamics and Topology of the KCNE1 Membrane Protein in Lipid Bilayers via Site-Directed Spin Labeling and Electron Paramagnetic Resonance Spectroscopy

KCNE1 is a single transmembrane protein that modulates the function of voltage-gated potassium channels, including KCNQ1. Hereditary mutations in the genes encoding either protein can result in diseases such as congenital deafness, long QT syndrome, ventricular tachyarrhythmia, syncope, and sudden cardiac death. Despite the biological significance of KCNE1, the structure and dynamic properties of its physiologically relevant native membrane-bound state are not fully understood. In this study, the structural dynamics and topology of KCNE1 in bilayered lipid vesicles was investigated using site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) spectroscopy. A 53-residue nitroxide EPR scan of the KCNE1 protein sequence including all 27 residues of the transmembrane domain (45-71) and 26 residues of the N- and C-termini of KCNE1 in lipid bilayered vesicles was analyzed in terms of nitroxide side-chain motion. Continuous wave-EPR spectral line shape analysis indicated the nitroxide spin label side-chains located in the KCNE1 TMD are less mobile when compared to the extracellular region of KCNE1. The EPR data also revealed that the C-terminus of KCNE1 is more mobile when compared to the N-terminus. EPR power saturation experiments were performed on 41 sites including 18 residues previously proposed to reside in the transmembrane domain (TMD) and 23 residues of the N- and C-termini to determine the topology of KCNE1 with respect to the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) lipid bilayers. The results indicated that the transmembrane domain is indeed buried within the membrane, spanning the width of the lipid bilayer. Power saturation data also revealed that the extracellular region of KCNE1 is solvent-exposed with some of the portions partially or weakly interacting with the membrane surface. These results are consistent with the previously published solution NMR structure of KCNE1 in micelles.
Mitochondrial Energetics in the Heart in Obesity-Related Diabetes: Direct Evidence for Increased Uncoupled Respiration and Activation of Uncoupling Proteins

OBJECTIVE— In obesity and diabetes, myocardial fatty acid utilization and myocardial oxygen consumption (M Vo 2 ) are increased, and cardiac efficiency is reduced. Mitochondrial uncoupling has been proposed to contribute to these metabolic abnormalities but has not been directly demonstrated. RESEARCH DESIGN AND METHODS— Oxygen consumption and cardiac function were determined in db/db hearts perfused with glucose or glucose and palmitate. Mitochondrial function was determined in saponin-permeabilized fibers and proton leak kinetics and H 2 O 2 generation determined in isolated mitochondria. RESULTS— db/db hearts exhibited reduced cardiac function and increased M Vo 2 . Mitochondrial reactive oxygen species (ROS) generation and lipid and protein peroxidation products were increased. Mitochondrial proliferation was increased in db/db hearts, oxidative phosphorylation capacity was impaired, but H 2 O 2 production was increased. Mitochondria from db/db mice exhibited fatty acid–induced mitochondrial uncoupling that is inhibitable by GDP, suggesting that these changes are mediated by uncoupling proteins (UCPs). Mitochondrial uncoupling was not associated with an increase in UCP content, but fatty acid oxidation genes and expression of electron transfer flavoproteins were increased, whereas the content of the F1 α-subunit of ATP synthase was reduced. CONCLUSIONS— These data demonstrate that mitochondrial uncoupling in the heart in obesity and diabetes is mediated by activation of UCPs independently of changes in expression levels. This likely occurs on the basis of increased delivery of reducing equivalents from β-oxidation to the electron transport chain, which coupled with decreased oxidative phosphorylation capacity increases ROS production and lipid peroxidation.
THE WAY I SEE IT: Library research as a transgressive activity

La recherche electronique a radicalement transforme le role du bibliothecaire, ici dans le cadre d'une institution universitaire. Pour repondre a sa requete, il aide l'usager, par mot-cles et operateurs booleens, a creer sa propre bibliotheque et a en repousser les murs, participant de ce fait a une activite transgressive, ou il est tout aussi important de demeler le vrai du faux que d'obtenir un resultat.
Issues and opportunities for agent-based modeling in air transportation

Characterizing the envelope of most probable future air transportation architectures requires a system-of-systems approach. Such an approach is intended to produce both tactical and strategic level decisions and do so in consideration of technological, policy, and socio-economic aspects. Agent-based modeling has found productive use in this domain by providing flexible tool for analysis of large-scale interacting systems. Following from the system-of-systems nature of air transportation, existing models can be readily categorized by their level of abstraction. Four existing agent-based models and one model under development are reviewed in this paper, identifying and generalizing four major methodological issues in their application of ABM. Subsequently, implications from these applications on augmentations such as game theory, agent-based optimization, intelligent agents, and treatment of uncertainty are presented. All these issues exist even beyond the scope of air transportation and could be of value for common application of ABM.
Dielectric properties of PLZT ceramics

The dielectric behavior of ferroelectric ceramics are of special importance in determining their electro-optic properties. An electro-optic ceramic is a transparent or partially transparent polycrystalline ferroelectric material. It is composed of an aggregate of ferroelectric single crystal grains, with a typical grain size varying from 0.5 to 40 μm depending on the method of fabrication and the temperature of annealing.
A methodological study of genome-wide DNA methylation analyses using matched archival formalin-fixed paraffin embedded and fresh frozen breast tumors

// Allyson C. Espinal 1, * , Dan Wang 2, * , Li Yan 2 , Song Liu 2 , Li Tang 3 , Qiang Hu 2 , Carl D. Morrison 4 , Christine B. Ambrosone 4 , Michael J. Higgins 1, # , Lara E. Sucheston-Campbell 5, 6, # 1 Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Buffalo NY, USA 2 Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA 3 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA 4 Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA 5 College of Pharmacy, The Ohio State University, Columbus, OH, USA 6 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA * These authors contributed jointly as first authors # These authors contributed jointly as senior authors Correspondence to: Lara E. Sucheston-Campbell, email: sucheston-campbell.1@osu.edu Michael J. Higgins, email: Michael.Higgins@roswellpark.org Keywords: DNA methylation/epigenetics, breast cancer, estrogen receptor negative Received: May 27, 2016 Accepted: January 10, 2017 Published: January 19, 2017 ABSTRACT Background: DNA from archival formalin-fixed and paraffin embedded (FFPE) tissue is an invaluable resource for genome-wide methylation studies although concerns about poor quality may limit its use. In this study, we compared DNA methylation profiles of breast tumors using DNA from fresh-frozen (FF) tissues and three types of matched FFPE samples. Results: For 9/10 patients, correlation and unsupervised clustering analysis revealed that the FF and FFPE samples were consistently correlated with each other and clustered into distinct subgroups. Greater than 84% of the top 100 loci previously shown to differentiate ER+ and ER– tumors in FF tissues were also FFPE DML. Weighted Correlation Gene Network Analyses (WCGNA) grouped the DML loci into 16 modules in FF tissue, with ~85% of the module membership preserved across tissue types. Materials and Methods: Restored FFPE and matched FF samples were profiled using the Illumina Infinium HumanMethylation450K platform. Methylation levels (β-values) across all loci and the top 100 loci previously shown to differentiate tumors by estrogen receptor status (ER+ or ER−) in a larger FF study, were compared between matched FF and FFPE samples using Pearson's correlation, hierarchical clustering and WCGNA. Positive predictive values and sensitivity levels for detecting differentially methylated loci (DML) in FF samples were calculated in an independent FFPE cohort. Conclusions: FFPE breast tumors samples show lower overall detection of DMLs versus FF, however FFPE and FF DMLs compare favorably. These results support the emerging consensus that the 450K platform can be employed to investigate epigenetics in large sets of archival FFPE tissues.
Fault detection of nonlinear dynamic systems with emperical input/output models

Abstract Predictive maintenance has become a familiar concept in industrial fault detection regime. The ability to detect early warning signals in systems in the form of small changes in dynamic behavior is essential to anticipate failures. This implies that the fault detection method must be well tuned to a particular process. In general, accurate system models are an essential part in residual based fault detection. However, in complex nonlinear systems, the development of accurate models can be very difficult, thus usually other approaches are often selected. As an alternative to the nonlinear analytical models, neural networks have shown significant potential in accurately representing nonlinear systems. This paper utilizes a non-typical model structure which includes internal states, so that the identification method is similar to a nonlinear extension to (linear) subspace identification. This model is then used with a moving horizon observer to generate residuals. The experimental section shows the observer implemented on a thermo fluid system, with several introduced faults.
Insights from structures of cancer-relevant pre-mRNA splicing factors

Pre-mRNA splicing factors recognize consensus signals within preliminary transcripts, and as cogs of the spliceosome machine, orchestrate the excision and rejoining of pre-mRNA regions for gene expression. Large-scale sequencing has demonstrated that mutations in key genes encoding pre-mRNA splicing factors are common among myeloid neoplasms and also occur in a variety of other cancers. This revelation offers new therapeutic opportunities to target pre-mRNA splicing vulnerabilities in hematologic and other malignancies. The mutated residues typically alter 3' splice site choice for a subset of transcripts. In this review, we highlight mechanistic insights from recent 3D structures that reveal the affected residues poised for pre-mRNA recognition.
Is ciliary Hedgehog signalling dispensable in the kidneys

An unbiased functional gene knockout screen to identify genes implicated in Hedgehog signalling in primary cilia detected most components of the ciliary machinery and ciliopathy-associated genes, but no kidney-related ciliopathy genes. The 472 hits are a tremendous resource for identifying potential ciliopathy genes and for analysing ciliary function and signalling pathways.
Clinical Chemistry Applications of Capillary Electromigration Methods

Abstract Capillary electrophoresis (CE) and related electromigration techniques have a wide range of potential applications in clinical laboratories. Advantages of these methods versus traditional electrophoretic techniques for clinical testing include their efficiency, speed, small sample requirements, ease of automation, and ability to be used with a variety of detection schemes. This chapter provides a review on the use of CE and related techniques for various types of analytes that are of interest in clinical testing. Methods that have been used in this work have included capillary zone electrophoresis, CE-based enzyme assays, CE immunoassays, micellar electrokinetic chromatography, nonaqueous CE, capillary gel electrophoresis, affinity CE, and capillary isoelectric focusing. Areas of clinical chemistry in which these methods have been employed, and which will be discussed in this review, include protein profiling, hematology, enzymology, immunology, endocrinology, therapeutic drug monitoring, toxicology, the detection of tumor biomarkers, and DNA diagnostics.
Fungi in megakaryocytes. An unusual manifestation of fungal infection of the bone marrow

When fungi infect the bone marrow, typically they are associated with granuloma formation and/or necrosis, and the fungi are found within histiocytes or admixed with necrotic debris. Recently two bone marrow biopsy specimens were encountered in which fungi were confined to the cytoplasm of megakaryocytes, a finding not previously reported in the literature. The first case was that of a 46-year-old man with pulmonary histoplasmosis and no known immunodeficiency. The second was that of a 38-year-old man with the acquired immune deficiency syndrome and cryptococcal meningitis. In the first case, many megakaryocytes contained fungal forms consistent with Histoplasma. In the second, one small cluster of megakaryocytes contained several budding yeast consistent with Cryptococcus. Neither marrow biopsy specimen had necrosis, granulomas, or histiocytic infiltration. In both cases, because of the unusual localization of the fungi, they were initially overlooked. The bone marrow may contain fungi even in the absence of abnormalities suggesting fungal infection on routinely stained sections. A silver stain or a periodic acid--Schiff stain should be performed on all marrow biopsy specimens in cases of known or suspected fungal infection outside the marrow. The phenomenon of megakaryocyte emperipolesis is well known, and this process may be responsible for the apparent ability of megakaryocytes to internalize fungi.
Measurements and modeling of coherent synchrotron radiation and its impact on the Linac Coherent Light Source electron beam

In order to reach the high peak current required for an x-ray free electron laser, two separate magnetic dipole chicanes are used in the Linac Coherent Light Source (LCLS) accelerator to compress the electron bunch length in stages. In these bunch compressors, coherent synchrotron radiation (CSR) can be emitted either by a short electron bunch or by any longitudinal density modulation that may be on the bunch. In this paper, we report detailed measurements of the CSR-induced energy loss and transverse emittance growth in these compressors. Good agreement is found between the experimental results and multi-particle tracking studies. We also describe direct observations of CSR at optical wavelengths and compare with analytical models based on beam microbunching.
Abstract 4756: Secretory IgM exacerbates tumor progression by inducing accumulations of myeloid-derived suppressor cells in mice

To explore the role of B cell receptor (BCR) in promoting malignant progression of chronic lymphocytic leukemia (CLL) in mice, we generate MD4/Eμ-TCL1 mice, whose B cells harbor a monoclonal BCR against hen egg lysozyme (HEL) and secrete IgM against HEL. MD4/Eμ-TCL1 mice survive significantly shorter than Eμ-TCL1 mice. While precancerous B cells in young MD4/Eμ-TCL1 mice recognize HEL, CLL cells developed in older MD4/Eμ-TCL1 mice fail to recognize HEL. Nevertheless, MD4/Eμ-TCL1 CLL cells can be activated by goat F(ab9)2 anti-mouse IgM and respond by phosphorylation of Igα, Syk and ERK1/2, indicating reactivation of a parental Ig gene allele. MD4/Eμ-TCL1 CLL cells also produce large quantities of secretory IgM (sIgM), which does not react with HEL. Compared with age-matched Eμ-TCL1 mice, MD4/Eμ-TCL1 mice also generate a significantly increased population of CD11b+/Ly6G+ granulocytic cells in the peripheral blood, spleens and bone marrow. CD11b+/Ly6G+ granulocytic cells purified from spleens of MD4/Eμ-TCL1 mice can suppress CD3/CD28-mediated proliferation of CD8+ T cells and gp100-loaded class I MHC-mediated proliferation of CD8+ T cells from PMEL-1 mice, qualifying these cells as myeloid-derived suppressor cells (MDSCs). Increased MDSCs may account for significantly decreased T cells and poor prognosis in CLL-bearing MD4/Eμ-TCL1 mice. Because MD4/Eμ-TCL1 mouse CLL cells and human CLL cells can produce sIgM, we hypothesize that sIgM may account for the accumulation of MDSCs. To test this hypothesis, we cross μS-/- mice, which cannot produce sIgM, with Eμ-TCL1 mice. The μS-/-/Eμ-TCL1 mice indeed develop significantly lower numbers of MDSCs, and survive significantly longer than Eμ-TCL1 mice. We decide to target the synthesis of sIgM by deleting the function of XBP-1, because the synthesis of sIgM is tightly regulated by a mechanism called regulated IRE-1-dependent decay (RIDD), which is hyperactivated in B cells as a response to XBP-1 deficiency. We cross B cell-specific XBP-1KO mice with MD4/Eμ-TCL1 mice, and the resultant XBP-1KO/MD4/Eμ-TCL1 mice indeed produce significantly reduced amounts of sIgM and decreased numbers of MDSCs. In addition, μS-/- mice grafted with Lewis lung carcinoma exhibit reduced functions of MDSCs in suppressing T cells, resulting in significantly slower tumor growth. These results clearly demonstrate that sIgM produced by B cells can upregulate the immunosuppressive functions of MDSCs in tumor-bearing mice to aggravate cancer progression. Citation Format: Chih-Hang Tang, Shiun Chang, Ayumi Hashimoto, Yi-Ju Chen, Chang Won Kang, Anthony Mato, Juan Del Valle, Dmitry Gabrilovich, Chih-Chi Andrew Hu. Secretory IgM exacerbates tumor progression by inducing accumulations of myeloid-derived suppressor cells in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4756.
Transformational leadership to promote nurse practitioner practice in primary care

Aim This study investigated transformational leadership from the perspectives of primary care nurse practitioners. Background The growing workforce of nurse practitioners in the United States could play a critical role in meeting the increasing demand for primary care. Little is known about how leadership within primary care practices could promote nurse-practitioner care. Transformational leadership is a widely recognized leadership style that affects clinician practice and outcomes. Method A cross-sectional survey design was used to collect data from nurse practitioners in New York state in 2012. The online survey containing measures of nurse practitioners and leadership relationships was completed by 278 nurse practitioners. Results The four factors of transformational leadership-idealized influence, inspirational motivation, intellectual stimulation, and individual consideration-were recognized by nurse practitioners. Almost half of nurse practitioners reported that leadership did not share information equally between nurse practitioners and physicians (idealized influence), and 45.9% reported that nurse practitioners were not represented on important organisational committees (intellectual stimulation). Conclusion Transformational leadership can be applied to promote nurse practitioner practice in primary care. Future research should explore how transformational leadership affects nurse practitioner care and outcomes. Implications for nursing management Leaders in primary care practices should consider applying transformational leadership principles to promote nurse practitioner practice.
58 – Overview of Risk Factors for Cardiovascular Disease

Coronary heart disease (CHD) is a chronic condition that requires medication and causes activity limitations due to ongoing angina or congestive heart failure. This chapter discusses various risk factors for CHD. Family history of CHD, cigarette smoking, hypertension, diabetes mellitus, sedentary lifestyle, levels of high and low density lipoprotein cholesterol, and obesity are major risk factors for CHD in women, although observational studies support racial/ethnic differences in the relative contributions of these factors to CHD risk. Low folate and high homocysteine levels are emerging as potentially important factors as well. The public health implications of these CHD risk factors in women are tremendous in their social, emotional, and fiscal impact on individuals and to the larger health care system. Randomized trials are urgently needed to develop interventions that will assist women in modifying known CHD risk factors and to test the efficacy of such changes on CHD risk. Trials are particularly crucial for minority women, where the CHD burden is greatest.
Restoring Fertility with Human Induced Pluripotent Stem Cells: Are We There Yet?

Overcoming infertility with assisted reproduction requires high-quality eggs and sperm. For those young women who no longer make functional eggs, the hope of conceiving a biological child just got one step closer with a recent publication in Science from Yamashiro et al. (2018).
Maternal smoking and gestational hypertension: Heterogeneous effect by timing of the exposure.

Abstract Objectives The objective of this study was to examine whether the association between maternal smoking and gestational hypertension varies by the timing of exposure. Study design Retrospective cohort study of women identified in 2015 US natality records for singleton births. Main outcome measures Our outcome was whether a woman was diagnosed with gestational hypertension (GH) on the birth record, a category which includes preeclampsia. Results Women who smoked before and during pregnancy had a reduced risk for GH relative to non-smokers (adjusted RR 0.92, 95% CI 0.90–0.94). In contrast, women who apparently quit just before the start of pregnancy had higher risk than non-smokers (adjusted RR 1.02, 95% CI 1.00–1.05). When the trimester-specific effects were examined, only women who smoked before pregnancy and in all three trimesters had reduced risk for GH. Smoking mothers who quit just before the start of the 3rd trimester had an increased risk for GH compared to non-smokers (adjusted RR 1.08, 95% CI 1.02–1.16). Conclusion In our analysis, women who smoked before pregnancy and in all three trimesters have reduced risk of GH compared to non-smokers, while smokers who reported quitting before pregnancy were at an increased risk. Our results offer new insights into the importance of timing of smoking in pregnancy on risk of GH, and challenge the notion that any smoking during pregnancy has a protective effect.
“The Click-Clack of Her Heels and the Jingle of Her Keys”: Exploring the Tensions in the Leadership of a Successful Turnaround Principal:

This qualitative case study explores the practices and tensions of being an effective principal in a turnaround school through an in-depth analysis of one principal who has been successful in sever...
Treating Hodgkin lymphoma in the new millennium: Relapsed and refractory disease

Although the majority of patients with Hodgkin lymphoma are cured with initial therapy, 10% to 15% of patients with early stage disease and 15% to 30% of patients with advanced disease have primary refractory or relapsed lymphoma. For younger patients whose disease is sensitive to second-line therapy, more than half of patients will experience long-term disease control with high-dose chemotherapy/autologous stem cell rescue (ASCT). For those patients who are chemotherapy refractory, relapse after, or are ineligible for ASCT, brentuximab vedotin, and checkpoint, inhibitors are highly active, although the majority of patients will ultimately experience recurrent lymphoma. Allogeneic transplant is curative in a subset of patients but may be associated with significant toxicity. Novel targeted and immunotherapy approaches, including chimeric antigen receptor T-cell therapy, are currently being studied in clinical trials with promising early results.
What Is Leadership

The primary purpose of a leader in an academic healthcare center is to inspire the multidisciplinary members of the organization to willingly engage together to deliver on the missions of providing high quality patient care, educating and training the next generation of healthcare providers, and creating new knowledge to advance the fields of science and medicine to improve patient care. Effective and valued leaders in the healthcare domain are inspired by moral purpose and social justice and must also be prepared to craft solutions in the challenging framework of conflicting priorities and resource limitation. Personal traits of optimism, humility, and integrity, coupled to mature emotional intelligence and a commitment to equity and inclusion are essential qualities of modern healthcare leaders.
The Effect of Secondary Cognitive Task Difficulty on Headway Maintenance and Perceived Workload While Using Lane Keeping Systems

Vehicle automation is developing at a rapid rate worldwide. However, even lower levels of automation, such as SAE Level-1, are expected to reduce drivers’ workload by controlling either speed or la...
Selection of Korean heat tolerant rice lines in West Java irrigated lowland agro-ecosystem

One condition in global climate change era is increasing of world temperature which is approaching critical point of rice plant adaptation. Thus, heat tolerant rice variety is needed. Indonesian Centre for Rice Research (ICRR) and RDA (Rural Development Administration) of Korea through ASEAN-Korean Economic Cooperatives collaborates to breed heat tolerant rice variety. In this regard, 150 BC1F5 recombinant inbred lines (RIL) along with 5 checks was tested following Augmented Design of five blocks. Transplanting was conducted at 21 days after sowing on 25 cm x 25 cm planting space in 2 m x 5 m square plots. The results showed that SR34132(41)-1-1-1 (13.00 t/ha) and SR34132(11)-1-1 -1 (11.65 t/ha) had higher yield than the best check Inpari 42 Agritan GSR (8.23 t/ha). The first line had big grain size (27.72 g) and medium productive tiller (15 tillers), while the second had more productive tiller (23 tillers) even though had low filled grain/panilce, seed set, and grain size (21.60 g). There were 69 lines having comparable yield with Inpari 42 Agritan GSR. Combining high yield with heat tolerance traits is feasible for Indonesian agro ecosystem condition. Further testing to confirm the tolerance of the lines to heat stress is needed.
Biomechanical comparison of locking compression plate fixation and a novel pedicle screw external fixation to repair equine mandibular fractures

OBJECTIVE: To determine the biomechanical properties of pedicle screw external fixation (PDW) for equine mandibular fracture repair and compare PDW to locking compression plates (LCP). STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Sixteen adult equine mandibles. METHODS: Four mandibles were kept intact, while 12 were osteotomized and stabilized with the LCP or PDW construct (6 mandibles/group). Failure, stiffness, and yield were calculated from quasi‐static ramp to failure and compared with previous analysis of mandibular fracture constructs. Tooth root involvement and method of failure were determined from radiographs and videos. RESULTS: Locking compression plate constructs achieved greater stiffness and load at failure (4656 ± 577 N‐m/radian, 558 ± 27 N‐m P < .05) compared with PDW constructs (2626 ± 127 N‐m/radian, 315 ± 48 N‐m). Yield did not differ between types of fixation (369 ± 57 N‐m, 193 ± 35 N‐m, P = .145). Tooth involvement was noted in two LCP constructs with failure via bone fracture. Pedicle screw external fixation constructs failed via wire unraveling and screw bending. CONCLUSION: Locking compression plate fixation increased stiffness and failure of constructs but did not influence yield. It also increased the risk to tooth root involvement relative to fixation with PDW. Compared with another study, PDW offered stiffness and failure similar to an intraoral splint with interdental wires, external fixator (EF), and external fixator with wires (EFW) and yield similar to an EF, an EFW, and a dynamic compression plate. CLINICAL RELEVANCE: Pedicle screw external fixation offers biomechanical stability comparable to other relevant mandibular fixation techniques and reduces the risk of tooth root damage compared with LCP fixation.
The hepatocyte clock and feeding control chronophysiology of multiple liver cell types

Most cells of the body contain molecular clocks, but the requirement of peripheral clocks for rhythmicity and their effects on physiology are not well understood. We show that deletion of core clock components REV-ERBα and REV-ERBβ in adult mouse hepatocytes disrupts diurnal rhythms of a subset of liver genes and alters the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by nonhepatocytic cells, and the loss of hepatocyte REV-ERBs remodels the rhythmic transcriptomes and metabolomes of multiple cell types within the liver. Finally, alteration of food availability demonstrates the hierarchy of the cell-intrinsic hepatocyte clock mechanism and the feeding environment. Together, these studies reveal previously unsuspected roles of the hepatocyte clock in the physiological coordination of nutritional signals and cell-cell communication controlling rhythmic metabolism.
Comprehensive Quality Improvement Program for Intraoperative Transesophageal Echocardiography: Development, Implementation, and Initial Experience.

Objective To develop and implement a comprehensive transesophageal echocardiography (TEE) quality improvement (QI) program and assess for potential improvements in TEE performed by cardiac anesthesiologists. Design Prospective institutionally approved QI program. Setting Academic tertiary care center. Participants The study comprised cardiac anesthesiologists. Interventions An instrument comprising 15 quality measures to assess TEE examinations pre- and post-cardiopulmonary bypass (CPB) was developed for the present study. TEE examinations before the introduction of the QI program were assessed retrospectively, and examinations performed after its introduction were reviewed prospectively over a 2-year period. Measurements and Main Results A total of 118 TEE studies were analyzed, 48 and 70 studies before and after introduction of the TEE QI program, respectively. Half of the studies were performed pre-CPB, and half of them were performed post-CPB. Multivariate linear mixed regression models were used to assess the effect of the QI program. Interrater variability was assessed among internal reviewers by means of the Shrout-Fleiss reliability intraclass correlation coefficient. Five quality measures demonstrated a significant improvement in studies after CPB after implementation, including 3 imaging criteria (left ventricle, tricuspid valve, and pulmonary artery) and 2 documentation criteria (completeness of demographic/clinical data and timely reporting of documentation). The inter-rater variability analysis yielded an average intraclass correlation coefficient of 0.90 before and 0.78 after the QI program initiation, consistent with excellent agreement among the 4 reviewers. Conclusions The present study demonstrated the ability to create and implement a formal QI program for intraoperative TEE in an academic tertiary care cardiac surgical group. The initial data showed significant improvement in several quality measures related to TEE performance.
Effects of Teachers as Coaches for Paraprofessionals Implementing Functional Communication Training

Young children with intensive behavioral needs are often served by paraprofessionals, who are typically among the least trained and least supported staff in the school. While professional developme...
The rise of open architectures in the U.S. Department of Defense

For decades the U.S. Department of Defense (DoD), has been trying to harness the power and rewards of Open Architectures (OA) to achieve flexible weapon systems with low costs of integration and rapid upgrade capabilities. OAs provide a method for rapidly applying cybersecurity to systems as part of standardization updates. Recently, the DoD has directly endorsed OAs as a game-changer for weapon system development and identified clear OA leaders. This sets the stage for a future generation of weapon systems that support rapid integration, modification, and upgrades to enable warfighter capabilities in the field. This paper presents the difference between open architecture and open systems, a short history of OAs in the DoD, discusses how the DoD has renewed its support of OA, and ideas to maintain the momentum.