cssi/SciSciGPT-SciSciNet huggingface dataset:
Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors

Respiratory syncytial virus (RSV) is a leading pediatric pathogen that is responsible for a majority of infant hospitalizations due to viral disease. Despite its clinical importance, no vaccine prophylaxis against RSV disease or effective antiviral therapeutic is available. In this study, we established a robust high-throughput drug screening protocol by using a recombinant RSV reporter virus to expand the pool of RSV inhibitor candidates. Mechanistic characterization revealed that a potent newly identified inhibitor class blocks viral entry through specific targeting of the RSV fusion (F) protein. Resistance against this class was induced and revealed overlapping hotspots with diverse, previously identified RSV entry blockers at different stages of preclinical and clinical development. A structural and biochemical assessment of the mechanism of unique, broad RSV cross-resistance against structurally distinct entry inhibitors demonstrated that individual escape hotspots are located in immediate physical proximity in the metastable conformation of RSV F and that the resistance mutations lower the barrier for prefusion F triggering, resulting in an accelerated RSV entry kinetics. One resistant RSV recombinant remained fully pathogenic in a mouse model of RSV infection. By identifying molecular determinants governing the RSV entry machinery, this study spotlights a molecular mechanism of broad RSV resistance against entry inhibition that may affect the impact of diverse viral entry inhibitors presently considered for clinical use and outlines a proactive design for future RSV drug discovery campaigns.
Brain hyperthermia during physiological and pathological conditions: causes, mechanisms, and functional implications.

Although brain metabolism consumes high amounts of energy and is accompanied by intense heat production, brain temperature is usually considered a stable, tightly regulated homeostatic parameter. Current animal research, however, has shown that different forms of functional neural activation are accompanied by relatively large brain hyperthermia (2-3°C), which has an intra-brain origin; cerebral circulation plays a crucial role in dissipating this potentially dangerous metabolic heat from brain tissue. Brain hyperthermia, therefore, reflects enhanced brain metabolism and is a normal physiological phenomenon that can be enhanced by interaction with common elements of an organism's environment. There are, however, instances when brain hyperthermia becomes pathological. Both exposure to extreme environmental heat and intense physical activity in a hot, humid environment restrict heat dissipation from the brain and may push brain temperatures to the limits of physiological functions, resulting in acute life-threatening complications and destructive effects on neural cells and functions of the brain as a whole. Brain hyperthermia may also result from metabolic activation induced by various addictive drugs, such as heroin, cocaine, and meth-amphetamine (METH). In contrast to heroin and cocaine, whose stimulatory effects on brain metabolism invert with increases in dose, METH increases brain metabolism dose- dependently and diminishes heat dissipation because of peripheral vasoconstriction. The thermogenic effects of this drug, moreover, are enhanced during physiological activation, resulting in pathological brain hyperthermia. Since brain hyperthermia exacerbates drug-induced toxicity and is destructive to neural cells, uncontrollable use of amphetamine-like drugs under conditions restricting heat dissipation from the brain may result both in acute life- threatening complications and clinically latent but dangerous morphological and functional brain destruction.
Extensive Coverage of Functional Verification of Hardware Designs

This paper presents the author's experience in teaching HDL concepts as part of a Digital Systems course and the conclusions regarding the importance of extensive coverage of functional verification of hardware designs. After almost four years of teaching this course and similar ones, the conclusions are that more time must be spent on functional verification rather than the traditional concepts of basic syntax and semantics to describe digital circuits. Such an approach may improve the learning process and the achievement of concepts and skills in digital design, encourage creative an analytical thinking, and overall assure more reliable designs. To prove the validity of this new approach, a research study regarding "Functional Verification in Digital Systems" was approved by The Institutional Research, Planning and Assessment department at Rose-Hulman Institute of Technology, Terre Haute, IN, and assessment data were gathered starting at the end of the winter quarter 2006-2007.
An experiment on the modification procedures of seasonal factors in exponential smoothing models

Abstract Adapting to changes over time is a primary point in any forecasting system. The quicker the adaptation the better the resulting forecasts. This is very important in computerized forecast-inventory control systems that manage thousands of parts. In such environments, it is difficult, if not impossible, to have all forecasts reviewed for possible changes in behaviour. This paper proposes two modifications to Winters' exponentially weighted moving-average model that provides improved forecasts for time series exhibiting seasonal behaviour. A set of tests is conducted to evaluate the performance of the original and modified Winters s models using 25 time series. The results indicate that average forecast errors have been reduced for the test series. The paper concludes with a discussion of the suitability of the proposed modifications under certain conditions.
Naive, effector, and memory CD8 T cells in protection against pulmonary influenza virus infection: Homing properties rather than initial frequencies are crucial

The goal of adoptive immunotherapy is to target a high number of persisting effector cells to the site of a virus infection or tumor. In this study, we compared the protective value of hemagglutinin peptide-specific CD8 T cells generated from the clone-4 TCR-transgenic mice, defined by different stages of their differentiation, against lethal pulmonary influenza infection. We show that the adoptive transfer of high numbers of Ag-specific unprimed, naive CD8 T cells failed to clear the pulmonary virus titer and to promote host survival. The same numbers of in vitro generated primary Ag-specific Tc1 effector cells, producing high amounts of IFN-gamma, or resting Tc1 memory cells, generated from these effectors, were protective. Highly activated CD62Llow Tc1 effectors accumulated in the lung with rapid kinetics and most efficiently reduced the pulmonary viral titer early during infection. The resting CD62Lhigh naive and memory populations first increased in cell numbers in the draining lymph nodes. Subsequently, memory cells accumulated more rapidly and to a greater extent in the lung lavage as compared with naive cells. Thus, effector cells are most effective against a localized virus infection, which correlates with their ability to rapidly distribute at the infected tissue site. The finding that similar numbers of naive Ag-specific CD8 T cells are not protective supports the view that qualitative differences between the two resting populations, the naive and the memory population, may play a major role in their protective value against disease.
Sensitivity to polyamine-induced growth arrest correlates with antizyme induction in prostate carcinoma cells.

High local polyamine concentrations may suppress cell growth of primary prostatic carcinomas. When cell growth assays were conducted in defined serum-free medium, spermine inhibited the growth of poorly metastatic rat prostate carcinoma cells, causing cell cycle arrest in the G1 phase. In contrast, highly metastatic prostate carcinoma cells were resistant to the growth inhibitory activity of spermine. Ornithine decarboxylase antizyme levels, measured by Western blotting, were elevated 1–2 h after spermine treatment of spermine-sensitive cells but not spermine-resistant cells. Spermine uptake was similar in both the sensitive and resistant cell lines. These results suggest that failure to induce antizyme correlates with spermine resistance in prostate carcinoma.
Note on Mark 6. 20

In the first part of this verse it is said that Herod feared John the Baptist, knowing him to be a just and holy man, and protected him; the second part presents some difficulties which can best be discussed with the text before us. In the Textus Receptus the words are καὶ ἀκούσας αὐτοῦ πολλὰ ἐποίeι, καὶ ἡδέως αὐτοῦ ἤκουeν. The authorities for the words with which we are concerned are reported as follows from Legg's critical apparatus, somewhat abbreviated: ηπορeι και א ΒLΘ Cop(bo), item ηπορeιτο και W: eποιeι και ACDNΠΣΦ ל Minusc. omn. Vss. pler.
siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster

Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm3 satellite related repeats (1.688X repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688X repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688X repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688X repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin.
Influence of Surgeon and Hospital Volume on Radical Prostatectomy Costs

Purpose: While higher radical prostatectomy hospital and surgeon volume are associated with better outcomes, the effect of provider volume on health care costs remains unclear. We performed a population based study to characterize the effect of surgeon and hospital volume on radical prostatectomy costs.Materials and Methods: We used SEER (Surveillance, Epidemiology and End Results)-Medicare linked data to identify 11,048 men who underwent radical prostatectomy from 2003 to 2009. We categorized hospital and surgeon radical prostatectomy volume into tertiles (low, intermediate, high) and assessed costs from radical prostatectomy until 90 days postoperatively using propensity adjusted analyses.Results: Higher surgeon volume at intermediate volume hospitals (surgeon volume low $9,915; intermediate $10,068; high $9,451; p = 0.021) and high volume hospitals (surgeon volume low $11,271; intermediate $10,638; high $9,529; p = 0.002) was associated with lower radical prostatectomy costs. Extrapolating nationally, ...
The Growth of Modern Finance

The U.S. financial services industry grew from 4.9% of GDP in 1980 to 7.9% of GDP in 2007. A sizeable portion of the growth can be explained by rising asset management fees, which in turn were driven by increases in the valuation of tradable assets, particularly equity. Another important factor was growth in fees associated with an expansion in household credit, particularly fees associated with residential mortgages. This expansion was itself fueled by the development of non-bank credit intermediation (or "shadow banking"). We offer a preliminary assessment of whether the growth of active asset management, household credit, and shadow banking - the main areas of growth in the financial sector - has been socially beneficial.
Disrupted posterior cingulate–amygdala connectivity in postpartum depressed women as measured with resting BOLD fMRI

Disengagement of emotion regulation circuits was previously shown in depressed mothers and was hypothesized to underlie the impaired maternal–infant sensitivity described in postpartum depression (PPD). We hypothesized similarly reduced resting-state functional connectivity in default mode network (DMN) regions involved in social cognition in PPD. Resting-state functional MRI, clinical and mother–infant attachment data were obtained from 14 unmedicated postpartum women with major depression and 23 healthy postpartum women. Posterior cingulate cortex (PCC) time series were extracted, filtered between 0.007 and 0.08 Hz and used as regressors in a whole brain general linear model analysis. PCC–right amygdala connectivity was significantly disrupted in depressed compared to healthy mothers for low-frequency neural activity, showing a negative (inverse) coupling in the depressed group but not in the controls. PCC–right amygdala connectivity was positively correlated with PCC–parahippocampus connectivity. Resting connectivity patterns of positive co-activations in postpartum women mirrored the canonical DMN. These findings of reduced PCC–amygdala coupling raise the possibility that PPD might involve the disruption of outward, preventative aspects of self-relevant thought and theory of mind/empathy processes. Further integrated studies of neural connectivity and these cognitive/behavioral dimensions are warranted.
Experimental methods in cancer therapeutics.

Abstract During the last 10 years, the search for methods of selectively targeting antineoplastic agents has increased significantly. Because of the lack of tumor specificity of systemically administered antitumor drugs, toxic side effects are common, often resulting in greater harm to the host tissue than to the neoplastic process. Currently, the therapeutic index of most antineoplastic agents used in systemic therapy remains marginal, despite efforts to achieve tumor specificity. Despite various chemical modifications of chemotherapeutic agents (e.g., altering their partition coefficient, attaching immunologic ligands, or altering charge density), only variable success has been achieved in increasing specificity. An alternative approach for increasing the effectiveness of antitumor drugs is to alter their distribution in the body by incorporating them into particulate carriers, which theoretically can be concentrated at the tumor site. In this way, the toxicity of the drug for the tumor might be enhanced while the systemic toxicity is minimized.
Progressive Kidney Degeneration in Mice Lacking Tensin

Tensin is a focal adhesion phosphoprotein that binds to F-actin and contains a functional Src homology 2 domain. To explore the biological functions of tensin, we cloned the mouse tensin gene, determined its program of expression, and used gene targeting to generate mice lacking tensin. Even though tensin is expressed in many different tissues during embryogenesis, tensin null mice developed normally and appeared healthy postnatally for at least several months. Over time, −/− mice became frail because of abnormalities in their kidneys, an organ that expresses high levels of tensin. Mice with overt signs of weakness exhibited signs of renal failure and possessed multiple large cysts in the proximal kidney tubules, but even in tensin null mice with normal blood analysis, cysts were prevalent. Ultrastructurally, noncystic areas showed typical cell– matrix junctions that readily labeled with antibodies against other focal adhesion molecules. In abnormal regions, cell–matrix junctions were disrupted and tubule cells lacked polarity. Taken together, our data imply that, in the kidney, loss of tensin leads to a weakening, rather than a severing, of focal adhesion. All other tissues appeared normal, suggesting that, in most cases, tensin's diverse functions are redundant and may be compensated for by other focal adhesion proteins.
Analytical and clinical validity of whole-genome oligonucleotide array comparative genomic hybridization for pediatric patients with mental retardation and developmental delay.

We performed a pilot study to establish the analytical and clinical validity of whole genome oligonucleotide array comparative genomic hybridization (oaCGH) using the 44,000 oligonucleotide array from Agilent Technologies. DNA specimens from 10 patients with different chromosomal abnormalities were used as the test group and sex mismatched normal male or female DNA as references. A series of DNA mixtures containing 50%, 33%, and 25% of a known deletion was generated to evaluate the analytical capacity of oaCGH on detecting mosaic pattern. Receiver operating characteristic (ROC) curves were computed to evaluate sensitivity, specificity, and analytical resolution for detecting deletions, duplications, and mosaic patterns. The oaCGH detected the chromosomally recognized deletions, duplications, and additional genomic aberrations. Flurorescent in situ hybridization (FISH) assays using targeted BAC clone probes confirmed oaCGH findings. Failure in detecting marker chromosomes, a polymorphic inversion, and a Robertsonian translocation was also noted. The oaCGH achieved 99% sensitivity and 99% specificity with a resolution of 300–500 Kb. It also demonstrated 85% sensitivity and 95% specificity in detecting 50% mosaicism; however, increased test-to-test variations and reduced sensitivity were noted as the mosaic percentage decreased. Chromosome and oaCGH analyses on 50 pediatric patients with mental retardation (MR) and developmental delay (DD) delineated the genomic content of chromosomal abnormalities in nine cases, pathogenic genomic disorders in three cases and benign genomic variants in six cases. These results affirmed the analytical and clinical validity of oaCGH and prompted a cytogenomic algorithm to integrate oaCGH, chromosome and FISH analyses for genetic diagnosis. © 2008 Wiley-Liss, Inc.
Effects of surface roughness and oxide layer on wafer bonding strength using transmission laser bonding technique

The reliability of wafer bonding techniques is highly dependent on the surface conditions of the two wafers to be bonded. In this paper, a wafer bonding technique called transmission laser bonding (TLB) focusing on the effects of surface roughness and interface oxidations on the bonding strength. The TLB is implemented for bonding Pyrex glass-to-silicon wafers, both with and without interface oxide layers, utilizing an ns-pulsed Nd:YAG laser. The tensile strengths of the TLB bonded specimens are comparable to existing major wafer bonding techniques. The surface roughness is quantified by atomic force microscopy (AFM). The bonded interfaces are analyzed by x-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) to study the bonding mechanism by evaluating the migration and diffusion of different atoms among the glass wafer, silicon substrate, and oxide layer during the bonding process.
Orange-Fleshed Sweet Potato: Successes and Remaining Challenges of the Introduction of a Nutritionally Superior Staple Crop in Mozambique

Background:Chronic vitamin A deficiency affects both women and children in Mozambique and populations worldwide and cannot be addressed through supplementation alone. Food-based approaches encouraging the consumption of vitamin A-rich foods, such as the orange-fleshed sweet potato (OFSP), have the potential to positively affect vitamin A status. A range of OFSP varieties have been introduced in sub-Saharan Africa in rural and urban environments and emergency and nonemergency contexts.Objective:To highlight the successes to date and remaining challenges of the introduction of OFSP to increase vitamin A consumption in Mozambique, collating a time line of key events.Methods:A systematic review of literature using The Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Results:The systematic search resulted in 20 studies that met inclusion criteria. Data extracted include author and year, study location and duration, project partners, project title, sample size and characteristics, objectives, ...
Globalization, Time, and Aging

For the most part, social gerontology has emphasized one temporal orientation. The idea that social gerontology has a penchant for linear, chronological time is well-documented (Adam 1990; Hendricks and Peters 1986; Seltzer 1976; Kastenbaum 1966). Despite efforts to include personal and sociocultural renditions of temporality, gerontological research continues to use chronological age as the primary way to define their population and understand life changes.
Abstract W MP58: The Relationship Between Carotid Stiffness, Diastolic Diameter, and White Matter Hyperintensity Volume: The Northern Manhattan Study

Background: Changes in the extracranial vasculature may be associated with small vessel disease in the brain. We sought to examine the association of carotid stiffness and carotid diastolic diameter with white matter hyperintensity volume (WMHV), a magnetic resonance imaging (MRI) measure for cerebral small vessel disease, in a multi-ethnic community-based cohort. Methods: We evaluated 1140 stroke-free participants in the Northern Manhattan study who underwent brain MRIs and high-resolution carotid ultrasounds. We used linear regression to examine carotid stiffness and diastolic diameter with WMHV after adjusting for sociodemographics, lifestyle behaviors, and traditional vascular risk factors. Results: Among 1140 participants (mean age: 70.6±9.0 years; 61% women; 15% White, 16% Black, 59% Hispanics), the mean carotid stiffness was 8.19 ± 5.39, mean carotid diastolic diameter was 6.16 ± 0.93 mm, and mean WMHV 0.68 ± 0.84. In a fully adjusted model, diastolic diameter was associated with log-WMHV (β=0.10, ...
Short-Term Outcomes and Complications of Damage Control and Definitive Laparotomy in Deployed Combat Environments: 2002 to 2011

ABSTRACT Introduction: Damage control laparotomy (DCL) in an austere environment is an evolving surgical modality. Methods: A retrospective evaluation of all patients surviving 24 hours who underwent a laparotomy from 2002 to 2011 in Iraq and Afghanistan was performed. DCL was defined as a patient undergoing laparotomy at two distinct North American Treaty Organization (NATO) Role 2 or 3 medical treatment facilities (MTFs); a NATO Roles 2 and 3 MTFs, and/or having the International Classification of Diseases, 9th Revision, Clinical Modification procedure code 54.12, for reopening of recent laparotomy site. Definitive laparotomy (DL) was defined as patients undergoing one operative procedure at one NATO Role 2 or 3 MTF. Demographic data including injury severity scores, hematological transfusion, mortality, intraperitoneal or retroperitoneal operative interventions, and complications were compared. Results: DCL composed of 26.5% (n = 331) of all 1,248 laparotomies performed between March 2002 and September...
Unnatural Selection: Intelligence Testing, Eugenics, and American Political Cultures

The "myth ofthe menace ofthe feeble-minded" blamed early twentieth-century social problems on a rising tide of feeble-minded men and women who were said to be filling America's custodial institutions, while even greater numbers of unrecognized morons were loosed to reproduce in the streets.1 Conflicting interpretations of this myth have been central to the debates among historians of mentai retardation and psychological testing for over two decades.2 One school of historical research has stressed growing altruism in the care of the mentally retarded and portrayed the menace myth as an exceptional episode distinct from the origins of intelligence testing.3 They use the term "myth" to denote falsehood. For them, the menace myth was merely a bad theory proven wrong by interwar scientists. An opposing group of historians has claimed that knowledge about intelligence is constructed to meet the needs of social control.4 A "myth," for them, exposes something essential about the world views of its believers. They say the menace myth is a recurring theme in the enduring undemocratic defense of social hierarchy. This essay charts a new direction in the way we interpret the meaning of the menace myth by altering the dominant research questions, and under this new framework pursuing a case study ofthe relationships between eugenics, testing technology, and youth custody policy in early twentieth-century Ohio. Although the dichotomy between altruistic progress and social control of? fered vital energy to historical work for a time, partisans of both approaches have drawn broad conclusions from a narrow history of intellectuals without properly working through the social and policy contexts.5 Fortunately, recent work by James W. Trent has provided a sharper sense of the impact that so? cial policies have had upon the lives of the mentally retarded. Trent's main argument that, "control and care merged as interrelated and interdependent factors in specialized services for retarded people," was an important attempt to bridge the gap between progressive altruism and social control. However, he did not consistently follow a narrative course that might allow one to see clearly how it is that care and control are part of the same social processes. When he examined the menace myth he retreated to the old framework of reformer motivations and argued that physicians and psychologists used the menace myth to capitalize on xenophobic class fears. When they found it in their professional interests to abandon eugenic rhetoric in favor ofthe therapeutic language ofthe mentai hygiene movement, the menace myth disappeared. Trent deftly exposed the political maneuvering of the philanthropists and scientists who advanced the menace myth, but the concept of self-interest stripped his interpretation of broader historical significance, while failing to further our understanding of how difficult it has been to "care" for the mentally retarded in a non-"controlling," apolitical, scientific way.
Asherman's Syndrome

Asherman's syndrome is being diagnosed with increasing frequency. Although it usually occurs following curettage of the pregnant or recently pregnant uterus, any uterine surgery can lead to intrauterine adhesions (IUA). Most women with IUA have amenorrhea or hypomenorrhea, but up to a fourth have painless menses of normal flow and duration. Those who have amenorrhea may also have cyclic pelvic pain caused by outflow obstruction. The accompanying retrograde menstruation may lead to endometriosis. In addition to abnormal menses, infertility and recurrent spontaneous abortion are common complaints. Hysteroscopy is the standard method to both diagnose and treat this condition. Various techniques for adhesiolysis and for prevention of scar reformation have been advocated. The most efficacious appears to be the use of miniature scissors for adhesiolysis and the placement of a balloon stent inside the uterus immediately after surgery. Postoperative estrogen therapy is prescribed to stimulate endometrial regrowth. Follow-up studies to assure resolution of the scarring are mandatory before the patient attempts to conceive as is careful monitoring of pregnancies for cervical incompetence, placenta accreta, and intrauterine growth retardation.
Individual Differences in Criterion Task Set Performance

As part of a larger standardization study of the U.S. Air Force Criterion Task Set (CTS), a number of individual difference variables were assessed to evaluate their relationship to CTS performance. The selection of these individual difference variables was based on their known or hypothesized relationship to performance or perceptual abilities. This paper reports some of the preliminary findings with regard to these individual difference variables. Of the variables measured, Stimulus Screening, Thrill and Adventure Seeking, Neuroticism, Type–A Behavior, and General Intelligence showed the most promising relationships to CTS performance variables.
Specific repression of granulocyte-macrophage and granulocyte colony-stimulating factor gene expression in interleukin-1-stimulated endothelial cells with antisense oligodeoxynucleotides.

Antisense oligodeoxynucleotides (ODNs) have been used to effect the specific inhibition of cellular gene expression. We have evaluated the application of this approach to the inhibition of interleukin-1 (IL-1)- induced granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) expression in cultured human umbilical vein endothelial cells. Antisense ODNs or control ODNs (sense ODNs or missense ODNs containing random base substitutions) were added to cultures of endothelial cells, the cells were induced with IL- 1 alpha, and the conditioned media were assayed for GM-CSF and G-CSF by quantitative bioassays and for immunoreactive GM-CSF by enzyme immunoassay. Antisense ODNs complementary to the first 15 or 18 bases of the translation start sites of GM-CSF or G-CSF mRNAs inhibited, in a concentration-dependent fashion, the IL-1-stimulated expression of the corresponding factor, but did not affect expression of the other factor. Control ODNs did not affect GM-CSF or G-CSF expression. Exposure to a GM-CSF antisense ODN, but not a control ODN, substantially reduced cytoplasmic GM-CSF mRNA levels in IL-1-stimulated endothelial cells. Neither ODN affected levels of endothelial leukocyte adhesion molecule (ELAM)1 or glyceraldehyde-3-phosphate dehydrogenase mRNAs. We conclude that antisense ODNs complementary to the translation start sites of GM-CSF or G-CSF mRNAs inhibit expression of the corresponding factor in a sequence-specific fashion and this effect is mediated, at least in part, by reduction in the cytoplasmic level of the targeted mRNA. Moreover, IL-1-induced GM-CSF or G-CSF expression does not depend on expression of the other factor.
A myelodysplastic syndrome with marrow eosinophilia terminating in acute nonlymphocytic leukemia, associated with an abnormal chromosome 16

A patient presented with a myelodysplastic syndrome and bone marrow eosinophilia that evolved six months later into an acute nonlymphocytic leukemia (ANLL). Cytogenetic analyses of the bone marrow revealed 86% of the metaphases with 45,X-Y,inv(16)(p13;q22),t(11;17) (q11;q25),del(21)(q13) and 14% of the metaphases with the same abnormalities but with a Y chromosome. The association of ANLL, bone marrow eosinophilia, and abnormal chromosome 16 has previously been reported and has been suggested to have a favorable prognosis. Our patient is unique in that ANLL was preceded by a preleukemic phase associated with bone marrow eosinophilia. When complete remission was achieved, the bone marrow cytogenetics returned to normal, and the eosinophilia disappeared.
Cortical asymmetries direct the establishment of cell polarity and the plane of cell division in the Fucus embryo.

External gradients, such as unilateral light, applied to apolar zygotes of Fucus result in a cortical asymmetry expressed as the actin-dependent translocation of existing plasma membrane molecules (e.g., DHP receptors) to the shaded side (Fig. 1a). This process corresponds to the alignment of the polar axis. The localized cortical domain identified by the accumulation of DHP receptors, F-actin, and free calcium forms a target site for Golgi vesicle (F granule) secretion. Localized secretion of F granules is essential to stabilize the polar axis (Fig. 1b), and to complete a structural complex at the site for polar growth, postulated to span the plasma membrane, from the actin cytoskeleton to the cell wall (Fig. 2). Furthermore, targeted secretion of the contents of F granules into the plasma membrane and/or cell wall appears to provide localized positional information required to orient the first cell division plane and to differentiate the rhizoid and thallus cells of the two-celled embryo (Fig. 1c). Our cytological approaches using Fucus zygotes point to the importance of directed vesicle movement and secretion in creating asymmetries in the plasma membrane/cell wall during embryogenesis, which appear to have a critical role in cell morphogenesis. Conclusions drawn from these results may provide a useful paradigm for the study of cell morphogenesis and pattern formation in higher plant embryos and vegetative tissues.
Self-concealment in obsessive-compulsive disorder: Associations with symptom dimensions, help seeking attitudes, and treatment expectancy

Abstract Obsessive-compulsive disorder (OCD) is characterized by unwanted and upsetting thoughts, images, or urges (obsessions). Some individuals with OCD feel compelled to conceal the content and frequency of their obsessions, and theoretical accounts suggest that self-concealment may contribute to OCD symptoms. Yet, empirical investigation in this area is lacking. The present study investigated individual differences in dispositional self-concealment (the behavioral tendency to keep distressing and potentially embarrassing personal information from others) in relation to OCD symptoms. Individuals who self-identified as having OCD ( N =115) were compared to unscreened community controls ( N =513) on a validated measure of self-concealment. The OCD group reported higher levels of self-concealment than the control group, and this difference remained significant after controlling for group differences in anxiety, depression, and stress symptoms. Among the OCD group, self-concealment was significantly related to OCD severity, though only for some symptom dimensions. Specifically, self-concealment was associated with symptoms pertaining to unacceptable thoughts, fears of being responsible for harm and symmetry/ordering, but not contamination symptoms. In addition, OCD participants with higher levels of self-concealment reported more negative attitudes about seeking professional help and lower levels of expected benefits of receiving cognitive behavioral therapy for their OCD. Clinical implications and future directions are discussed.
A survey of the historical scope and current trends of wearable technology applications

The field of wearable technology has undergone significant growth in the last few years. Along with this growth come trends in consumer application development, which may be indicative of structural influences on the design and development of products as well as social influences among consumers. Here, we present a two-phase survey of the application space of wearable technology, by assessing applications observed in research or industrial activities from two time periods: initially with a historical focus (mapping the space up to 2014) and subsequently through a 1-year snapshot by mapping developments between 2014 and 2015. We evaluate distribution in application instances over the body surface, over a range of product types, and within a set of application categories, as well as differences in product price and gender target. The implications of changes in product focus areas over these two time frames are discussed.
Abstract P052: Homocysteine Increases Macrophage-Derived Paraoxonase -1 Expression Independent of CD68

Although atherosclerotic plaque rupture is the leading cause of myocardial infarction, the mechanisms are unclear. Macrophages burdened with oxidized LDL (oxLDL) become foam cells: hallmarks of plaque progression and instability. One of the main macrophage-specific receptors for oxLDL is CD68. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated lactonase capable of retarding/inhibiting LDL oxidation. Elevated levels of homocysteine (Hcy), an amino acid homologue and independent cardiovascular risk factor, is metabolized by Pon1. Given the literature connections of oxLDL, Pon1, Hcy, and macrophages to atherosclerosis, we hypothesized that Pon1 is produced by murine macrophages and its expression is increased by Hcy via CD68. Murine J774a.1 macrophages were treated with LDL, oxLDL, Hcy, or oxLDL+Hcy. Also, separate treatment groups included macrophages that had CD68 silenced by CD68 siRNA transfection. Cell lysates were analyzed for CD68 and Pon1 expression via Western blotting. Pon1 is present in macrophages. Hcy along with oxLDL significantly increases Pon1 (51%, 1.51 vs 0.97) expression compared to controls than oxLDL alone. Pon1 expression is significantly decreased (33%, 0.67 vs 1) with silencing of CD68. Pon1 expression is significantly decreased more with oxLDL (82% 0.17 vs 1) in presence of CD68 silencing but is significantly increased with oxLDL+Hcy (24% 1.24 vs 1). CD68 expression tends to increase more with oxLDL+Hcy than oxLDL alone when compared to control and the tendency follows with silencing of CD68. Our results conclude that Hcy increases macrophage-derived Pon1 expression independent of CD68.
Evolving Learning: The Changing Effect of Internet Access on Political Knowledge and Engagement (1998–2012)

This study addresses the changing role of Internet usage on the political knowledge and participation gap between individuals of low and high socioeconomic status (SES). Analysis of data collected by the Pew Research Center's Biennial Media Consumption Studies (1998–2012) shows that the percentage of the population that accidentally encounters political information online has risen dramatically. Results show that accidental exposure and SES are positively related to political knowledge, and that accidental exposure reduces the SES knowledge gap. Moreover, accidental exposure appears to be mitigating the SES voting gap at an increasing rate over time.
Meta-analysis of disease free survival (DFS) as a surrogate for overall survival (OS) in localized renal cell carcinoma (RCC).

459Background: OS is a critical endpoint for adjuvant RCC trials testing the benefit of early systemic therapy to increase cure rates, but requires long duration and significant patient resources. We explored the potential use of DFS as a surrogate for OS when assessing the efficacy of adjuvant therapy in localized RCC. Methods: We performed a systematic literature review following the PRISMA statement. Inclusion criteria required randomized controlled trials (RCT) for adjuvant systemic therapy in localized RCC, which reported on both DFS and OS. DFS was defined from randomization or nephrectomy (R/N) to the first evidence of clinical recurrence (loco-regional or distant) or death from any cause. OS was defined from R/N to death from any cause. We extracted data on hazard ratio (HR) and 5-year event free rate from Kaplan Meier estimates. We performed a meta-analysis and correlated these estimates for OS and DFS, weighted by number of DFS events. R-square >0.7 would indicate a strong correlation and potent...
Study of advancement to higher temperature membrane distillation

Abstract It is well known that the mass flux (J) and the membrane thermal efficiency (η) of membrane distillation increase with the feed flow temperature. A comprehensive laminar and turbulent flow model for simulating and evaluating the performance of direct contact membrane distillation (DCMD) when operated at inlet feed temperature (Tf,i) from 80 °C to 180 °C, higher than the customary maximum of ~ 80 °C, was developed and used to explain and assess the performance of such high temperature DCMD, as well as the potential associated problems of the needed higher operating pressure, and provide knowledge useful for their future design and optimization. Some of the key results are that raising Tf,i from 80 °C to 180 °C, increases J 9.4-fold, and η 2.1-fold, and decreases the specific energy consumption (SEC) 2.9-fold. Raising the flow Reynolds number from 1200 to 7000 increases J 2.6-fold and η by 15%, but SEC increases 2.3-fold. The needed system pressurization does not affect the process performance significantly. The higher operating temperatures also provide more practical opportunities for heat recovery, which could significantly further raise overall system efficiency.
Pial Microcirculation Evaluated by Closed Cranial Window Method 7 Days After Impact Acceleration Injury in Rats: Does Post-Traumatic Hypothermia Provide Persisting Pial Vascular Protection?

Recently our group demonstrated, in rats, that moderate hypothermia followed by gradual rewarming exerted significant cerebrovascular-protection when assessed up to 6 h following traumatic brain injury (TBI). However, as these studies were confined to the acute postinjury period, we questioned whether this same cerebrovascular protection persisted with more prolonged survival. To explore this issue 18 male Sprague-Dawley rats were randomized into three groups: TBI without hypothermia, TBI with post-traumatic hypothermia, and sham. Seven days later, the pial arteriolar responsiveness to various vasodilator agents (acetylcholine, pinacidil, sodium nitroprusside, and hypercapnia) were assessed through a closed cranial window. The sham and TBI with hypothermia groups showed essentially normal vasoreactivity; however, the nonhypothermic TBI rats showed significantly reduced responsiveness to these agents. These results confirm that TBI causes prolonged cerebrovascular impairment to various known vasodilatory agents. Moreover, this study also demonstrates that the use of post-traumatic moderate hypothermia provides enduring protective effects for the injured pial microcirculation.
"Impact Investing: Actors, Metrics and Interactions"

This study aims to examine the current landscape of impact investing. A background on social finance is provided, and impact investing is introduced and defined. An examination is offered of the va...
Philosophical Issues and Nursing Science

The author of this article introduces a new column that will explore philosophical issues of concern to nurse scientists. In this initial column, I review the general terrain of philosophy in nursing science and explore some philosophical issues relevant to theory development. One conclusion is that inquiry into philosophical issues may help expand our repertoire of conceptual tools useful in building scientific knowledge and facilitating theoretical progress.
Reliability perspective of resistive synaptic devices on the neuromorphic system performance

Emerging non-volatile memory (eNVM) based synaptic devices are attractive for the replacement of SRAM in the hardware implementation of artificial neural networks (ANNs). However, one of the critical challenges for eNVM is the reliability concerns due to data retention and write endurance failures. This paper investigates the impact of these two failures in the multilayer perceptron (MLP) using our developed NeuroSim+ simulator. For the retention failure in offline classification, we consider various possible conductance drift scenarios and the reported physical model based on conductance variation. The results confirm that faster degradation on the classification accuracy is highly correlated with larger deviation in the weighted sum. For the endurance failure in online learning, the strength of conductance tuning is assumed to become weaker over write pulse cycles. The analysis suggests that the learning accuracy is less impacted because the network is able to adapt itself and activate more synapses to participate in the weight update when the tuning capability of synapses are degraded.
Mother and Community College Professor

When do you decide you want to be a chemist or to teach chemistry or to be a professor? I wasn’t sure what I wanted to do even after arriving in graduate school. Then suddenly I did. But that’s the middle of the story, so let’s go back to the beginning.
A Decision Analysis Approach for Coordinating Design, Manufacturing and Marketing in New Product Decisions

In the late 1800’s, Faber pencils dominated the market. By one estimate, by the end of the 19th century Faber made 250 million pencils per year. L. & C. Hardmuth Company, facing stiff competition from Faber, designed a top-quality pencil that would sell for three times the price of any other pencil in the market. They named it Koh-I-Noor after the great diamond of history and painted the pencil golden yellow to suggest the Oriental source of the then-finest graphite. The pencil was a huge success. Was it simply designing and making a better pencil or was it also selecting a name and a color to connote quality and value that made the Koh-I-Noor pencil so successful? This example, though of a relatively simple product, demonstrates that a creative fusion of marketing insights with design and high quality production could reap a firm substantial success in the market place.
Determining elastic modulus from dynamic mechanical analysis data: Reduction in experiments using adaptive surrogate modeling based transform

Abstract A transform was proposed in the earlier work to convert the frequency domain storage modulus obtained from dynamic mechanical analysis (DMA) to elastic modulus over a wide range of temperatures and strain rates (Polymer, 2016, 101, 1–6) from testing of a single specimen. However, the method still required conducting temperature and frequency sweeps in DMA experiments. The present work is focused on developing an adaptive DMA experimental scheme for achieving further reduction in experimentation required to characterize a material using adaptive design of experiments (DoE) method. First, the surrogate model is established based on time-temperature superposition principle using the Particle Swarm Optimization. Then four sampling methods are used to fit the data on the surrogate model. The Sobol Quasi Monte Carlo (QMC) method converges faster and has better accuracy than other methods. Then, using integral relations of viscoelasticity, the surrogate model is transformed to time domain for obtaining a temperature dependent relaxation function from which the strain rate sensitive elastic modulus is extracted and validated with tensile test results. The error is found to be below 3.9% for 5% magnitude of noise and 4.4% for 10% magnitude of noise in the strain rate range 10−5 to 10−2 s−1 using Sobol QMC method. The close agreement indicates that the adaptive DMA scheme can significantly reduce the time and cost involved in materials characterization and eliminate the need for tensile tests for measuring material modulus.
Outcomes of kidney transplants in pediatric patients with the vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities association

In this single-center retrospective study, we analyzed kidney transplant outcomes in nine pediatric patients with VACTERL [vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities] association-making this the largest study of its kind. Of 743 pediatric kidney transplant recipients at our center (1980-2017), nine had documented diagnoses of VACTERL association. All nine had congenital anorectal malformations and renal anomalies, five had vertebral defects, and one had a bifid thumb and tracheoesophageal fistula. Renal anomalies included dysplasia (n = 6), aplasia (n = 3), and horseshoe kidney (n = 2). Congenital lower urinary tract anomalies included neurogenic bladder (n = 6), obstructive uropathy (n = 4), anovesicular fistula (n = 1), rectourethral fistula (n = 1), and posterior urethral valves (n = 1). Age at transplant ranged from 1.2 to 15 years (mean, 7.3; standard deviation [SD], 5.5); 6 (67%) were male, and 3 (33%) were female; 6 (67%) had a living related donor, and 3 (33%) had a deceased donor. The overall graft survival rate was 78% (range, 1.5 to 25.2 years; mean, 10.5; SD, 8.9). One month post-transplant, one recipient died with a functioning graft. At 3.7 years post-transplant, one graft failed because of recurrent pyelonephritis. Post-transplant urologic complications included pyelonephritis (n = 6), vesicoureteral reflux (n = 5), and graft hydronephrosis (n = 4). We conclude that pediatric patients with VACTERL association can be safely transplanted-careful patient selection with vigilance and intervention for pre- and post-transplant urologic complications is essential.