cssi/SciSciGPT-SciSciNet huggingface dataset:
Fcγ receptor-dependent effector mechanisms regulate CD19 and CD20 antibody immunotherapies for B lymphocyte malignancies and autoimmunity

Immunotherapy using Rituximab, an unconjugated CD20 monoclonal antibody, has proven effective for treating non-Hodgkin’s lymphoma and autoimmune disease. CD19 antibody immunotherapy is also effective in mouse models of lymphoma and autoimmunity. In both cases, mouse models have demonstrated that effector cell networks effectively deplete the vast majority of circulating and tissue B lymphocytes through Fcγ receptor-dependent pathways. In mice, B cell depletion is predominantly, if not exclusively, mediated by monocytes. CD20 mAbs rapidly deplete circulating and tissue B cells in an antibody isotype-restricted manner with a hierarchy of antibody effectiveness: IgG2a/c > IgG1 > IgG2b >> IgG3. Depending on antibody isotype, mouse B cell depletion is regulated by FcγRI-, FcγRII-, FcγRIII-, and FcγRIV-dependent pathways. The potency of IgG2a/c mAbs for B cell depletion in vivo results from FcγRIV interactions, with likely contributions from high-affinity FcγRI. IgG1 mAbs induce B cell depletion through preferential, if not exclusive, interactions with low-affinity FcγRIII, while IgG2b mAbs interact preferentially with intermediate-affinity FcγRIV. By contrast, inhibitory FcγRIIB-deficiency significantly increases CD20 mAb-induced B cell depletion at low mAb doses by enhancing monocyte function. Thus, isotype-specific mAb interactions with distinct FcγRs contribute significantly to the effectiveness of CD20 mAbs in vivo. These results provide a molecular basis for earlier observations that human FcγRII and FcγRIII polymorphisms correlate with the in vivo effectiveness of CD20 antibody therapy. That the innate monocyte network depletes B cells through FcγR-dependent pathways during immunotherapy has important clinical implications for CD19, CD20, and other antibody-based therapies for the treatment of diverse B cell malignancies and autoimmune disease.
De novo single exon deletion of AUTS2 in a patient with speech and language disorder: a review of disrupted AUTS2 and further evidence for its role in neurodevelopmental disorders.

The autism susceptibility candidate 2 (AUTS2) gene is suggested to play a critical role in early brain development, and its association with intellectual disability (ID), autism spectrum disorders, and other neurodevelopmental disorders (NDDs) has recently gained more attention. Genomic rearrangements and copy number variations (CNVs) involving AUTS2 have been implicated in a range of NDDs with or without congenital malformations and dysmorphic features. Here we report a 62 kb de novo deletion encompassing exon 6 of AUTS2 detected by chromosomal microarray analysis (CMA) in a 4.5 year-old female patient with severe speech and language disorder, history of tonic–clonic movements, and pes planus with eversion of the feet. This is one of the smallest de novo intragenic deletions of AUTS2 described in patients with NDDs. We reviewed previously reported small pathogenic CNVs (<300 kb) in 19 cases, and correlated their specific locations within AUTS2 as well as presence of enhancers, regulatory elements, and CpG islands with the clinical findings of these cases and our patient. Our report provides additional insight into the clinical spectrum of AUTS2 disruptions. © 2014 Wiley Periodicals, Inc.
Live Cell Imaging of Src/FAK Signaling by FRET

The Src/FAK complex is involved in many signaling pathways and plays crucial roles in cell adhesion/migration. It becomes clear that the subcellular localization of Src and FAK is crucial for their activities and functions. In this article, we first overview the molecular mechanisms and functions of Src and FAK involved in cell adhesion/migration. We then introduce the development of genetically encoded biosensors based on fluorescence resonance energy transfer (FRET) to visualize the activities of Src and FAK in live cells with high spatiotemporal resolutions. Different kinds of signal peptides targeting subcellular compartments are also discussed. FRET-based biosensors fused with these targeting signals peptides are further introduced to provide an overview on how these targeting signals can facilitate the localization of biosensors to continuously monitor the local activity of Src and FAK at subcellular compartments. In summary, genetically-encoded FRET biosensors integrated with subcellular compartment-targeting signals can provide powerful tools for the visualization of subcellular Src and FAK activities in live cells and advance our in-depth understanding of Src/FAK functions at different subcellular compartments.
Small-scale heterogeneity of fertilization success in a broadcast spawning octocoral

Fertilization rates of many broadcast spawning marine taxa are highly variable and exhibit marked variation even on scales of seconds and centimeters. Variance in fertilization rates of the broadcast spawning Caribbean gorgonian Plexaura kuna Lasker, Kim, and Coffroth was examined in the San Blas Islands, Panama in a series of field experiments that compared fertilization rates at set distances from spawning male colonies. Quadruplicate samples of water were collected from each of five positions around spawning male colonies during spawning events in June and July 1994–1995. All samples were analyzed for their ability to fertilize eggs. In 1995, sperm densities also were measured. The average fertilization was very low (15%), and 74% of the samples yielded less than 20% fertilization rates. Fertilization rates dropped by 44% 1 m from a spawning male. Current speeds ranged from 1.9–5.5 cm s−1 during the experiments and were negatively correlated with fertilization rates. Samples collected from identical locations within seconds of each other varied in fertilization rates by as much as 56%. Sperm densities in the quadruplicate samples differed by as much as two orders of magnitude. Average fertilization rates are most affected by current speed and rates of sperm release. However, finer scale variance is probably related to heterogeneities in mixing processes that occur on scales of centimeters and seconds. Mean fertilization rates may be driven by heterogeneity in dilution processes that produce patches of high sperm density.
The structure and solid-state reactivity of a new polymorph of tetrakis(4-vinyl-pyridine)diisothiocyanatocobalt(II)

Abstract The crystal structure of Co(NCS) 2 [4-vinylpyridine] 4 has been determined by X-ray diffraction methods. The complex crystallizes in space group Pbca , with a = 32.293(15) A, b = 11.416(6) A, c = 17.033(10) A , and Z = 8. Full-matrix least-squares refinement of positional and thermal parameters for all atoms (H atoms fixed at calculated positions), with 1458 reflections ( F >; 3.92 σ (F) ) led to R = 0.075 and R w = 0.079. The trans -octahedral complex consists of four vinylpyridine ligands, arranged in a propeller-shape, and two isothiocyanate ligands. Powder diffraction of Co(NCS) 2 (4-vinylpyridine) 2 indicates an isomeric cell, with a = 13.77 A . The analogous Ni(II) complexes are isomorphous with the Co(II) complexes, suggesting that the yellow–green complex Ni(NCS) 2 (4-vpy) 2 , previously thought to be polymeric, is in fact tetrahedral.
A simple method for finding the Jordan form of a matrix

A conceptually simple algorithm is presented for determining the orders of the minor blocks in the Jordan canonical form of a given matrix whose eigenvalues are known.
Numerical treatment of fully developed laminar flow in helically coiled tubes

Laminar flow in helically coiled tubes is treated numerically. Fully developed axial and secondary velocities are calculated for both circular and elliptical cross sections. Only closely wrapped helices, that is, helices with modest pitch, are considered. Ten solutions with Deans numbers up to 200 have good accuracy. Two additional solutions with Deans numbers up to 280 are approximate.
Evaluating the Efficacy of the PEAK Relational Training System Using a Randomized Controlled Trial of Children with Autism

The present investigation sought to examine the efficacy of the instructional curriculum described in the Direct Training Module of the PEAK Relational Training System on the language repertoires, as measured by the PEAK direct assessment, of children diagnosed with autism or related developmental disabilities. Twenty-seven children diagnosed with pervasive developmental disorders were evaluated using the PEAK direct training assessment protocol prior to assignment to control and experimental groups. Participants in the experimental group received additional language instruction derived from the curriculum programs of the Direct Training Module, while participants in the control group received treatment as usual. Both groups were then re-assessed using the PEAK direct assessment after 1 month. A repeated measures ANOVA indicated that participants in the experimental group made significantly more gains in language skills than those who were assigned to the control group, F(1, 22) = 9.684, p = .005. Implications for evidence-based practice and future research are discussed.
Rapid identification of mutation-complementing restriction fragments from Aspergillus nidulans cosmids

Abstract We isolated recombinant DNA cosmid clones that complemented certain mutations in Aspergillus nidulans when covalently closed circular DNA was used to transform cells. We found that DNA from the cosmids was capable of genetic complementation even after digestion to completion with restriction endonucleases that recognize six base pair sequences. Individual restriction fragments were isolated from agarose gels and tested for their ability to complement mutations in cotransformation experiments by using either the A. nidulans trpC or argB gene as selective marker. Specific fragments complemented the mutations. This procedure permits rapid identification of small DNA fragments, from large cosmid inserts, that contain all or part of specific genes, without subcloning the fragments or constructing restriction maps for the cosmids. It therefore significantly simplifies mapping of genes cloned by cosmid complementation or mutations in Aspergillus by providing a starting point for the application of conventional molecular mapping techniques.
Haptic Feature Extraction

This study examined the process by which the shape of a haptically explored object is synthesized from the geometric characteristics of simpler constituent elements, such as arcs and ellipses. Subjects traced the outlines of virtual objects by means of whole arm movements. Each object consisted of the union of a large central ellipse and two smaller circles, extending upward and outward from the top left and right sides of the base. The sizes of the two circles and the eccentricity of the elliptical base were varied. After exploring the object's contour in the absence of vision, subjects reproduced the sensed shape by means of freehand drawing. Speed and force were modulated during the exploratory phase in a manner that suggested that subjects reacted to rather than predicted changes in curvature. Also, subjects typically devoted more time to exploring the part of the contour encompassing the two smaller circles. During drawing, individual features of the explored shape were reproduced with varying degrees of fidelity. Aspects related to the size and location of the smaller circles were reproduced better than was the eccentricity of the ellipse forming the base. Since subjects spent proportionally less time exploring the base, these results suggest that subjects selectively focused attention to regions of high spatial contrast and that the exploratory strategy introduced distortions in the haptically sensed shapes.
Mother’s Education, Learning‐by‐Doing, and Child Health Care in Rural India

This study analyzes the determinants of the use of prenatal care and child immunization in rural India relying primarily on the 1993/94 National Family Health Survey. The key question addressed is whether learning-by-doing is an important feature of the health care system. More specifically, are women who use prenatal care as a result more likely to immunize their children? We conclude that important unobserved traits influence the utilization of both prenatal and immunization services. Once these are controlled, learning-by-doing is important for educated women, but not for uneducated women. There are two possible interpretations of this finding. One is that a lack of education limits the ability of women to effectively learn from the prenatal experience. The other is failings of the health care system limits its effectiveness with uneducated women. We also find strong evidence of gender bias in the demand for immunization services particularly among uneducated women. In addition, the analysis provides estimates of the effects on prenatal care and immunization of formal education, media exposure, economic status, family composition, access to services, and other variables.
Recharge Estimations for Laguna Pond at Freeman Ranch, San Marcos, Texas

Laguna Pond is an irregularly shaped pond located on Freeman Ranch in the Edwards Aquifer Recharge Zone of south-central Texas. To determine the potential usefulness of Laguna Pond for the management of Freeman Ranch, the pond's drainage area, storage capacity, and yearly water budget were determined using a Global Positioning System unit and geographic information systems analytical tools. Preliminary analysis of the data revealed a negligible drainage area and a storage capacity of 3.71 acre-feet (161,608 cubic feet or 1,208,908.79 gallons) with a surface area of 0.29 acres (12,632 ft2). The preliminary water budget revealed a deficit of approximately 29 in per year, which would require the ranch to pump 8.97 af/year (2, 921,529.604 gallons/year) to create a perennial pond. The exorbitant amount of water required to maintain the pond makes the Laguna an unlikely candidate for utilization as a stock pond or source of recreation for the ranch.
A projection transform for non-Euclidean relational clustering

The duality theory for the relational c-means algorithms, relational Gaussian mixture model, etc. requires that a distance matrix R correspond to a set of vector object data whose squared A-norm distances (or less generally, squared Euclidean distances) match the elements of R. For most datasets, this is an unrealistic constraint. As such, this paper proposes an alternating projection-based transform for converting non-Euclidean distance matrices into Euclidean distance matrices. Two synthetic and six real-world non-Euclidean datasets are used to illustrate that this method preserves cluster structure well.
Fluid–structure interaction for aeroelastic applications

Abstract The interaction between a flexible structure and the surrounding fluid gives rise to a variety of phenomena with applications in many areas, such as, stability analysis of airplane wings, turbomachinery design, design of bridges, and the flow of blood through arteries. Studying these phenomena requires modeling of both fluid and structure. Many approaches in computational aeroelasticity seek to synthesize independent computational approaches for the aerodynamic and the structural dynamic subsystems. This strategy is known to be fraught with complications associated with the interaction between the two simulation modules. The task is to choosing the appropriate models for fluid and structure based on the application, and to develop an efficient interface to couple the two models. In the present article, we review the recent advancements in the field of fluid–structure interaction, with specific attention to aeroelastic applications. One of the key aspects to developing a robust coupled aeroelastic model is the presence of an efficient moving grid technique to account for structural deformations. Several such techniques are reviewed in this paper. Also, the time scales associated with fluid–structure interaction problems can be very different; hence, appropriate time stepping strategies and/or sub-cycling procedures within the individual field need to be devised. The flutter predictions performed on an AGARD 445.6 wing at different Mach numbers are selected to highlight the state-of-the-art computational and modeling issues.
Real-time data retrieval and new visualization techniques for the energy industry

Effective power system operation requires power system engineers and operators to analyze vast amounts of information. The authors have developed several techniques for visualizing large amounts of data including contouring, animated flows, and 3D visualization. These techniques have been completely integrated into PowerWorld Simulator, an offline system study tool for use in the energy industry. Integrating these visualization techniques with real-time data sources, such as those available in energy control centers, however, has presented a separate challenge to the wide dissemination of these visualization abilities. The paper presents a case study of integrating these abilities with control centers that utilize the Plant Information (PI) System for data storage and archival. Projects have been completed that integrate these visualization techniques into control centers for Commonwealth Edison in Lombard, Illinois and City Water Light and Power in Springfield, Illinois. A separate pilot project has also been completed with the Tennessee Valley Authority.
A Values Constraint in Internationalizing the Business Curriculum

Abstract Research on worldminded-ness and related work on international adjustment and effectiveness suggest that highly worldminded individuals will be more productive in international business. This study of worldminded attitudes in a university student population reveals that business majors are less worldminded than majors in other fields. In addition, the gap between business majors and other majors widens with class progression and student age, as business student worldmindedness declines while that of other students increases. The contribution of the total program of business studies to the evolution of student attitudes appropriate for international business has to be considered in efforts to internationalize the curriculum. International business courses alone may not be adequate to alter student attitude trends unfavorable to international work. Further examination of student worldminded attitudes suggests that required language classes and study abroad programs are not likely to have a signific...
Symplasmic networks in secondary vascular tissues: parenchyma distribution and activity supporting long-distance transport

Stems that develop secondary vascular tissue (i.e. xylem and phloem derived from the vascular cambium) have unique demands on transport owing to their mass and longevity. Transport of water and assimilates must occur over long distances, while the increasing physical separation of xylem and phloem requires radial transport. Developing secondary tissue is itself a strong sink positioned between xylem and phloem along the entire length of the stem, and the integrity of these transport tissues must be maintained and protected for years if not decades. Parenchyma cells form an interconnected three-dimensional lattice throughout secondary xylem and phloem and perform critical roles in all of these tasks, yet our understanding of their physiology, the nature of their symplasmic connections, and their activity at the symplast-apoplast interface is very limited. This review highlights key historical work as well as current research on the structure and function of parenchyma in secondary vascular tissue in the hopes of spurring renewed interest in this area, which has important implications for whole-plant transport processes and resource partitioning.
Dependent personality, separation anxiety disorder and other anxiety disorders in OCD

Background The purpose of this study was to investigate whether dependent personality and/or general personality dimensions might explain the strong relationships between separation anxiety disorder (Sep-AD) and three other anxiety disorders (agoraphobia, panic disorder and social anxiety disorder) in individuals with obsessive compulsive disorder (OCD). Methods Using data from 509 adult participants collected during the OCD Collaborative Genetic Study, we used logistic regression models to evaluate the relationships between Sep-AD, dependent personality score, general personality dimensions and three additional anxiety disorders. Results The dependent personality score was strongly associated with Sep-AD and the other anxiety disorders in models adjusted for age at interview, age at onset of OC symptoms and worst ever OCD severity score. Several general personality dimensions, especially neuroticism, extraversion and conscientiousness, were also related to Sep-AD and the other anxiety disorders. Sep-AD was not independently related to these anxiety disorders, in multivariate models including general personality and dependent personality disorder scores. Conclusions The results suggest that Sep-AD in childhood and these other anxiety disorders in adulthood are consequences of dependent personality disorder (for agoraphobia and panic disorder) or introversion (for social phobia). It is unknown whether these results would be similar in a non-OCD sample. Copyright © 2015 John Wiley & Sons, Ltd.
Evidence for sex differences in cardiovascular aging and adaptive responses to physical activity

There are considerable data addressing sex-related differences in cardiovascular system aging and disease risk/progression. Sex differences in cardiovascular aging are evident during resting conditions, exercise, and other acute physiological challenges (e.g., orthostasis). In conjunction with these sex-related differences—or perhaps even as an underlying cause—the impact of cardiorespiratory fitness and/or physical activity on the aging cardiovascular system also appears to be sex-specific. Potential mechanisms contributing to sex-related differences in cardiovascular aging and adaptability include changes in sex hormones with age as well as sex differences in baseline fitness and the dose of activity needed to elicit cardiovascular adaptations. The purpose of the present paper is thus to review the primary research regarding sex-specific plasticity of the cardiovascular system to fitness and physical activity in older adults. Specifically, the paper will (1) briefly review known sex differences in cardiovascular aging, (2) detail emerging evidence regarding observed cardiovascular outcomes in investigations of exercise and physical activity in older men versus women, (3) explore mechanisms underlying the differing adaptations to exercise and habitual activity in men versus women, and (4) discuss implications of these findings with respect to chronic disease risk and exercise prescription.
Conclusion: the powers of ignorance: on finding out what to do next

This afterword places the three articles in the context of recent developments in the anthropology of knowledge as it relates to sociability. The articles illustrate again that sociability is more a matter of finding out what is happening, and then doing something about it, than a matter of applying earlier knowledge. The papers are part of a movement in anthropology with roots in the work of people like Garfinkel, Ranciere, de Certeau, Lave, etc. In various ways they focused our attention on the matters that appear in the three papers included here: the acknowledgment of ignorance is always productive, though what is done next can be quite dangerous for many of those involved. Furthermore, the learning that participation produces soon reveals itself insufficient and a new form of ignorance. In all events, ignorance leads to social interaction in all its modalities. Ignorance is not a barrier to sociability.
A second generation linear low voltage BiCMOS OTA

A multiple-output linear BiCMOS operational transconductance amplifier (OTA) with independent gain control on each output, approximately constant bandwidth and input range and low supply requirements is introduced. Experimental and simulated results verifying the operation of the OTA are presented. >
Thin-plate splines for printer data interpolation

Thin-plate spline models have been used extensively for data-interpolation in several problem domains. In this paper, we present a tutorial overview of their theory and highlight their advantages and disadvantages, pointing out specific characteristics relevant in printer data interpolation applications. We evaluate the accuracy of thin-plate splines for printer data interpolation and discuss how available knowledge of printer's physical characteristics may be beneficially exploited to improve performance.
Fatal hemorrhagic pneumonia concomitant with Chlamydia pneumoniae and parainfluenza virus 4 infection.

Abstract Context.—Cases of fatal hemorrhagic pneumonia need to be investigated for highly contagious viral causes. While not all hemorrhagic pneumonias are caused by very contagious agents, the etiology must be correctly determined in order to administer appropriate patient care. Objective.—To determine whether chlamydia, paramyxovirus, or mycoplasma was the causative agent in a case of fatal hemorrhagic pneumonia, and to evaluate the possibility that this was the first case of hantavirus pulmonary syndrome in Illinois. Design.—Nonroutine virological and molecular analyses were performed on lung tissue taken during an unrestricted autopsy of a patient who died in 2002. Setting and Patient.—An elderly, male, Chicago-area resident with a 3-week history of nonspecific, mild upper respiratory tract infection was admitted for hospital treatment of the respiratory infection and viral myositis without cardiac involvement. The patient became febrile, hypoxic, developed hemorrhagic pneumonia, and died. Because he ...
Metabolism of Nω-methylserotonin, a serotonergic constituent of black cohosh (Cimicifuga racemosa, L. (Nutt.)), by human liver microsomes

The roots/rhizomes of black cohosh (Cimicifuga racemosa L. (Nutt.) (syn. Actaea racemosa L.) have been used traditionally by Native Americans to treat colds and rheumatism as well as for alleviating menopausal symptoms such as hot flashes (McKenna et al., 2001). Because of health risks associated with hormone replacement therapy (Rossouw et al., 2002), black cohosh preparations are popular among women seeking alternative treatments for menopausal complaints (Mahady et al., 2003). Extensive preclinical and clinical investigations have provided conflicting evidence regarding the efficacy of black cohosh for relieving hot flashes (Borrelli and Ernst, 2008). While early studies suggested that black cohosh extracts were effective in reducing the frequency and intensity of hot flashes among perimenopausal and postmenopausal women (Frei-Kleiner et al., 2005; Kronenberg and Fugh-Berman, 2002; Osmers et al., 2005; Wuttke et al., 2003), recent trials including double-blind placebo-controlled studies demonstrated no vasomotor symptom benefits (Geller et al., 2009; Jacobson et al., 2001; Liske et al., 2002; Newton et al., 2006). The mechanism(s) of action of black cohosh is still a matter of intense research. Several in vitro and in vivo studies have established that black cohosh extracts are not estrogenic (Liske et al., 2002; Liu et al., 2001; Onorato and Henion, 2001; Overk et al., 2008; Ruhlen et al., 2007). A serotonergic hypothesis was put forward by our group after it was found that crude extracts of black cohosh acted as partial agonists of serotonin 5-HT1A and 5-HT7 receptors (Burdette et al., 2003). Subsequent bioassay-guided fractionation studies identified Nω-methylserotonin (Nω-MeSer) as a potent agonist of the serotonin receptors 5-HT1A and 5-HT7 with IC50 values of 2 and 0.02 nM, respectively (Powell et al., 2008). This compound also exhibited potent selective serotonin reuptake inhibition activity with an IC50 value of 490 nM. Because of the significance of Nω-MeSer as a potential active ingredient in black cohosh, it is of interest to understand its human metabolism, bioavailability and pharmacokinetics. In this study, we investigated the in vitro metabolism of Nω-MeSer using pooled human liver microsomes. The metabolites were identified by using liquid chromatography-tandem mass spectrometry (LC-MS) and by comparison with authentic standards.
Genetic Research in Schizophrenia: New Tools and Future Perspectives

Genetically, schizophrenia is a complex disease whose pathogenesis is likely governed by a number of different risk factors. While substantial efforts have been made to identify the underlying susceptibility alleles over the past 2 decades, they have been of only limited success. Each year, the field is enriched with nearly 150 additional genetic association studies, each of which either proposes or refutes the existence of certain schizophrenia genes. To facilitate the evaluation and interpretation of these findings, we have recently created a database for genetic association studies in schizophrenia ("SzGene"; available at http://www.szgene.org). In addition to systematically screening the scientific literature for eligible studies, SzGene also reports the results of allele-based meta-analyses for polymorphisms with sufficient genotype data. Currently, these meta-analyses highlight not only over 20 different potential schizophrenia genes, many of which represent the "usual suspects" (eg, various dopamine receptors and neuregulin 1), but also several that were never meta-analyzed previously. All the highlighted loci contain at least one variant showing modest (summary odds ratios approximately 1.20 [range 1.06-1.45]) but nominally significant risk effects. This review discusses some of the strengths and limitations of the SzGene database, which could become a useful bioinformatics tool within the schizophrenia research community.
Presence of a carcinoma‐associated antigen(s) in the spent chemically defined medium of a human colon carcinoma cell line

The human colon carcinoma cell line HT-29 was adapted to grow in chemically defined medium (CDM). The spent CDM (S-CDM) was concentrated by Amicon filtration and the crude HT-29 S-CDM purified by 40% saturated(NH4)2 SO4 precipitation. The purified antigen was tested by a micro-complement fixation (MCF) assay against the sera of cancer patients of various histologic types and against the sera of normal donors. Fifteen of 20 (75%) colon cancer, 16/20 (80%) breast cancer sera, 14/19 (74%) lung cancer sera, and 13/20 (65%) miscellaneous carcinoma sera were positive in the MCF. By contrast, 2/21 (10%) melanoma sera, 7/20 (35%) sarcoma sera, and 2/19 (11 %) normal sera were positive. These data suggest the presence of a carcinoma-associated antigen in the spent CDM of the HT-29 colon carcinoma cell line adapted to grow in CDM.
Endothelin Expression and the Progression of Heart Failure Exemplifying the Vagaries of Therapeutic Development

Increased expression of endothelin (ET)–1 has been well described in heart failure and has been thought to potentiate the progression of this disorder through hemodynamic effects as well as vascular and cardiac remodeling.1,2 Investigations of heart failure animal models3,4 as well as early clinical studies5–7 supported a potential beneficial effect of ET-1 blockade in heart failure. On the basis of these observations, it is surprising that larger-scale clinical trials failed to support the value of chronic endothelin receptor blockade in reducing symptoms or adverse clinical outcomes for patients with heart failure.8,9 In fact, there was evidence for harm, in part mediated through increased fluid retention. The study by Schirger et al10 in this issue provides us with important new insights into the role of ET-1 in the progression of cardiovascular remodeling to clinical heart failure. This study also reminds us of the caution required in navigating the complex road from a partial understanding of pathophysiology to achieving clinical benefit through pharmacological intervention. See p 249 Schirger et al10 observe, first, that during a phase of “transition” from experimental ventricular remodeling and dysfunction to the earliest signs of sodium retention, ET-1 expression is upregulated, without evidence of either systemic or tissue activation of the renin-angiotensin system (RAS). Second, they find that blockade of the ETA receptor in the presence of experimental heart failure produced no improvement in sodium excretion but increased plasma renin activity (PRA) and further increased plasma ET-1. In adding to our understanding of the complexity of interactions between endothelin and other neurohormonal systems in mediating structural and functional manifestations of progressive heart failure, the …
The Zen of quality improvement: the waves and the tide form a unity

Multiple problems arise when the logic of the randomised controlled trial (RCT) is used to dismiss the success of an intervention when measurable improvement occurs in the intervention groups but an equivalent improvement also occurs in the control groups. When groups both inside and outside a programme improve over the same period to the same degree according to an assigned metric, there is a secular trend that may exhibit the features of what Chen et al 1 label a ‘rising tide’. But when organisations in the control groups improve just as much as those that are the subject of targeted interventions, how do we know any intervention was necessary? The rising tide phenomenon presents a confusion, a contradiction and a conundrum for logic model of the RCT, since it is constructed to eliminate bias by blinding both the researcher and subjects as to who has been randomised to the treatment arm and who the control arm, and assumes as well that the control group's data will not be contaminated by the intervention. Quality improvement programmes, as Chen et al point out, are very different. They are rarely introduced into a vacuum; rather, they are introduced into fields …
Enhanced detection of EGFR mutations in plasma from non-small cell lung cancer (NSCLC) patients using Scorpion primers

7682 Background: Activating epidermal growth factor receptor (EGFR) mutations identified in NSCLC patient tumors are often associated with rapid and profound response to EGFR tyrosine kinase inhibi...
Microcavity vacuum-field configuration and spontaneous-emission power

Vacuum-electromagnetic-field modes in microcavities are redistributed and renormalized, and hence the pattern and the rates of the spontaneous emission are modified. Consequently, the conventional technique for calculating cavity spontaneous- emission power based on the scalar (isotropic) energy mode density formalism is not applicable to vertical-cavity lasers (VCLs). A comprehensive model for spontaneous emission from three-dimensional dielectric microcavities is dearly needed. Such a model must account for radiation intensity along both axial and lateral emission directions. The utility of such a model is greatly enhanced if it is primarily analytical in its formalism and can quantitatively predict the measured intensities. This paper presents the development of the above prescribed model and compares its predictions to the experimental data from air-post index-guided VCLs, for which both axial and lateral spontaneous-emission intensities can be readily measured.
Polytobacco Use of Cigarettes, Cigars, Chewing Tobacco, and Snuff Among US Adults

Author(s): Sung, Hai-Yen; Wang, Yingning; Yao, Tingting; Lightwood, James; Max, Wendy | Abstract: IntroductionTobacco use prevalence has been commonly estimated on a product by product basis and the extent of polytobacco use among current users of each tobacco product is not well understood. This study aimed to examine the prevalence, trends, and correlates of polytobacco use among current users of cigarettes, cigars, chewing tobacco, and snuff in US adults aged ≥18.MethodsWe used pooled data from the 1998, 2000, 2005, and 2010 Cancer Control Supplements of the National Health Interview Survey (N = 123 399 adults). Multivariate logistic regression models were estimated to determine significant factors associated with polytobacco use.ResultsIn 2010, the prevalence of polytobacco use was 8.6% among current cigarette smokers, 50.3% among current cigar users, 54.8% among current chewing tobacco users, and 42.5% among current snuff users. After controlling for other covariates, gender and race/ethnicity did not show consistent associations with poly-use across these four groups of current tobacco users; however, a positive association of young adulthood, less than high school education, and binge drinking with poly-use was consistently found among all these groups.ConclusionsPolytobacco use is extremely popular among current users of non-cigarette tobacco products. Polytobacco use patterns differ across sociodemographic subpopulations, and the gender and racial/ethnic profiles in poly-users vary across different groups of current tobacco users. Tobacco control strategies need to consider the interrelationships in the use of different tobacco products and the diverse profiles of poly-users in order to develop tailored tobacco prevention and intervention policies to further reduce the burden of tobacco use.
Ground Target Localization and Tracking in a Riverine Environment from a UAV with a Gimbaled Camera

This paper develops a framework for ground target localization and tracking in a riverine environment from a UAV with a two axis gimbaled camera. Accurately determining the position of targets is a critical technology for reconnaissance, cooperative multi-vehicle formation operation, and path-planning through hostile environments. We assume that the UAV is operating in a riverine environment, which implies that the altitude of the target is a known constant. This simplification removes the range ambiguity, and target positions can be uniquely determined from pixel coordinates in a single image. An extended Kalman filter (EKF) and an unscented Kalman filter (UKF) are developed to localize the inertial position of a target identified by pixel coordinates in an image. In Monte Carlo simulations, the performance of the filters is virtually identical, and localization accuracy is limited by uncertainty in the aircraft position and orientation. Flight test results verify the performance of the target localization filters. In addition, an estimation-based approach is used to develop a gimbal control law that drives the target to the center of the camera field of view. In combined simulations with the EKF, the control law maintains the target in the center of the camera field of view while tracking a moving target from a maneuvering aircraft.
Enhancing the Interfacial Bond Strength of Lignocellulosic Fiber Dispersed in Synthetic Polymer Matrices

Wood-plastic composites have been produced utilizing a phenol-formaldehyde pretreatment of the wood. The use of additives to cross link the plastics and increase the interfacial bond between the wood and plastic were also investigated. These preliminary results suggest that pretreatment of the wood with a thermosetting resin may increase the stiffness of the composite. The use of an octylphenol as a plastic compatabilizer did not reliably increase stiffness in this system, although additional study is warranted. An interaction between the wood and the polystyrene in the plastic mixture may be indicated.
The Development of a Human Gait Model With Predictive Capability and the Simulation of Able-Bodied Gait

The development of current prostheses and orthoses typically follows a trial and error approach where the devices are designed based on experience, tried on human subjects and then redesigned iteratively. This design approach is costly, risky and time consuming. A predictive human gait model is desired such that prostheses can be virtually tested so that their performance can be predicted qualitatively, the cost can be reduced, and the risks can be minimized. The development of such a model is explained in this paper. The developed model includes two parts: a plant model which represents the forward dynamics of human gait and a controller which represents the central nervous system (CNS). The development of the plant model is explained in a different paper. This paper focuses on the control algorithm development and able-bodied gait simulation. The controller proposed in this paper utilizes model predictive control (MPC). MPC uses an internal model to predict the output in advance, compare the predicted output to the reference, and optimize control input so that the error between them is minimal. The developed predictive human gait model was validated by simulating able-bodied human gait. The simulation results showed that the controller is able to simulate the kinematic output close to experimental data.Copyright © 2015 by ASME
Geometry Preparation for High School Mathematics Teachers

The high rate of return in the survey of colleges and universities was interpreted as an indication of interest in and concern for the problem of teacher preparation in geometry. at the same time t...
Pulmonary reactions to drugs

Reactions to drugs may take many forms, most commonly skin and gastrointestinal reactions. Often forgotten are the pulmonary toxic effects, which can be devastating. Unfortunately, treatment of many of these iatrogenically produced diseases is unsatisfactory. Supportive pulmonary care and corticosteroids, in some cases, are the major modalities of therapy. The physician must be aware of the serious pulmonary consequences of many commonly used agents. Judicious use of these drugs coupled with careful pulmonary monitoring will prevent serious toxicity.
Where Are Limits Needed in Calculus

A method introduced in the 17th century by Descartes and van Schooten for finding tangents to classical curves is combined with the point-slope form of a line in order to develop the differential c...
Esophageal and Colon Changes in Myotonia Dystrophica

Myotonia dystrophica is a rare cause of gastrointestinal dilation and abnormal peristalsis. This disease entity should be considered in any instance of esophageal and colon dilation of adult onset in which no obvious congenital, inflammatory, obstructive, metabolic, or iatrogenic etiology can be found. A case of megacolon associated with abnormal esophageal motility that resulted from myotonia dystrophica in a 21-year-old man is described, and the differential ro- entgenographic diagnosis is reviewed. This case is unique in that signs and symptoms of megacolon were the first indication of myotonia dystrophica.
Functional Forms of Optimum Spoofing Attacks for Vector Parameter Estimation in Quantized Sensor Networks

Estimation of an unknown deterministic vector from quantized sensor data is considered in the presence of spoofing attacks, which alter the data presented to several sensors. Contrary to the previous work, a generalized attack model is employed which manipulates the data using transformations with arbitrary functional forms determined by some attack parameters whose values are unknown to the attacked system. For the first time, necessary and sufficient conditions are provided under which the transformations provide a guaranteed attack performance in terms of Cramer–Rao Bound (CRB) regardless of the processing the estimation system employs, thus defining a highly desirable attack. Interestingly, these conditions imply that, for any such attack when the attacked sensors can be perfectly identified by the estimation system, either the Fisher information matrix (FIM) for jointly estimating the desired and attack parameters is singular or that the attacked system is unable to improve the CRB for the desired vector parameter through this joint estimation even though the joint FIM is nonsingular. It is shown that it is always possible to construct such a highly desirable attack by properly employing a sufficiently large dimension attack vector parameter relative to the number of quantization levels employed, which was not observed previously. To illustrate the theory in a concrete way, we also provide some numerical results which corroborate that under the highly desirable attack, attacked data are not useful in reducing the CRB.
Chemical and isotopic changes in Williston Basin brines during long-term oil production: An example from the Poplar dome, Montana

Brine samples were collected from 30 conventional oil wells producing mostly from the Charles Formation of the Madison Group in the East and Northwest Poplar oil fields on the Fort Peck Indian Reservation, Montana. Dissolved concentrations of major ions, trace metals, Sr isotopes, and stable isotopes (oxygen and hydrogen) were analyzed to compare with a brine contaminant that affected groundwater northeast of the town of Poplar. Two groups of brine compositions, designated group I and group II, are identified on the basis of chemistry and 87Sr/86Sr ratios. The solute chemistry and Sr isotopic composition of group I brines are consistent with long-term residency in Mississippian carbonate rocks, and brines similar to these contaminated the groundwater. Group II brines probably resided in clastic rocks younger than the Mississippian limestones before moving into the Poplar dome to replenish the long-term fluid extraction from the Charles Formation. Collapse of strata at the crest of the Poplar dome resulting from dissolution of Charles salt in the early Paleogene probably developed pathways for the ingress of group II brines from overlying clastic aquifers into the Charles reservoir. Such changes in brine chemistry associated with long-term oil production may be a widespread phenomenon in the Williston Basin.
Prevention is better: the case of the underutilized failure mode effect analysis in patient safety.

Prospective hazard analysis methodologies, like failure modes and effects analysis (FMEA), have been tried and tested in the engineering industry and are more recently gaining momentum in healthcare. Considering FMEA’s evidence based successes, this commentary makes the case that healthcare is underutilizing the methodology by relying on retrospective hazard analysis. Healthcare leaders should determine where prospective hazard analysis principles could be better built into care delivery planning and processes that will enhance patient safety.
Orthostatic Edema: Clinical Features

Orthostatic edema is a disorder seen mainly if not exclusively in females. This fact may or may not be related to ovarian function; although orthostatic edema seldom, if ever, becomes evident before puberty, it frequently persists after the menopause or after bilateral oophorectomy. In fact, the disorder first became evident after the menopause in 13 (7.8%) of our patients (see Appendix I, patients #4, 27, 30, 43, 68, 73, 85, 94, 97, 117, 131, 142, and 155). On the other hand, orthostatic edema is clearly affected by changes in the physiology of the reproductive organs of women, since it commonly appears to start with or to be aggravated by premenstrual fluid retention, and it frequently begins during pregnancy, as it did in 24 of 153 patients (16%) (identified as P in the symptoms column in Appendix I).