cssi/SciSciGPT-SciSciNet huggingface dataset:
Stable and reproducible transgene expression independent of proliferative or differentiated state using BAC TG-EMBED.

Reproducible and stable transgene expression is an important goal in both basic research and biotechnology, with each application demanding a range of transgene expression. Problems in achieving stable transgene expression include multi-copy transgene silencing, chromosome-position effects, and loss of expression during long-term culture, induced cell quiescence, and/or cell differentiation. Previously, we described the “BAC TG-EMBED” method for copy-number dependent, chromosome position-independent expression of embedded transgenes within a BAC containing ~170 kb of the mouse Dhfr locus. Here we demonstrate wider applicability of the method by identifying a BAC and promoter combination that drives reproducible, copy-number dependent, position-independent transgene expression even after induced quiescence and/or cell differentiation into multiple cell types. Using a GAPDH BAC containing ~200 kb of the human GAPDH gene locus and a 1.2 kb human UBC promoter, we achieved stable GFP-ZeoR reporter expression in mouse NIH 3T3 cells after low-serum-induced cell cycle arrest or differentiation into adipocytes. More notably, GFP-ZeoR expression remained stable and copy-number dependent even after differentiation of mouse ESCs into several distinct lineages. These results highlight the potential use of BAC TG-EMBED as an expression platform for high-level but stable, long-term expression of transgene independent of cell proliferative or differentiated state.
Functions and the IF Statement

This chapter describes the functions and the IF statements. When a function appears in an expression in FORTRAN, the argument of the function is evaluated first. Then, the function itself is evaluated. If there is more than one function in an expression, the functions are evaluated from left to right. Finally, the remaining operations in the expression are evaluated according to their priorities. A function can be used in an expression in the same manner as a variable. The FLOAT function floats the value of its argument, and, therefore, allows the use of its argument in a REAL expression. The IFIX function allows the use of a REAL constant or variable in an expression involving INTEGERS. However, IFIX first truncates the value of its argument. In a program, calculating the polynomial for many sets of data, the execution of the statements in the loop continues until the last data card is processed. The chapter discusses a statement called the logical IF that enables to terminate a loop from within the program.
Renin-Angiotensin System Proteases and the Cardiometabolic Syndrome: Pathophysiological, Clinical and Therapeutic Implications

Obesity, Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Disease (CVD) are worldwide leading causes of morbidity and mortality. Once considered as separate metabolic and hemodynamic/cardiovascular entities respectively, it has become nowadays clear that the relationship between these conditions is not coincidental, and has common pathophysiological features that allows considering both obesity and T2DM as part of the cardiovascular diseases spectrum. Furthermore, from a clinical standpoint it is also clear that cardiovascular risk factors seldom are isolated findings, but frequently present as a clustering of different conditions, including abnormalities in blood pressure, body weight, glucose homeostasis and albuminuria. The tendency of CVD risk factors to cluster has been described in the medical literature since the decade of 1920s (Avogaro et al 1967). However, the concept of Cardiometabolic Syndrome (CMS) is still evolving, and makes reference to a group of cardiovascular /metabolic risk factors, including hypertension (HTN), dysglycemia, atherogenic dyslipidemia, albuminuria and obesity, which confer an excess high risk for CVD than its individual components. Several names have been given to the condition, including Syndrome X, Dysmetabolic Syndrome, Insulin Resistance Syndrome, Metabolic Syndrome and more recently Cardiometabolic Syndrome. In addition, numerous worldwide organizations have described the CMS and have used different definition criteria, which take into account the current epidemiologic, clinic and pathophysiological evidence available about the condition. These include the National Cholesterol Education
McKinney v. Saviego

In McKinney v. Saviego, the US Supreme Court concluded that the 1848 Treaty of Guadalupe Hidalgo, which ended the US-Mexican War, did not protect the property rights of Pilar Saviego, the heir of a Mexican landowner who fled Texas shortly after the outbreak of hostilities between Mexico and Texas insurrectionists, but before Texas declared its independence in 1836. The landowner’s departure, the Court said, constituted an abandonment of her property, and under Texas law she could not bequeath it to her daughter, also a Mexican citizen. The Court ruled that, because Texas was already a US state at the time the 1848 Treaty was signed, it was not one of the “territories” to which the treaty provisions protecting the rights of Mexican landowners applied.The case is one of many examples of the federal courts construing ambiguous provisions in the Treaty of Guadalupe Hidalgo in ways that benefited Anglo land claimants while leading to the alienation of the property rights of Mexican landholders. The case is also a profound illustration of some of the ways in which US policy makers at the time took a treaty intended to protect the property rights of Mexican landholders and, through the Senate ratification process, eliminated core protections. This diluted version of the Treaty would later enable the federal judiciary in McKinney v. Saviego and many other cases to interpret its provisions in ways that resulted in the displacement of scores of Mexicans from their lands, thus returning such property to the public domain and fulfilling the United States’ Manifest Destiny. As Guadalupe Luna has pointed out, this alienation of Chicanos/Chicanas from their property transformed many Mexican Americans from landholders into dispossessed farmworkers.
Conversions of Methane to Synthesis Gas over Co/γ-Al2O3 by CO2 and/or O2

The goal of the paper was to investigate the effect of the catalyst precursor on the catalytic activity. For this reason, the structure, the reducibility and the reaction behavior of γ-Al2O3-supported Co (24 wt%) catalysts as a function of calcination temperature (Tc) were investigated using X-ray diffraction, temperature-programmed reduction, CO chemisorption, pulse reaction with pure CH4, and the catalytic reactions of methane conversion to synthesis gas. Depending on Tc, one, two, or three of the following Co-containing compounds, Co3O4, Co2AlO4, and CoAl2O4, were identified. Their reducibility decreased in the sequence: Co3O4>Co2AlO4>CoAl2O4. Co3O4 was generated as a major phase at a Tc of 500°C and Co2AlO4 and CoAl2O4 at a Tc of 1000°C. The reduced Co/γ-Al2O3 catalysts, obtained via the reduction of the 500 and 1000°C calcined catalysts, provided high and stable activities for the partial oxidation of methane and the combined partial oxidation and CO2 reforming of methane. They deactivated, however, rapidly in the CO2 reforming of methane. Possible explanations for the stability are provided.
Superplastic Deformation of CuO-Doped 3Y-TZP

The superplastic deformation of ceramics has been the subject of much study since Wakai et al.1 demonstrated in 1986 that yttria stabilized tetragonal zirconia polycrystals (Y-TZP) could be deformed superplastically in tension. Many other ceramics have since been found to deform superplastically,2 although Y-TZP is particularly well suited for superplastic deformation due to its inherently slow grain growth at typical deformation temperatures. A grain size below 1 µm is a critical requirement for superplastic deformation in ceramics.
Schedule and magnitude of reproductive investment under immune trade-offs explains sex differences in immunity

Sex differences in immunity are found in many species. Known immune mechanisms in birds and mammals suggest that pathogen detection may be amplified in females, whereas in males, pathogen killing is amplified. We show that these immunological profiles emerge as distinct peaks on a fitness landscape defined by sensitivity-specificity and infection-immunopathology immune tradeoffs. What selection pressures might drive males and females towards separate peaks? Surprisingly, modeling immune trade-offs alone results in a pattern of sex differences that is the reverse of what is observed. By integrating these trade-offs into a life-history framework, where the schedule and magnitude of reproductive investment differs between the sexes, we find that increased age-specific infection and mortality risks during parental investment can push females towards the peak that aligns with empirical observations. Overall, our model suggests enhanced pathogen detection (in females) versus enhanced pathogen killing (in males) is best explained if shared immune tradeoffs interact with sex-specific reproductive schedules and risks. We suggest ways to test this framework empirically.
Summary on DHM Methods

In this work, the combination of optical methods, mainly based on holographic principles for marker-free imaging, real-time trapping, identification and tracking of micro objects is investigated. Therefore, first an overview of Digital Holographic Microscopy (DHM) and holographic optical tweezers as well as non diffracting beam types is given for minimal-invasive, real-time and marker free imaging of micro and nano objects.
Corynebacterium striatum prosthetic valve endocarditis with severe aortic regurgitation successfully treated with transcatheter aortic valve replacement.

We describe the case of a 69-year-old man with a history of bioprosthetic aortic valve replacement who presented with Corynebacterium striatum prosthetic valve endocarditis (PVE) complicated by severe aortic insufficiency with refractory cardiogenic shock despite antibiotic therapy. He was considered a prohibitive-risk surgical candidate due to co-morbid conditions and off-label valve-in-valve transcatheter aortic valve replacement (TAVR) was performed after detailed multidisciplinary evaluation. He recovered well without recurrent infection following completion of antibiotics and transthoracic echocardiogram at 12 months showed a normal functioning prosthetic valve. To our knowledge, this is the first reported case of native or PVE treated with TAVR.
Effect of Stress Biaxiality on the Transverse Tensile Strain-to-Failure of Composites

Thermoplastic matrices are now available with neat resin strain-to-failure values of up to 100%. These high strain-to-failure values could be expected to result in dramatically higher transverse strain-to-failure values in thermoplastic composites than epoxy composites. However, measurements of the transverse strain-to-failure of some thermoplastic composites have revealed only a modest increase in transverse strain capability. The objective of this work was to show that the matrix is biaxially stressed in a transverse tension test and that this significantly reduced strain-to-failure values. To accomplish this objective, a specimen configuration was designed to introduce biaxial stresses into the neat resin. Data was generated on polyetheretherketone and polycarbonate, both ductile thermoplastics. Test results showed that biaxial stresses reduced the strain-to-failure of these materials by well over an order of magnitude. Thus, this work shows that, while a thermoplastic matrix's ductility may translate into composite toughness and delamination resistance, it does not necessarily translate into dramatically increased composite transverse strain-to-failure values.
Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases

ABSTRACT Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients.
Student knowledge and confidence with prescribing hormonal contraception.

Abstract Introduction Pharmacists' scope of practice has expanded in several states to include independently prescribing and dispensing hormonal contraceptive products. The objective of this research was to assess student knowledge and confidence with prescribing hormonal contraception following a simulated patient case activity. Methods This was a descriptive, exploratory, nonexperimental study utilizing educational assessments and survey data from second professional year students during the 2017 to 2018 and 2018 to 2019 academic years. Student performance was assessed using a five-question readiness assurance test at the beginning of class, documented patient assessment and plan, and five-question post-activity quiz. Student confidence with interpreting legal regulations and following protocol instructions, performing a patient assessment, prescribing an appropriate contraceptive product, and providing verbal and written communication to patients and providers was assessed using a nine-question survey at the end of class. Results Average student performance was consistent on the readiness assurance test between the two years. Students scored an average of 84.2% and 91.6% on the documented assessment and plan and 96.4% and 91.2% on the post-activity quiz for each year, respectively. Students felt most confident with navigating and interpreting a prescription drug formulary, providing the patient with written documentation, and communicating with the patient's prescriber. Students were less confident with selecting an appropriate product based on patient-specific factors and providing education on missed doses. Conclusions This case-based activity demonstrated student knowledge and confidence with prescribing hormonal contraceptives.
Navigating a Traditionally Male-Dominated Specialty as a Woman

In our current, fast-paced society, the terms “work-life balance” and “burnout” have become a part of our daily vernacular. This chapter specifically addresses the challenges faced by women navigating traditionally male-dominated careers and the importance of recognizing the impact gender inequality has on the female workforce. Lastly, suggestions are offered as we strive for gender parity in the workplace.
Constraining Implicit Space with Minimum Description Length: An Unsupervised Attention Mechanism across Neural Network Layers

Inspired by the adaptation phenomenon of neuronal firing, we propose the regularity normalization (RN) as an unsupervised attention mechanism (UAM) which computes the statistical regularity in the implicit space of neural networks under the Minimum Description Length (MDL) principle. Treating the neural network optimization process as a partially observable model selection problem, UAM constrains the implicit space by a normalization factor, the universal code length. We compute this universal code incrementally across neural network layers and demonstrated the flexibility to include data priors such as top-down attention and other oracle information. Empirically, our approach outperforms existing normalization methods in tackling limited, imbalanced and non-stationary input distribution in image classification, classic control, procedurally-generated reinforcement learning, generative modeling, handwriting generation and question answering tasks with various neural network architectures. Lastly, UAM tracks dependency and critical learning stages across layers and recurrent time steps of deep networks.
Racial/ethnic and gender inequalities in third grade children’s self-perceived STEM competencies

Studies have sought to understand the underrepresentation of women and racial/ethnic minority groups in STEM, but less attention has been paid to primary school students. Using data from a national...
Sexual Minority Women of African Descent

Women of African descent who are same gendered loving represent a broad and diverse group. As such, in doing research on the population or providing services to them, the cultural context and social positions of the women’s experiences is significant. The cultural context may impact how the women desire to be labeled or identified, or perhaps not identified by a label at all. More research into this area is necessary, particularly to expand upon the gendered structure of labeling, dating, and sexual expression that has been found to exist among some Black urban lesbians. Thus far, research has demonstrated consistency in identity labeling for the cities of Chicago and New York (Wilson, 2009; Moore, 2006); obtaining information about Black lesbians of other cities would also enrich the literature. Also, some women will clearly reflect life outcomes of positive marginality that are worthy of empirical investigation, such that more can be learned about women at the margins who have successfully integrated and embraced all aspects of themselves. Empirical investigations into Black lesbian mother-daughter relationships, with a goal of understanding how the women’s relationships with their mothers may impact their psychological development and interpersonal relationships, is valuable. Greene’s attention to the use of psychodynamic perspectives in work with Black lesbians is also summarized here. Unfortunately, there is still relatively limited empirical research available on Black sexual minority women, and even moreso for those residing outside of the United States, thus the research presented here on Black Cuban lesbians is illuminating.
GIS uses and constraints on diffusion in Eastern European and the former USSR.

A team of American specialists, headed by a prominent human/political geographer, examines the emerging uses of geographic information systems (GIS) in Eastern Europe and the former USSR as well as constraints to their further dissemination. The paper, based on a communications survey, conference participation, and local sources, devotes particular attention to GIS applications in planning and services delivery and to variable rates of adoption of GIS technology in the region, as documented in a table of public-sector applications compiled by the authors. Factors limiting the utility of traditional innovation-diffusion models in understanding current patterns are identified. Journal of Economic Literature, Classification Numbers: C80, O31, O32. 2 figures, 2 tables, 64 references.
Isolation and characterization of a 58-kDa membrane- and microfilament-associated protein from ascites tumor cell microvilli.

Abstract A 58-kDa protein is found in microvilli and in actin-containing transmembrane complexes of 13762 ascites tumor cells with immobile surface receptors; it is absent from sublines with mobile receptors. 58-kDa protein has been proposed to stabilize microvilli and restrict receptor mobility by stabilizing membrane-microfilament interactions. Antibodies against 58-kDa protein were blot-purified from antisera of rabbits injected with crude transmembrane complex and were used to monitor purification of the protein. 58-kDa protein was extracted from EDTA/EGTA-stripped microvillar microfilament cores with 1 M NaCl. A single depolymerization-polymerization cycle of the microfilaments, followed by solubilization of 58-kDa protein in 1 M NaCl and chromatography on hydroxyapatite-Sephadex G-150, purified the protein to greater than 95% homogeneity. The native molecular weight and frictional coefficient indicated a monomeric, asymmetric structure. 58-kDa protein bound F-actin in pelleting assays and inhibited polymerization of pyrenyl-actin. It also bound phosphatidylserine, phosphatidylinositol, and phosphatidylcholine vesicles in pelleting studies. Immunoblot analyses of endogenously and exogenously proteolyzed microvilli and their membranes and microfilament cores showed specific membrane and microfilament binding fragments of 28-30 kDa. The microfilament- and phospholipid-binding properties of 58-kDa protein and the localization of its proteolysis products are consistent with its proposed role in stabilizing membrane-microfilament interactions in the ascites cell microvilli.
Robust Registration of Aerial Image Sequences

We describe techniques for registering images from sequences of aerial images captured of the same terrain on different days. The techniques are robust to changes in weather, including variable lighting conditions, shadows, and sparse intervening clouds. The primary underlying technique is robust feature matching between images, which is performed using both robust template matching and SIFT-like feature matching. Outlier rejection is performed in multiple stages to remove incorrect matches. With the remaining matches, we can compute homographies between images or use non-linear optimization to update the external camera parameters. We give results on real aerial image sequences.
Chapter 24 Econometric analysis of qualitative response models

Publisher Summary This chapter has surveyed the current state of econometric models and methods for the analysis of qualitative dependent variables. It discusses that the models of economic optimization that are presumed to govern conventional continuous decisions are equally appropriate for the analysis of discrete response. While the intensive marginal conditions associated with many continuous decisions are not applicable, the characterization of economic agents as optimizers implies conditions at the extensive margin and substantive restrictions on functional form. Unless the tenets of the behavioral theory are themselves under test, it is good econometric practice to impose these restrictions as maintained hypotheses in the construction of discrete response models. As a formulation in terms of latent variable models makes clear, qualitative response models share many of the features of conventional econometric systems. Thus the problems and methods arising in the main stream of econometric analysis mostly transfer directly to discrete response. Divergences from the properties of the standard linear model arise from nonlinearity rather than from discreteness of the dependent variable. Thus, most developments in the analysis of nonlinear econometric systems apply to qualitative response models. In summary, methods for the analysis of qualitative dependent variables are part of the continuing development of econometric technique to match the real characteristics of economic behavior and data.
Self-organizing dynamics for optimization

Motivated by noise-driven cellular automata models of self-organized criticality (SOC), a new paradigm for the treatment of hard combinatorial optimization problems is proposed. An extremal selection process preferentially advances variables in a poor local state. The ensuing dynamic process creates broad fluctuations to explore energy landscapes widely, with frequent returns to near-optimal configurations.
THE EARLY DIVERSIFICATION HISTORY OF DIDELPHID MARSUPIALS: A WINDOW INTO SOUTH AMERICA'S “SPLENDID ISOLATION”

The geological record of South American mammals is spatially biased because productive fossil sites are concentrated at high latitudes. As a result, the history of mammalian diversification in Amazonia and other tropical biomes is largely unknown. Here we report diversification analyses based on a time-calibrated molecular phylogeny of opossums (Didelphidae), a species-rich clade of mostly tropical marsupials descended from a Late Oligocene common ancestor. Optimizations of habitat and geography on this phylogeny suggest that (1) basal didelphid lineages inhabited South American moist forests; (2) didelphids did not diversify in dry-forest habitats until the Late Miocene; and (3) most didelphid lineages did not enter North America until the Pliocene. We also summarize evidence for an Early- to Middle-Miocene mass extinction event, for which alternative causal explanations are discussed. To the best of our knowledge, this study provides the first published molecular-phylogenetic evidence for mass extinction in any animal clade, and it is the first time that evidence for such an event (in any plant or animal taxon) has been tested for statistical significance. Potentially falsifying observations that could help discriminate between the proposed alternative explanations for didelphid mass extinction may be obtainable from diversification analyses of other sympatric mammalian groups.
Avoiding ageism at Coca‐Cola

Purpose – This article describes how Coca‐Cola Enterprises has established forward‐thinking, diverse anti‐ageism policies in order to comply with new UK legislation and achieve age positive “employer champion” status.Design/methodology/approach – Outlines the steps the company followed in order to combat ageism in all its forms.Findings – Reveals that, over the last six months, 12 percent of the people the company has recruited – mostly on the sales side of the business – are over the age of 40. Not only is the business hiring more people across the age spectrum, but also potential candidates view Coca‐Cola Enterprises as an employer focused on skills, not age.Practical implications – Deals with a topic that will become increasingly important in countries where the average age of the workforce is increasing.Originality/value – Highlights the fact that age diversity is not something that can be introduced to a company overnight. It involves a complete change in culture, with a real understanding from acros...
Genetic polymorphisms in the Hmong population: implications for cancer etiology and survival.

BACKGROUND The Hmong, an isolated, agrarian people from southern China, migrated to the mountainous regions of what are today Vietnam, Cambodia, and Laos. Minnesota has the second largest Hmong population in the United States. The authors compared frequencies of common genetic polymorphisms believed to influence risk of malignancy to determine whether frequencies in the Hmong are different from those in other Asian populations and in white Minnesotans. METHODS Genotyping for glutathione S-transferase μ1 (GSTM1), glutathione S-transferase θ1 (GSTT1), myeloperoxidase (MPO) (C−463T), nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase (NQO1) (C609T), 5,10-methylenetetrahydrofolate reductase (MTHFR) (C677T), MTHFR (A1298C), methionine synthase reductase (MTRR) (A66G), X-ray repair cross complementing 1 (XRCC1) 194 (Arg194Trp), XRCC1 280 (Arg280His), and XRCC1 399 (Arg399Gln) alleles was performed by TaqMan analysis using DNA isolated from newborn heel-stick spots provided by the Minnesota Department of Health. RESULTS The Hmong had significantly higher frequencies of the NQO1 T allele and the XRCC1 Trp polymorphism (Arg194Trp) and had significantly lower frequencies of the G allele in MTRR (A66G) and the T allele in MTHFR (C677T) compared with white Minnesotans. The Hmong also were significantly more likely to lack the GSTM1 and GSTT1 genes compared with whites (82% vs. 54% and 61% vs. 18%, respectively). Genotype frequencies were similar for MTHFR (A1298C), MPO (C−463T), and XRCC1 (Arg280His, Arg399Gln). Genotype frequencies at these loci also were compared with those reported for other Asian populations and showed notable differences between the Hmong and Chinese/Taiwanese, Korean, and Japanese populations. CONCLUSIONS The genetic differences identified have implications for both cancer etiology and prognosis in this unique population. Cancer 2004;100:411–7. © 2003 American Cancer Society.
International Debt Forgiveness and Global Poverty Reduction

This article discusses the relationship between the international debt crisis and global poverty. The author argues for an expansion of coordinated international effort, bolstered by fundamental principles of public international law, to address global poverty by substantially reducing the foreign-denominated debt owed by developing countries to modernized countries and financial institutions.
A hierarchy of clinical observations.

When I was a house officer at Boston Children9s Hospital, Herb Needleman was in great demand as a consultant for hospitalized children in emotional crisis. He was eclectic in approach, being trained in both pediatrics and child psychiatry, and down-to-earth in his recommendations. Herb also made a point of involving housestaff in his interviews and deliberations. I was repeatedly impressed by one inevitable occurrence in these interactions. Facile in our presentation of the pertinent medical history, physical findings, and laboratory tests, we would suddenly be at a complete loss for words when of person is she?" This loss of expressive function afflicted almost everyone, from medical student to senior resident to attending physician.
The Impact of Negative Life Events on Young Adolescents: Comparing the Relative Vulnerability of Middle Level, High School, and College-Age Students.

(2014). The Impact of Negative Life Events on Young Adolescents: Comparing the Relative Vulnerability of Middle Level, High School, and College-Age Students. RMLE Online: Vol. 38, No. 2, pp. 1-13.
Pulmonary immunoglobulin E levels and the response to anti-immunoglobulin E antibody therapy in paediatric severe therapy resistant asthma

Background: Omalizumab is used in children with atopic, moderate to severe persistent asthma, but predictors of response are unknown. Broncho-alveolar lavage (BAL) or endobronchial biopsy (EB) immunoglobulin E (IgE) has not been reported. It has been proposed that pulmonary IgE levels may predict response to therapy. Hypothesis: there is no relationship between serum and pulmonary IgE; and pulmonary IgE levels predict response to omalizumab. Methods: We measured IgE levels in serum, induced sputum (IS), BAL and EB in 70 children (6-16 yr) with severe asthma. 15 underwent an omalizumab trial. IgE expression was determined in EB by immunohistochemistry and levels in IS and BAL were quantified using ELISA. Haematoxylin and eosin stained EB were used to quantify airway remodelling and eosinophilic inflammation was quantified using the congo red stain. Results: 54 subjects had at least one evaluable biopsy. There was no relationship between total serum IgE and EB IgE+ cells, Spearman r=0.4739. Non-responders had higher serum IgE (failed trial: median 1582 IU/ml, range [1324 - 11355] vs. successful trial: 386 IU/ml, range [105-2438], p<0.05). EB IgE+ cells did not predict omalizumab response. There was no association between EB IgE expression and airway remodelling or eosinophilic inflammation. Conclusions: There was no relationship between serum and pulmonary IgE. Very high serum IgE levels predicted a failed response to omalizumab, but EB IgE expression was not useful in predicting a response. There was no relationship between airway remodeling, eosinophilic inflammation and EB IgE+ cells. Funding: Asthma UK.
Bronchoalveolar Lavage Neutrophilia in Asthmatic and Healthy Volunteers After Controlled Exposure to Ozone and Filtered Purified Air

Study objective To characterize the pulmonary response of asthmatic and healthy nonsmoking adult men to 0.20 ppm ozone by controlled chamber exposure. Design A prospective, crossover study of five atopic asthmatic and five normal subjects randomly exposed to ozone and filtered purified air (FPA) for 6 h, consisting of 30-min alternating periods of rest and moderate exercise. The two exposures were separated by at least 30 days. Setting A controlled exposure in a stainless steel chamber. Patients Five atopic asthmatic and five normal subjects between 18 and 45 years of age. Treatment with medications was withheld from asthmatics prior to the exposures. All subjects were nonsmokers. Interventions Symptoms were assessed throughout the exposures. Pulmonary function was measured at baseline, hourly throughout an exposure, and after an exposure. Bronchoalveolar lavage (BAL) was performed 18 h after the completion of an exposure. The BAL fluid (BALF) was analyzed for cell count and differential; the cell-free supernatant was analyzed for albumin, tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), and interleukin 8 (IL-8). Results There were statistically significant increases in IL-8 levels, as well as percent polymorphonuclear neutrophils (PMNs) and PMNs per milliliter of lavage in asthmatics exposed to ozone as compared with the same asthmatics exposed to FPA and the same normal subjects exposed to ozone and FPA. Interleukin 6 was also significantly increased in asthmatics exposed to ozone. The BALF albumin, TNF, and IL-1 levels were not significantly different among the four groups. There were no differences between asthmatics and healthy controls exposed to ozone or FPA in baseline to postexposure FEV 1 , FVC, FEV 1 /FVC, and sRaw. Conclusions We conclude that asthmatics exposed to ozone develop a significant BALF neutrophilia and increased levels of the cytokines, IL-8 and IL-6. These BALF findings occur even though the level of ozone exposure was not significant enough to reduce pulmonary function.
Rfg1, a Protein Related to the Saccharomyces cerevisiae Hypoxic Regulator Rox1, Controls Filamentous Growth and Virulence in Candida albicans

Candida albicans, the major fungal pathogen in humans, can undergo a reversible transition from ellipsoidal single cells (blastospores) to filaments composed of elongated cells attached end to end. This transition is thought to allow for rapid colonization of host tissues, facilitating the spread of infection. Here, we report the identification of Rfg1, a transcriptional regulator that controls filamentous growth of C. albicans in an environment-dependent manner. Rfg1 is important for virulence of C. albicans in a mouse model and is shown to control a number of genes that have been implicated in this process. The closest relative to Rfg1 in Saccharomyces cerevisiae is Rox1, a key repressor of hypoxic genes. However, Rfg1 does not appear to play a role in the regulation of hypoxic genes in C. albicans. These results demonstrate that a regulatory protein that controls the hypoxic response in S. cerevisiae controls filamentous growth and virulence in C. albicans. The observations described in this paper raise new and intriguing questions about the evolutionary relationship between these processes.
Semiclassical calculation of Franck-Condon intensities for reactive systems

Abstract A Filinov transformation of the initial value representation of the semiclassical propagator has been used to obtain Franck-Condon intensities for a model of the photodetachment of H 3 − → H+H 2 +e − . Resonance peak widths and heights are obtained which are in good agreement with quantum results.
Determining anchoring systems for ocean energy harvesting devices off the coast of southeast Florida

Confirmed ocean current and thermal resources off the coast of south east Florida have the potential to mitigate Florida's increasing energy needs with the deployment of marine renewable energy (MRE) technologies. Potential anchors have been selected in this work for use in mooring MRE systems in specific energy dense locations. Simulations of single point moored hydrokinetic turbines were created to extract anchor loading data for prototype to commercial sized systems enduring hurricane conditions. A basis for the environmental conditions occurring during storms with 100-year return periods was created for this location with the combination of offshore standards in the Gulf of Mexico and local maximum current measurements. High uplift angles and large vertical anchor loads of the taut moorings used in simulation create a difficult anchoring scenario in a location assumed to have stratified seafloors. As MRE systems move from prototype to commercial systems, increased drag due to increasing turbine rotor diameters create anchor loads that require anchor embedment or multiple anchor systems.
Possible impact-induced refractory-lithophile fractionations in EL chondrites

Abstract Literature data show that refractory-lithophile elements in most chondrite groups are unfractionated relative to CI chondrites; the principal exception is the EL-chondrite group whose observed falls (all of which are type 6) are depleted in Ca and light REE. In contrast, literature data and our new INAA data on EL3 PCA 91020, EL3 MAC 88136 and EL4 Grein 002 show that some replicates of these samples have nearly flat REE patterns (unlike those of EL6 chondrites); other replicates exhibit fractionated REE patterns similar to those of EL6 chondrites. Petrographic examination shows that many EL6 (and some EL3 and EL4) chondrites are impact-melt breccias or contain impact-melted portions. We suggest that the same impact processes that formed these breccias and produced melt are responsible for the observed bulk compositional fractionations in refractory-lithophile elements, i.e., EL6 chondrites were produced from initially unequilibrated EL3 material. When large amounts of impact heat were deposited, plagioclase and/or oldhamite (CaS) (the major REE carriers in enstatite chondrites) may have been melted and then transported appreciable (>10 cm) distances. EL6 chondrites represent the residuum that is depleted in REE (particularly in LREE) and Ca. Unlike the case for EL chondrites, our new INAA data on ALH 84170, EET 87746 and SAH 97096 (all EH3) show some scatter but are consistent with the EH group having uniform refractory-lithophile abundances.
High-temperature spectral emissivity of several refractory elements and alloys

Thermionic energy conversion has emerged as the method of choice for the direct space-based conversion of heat to electricity. An important parameter in the implementation of this method of direct energy conversion is the emissivity of the converter emitter and collector materials. This information is necessary to determine heat losses, heat transfer, and reservoir temperatures in the thermionic energy converter. Spectral normal emissivities were acquired at a wavelength of 0.65 ώm for a series of tungsten-rhenium alloys, tungsten-osmium alloys, and tungsten-iridium alloys in the temperature range 1400 to 2600 K. Additionally, the spectral normal emissivity for pure elements of molybdenum and ruthenium were obtained over the temperature range 1200 to 2600 K and 1400 to 2250 K, respectively. The spectral normal emissivities for a niobium-67% ruthenium (eutectic composition) in the temperature range 1400 to 2000 K were also obtained at the same wavelength. In all cases, the emissivity decreased linearly with increasing temperature. Both the tungsten-osmium and the tungsten-rhenium alloys exhibited emissivity values of 0.32 to 0.54 over the temperatures tested. The tungsten-iridium alloy yielded emissivity data of 0.35 to 0.47. The niobium-ruthenium emissivity data were within 0.34 and 0.36. The pure molybdenum and pure ruthenium experiments resulted in emissivity values ranging from 0.35 to 0.45 and 0.35 to 0.39, respectively.
WING PRODUCTION BY GROUPED AND ISOLATED APTERAE OF THE APHID MYZUS PERSICAE ON ARTIFICIAL DIET

Single and groups of plant-reared adult apterous Myzus persicae were transferred to an artificial diet and the progeny produced on subsequent days raised in groups on the diet. An enhancement in alata-production in response to interactions between the adult aphids was recorded. This would not have occurred or have been as marked if seedling hostplants (radish or mustard) had been used as larviposition and larval rearing substrates. Crowding the adult aphids at different densities and for various periods showed that relatively few contacts between them promote an increase in alata-production. Such increases are maintained for several days after the period of crowding. Isolated adults did not produce exclusively apterous progeny and their alata-production moreover increased to 80–90% after about a week on the diet despite the fact they were isolated from their progeny on a daily basis. Zusammenfassung GEFLUGELTEN-PRODUKTION VON IN GRUPPEN ODER ISOLIERT AUF KUNSTLICHER DIAT GEHALTENEN UNGEFLUGELTEN DER BLATTLAUS MYZUS PERSICAE Entweder in Gruppen oder einzeln auf Rettichkeimlingen herangezogene adulte Aptere von Myzus persicae wurden fur die Experimente an eine kunstliche Diat gesetzt und ihre taglich entnommenen Nachkommen gruppenweise mit dieser Diat aufgezogen. Als sofortige Reaktion auf die Vereinzelung war eine Steigerung der Apteren-Produktion festzustellen. Als Reaktion auf zeitweiser Gruppierung erhohte sich mit der Dauer dieses Vorganges die Geflugeltenzahl. Die Erhohung lies sich uber einige Tage nachweisen. Gruppierungsexperimente mit verschiedener Anzahl von Adulten oder fur verschieden lange Perioden zeigten, das schon relativ wenige Kontakte eine Alaten-Produktion forderten. Isolierte Adulte brachten nicht ausschlieslich ungeflugelte Nachkommen hervor und ihre Geflugelten-Produktion stieg nach einer Woche Aufenthalt auf der kunstlichen Diat daruber hinaus auf 80–90% an, auch wenn sie taglich von ihrer Nachkommenschaft getrennt wurden.
Selective downregulation of the high molecular weight form of adiponectin in hyperinsulinemia and in type 2 diabetes: differential regulation from nondiabetic subjects.

OBJECTIVE— Adiponectin is an adipocyte-specific secretory protein found in circulation in several different forms and is present at significantly lower levels in the plasma of diabetic patients compared with that of insulin-sensitive individuals. We wanted to test whether insulin per se is a contributing factor toward lower plasma adiponectin concentrations and, if so, whether the splanchnic bed contributes to this phenomenon. RESEARCH DESIGN AND METHODS— We sampled femoral artery and hepatic venous samples and measured the high–molecular weight (HMW) and low–molecular weight (LMW) fractions of adiponectin in 11 type 2 diabetic and 7 nondiabetic subjects matched for age, sex, and BMI during basal conditions and during a hyperglycemic (∼9.5 mmol/l) hyperinsulinemic (∼700 pmol/l) clamp. RESULTS— Under these conditions, total arterial adiponectin, HMW, and the ratio of HMW to total adiponectin all were lower ( P CONCLUSIONS— HMW adiponectin and the ratio of HMW to total adiponectin are lower in individuals with diabetes than in nondiabetic subjects. We conclude that HMW adiponectin is downregulated in hyperinsulinemia and type 2 diabetes.
Congress and the year 2000: Peering into the demographic future*

Some political implications of current U.S. demographic trends are explored. Five major areas of concern are identified which are "the circumstances of childrens families; the characteristics of the work force; the racial and ethnic makeup of local electorates; the aging of the population; and the populations geographic distribution." (EXCERPT)
Gangliogliomas: a clinicopathological study of 25 cases and review of the literature

The histopathological, clinical, and radiological findings in 25 patients (median age 20.5 years; range 1.7-64.2 years) with gangliogliomas were assessed to correlate degree of astrocytic anaplasia and proliferative potential with recurrence or survival. Most patients (64%) presented with seizures (median Karnofsky Performance Score 90%; range 70-100%). Computerized tomography and magnetic resonance imaging showed nonspecific abnormalities. Neoplastic ganglion cells were defined as heterotopic, irregularly grouped, or having more than one nucleus of bizarre shape or size. The astrocytic component was moderately anaplastic in 15 cases and highly anaplastic (HAA) in 10. Eight patients had gross total resection, 11 had subtotal resection, and six underwent biopsy. Ten patients (five gross total resection, three subtotal resection, two biopsy) had no further treatment, 15 underwent external irradiation, and five had adjuvant chemotherapy. Twenty-four patients are alive 15-394 weeks (median 203.5 weeks) postoperatively; one with ganglioglioma-HAA died at 65 weeks. No tumor recurred after gross total resection. Duration of preoperative symptoms 30 years at diagnosis may have increased the risk of recurrence after subtotal resection or biopsy by four, three, and two times, respectively (not significant). Bromodeoxyuridine labeling index (BUdR LI) was < 1% in eight non-recurring tumors and 1.3% in another recurring twice (second recurrence LI = 1.6%). Most patients with ganglioglioma have a good prognosis. After gross total resection, only observation is required. After subtotal resection or biopsy, recurrence is possible. BUdR labeling may guide further therapy.
Interleukin-1 beta, -1 alpha, and -6 and prostaglandins in vaginal/cervical fluids of pregnant women before and during labor

Interleukin-1 beta (IL-1 beta) is not detected in the amniotic fluid of normal human pregnancies before the initiation of parturition, but during labor, both at term and preterm, this cytokine is present in the amniotic fluid of 25-40% of pregnancies. A critical question, however, is whether this finding is indicative of a role for IL-1 beta (directly or indirectly) in the initiation of parturition or is the result of IL-1 beta formation and entry into amniotic fluid as a natural sequela of normal labor. The forebag of the amniotic sac is formed during labor in response to cervical dilatation, and on the decidual surface, the tissues of this structure become exposed and bathed by vaginal fluids as the cervix opens. Microorganisms and bacterial toxins are present in vaginal fluid before labor begins; these agents should act upon the exposed tissues of the forebag to cause inflammation and evoke an inflammatory response. This study was conducted to examine the likelihood that the inflammatory mediators foun...