cssi/SciSciGPT-SciSciNet huggingface dataset:
Prolactin negatively regulates caveolin-1 gene expression in the mammary gland during lactation, via a Ras-dependent mechanism.

Abstract Caveolin-1 is a 22-kDa integral membrane protein that has been suggested to function as a negative regulator of mitogen-stimulated proliferation in a variety of cell types, including mammary epithelial cells. Because much of our insight into caveolin-1 function has come from the study of human breast tumor-derived cell lines in culture, the normal physiological regulators of caveolin-1 expression in the mammary gland remain unknown. Here, we examine caveolin-1 expression in mice at different stages of mammary gland development. We show that caveolin-1 expression is significantly down-regulated during late pregnancy and lactation. Upon weaning, mammary gland expression of caveolin-1 rapidly returns to non-pregnant “steady-state” levels. Injection of virgin mice with a battery of hormones normally up-regulated during lactation demonstrates that prolactin is the main mediator of caveolin-1 down-regulation. Virtually identical results were obtained with human mammary epithelial cells (hTERT-HME1) in culture. In addition, we demonstrate that prolactin-mediated down-regulation of caveolin-1 expression occurs at the level of transcriptional control and via a Ras-dependent mechanism. Interestingly, in the mammary gland, both mammary epithelial cells and the surrounding mammary adipocytes show prolactin-mediated down-regulation of caveolin-1. This hormone-dependent regulation of caveolin-1 expression is specific to the mammary fat pad. Finally, we employed HC11 cells, a well-established model of mammary epithelial cell differentiation, to study the possible functional effects of caveolin-1 expression. In the presence of lactogenic hormones, recombinant expression of caveolin-1 in HC11 cells dramatically suppresses the induction of the promoter activity and the synthesis of β-casein, an established reporter of lactogenic differentiation and milk production. These findings may explain why caveolin-1 levels are normally down-regulated during lactation. This report is the first demonstration that caveolin-1 levels are down-regulated during a normal physiological event in vivo, i.e. lactation, because previous reports have only documented that down-regulation of caveolin-1 occurs during cell transformation and tumorigenesis.
Bombesin Stimulates Nuclear Factor κB Activation and Expression of Proangiogenic Factors in Prostate Cancer Cells

The majority of deaths from prostate cancer occur in patients with androgen-insensitive metastatic disease. An important early event in the development of the metastatic phenotype is the induction of genes that promote angiogenesis, such as vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), which are released from tumor cells into their microenvironment. Coincident with progression from prostatic carcinoma in situ to metastatic disease is an increase in the number of tumor cells exhibiting neuroendocrine (NE) differentiation. NE cells express a variety of peptide hormones, including the bombesin (BBS)-like peptide, gastrin-releasing peptide (GRP), and its cognate receptor, GRP-R. Although there is a strong positive correlation between the degree of NE differentiation and the metastatic potential of prostate cancers, a mechanistic link between increased expression of peptide hormone receptors, such as GRP-R, and proangiogenic gene expression has not been established. Here we report that BBS stimulates nuclear factor kappa B (NF kappa B) activation and proangiogenic gene expression in the androgen-insensitive prostate cancer cells lines, PC-3 and DU-145. In PC-3 cells, BBS stimulation of GRP-R resulted in the up-regulation of IL-8 and VEGF expression through a NF kappa B-dependent pathway. We show that BBS treatment induced inhibitor of NF kappa B degradation, NF kappa B translocation to the cell nucleus, increased NF kappa B binding to its DNA consensus sequence, and increased IL-8 and VEGF mRNA expression and protein secretion. Treatment with the proteasome inhibitor, MG-132, blocked BBS-stimulated NF kappa B DNA binding, and IL-8 and VEGF expression and secretion. Finally, media collected from PC-3 cell cultures, after BBS treatment, stimulated an NF kappa B-dependent migration of human umbilical vascular endothelial cells in vitro. Together, our data demonstrate a role for BBS and GRP-R in the NF kappa B-dependent up-regulation of proangiogenic gene expression, and suggest a possible molecular mechanism linking NE differentiation and the increased metastatic potential of androgen-insensitive prostate cancers.
Repositioning Ourselves: acknowledging contradiction

The essence of this paper is to present a self-study that resulted in the awareness of discrepancies that existed between our beliefs and practices as teacher educators and educational researchers. On the one hand, we assessed the impact of our teaching on participants of a professional development program. We analyzed the participants’ abilities to explore student voices as input for improving the teaching of mathematics. On the other hand, as we categorized and characterized our participants’ reflections using the tools of qualitative inquiry, the end effect was to distort and even silence those voices as an input for improving our own instruction, denying participants both agency and identity. This presented us with a living contradiction since this stance conflicted with our belief that learners deserve both agency and identity.
Insurance Purchase for Low-Probability Losses

It is widely accepted that individuals tend to underinsure against low-probability, high-loss events relative to high-probability, low-loss events. This conventional wisdom is based largely on field studies, as there is very little experimental evidence. We reexamine this issue with an experiment that accounts for possible confounds in prior insurance experiments. Our results are counter to the prior experimental evidence, as we observe subjects buying more insurance for low-probability events than the higher-probability events, given a constant expected loss and load factor. Our results suggest that, to the extent underinsurance for catastrophic risk is observed in the field, it can be attributed to factors other than the relative probability of the loss events.
A Comparison of WordNet and Roget's Taxonomy for Measuring Semantic Similarity

This paper presents the results of using Roget's International Thesaurus as the taxonomy in a semantic similarity measurement task. Four similarity metrics were taken from the literature and applied to Roget's The experimental evaluation suggests that the traditional edge counting approach does surprisingly well (a correlation of r=0.88 with a benchmark set of human similarity judgements, with an upper bound of r=0.90 for human subjects performing the same task.)
Whole Blood Analysis of Leukocyte‐Platelet Aggregates

In inflammatory and thrombotic syndromes, platelets aggregate with circulating leukocytes, especially monocytes and neutrophils. This leukocyte-platelet aggregate formation is initiated primarily through platelet surface expression of P-selectin (CD62P), following activation-dependent degranulation of α-granules, binding to its constitutively expressed counter-receptor, P-selectin glycoprotein ligand 1 (PSGL-1), on leukocytes. Monocyte-platelet aggregates are a more sensitive marker of platelet activation than platelet surface P-selectin. Detection of leukocyte-platelet aggregates is relatively simple by whole-blood flow cytometry. Light scatter and at least one leukocyte-specific antibody are used to gate the desired population, and the presence of associated platelets is detected by immunostaining for abundant platelet-specific markers. © 2016 by John Wiley & Sons, Inc.
Early Childhood Education: Improving Outcomes for Young Children and Families

Children's early experiences form the foundation on which later cognitive and academic outcomes are layered. Quality, stimulating environments and sensitive, responsive caregivers and teachers contribute to a child's success in later school and career settings. Early childhood education is reviewed in this chapter, including the benefits of early intervention, a history of early childhood programs including philosophical and historical foundations, developmentally appropriate practice, and empirically based approaches. Response to intervention preschool models are also summarized as well as technological applications in early childhood settings. Finally, future directions including the importance of wide scale developmental screening and universal access to pre-kindergarten programs are described. Keywords: early childhood education; early intervention; universal preschool; developmentally appropriate practice
NONCARDIAC THORACIC ANOMALIES

FHT is a rare diagnosis that may be an isolated finding or associated with multiple fetal anomalies, congenital infection or isoimmunization. The natural history of the lesion is variable. The effusion may regress spontaneously; remain stable in size; or progress to involve both sides of the chest and produce fetal hydrops, pulmonary hypoplasia, and fetal or neonatal demise. Hydrops is associated with significant fetal mortality. Antenatal decompression of the hydrothorax with pleuroamniotic shunting or thoracocentesis may result in a significant decrease in perinatal morbidity and mortality. Persistent hydrothorax can usually be treated with noninvasive measures in the newborn period.
The Emergence of Feminism in India, 1850–1920

PADMA ANAGOL Hampshire and Burlington: Ashgate, 2006 Pp. x + 264. £60.00. ISBN 978 0 7546 3411 9 Padma Anagol begins The Emergence of Feminism in India, 1850–1920 by recalling the tales of Maharash...
Factors affecting selection of operative approach and subsequent short-term outcomes after anatomic resection for lung cancer

Background Previous studies evaluating video-assisted thoracoscopic surgery (VATS) for lung cancer are single-institution series, suffer from small sample size, or use administrative or self-reported databases. Using a multi-institutional, standardized, and audited surgical outcomes database, our objectives were to examine preoperative factors associated with undergoing VATS vs open resection and assess subsequent perioperative outcomes. Study Design The American College of Surgeons National Surgical Quality Improvement Program Participant Use File was used to identify patients who underwent anatomic resection (eg, segmentectomy, lobectomy, and bi-lobectomy) for primary lung cancer (2005 to 2010). Multiple logistic regression models, including propensity scores, were developed to assess preoperative factors associated with undergoing VATS and the risk-adjusted association between operative approach and 30-day outcomes. Results Of 2,353 patients undergoing resection, 74% underwent open thoracotomy (OT) and 26% underwent VATS. After regression for confounders, factors associated with undergoing a VATS were patient age older than 75 years (odds ratio [OR] = 1.41; 95% CI, 1.05–1.90), Hispanic ethnicity (OR = 2.52; 95% CI, 1.69–3.77), and cardiothoracic surgery training (OR = 1.68; 95% CI, 1.37–2.07). Patients undergoing OT had a higher likelihood of any adverse event developing (24% vs 14%; OR=1.76; 95% CI, 1.35–2.29), specifically pneumonia and sepsis/septic shock. Median length of stay was significantly longer in the OT group (7 vs 4 days; p Conclusions In addition to patient factors, surgeon training can play a role in determining the operative approach offered to patients. Patients selected for VATS had a lower 30-day morbidity and shorter length of stay compared with OT anatomic resection for primary lung cancer.
Coplanarity in twistor space of N = 4 next-to-MHV one-loop amplitude coefficients

Abstract Next-to-MHV one-loop amplitudes in N = 4 gauge theory can be written as a linear combination of known multivalued functions, called scalar box functions, with coefficients that are rational functions. We consider the localization of these coefficients in twistor space and prove that all of them are localized on a plane. The proof is done by studying the action of differential operators that test coplanarity on the unitarity cuts of the amplitudes.
Finite Linnaean structures.

This paper considers a class of set-theoretical entities, calledn-rank Linnaean structures, which are intended as abstract models of the taxonomic classificatory systems of biology. In the first part, devoted to formalism, finite Linnaean structures are discussed in complete generality; but, in addition, eight distinct subclasses are noted and some of the properties of their elements are explored. In the second part, concerned with applications, it is shown that taxonomic systems may be recast in the form of finite Linnaean structures, and an effort is made to show that some undesirable features of earlier models are avoided without artificiality and without abandoning extensional mathematics.
Thermal Loading of Optical Resonators for Future Gravitational-Wave Detectors

Illuminating a Fabry-Perot ring cavity with high-power laser light demonstrates the effects of thermal distortion of the cavity’s optics, allowing estimations of power handling limitations of resonators for future gravitational-wave detectors.
A dual formulation of the algebraic Riccati equation problem

By introducing a set of matrix transformations, the algebraic Riccati equation (ARE) is converted into a ‘dual’ matrix quadratic equation (DARE) where the unknown belongs to the field of skew-symmetric matrices. As a consequence of this reformulation for a matrix space Rnxn the system of n(n+ 1)/2 coupled quadratic equations associated to ARE is shown to be equivalent to another system of n(n-1)/2 coupled quadratic equations. An efficient computational algorithm is given for solving the dual Riccati equation and closed form analytical solutions of ARE are derived for the case in which n=2 or when some special, but non-trivial, commutativity conditions are fulfilled in the transformed space.
Health City Cayman Islands and the globalization of health services delivery

We describe a new health care campus under development in the Cayman Islands, Health City, based on the low-cost "focused factory" model. The construction of a multispecialty hospital opening in February 2014 less than a 4-hour flight away from the United States and convenient to both Central and South America for patients who already travel to the United States for clinical care could reshape the US health care marketplace and enhance access to affordable specialty health care in the region.
Development and validation of in vitro bioassays for 2,3,7,8-TCDD equivalents

Abstract Toxic halogenated aryl hydrocarbons are industrial compounds and/or by-products which have been detected as complex mixtures in almost every component of the global ecosystem. Included in this class of chemical pollutants are the halogenated (Cl/Br) biphenyls (PCBs/PBBs), dibenzo-p-dioxins (PCDDs/PBDDs) and dibenzofurans (PCDFs/PBDFs). Rat hepatoma H-4-II E cells are highly sensitive to the induction of aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) by 2,3,7,8-TCDD and related toxic halogenated aromatics and for > 25 of these compounds there was an excellent correlation (r = 0.85 to 0.93) between their in vitro pEC 50 values for induction and their pED 50 values for in vivo effects in the rat (AHH induction, body weight loss and thymic atrophy). Moreover, for selected PCB, PCDD and PCDF congeners comparable linear correlations between in vitro induction activity and in vivo toxicities in the guinea pig (AHH induction and body weight loss) and mouse (immunotoxicity) were also observed. The data confirm the utility of the in vitro induction bioassay for toxic halogenated aromatics. The results of these studies permit the calculation of estimated “2,3,7,8-TCDD equivalent ranges” for most of the important toxic halogenated aromatics and provide a more rational basis for risk assessment of these compounds and their mixtures.
Bragg and non-Bragg Diffraction from Single Beam Writing and Readout in Photorefractive Barium Titanate

We demonstrate anisotropic self-diffraction in cerium doped barium titanate crystal using one incident beam. The second writing beam is derived from the internal reflection, at the incident surface, of the generated contra-propagating self-phase conjugate inside the crystal. Experimental measurements of the permissible angle(s) of incidence fit the theoretical and experimental results using two incident beams investigated by Kukhtarev et al [1]. The result also shows that anisotropic higher orders can be observed even when the ratio between both writing beams (induced and incident) is less than 10%. In the second part of the paper, we investigate the gratings created during self-diffraction originating from two writing beams in cerium doped barium titanate, using a reading beam of different wavelength. We have previously used anisotropic self-diffraction using two incident beams for image correlation [2]. The results can be separated to two different regimes, Bragg-like regime and Raman-Nath like regime. In the Raman-Nath regime, the polarizations of the generated higher order(s) are orthogonal to the polarization of the reading beam. In the Bragg like regime, the polarizations are the same. Finally the reading of self-diffraction gratings created by one writing beam will be investigated using one beam at a different wavelength.
Alterations in cerebrovascular reactivity after positive pressure ventilation.

ABSTRACT: Pressure ventilation of the newborn can adversely affect the cardiovascular system. Increasing airway pressure increases cerebral venous pressure, thus stressing brain vasculature. To test the hypothesis that cerebral venous distension caused by mechanical ventilation alters cerebral microvascular responses, we studied cerebrovascular responses before, during, and after positive pressure ventilation. Anesthetized newborn pigs were ventilated with a standard time-cycled, pressure-limited infant respirator. Pial arterioles were measured in response to hypercapnia, topical isoproterenol, and topical norepinephrine during control [mean airway pressure (Paw) = 0.9 ± 0.05 kPa (4.8 ± 0.3 cm H2O)] conditions, during 40–60 min of increased Paw [2.5 ± 0.2 kPa (13.9 ± 1.3 cm H2O)], and when the Paw was lowered again. Pial arteriolar dilation in response to hypercapnia was not changed by increasing Paw. Similarly, responses to isoproterenol and norepinephrine were unaltered during raised Paw. However, a significant decrease in responses to topical isoproterenol and norepinephrine was observed after increased Paw. These experiments show that specific prostanoid-independent cerebrovascular responses are altered subsequent to pressure ventilation, whereas prostanoid-dependent dilation to hypercapnia was not affected. These changes suggest that the newborn cerebral vasculature is affected by positive pressure ventilation, further raising the possibility that ventilation-induced alterations in microvascular responses could make the brain more vulnerable to added stresses after pressure ventilation.
Community-based screening for cardiovascular disease and diabetes using HbA1c.

Abstract Background Persons from inner-city immigrant and mixed-ethnic communities are known to be at high risk for cardiovascular disease and diabetes. Such communities may also be underserved for preventive medical care. The authors hypothesized that hemoglobin A1c (HbA1c) could be used as a screening test for a community-based program to detect new cases of diabetes and persons at risk for diabetes and cardiovascular disease. Methods Screenings took place in churches, group homes, shelters, community centers, and street corners of the Bronx. Screening data included history of diabetes, age, ethnicity, body mass index, blood pressure, lipid panel, random glucose, and HbA1c. Data were analyzed for number of cases of new diabetes (HbA1c ≥7%), for patients at risk for diabetes (HbA1c 6%–6.99%), and for associations between HbA1c and other variables. The effect of location of screening and self-reported ethnicity on outcome variables was also analyzed. Results Seven hundred four persons were screened in 25 different sessions. HbA1c and lipid profile were obtained on 539 persons, which formed the cohort for analysis. Mean HbA1c for the cohort was 6.00%. Thirty-two percent of the cohort had HbA1c of more than 6%, and 11.4% had HbA1c of more than 7%. Excluding known diabetics (13% of cohort), 24% had HbA1c of more than 6%, and 3.4% had HbA1c of more than 7%. HbA1c was significantly correlated with total cholesterol, triglycerides, low-density lipoprotein, systolic blood pressure, body mass index, and age; in all cases, correlation coefficients were higher with HbA1c than with random glucose. In addition, significantly higher cardiovascular disease risk factors were found in persons with HbA1c of more than 6%; 6% may be a threshold value for the metabolic syndrome. Mean HbA1c was higher in persons from the South Bronx (which has a higher poverty rate) than the North Bronx (6.08% v 5.74%, p =0.013). There were no statistically significant differences between self-reported ethnic groupings. Conclusions There was a high prevalence of undiagnosed diabetes, and of patients at risk for diabetes, in this community setting. Community-based screening can be used as a method for identifying high percentages of patients at risk for diabetes or with undiagnosed diabetes in an inner city, immigrant, mixed-ethnic population.
Electrostatically controlled isolation of debundled single-walled carbon nanotubes from nanoplatelet dispersant

Individually dispersed single-walled carbon nanotubes (SWCNTs) were isolated and stabilized from electrostatically tethered nanoplatelets in aqueous solution, following nanoplatelet-assisted exfoliation. SWCNT isolation was achieved by precipitating nanoplatelets with cations and by concurrent usage of appropriate surfactants to stabilize SWCNTs. It was found that the precipitation of nanoplatelets induced by monovalent cations was due to the ionic screening effect, whereas ion exchange was the main cause for nanoplatelet aggregation when divalent cations were used. When the above processes are optimized, isolation of pure SWCNTs with yield greater than 90% can be achieved. Effects of ion valency, ion size, reaction time, concentration of SWCNTs and surfactant type for the separation process are discussed. The structure and composition of the exfoliated SWCNTs were characterized using various microscopy and spectroscopy tools. The above exfoliation and separation approach does not noticeably affect the electronic state of the SWCNTs, and is thus highly attractive for applications where optimal SWCNT properties are desired.
THE INFLUENCE OF MATING SYSTEM AND OVERLAPPING GENERATIONS ON EFFECTIVE POPULATION SIZE.

The effective population size (Ne ) depends strongly on mating system and generation time. These two factors interact such that, under many circumstances, Ne is close to N/2, where N is the number of adults. This is shown to be the case for both simple and highly polygynous mating systems. The random union of gametes (RUG) and monogamy are two simple systems previously used in estimating Ne , and here a third, lottery polygyny, is added. Lottery polygyny, in which all males compete equally for females, results in a lower Ne than either RUG or monogamy! Given nonoverlapping generations the reduction is 33% for autosomal loci and 25% for sex-linked loci. The highly polygynous mating systems, harem polygyny and dominance polygyny, can give very low values of Ne /N when the generation time (T) is short. However, as T is lengthened, Ne approaches N/2. The influence of a biased sex ratio depends on the mating system and, in general, is not symmetrical. Biases can occur because of sex differences in either survival or recruitment of adults, and the potential for a sex-ratio bias to change Ne is much reduced given a survival bias. The number of juveniles present also has some influence: as the maturation time is lengthened, Ne increases.
Molecular events in late stages of T-cell functional maturation.

Peripheral blood lymphocytes activated with either the calcium ionophore A23187 or the combination of anti-CD2 monoclonal antibodies, 9.6 + VIT13, undergo blast formation and proliferation but do not develop cytolytic activity. These proliferating blasts, referred to as pre-effector blasts because they do not yet express cytolytic function, respond to stimulation with interleukin-2 (IL-2) by further proliferation and development of cytolytic activity, i.e. they become effector cells. Pre-effector blasts activated with 9.6 + VIT13, but not A23187-activated pre-effector blasts, also respond to stimulation with interferon-gamma (IFN-gamma) by becoming cytolytic effector cells. This report examines gene expression (by Northern blot analysis) in pre-effector blasts and during the transition from the pre-effector to the effector stage. The data presented here provide further support for the concept that A23187 activation drives T cells to become dividing blasts that are appropriately referred to as 'pre-effector' cells in that these blasts do not express transcripts for granzyme A or perforin mRNA but are driven by IL-2 to do so in parallel with the acquisition of cytotoxic function. Cells are apparently driven by 9.6 + VIT13 to a later stage of functional maturation than by A23187 activation; 9.6 + VIT13-activated pre-effector blasts express mRNA for both granzyme A and perforin, even though these blasts do not express cytolytic activity. Activation via A23187 results in lower expression of the proto-oncogene c-myb relative to that found in either 9.6 + VIT13 or OKT3-activated cells.
Bilirubin Inhibition of Heme Biosynthesis

The conversion of protoporphyrin and iron to heme is catalyzed by a soluble enzyme prepared from rat liver. This reaction is inhibited by bilirubin, and initial kinetic studies suggest that the inhibition is due in part to a competition between protoporphyrin and the bile pigment. Implications of this finding in hyperbilirubinemia are mentioned.
Child and Parent Reaction to the Three Mile Island Nuclear Accident

Thirty-five local children and their parents were studied 1 1/2 years after the Three Mile Island (TMI) nuclear accident. On a standardized self-report measure, the children were found to have a level of residual anxiety that was not identified by their parents. These children also consistently reported stronger and more symptomatic responses to the TMI accident for themselves than their parents did for them. Child intensity-of-reaction scores were significantly related to mother-father discordance in mood and reaction to the event. Four of the children who were psychiatrically disturbed showed significantly high or low intensity-of-reaction levels.
Morphometric Description of the Wandering Behavior in Drosophila Larvae: Aberrant Locomotion in Na+ and K+ Channel Mutants Revealed by Computer-Assisted Motion Analysis

Wandering is a simple behavior in Drosophila larvae prior to metamorphosis. Using the Dynamic Image Analysis System (DIAS) initially developed for analyzing amoeboic movements of single cells, we have analyzed videotaped behaviors of Drosophila larvae at the wandering stage. Previous studies show that mutations in the Na+ channel gene paralytic (para) cause paralysis at 29 degrees C, and mutations in the K+ channel beta subunit gene Hyperkinetic (Hk) lead to leg-shaking under ether anesthesia. The application of DIAS revealed quantifiable abnormalities in the larval locomotion of both ion channel mutants even under "permissive" conditions. Analysis of centroid movement indicates that, compared to wild type, both Hk and para larvae crawled at a slower average speed, but a similar peak instantaneous speed during a contraction cycle. Nevertheless, contraction in the body length was greater in mutants, implying a lower efficiency in conversion of muscular contraction to distance translocation. In addition, each mutant produced a characteristic crawling pattern distinct from the wild-type control. The larval crawling pattern was determined by periods of linear locomotion interposed by non-locomotive, "searching and decision-making" episodes, after which the crawling was resumed in a new direction. Our results demonstrate that mutations in single ion channel subunits resulted in stereotypic modifications in locomotion control and crawling patterns, and that DIAS is a powerful tool in revealing subtle differences in animal behavior and quantifying mutational effects on the interplay of discrete behavioral components.
Bioterrorism, Public Health, And Human Rights

It is unnecessary and counterproductive to sacrifice basic human rights to respond to bioterrorism. Constructive public health legislation, which must be federal, cannot be carefully drafted under panic conditions. When it is, like the “model act,” it will predictably rely on broad, arbitrary state authority exercised without public accountability. Public health should resist reverting to its nineteenth-century practices of forced examination and quarantine, which will simply encourage people to avoid physicians, hospitals, and public health practitioners they now trust and actively seek out in emergencies. Upholding human rights is essential to public trust and is ultimately our best defense against the threat of terrorism in the twenty-first century.
Plasma and Pulmonary Fluid Endothelin in Horses with Seasonal Recurrent Airway Obstruction

Background: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves. Hypothesis: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission. Animals: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected. Methods: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA. Results: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7–1.8) and venous (1.3, 1.2–1.7) plasma and in BALF (0.3, 0.2–0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21–50) were greater in affected horses during clinical exacerbation compared with remission (P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses (P < .05). Conclusions and Clinical Importance: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.
Mechanisms of Intrinsic Bioremediation of Gas Condensate Hydrocarbons in Saturated Soil

The addition of gas condensate hydrocarbons to saturated soil from a gas production site stimulated sulfate reduction under anaerobic and oxygen-limiting conditions, and nitrate and Fe(III) reduction under oxygen-limiting conditions, compared to biotic controls that lacked hydrocarbon and sterile controls. The sulfate reduction corresponded to a reduction in the amount of toluene relative to other hydrocarbons. These results suggest that subsurface soils at the gas production site have the potential for intrinsic bioremediation of hydrocarbons.
Conformational and dynamic considerations in the design of peptide hormone analogs.

Efforts to understand the chemical-physical basis for peptide hormone and neurotransmitter action requires integration of conformational parameters and biological properties. Since most peptide hormones are conformationally flexible, the question arises as to which of the manifold of conformations is of biological significance. In molecular terms, it is necessary to carefully distinguish chemical-physical features important to binding (the binding message) from those involved in transduction (the biological activity message). One approach to this involves the design, synthesis, and conformational analysis of semirigid hormone analogs. The distinction between binding and transduction can best be examined by evaluation of full biological profiles of partial agonists, antagonists, and analogs with prolonged biological activity. Using this multidisciplinary approach, we have prepared several semirigid [Pen1]-oxytocin antagonist analogs and evaluated their conformational properties and biological activities. Specific conformational features can be related to inhibitory activities in several cases. On the basis of structure–activity relationships and conformational considerations, we have designed a series of conformationally restricted cyclic and acyclic analogs of the linear peptide α-melanotropin. Some of these peptides have exceptionally prolonged in vivo activity (weeks), and others exhibit superagonist potency (10,000 times the native hormone). We have evidence that potency and prolonged activity have different structural and conformational requirements. It is suggested that potency is primarily a function of receptor recognition (the binding message), whereas prolonged activity is related to transduction (the biological activity message).
Free cholesterol enhances adenoviral vector gene transfer and expression in CAR-deficient cells.

Efficient adenovirus vector-mediated gene transfer depends on the presence of sufficient amounts of the high-affinity coxsackie–adenovirus (Ad) receptor (CAR) on the surface of the target cell leading to receptor-mediated endocytosis of the vector. The present study evaluates the effect of free cholesterol, a lipid component of endocytic vesicles, on Ad uptake into CAR-deficient cells. Infection in the presence of free cholesterol at its maximum solubility in water led to increased binding, uptake, and expression of Ad in human skin fibroblasts and alveolar macrophages, two primary human cells known to be deficient in CAR. The effect of free cholesterol was maximal at its solubility maximum in aqueous solution. Increase of Ad vector-mediated gene transfer with cholesterol was dependent on the lack of CAR receptor expression on the surface and was diminished by overexpression of CAR in CAR-deficient cells. Cholesterol-mediated increase of Ad-mediated gene expression was dependent on coincubation of both cholesterol and Ad and was not dependent on the cholesterol content of the cell. Increased Ad vector-mediated gene expression in the presence of free cholesterol was also observed in murine skin in vivo. Structural analysis of the Ad–cholesterol mixture showed complexation between Ad particles leading to formation of multivirus aggregates due to hydrophobic interaction. The addition of free cholesterol with Ad vectors may be a simple way to increase Ad-mediated gene transfer to cells that are poor targets due to their lack of a sufficient number of Ad receptors.
Concurrent design and economic justification in developing a product

SUMMARY In today's globally competitive world it is essential to design products with maximized functionality and minimized costs. An environment that facilitates the interactions between design and justification would enhance such a decision process. A conceptual framework for such a concurrent design and justification system is presented in this paper. A prototype implementation was developed to explore the usefulness of the design justification concept Actual data from the design of an electromagnetic/radio frequency shield, a component in electrical metering equipment, was used. In this implementation the design justification environment allowed the decision maker to see the potential economic implications of different design alternatives. It also enabled the decision maker to take advantage of their present knowledge and combine it with that of the environment to better analyse the design of the shield throughout the entire product development period.
Fabrication and electronic characterization of single molecular junction devices: a comprehensive approach.

We demonstrated a new comprehensive method to combine scanning probe microscopy (SPM) nanolithography and modified SPM break junction techniques to fabricate and characterize single molecular break junction devices. By patterning alkanedithiol and alkanediamine molecules in the alkanethiol template and measuring the conductance of the two kinds of molecular junctions, we have shown the following: (1) the new “stretch-hold” approach produced four groups of conductance values for each molecular junction, for the first time realizing the less populated conductance values that correspond to different contact configurations; (2) the electronic transport mechanism for such molecular junctions is electronic tunneling with similar decay constants for each conductance group of the same kind of molecules. The conductance differences among different groups are due to the molecule−electrode contact configuration difference, which was shown by the extrapolated contact resistances. This new approach also allows one to ...
Management of peripheral pain generators in fibromyalgia

Fibromyalgia is a widespread chronic pain disorder that is characterized in part by central sensitization and increased pain response to peripheral nociceptive and non-nociceptive stimuli. Part of the comprehensive pain management of patients with fibromyalgia should include a thoughtful evaluation and search for peripheral pain generators that either are associated with fibromyalgia or are coincidentally present. The identification and treatment of these pain generators lessens the total pain burden, facilitates rehabilitation and decreases the stimuli for ongoing central sensitization.
Integrating seabird restoration and mammal eradication programs on islands to maximize conservation gains

Colonial nesting seabirds frequently drive island ecosystem biodiversity by maintaining ecosystem functioning and community dynamics. Invasive mammal introductions to most of the world’s islands have ravaged insular seabird populations and had associated devastating ecosystem-wide effects. Eradication programs remove invasive mammals from islands, with the goal of conserving and restoring island species and systems. However, most eradication programs rely almost exclusively on passive seabird recovery to achieve these goals. Unfortunately, the life histories of most seabird species are not conducive to passive recovery within a contemporary timeframe. Seabird restoration techniques can effectively overcome life history related issues and significantly reduce recovery times for insular seabird populations, thereby reducing associated ecosystem-wide recovery times. By integrating seabird restoration and eradication programs, practitioners can maximize conservation gains, expand funding opportunities, and restore island ecosystems and the biodiversity they support.
Three decades of caring for the Venezuelan Huntington's disease families.

738 www.thelancet.com/neurology Vol 12 August 2013 a uniquely dedicated person who has devoted the past 25 years of her life to the Huntington’s disease community. Working with her are two dedicated and highly trained nurses. They have been exceptionally loyal and committed, doing very diffi cult jobs for more than 14 years. The core staff of the Casa Hogar consists of 30 auxiliary nursing staff , all of whom are family members of people with Huntington’s disease. We require that only such individuals serve as staff . They know how best to take care of their mothers, fathers, and children, who live with dignity in the Casa Hogar. They understand and intuitively know how to care for the complex array of problems that confront every patient. Families of people with Huntington’s disease are ostracised by the wider community, and cannot fi nd work. Working with us provides an income and safe haven if they become ill in the future. Ours is the only nursing home in the world where staff are required to be from families of people with Huntington’s disease. We provide the full salary for Margot de Young, the two nurses, and 30 staff members of the Casa Hogar, totalling almost $750 000 annually. Including drugs and food, we provide almost $1 000 000 annually to cover the home’s expenses. Several videos about our work at the Casa Hogar have been produced, including a piece from the British Broadcasting Corporation’s Newsnight programme, “Venezuela village key in search of Huntington’s cure”, which can be watched online. We are in the midst of fundraising to secure additional resources for the Casa Hogar and other research activities. Details of our work can be found on the Hereditary Disease Foundation website.
Competitive bank pricing and adverse selection, with implications for testing the SCP hypothesis

Abstract Adverse borrower selection implies that competitive interest rates on bank loans will be an increasing function of the number of banks in the market, whenever the marginal cost of lending does not rise too sharply with market concentration (a condition supported by a variety of empirical evidence). Moreover, this linkage is stronger during economic recessions when more loans default. These findings suggest a need to reinterpret many prior empirical studies of loan price versus concentration, as well as raising new considerations in the appropriate construction of future empirical tests.
Near-Infrared Heavy-Atom-Modified Fluorescent Dyes for Base-Calling in DNA-Sequencing Applications Using Temporal Discrimination

A series of near-IR fluorescent dyes were prepared which contained an intramolecular heavy atom for altering the fluorescence lifetimes to produce a set of probes appropriate for base-calling in a single-lane DNA sequencing format. The heavy-atom modification consisted of an intramolecular halogen situated on a remote section of the chromophore in order to minimize the perturbation on the lifetimes and fluorescence quantum yields. In addition, the dye series possessed an isothiocyanate functional group to allow facile attachment to sequencing primers. The unconjugated dyes showed similar absorption and emission maxima (λabs = 765−768 nm; λem = 794−798 nm) as well as fluorescence quantum yields that were invariant, within experimental error, with the heavy atom. However, the lifetimes of these dyes were found to vary with the identity of the halogen substitution (I, τf = 947 ps; F, τf = 843 ps, measured in methanol), with an average variation within the dye series of 35 ps. The spectroscopic properties of ...
Automatic identification of heart failure diagnostic criteria, using text analysis of clinical notes from electronic health records

Objective Early detection of Heart Failure (HF) could mitigate the enormous individual and societal burden from this disease. Clinical detection is based, in part, on recognition of the multiple signs and symptoms comprising the Framingham HF diagnostic criteria that are typically documented, but not necessarily synthesized, by primary care physicians well before more specific diagnostic studies are done. We developed a natural language processing (NLP) procedure to identify Framingham HF signs and symptoms among primary care patients, using electronic health record (EHR) clinical notes, as a prelude to pattern analysis and clinical decision support for early detection of HF.
Partitioning and thermodynamics of dipyridamole in the n‐octanol/buffer and liposome systems

The thermodynamics of partitioning (K) of dipyridamole has been determined in n-octanol/buffer and liposome-buffer systems at pH 7.4. Dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) were used to prepare multilamellar liposomes. Partitioning of dipyridamole did not depend on the amount of n-octanol employed, however, partitioning was dependent upon the quantity of DMPC employed to prepare liposomes. Plots of log K vs 1/T were linear in the n-octanol and liposome systems. Partitioning was generally greater in liposomes than in the n-octanol/buffer system. Among liposomes, the partitioning was greater in DMPC liposomes at all temperatures. The values of enthalpy (delta H) and entropy (delta S) were positive in both the n-octanol and liposome systems. These values were lower in DMPC liposomes and were comparable in the n-octanol and DPPC liposomes. Thus, the interaction of dipyridamole depends on the rigidity of lipid bilayers and liposomes constitute a more selective partitioning system than the n-octanol/buffer system.
Chemistry of Dimetallaboranes Derived from the Reaction of [Cp*MCl2]2 with Monoboranes (M = Ru, Rh; Cp* = η5-C5Me5)

In a single step, from [Cp*RuCl2]2 (Cp* = η5-C5Me5) and Li[BH4], nido-1,2-(Cp*Ru)2(μ-H)2B3H7, 1, is produced in high yield. Addition of BH3·THF to 1 results in conversion to nido-1,2-(Cp*Ru)2(μ-H)B...
Proteome and membrane fatty acid analyses on Oligotropha carboxidovorans OM5 grown under chemolithoautotrophic and heterotrophic conditions.

Oligotropha carboxidovorans OM5 T. (DSM 1227, ATCC 49405) is a chemolithoautotrophic bacterium able to utilize CO and H2 to derive energy for fixation of CO2. Thus, it is capable of growth using syngas, which is a mixture of varying amounts of CO and H2 generated by organic waste gasification. O. carboxidovorans is capable also of heterotrophic growth in standard bacteriologic media. Here we characterize how the O. carboxidovorans proteome adapts to different lifestyles of chemolithoautotrophy and heterotrophy. Fatty acid methyl ester (FAME) analysis of O. carboxidovorans grown with acetate or with syngas showed that the bacterium changes membrane fatty acid composition. Quantitative shotgun proteomic analysis of O. carboxidovorans grown in the presence of acetate and syngas showed production of proteins encoded on the megaplasmid for assimilating CO and H2 as well as proteins encoded on the chromosome that might have contributed to fatty acid and acetate metabolism. We found that adaptation to chemolithoautotrophic growth involved adaptations in cell envelope, oxidative homeostasis, and metabolic pathways such as glyoxylate shunt and amino acid/cofactor biosynthetic enzymes.
Hispanics in the United States, 1850–1990: Estimates of Population Size and National Origin

(2000). Hispanics in the United States, 1850–1990: Estimates of Population Size and National Origin. Historical Methods: A Journal of Quantitative and Interdisciplinary History: Vol. 33, No. 3, pp. 137-153.
Specific detection of Phytophthora cactorum in diseased strawberry plants using nested polymerase chain reaction.

Validated protocols for DNA purification and PCR amplification are reported for detection of Phytophthora cactorum in diseased strawberry plants. To remove PCR inhibitors, necrotic strawberry tissues were soaked in 5% alconox solution for >12 h before DNA extraction, and the extracted genomic DNA was embedded in an agarose gel chamber and subjected to electrophoresis. The purified DNA was amplified reliably by PCR. Nested PCR was used to detect a portion of the rRNA gene of P. cactorum in samples. In the first round of PCR, primers ITS1 and ITS4 amplified fragments of varying sizes from total genomic DNA from diseased strawberry plants. In the second round of PCR, a 1:25 dilution of the first-round PCR products was used as template with two P. cactorum-specific primer pairs (BPhycacL87FRG and BPhycacR87RRG, which amplified a 340-bp fragment and a 480-bp fragment from the rRNA gene; and BPhycacL89FRG and BPhycacR176RRG, which amplified a 431-bp fragment). Validation tests using culture-based isolations as a standard for comparison indicated that the DNA purification and PCR primers and amplification protocols were reliable and specifically amplified a portion of the rRNA gene of P. cactorum from necrotic root, crown and petiole tissues of strawberry naturally infected by the pathogen.