cssi/SciSciGPT-SciSciNet huggingface dataset:
A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets

// Ruli Gao 1,2 , Chunxia Cao 1 , Min Zhang 1 , Maria-Cecilia Lopez 3 , Yuanqing Yan 2 , Zirong Chen 3 , Yoshitsugu Mitani 4 , Li Zhang 5 , Maria Zajac-Kaye 6 , Bin Liu 7 , Lizi Wu 3 , Rolf Renne 3 , Henry V. Baker 3 , Adel El-Naggar 4 and Frederic J. Kaye 1,2 1 Department of Medicine, Division of Hematology and Oncology, College of Medicine, University of Florida, Gainesville, FL, USA 2 Genetics & Genomics Graduate Program, Genetics Institute, College of Medicine, University of Florida, Gainesville, FL, USA 3 Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA 4 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Department of Computational Biology and Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Department of Anatomy & Cell Biology, College of Medicine, University of Florida, Gainesville, FL, USA 7 Department of Molecular Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence: Frederic J. Kaye, email: // Keywords : MYB salivary gland cancer, adenoid cystic cancer, extracellular matrix Received : October 02, 2014 Accepted : December 09, 2014 Published : December 10, 2014 Abstract MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
SpatialHadoop: A MapReduce framework for spatial data

This paper describes SpatialHadoop; a full-fledged MapReduce framework with native support for spatial data. SpatialHadoop is a comprehensive extension to Hadoop that injects spatial data awareness in each Hadoop layer, namely, the language, storage, MapReduce, and operations layers. In the language layer, SpatialHadoop adds a simple and expressive high level language for spatial data types and operations. In the storage layer, SpatialHadoop adapts traditional spatial index structures, Grid, R-tree and R+-tree, to form a two-level spatial index. SpatialHadoop enriches the MapReduce layer by two new components, SpatialFileSplitter and SpatialRecordReader, for efficient and scalable spatial data processing. In the operations layer, SpatialHadoop is already equipped with a dozen of operations, including range query, kNN, and spatial join. Other spatial operations are also implemented following a similar approach. Extensive experiments on real system prototype and real datasets show that SpatialHadoop achieves orders of magnitude better performance than Hadoop for spatial data processing.
Suboptimal symbol-by-symbol demodulation of continuous phase modulated signals

This paper develops a class of suboptimum symbol-by-symbol demodulators called Bayesian conditional decision feedback estimators (BCDFEs), for the demodulation of continuous phase modulated (CPM) signals. The BCDFEs offer a trade-off between bit error performance (BEP) and computational complexity/the number of integrators used, by varying certain parameters. Some additional complexity reduction schemes, which can be used in conjunction with the BCDFEs, are given. These result in significant reduction in complexity, with little loss in the BEP performance at high SNRs. These demodulators are useful in cases where symbol-by-symbol demodulation is necessary.
Developmental, emotional and behavioral co-morbidities across the chronic health condition spectrum.

Aims Estimate the prevalence of specific developmental, emotional, and behavioral (DEB) problems across selected chronic health conditions; examine the relationship of chronic health conditions to functional activities and participation; determine the potential confounding effect of sociodemographic factors on the prevalence of DEB problems. Methods The 2007 National Survey of Children's Health, conducted by the Centers for Disease Control and Prevention, served as the primary data source for this study. A total of 91.642 interviews (66.6% response rate for identified households with children) were performed. Population-based estimates were obtained for variables of interest by assigning sampling weights to each child for whom an interview was completed. Results Parents were two to 30 times more likely to report DEB problems, such as Attention Deficit/Hyperactivity Disorder, depression, learning problems, and challenging behaviors, for children with chronic health conditions. These children had a greater number and range of difficulties with social interaction and school functioning as well as a lower rate of participation in community activities. Although highest rates of DEB problems were reported for those conditions involving the nervous or sensory systems, children with asthma, diabetes, and musculoskeletal conditions also had a higher rate of problems than children without the conditions. The higher prevalence of DEB problems remained after statistical adjustment for socio-demographic factors. Conclusions Children with a spectrum of chronic health conditions are at high risk for DEB problems that affect learning, behavior, and emotional well-being. As part of a comprehensive approach to the management of chronic health conditions, children should be screened for these problems and referred for appropriate further evaluation and remediation. Attention to these common co-morbidities will not only result in enhanced quality of life but will also promote better adherence to medical recommendations and, thereby, optimal disease control.
Incorporating Scottish Highland Games and Activities into Your Physical Education Classes

The purpose of this article is to introduce a potentially new and exciting group of activities that can be taught in physical education. Activities based on Scottish Highland Games can be an interesting way to incorporate history and literature into the curriculum, as well as introduce students to a variety of unique physical activities. This article will look at a brief history of Highland Games and provide basic rules and modifications for their safe and fun implementation in a physical education program.
Untangling the Interplay Among Navigational Strategies Used by the Ant Formica podzolica

Abstract Ants use a variety of navigational mechanisms in homing, including pheromone trails, landmarks, compasses, and visual “snapshots” of the landscape. In many cases, an ant has more than one of these information types available and may give priority to one mechanism over the others. We investigated how the ant Formica podzolica Francoeur makes use of polarized light during the initial stages of homing. When ants were displaced to an unfamiliar area, they spent significantly more time in the 90° arc centered on their perception of the direction to the nest. This preference was eliminated by modifying the ants’ view of the sky with a polarizing filter, suggesting that F. podzolica use polarized light information. However, the displacements also showed that the ants make use of nest-specific information (possibly landmarks or snapshot matching) to recalibrate their homeward paths. When confronted with incompatible orientation information from polarized light in the sky and landmarks, the ant seems to r...
Effects of prostate-rectum separation on rectal dose from external beam radiotherapy.

Purpose In radiotherapy for prostate cancer, the rectum is the major dose-limiting structure. Physically separating the rectum from the prostate ( e.g., by injecting a spacer) can reduce the rectal radiation dose. Despite pilot clinical studies, no careful analysis has been done of the risks, benefits, and dosimetric effects of this practice. Methods and Materials Using cadaveric specimens, 20 mL of a hydrogel was injected between the prostate and rectum using a transperineal approach. Imaging was performed before and after spacer placement, and the cadavers were subsequently dissected. Ten intensity-modulated radiotherapy plans were generated (five before and five after separation), allowing for characterization of the rectal dose reduction. To quantify the amount of prostate-rectum separation needed for effective rectal dose reduction, simulations were performed using nine clinically generated intensity-modulated radiotherapy plans. Results In the cadaveric studies, an average of 12.5 mm of prostate-rectum separation was generated with the 20-mL hydrogel injections (the seminal vesicles were also separated from the rectum). The average rectal volume receiving 70 Gy decreased from 19.9% to 4.5% ( p p Conclusion Prostate-rectum spacers can allow for reduced rectal toxicity rates, treatment intensification, and/or reduced dependence on complex planning and treatment delivery techniques.
Effects of Caddisfly Grazers on the Elemental Composition of Epilithon in a Boreal Lake

We examined how the intensity of benthic grazing affects the C:P stoichiometry of epilithon in an oligotrophic lake at the Experimental Lakes Area in northwestern Ontario, Canada. Caddisflies were enclosed over natural epilithon to compare epilithic C:P ratios along a grazer gradient (0, 1, 4, and 9 individuals/700 cm 2 enclosure) after 10 and 20 d. We also examined mechanisms that potentially explain changes in epilithic C:P ratios at different grazer levels by estimating algal biomass and taxonomic composition. After 10 d, no differences in epilithic C:P ratios were found among grazer levels. However, after 20 d, epilithic C:P ratios (∼500) at high grazer levels (9/enclosure) were significantly lower than C:P ratios (∼1200) in grazer-free enclosures. We also found that algal biomass was significantly reduced under intense grazing. No significant effects of grazer level were detected on epilithic C:chlorophyll ratios, the % contribution of algal C to epilithic organic C, or the taxonomic compos...
Isolation of viable type II alveolar epithelial cells by flow cytometry

We developed a new method for isolating viable type II cells from fractionated and unfractionated lung cell suspensions by flow cytometry using acridine orange (AO). Fischer-344 rat lungs were dispersed into single-cell suspensions by a technique that yields a high number of cells (4-5 X 10(8) cells/lung, congruent to 85% viable), congruent to 11% of which are type II cells. Elutriated fractions from the lung cell preparation and parent, unfractionated cell suspensions were incubated with 1.0-0.02 micrograms/ml AO and analyzed by flow cytometry. Parameters analyzed included axial light loss (ALL) and red fluorescence (RF). Based on their unique RF, attributable to AO staining of type II cell lamellar bodies, and their ALL characteristics, type II pneumocytes were sorted from elutriated fractions to greater than 95% purity. Using the same approach, type II pneumocytes were sorted from unfractionated lung cell suspensions at greater than or equal to 85% purity. The viabilities of the type II alveolar epithelial cells isolated by this method range from 85% to 95%, and the ultrastructural features of the sorted cells were unaltered by AO labeling or sorting.
Aggregating inductive expertise

The aggregation problem is to design an inferential agent that makes intelligent use of the theories offered by a team of inductive inference machines working in a common environment. The present paper formulates several versions of the aggregation problem and investigates them from a recursion theoretic point of view.
Segmental arrangement of reticulospinal neurons in the goldfish hindbrain.

The hindbrain is evolutionarily conserved among diverse vertebrate phyla. In vertebrate embryos, the hindbrain is segmentally organized as a series of overt swellings known as rhombomeres. In the larval zebrafish Brachydanio rerio, conspicuous and identifiable reticulospinal neurons are positioned in the center of rhombomeres. Segmentally homologous reticulospinal neurons that share a range of morphological, developmental, and biochemical features occupy adjacent rhombomeres. We have recently shown that reticulospinal neurons of the zebrafish survive ontogeny without considerable morphological modification and we suggested that homologous neurons may share similar functions at different stages of development (Lee and Eaton: Journal of Comparative Neurology 304:34–52, 1991). The goldfish Carassius auratus, a related cyprinid, is especially suited for neurophysiological and behavioral studies. However, it is not yet known if the various reticulospinal neurons of zebrafish are generalizable to other species such as the goldfish. Therefore, we sought to examine the extent to which reticulospinal neurons of the zebrafish are also present in the adult goldfish. Analysis of 45 brains retrogradely labeled with horseradish peroxidase (HRP) from the spinal cord showed that reticulospinal neurons are arranged as a series of seven segments within the hindbrain; a regular interval of approximately 200 μm separates adjacent segments. Although the goldfish reticulospinal system has more neurons than the zebrafish, many reticulospinal neuron types continue to be identifiable. Moreover, comparisons of dendritic arborizations and axon paths between the two species showed that the morphology between various neuron types is virtually identical. The cross-taxonomic similarities between the reticulospinal systems of these related cyprinids make it possible to pursue functional considerations of segmentally homologous neurons in the goldfish hindbrain. © 1993 Wiley-Liss, Inc.
Proton Upsets in Orbit

This paper presents a method of predicting proton-induced single event upset rates in spacecraft RAMs. The approach uses a sensitivity parameter A, determined from one or more experimental measurements of upset cross sections made at any proton energy above threshold. Parameter A uniquely determines a curve for the energy dependence of the upset cross section. This curve can be combined with the proton spectrum at the RAM to predict its upset rate. Predicted upset rates for 600 circular orbits are presented.
Dynamics of two atoms in a quantized radiation field

Abstract We study a model with two atoms interacting with a single-mode quantized radiation field. We show the detailed quantum collapse and “revivals” in our system.
Buried lysine, but not arginine, titrates and alters transmembrane helix tilt

The ionization states of individual amino acid residues of membrane proteins are difficult to decipher or assign directly in the lipid–bilayer membrane environment. We address this issue for lysines and arginines in designed transmembrane helices. For lysines (but not arginines) at two locations within dioleoyl-phosphatidylcholine bilayer membranes, we measure pKa values below 7.0. We find that buried charged lysine, in fashion similar to arginine, will modulate helix orientation to maximize its own access to the aqueous interface or, if occluded by aromatic rings, may cause a transmembrane helix to exit the lipid bilayer. Interestingly, the influence of neutral lysine (vis-a-vis leucine) upon helix orientation also depends upon its aqueous access. Our results suggest that changes in the ionization states of particular residues will regulate membrane protein function and furthermore illustrate the subtle complexity of ionization behavior with respect to the detailed lipid and protein environment.
Multiphase materials with lignin: 2. Blends of hydroxypropyl lignin with poly(vinyl alcohol)

Abstract Polymer blends consisting of hydroxypropyl lignin (HPL) and poly(vinyl alcohol) (PVA) hydrolysed to the extent of 75, 88 and 96% were prepared by casting from dimethylformamide solution. The resulting films were studied with regard to their morphology by scanning electron microscopy, differential scanning calorimetry and dynamic mechanical thermal analysis. Results suggest that HPL/PVA blends form homogeneous and at least partially miscible materials (with separated phases of A at any composition. This is attributed both to similarity in solubility parameter and to the formation of hydrogen bonds. Supporting evidence is derived from scanning electron microscopy of freeze-fractured surfaces, from quantitative melt endotherm measurements, and from measurements of the position and range of glass transition temperatures.
Still no demonstration that g is not unitary: Further comment on Kranzler and Jensen

Abstract In their reply to my critique (Carroll, 1991), Kranzler and Jensen (1991b) have still not demonstrated that a factor of general intelligence, g, depends on or “contains” a number of independent processes. All that they have demonstrated is that an estimate of g is predictable from a number of independent components statistically derived from a matrix of correlations among various elementary cognitive tasks (ECTs). But on the basis of correlations between ECTs and psychometric tests, the estimate of g derived from the psychometric tests is likely to contain variance identifiable with variance from ECTs that is independent of g, and to that extent, the estimate of g contains “impurities” which are predictable from ECTs. This does not necessarily imply that g itself contains a number of independent components. I point out sources of Kranzler and Jensen's misunderstanding of this argument, and make suggestions as to possible approaches to assessing whether g is unitary or not.
Multiple murine BRafV600E melanoma cell lines with sensitivity to PLX4032

The BRAFV600E mutation, which approaches 50% in human melanomas, constitutively activates pERK and contributes to disease progression. The BRAFV600E inhibitor, Vemurafenib (PLX4032), shows promising clinical responses, but resistance to PLX4032 usually develops within a year. Transgenic mouse models allow the study of BRafV600E melanoma in vivo, however in vitro models are necessary to better understand the molecular mechanism underlying disease progression and resistance. We established melanoma cell lines (D4M cells) from the conditional mouse model of metastatic melanoma: Tyr::CreER;BrafCA;Ptenlox/lox, which recapitulates human disease. Cultured D4M cells express high constitutive pERK. PLX4032 abrogates ERK phosphorylation, inhibits D4M proliferation, and increases expression of the melanoma associated antigen, pmel, in vitro, consistent with human BRAFV600E melanoma cell lines. D4M cells are transplantable in either immune-compromised or syngeneic B6 mice. Thus, D4M cell lines allow correlation of in vitro studies on molecular mechanisms of melanoma with in vivo investigations on pathology and immunology.
Heterogeneous Atomistic-Continuum Representations for Dense Fluid Systems

We present a formulation and numerical solution procedure for heterogeneous atomistic-continuum representations of fluid flows. The ingredients from atomistic and continuum perspectives are non-equilibrium molecular dynamics and spectral element, respectively; the matching is provided by a classical procedure, the Schwarz alternating method with overlapping subdomains. The technique is applied to microscale flow of a dense fluid (supercritical argon) in a complex two-dimensional channel.
Reliability of Methadone Plasma Levels in Methadone Maintenance

The authors investigated the intra-individual variability of methadone plasma levels in stable metbadone-mainte-nance patients. Methadone trough levels were obtained from 11 male subjects on Monday, Wednesday, and Friday of the same week. Urine toxicology screens, hematocrit, serum proteins, and liver function tests were obtained at the same time. There was no significant intra-individual variation in methadone levels. The mean coefficient of variation was 7.9%, and the coefficient of variation was inversely related to dose. Thus, the average range of plasma levels was ± 20 ng/ml across dosages. There was no relationship between the other blood studies and methadone level or variability. Therefore, a single methadone trough level may be used to determine adequacy of dosage in most cases.
New vector-like interactions: constraints from kaon physics and from μ→eγ

Abstract Bounds on rare processes can provide severe constraints on non-standard effective interactions which arise in certain extensions of the standard model. We point out how the K 0 − K 0 mass difference and the rate for μ → eγ can be used to constrain vector-like effective four-fermion operators, and discuss the effects of these operators on other rare kaon decays.
Existence of Solutions to the Hamilton–Jacobi–Bellman Equation under Quadratic Growth Conditions

Abstract In this paper we show the existence of solutions with quadratic growth to Hamilton–Jacobi–Bellman equations. We assume that the Hamiltonian has the quadratic growth both in x and p. We obtain the explicit Lipschitz bound of solutions in the weighted sup-norm. Also, we discuss the vanishing viscosity limit of solutions and show the existence of viscosity solutions to the resulting Hamilton–Jacobi equation.
Clinical pharmacokinetics of antibacterial drugs in the elderly. Implications for selection and dosage.

A review of the clinical pharmacokinetics of antibiotics in the healthy elderly reveals that for most compounds a decrease occurs in renal clearance (associated with age-related decreases in renal function), as well as a prolonged half-life and increased area under the plasma concentration-time curve. These changes are amplified in the sick infected elderly. It is important that the treating physician be aware of the potential side-effects of antimicrobial agents, and whenever possible choose those which are associated with the least adverse effects. Individual patient variability, including underlying diseases and other prescribed medications, must be taken into account when dosage is selected. beta-Lactam compounds have a remarkable safety record: specifically in the elderly, their therapeutic/toxic ratio is much higher than that observed with aminoglycosides. Regimens for this class of drugs in the elderly should maintain antibiotic concentrations above the minimum inhibitory concentrations for maximum efficacy. In the treatment of elderly patients, it is suggested that dosage and interval be based on estimated or measured creatinine clearance. Usually, for drugs that are excreted primarily by the kidney (i.e. amino-glycosides, beta-lactams and quinolones), dosage intervals must be increased when there is an associated fall in creatinine clearance. The pharmacokinetic parameters suggest that as an alternative to increasing dosage interval the usual dose may be decreased, but further studies are necessary for confirmation.
Sorption of water, carbon dioxide and nitrogen by sol—gel thorium oxide

Abstract Sol gel thoria is an agglomerate of microcrystallites held together in a semirigid matrix. A layer of sorbed water bridges the intercrystalline contacts. Prolonged evacuation is required to remove this sorbed layer. Prizing penetration can occur by again introducing a high relative pressure of water vapor. Stringent outgassing (
Jewish Women in Therapy: Seen But Not Heard

Contents Preface * Introduction * The Generation of Survivors * The Issue of Power: Some Notes on Jewish Women and Therapy * Therapy's Double Dilemma: Anti-Semitism and Mysogyny * Jewish Feminism and Women's Identity * How Is This Feminist Therapist Different from All Other Feminists? Or, My Journey from Pirke Avot to Feminist Therapy Ethics * Reflections of a Jewish Lesbian-Feminist Activist-Therapist Or, First of All I Am Jewish, the Rest Is Commentary * The Missing * Clearance Sale * But You Don't Look Jewish! * A Feminist Perspective on Intermarriage * Midlife Transitions Among Jewish Women: Counseling Issues * All in the Family: Violence in the Jewish Home * Cultural Undertones in Therapeutic Work with a Psychotic Jewish Patient * Anti-Semitism in the Therapy Room
A Brief Moment for a One-Person Remnant (2 Kings 5:2-3)

The positive use of "remnant" in the First Testament characteristically refers to a self-conscious, self-aware, and often self-serving community that claims the future of Israel for itself (see Hasel). This article considers a "remnant" figure who is not self-conscious or self-aware, and certainly not self-serving. It refers to the "young girl" in 2 Kings 5:2-3. Her appearance in Israel's text is brief. She is assigned no important role by the text and is given no name. Moreover, her appearance is confined to two verses, and she is nowhere remembered or cited in any subsequent text. She is so incidental in her one narrative appearance that she is scarcely noticed. And yet, the article suggests, she is the pivotal character who makes this entire narrative of chapter 5 possible.
Formaldehyde oxidation on Pt: Kinetic evidence for adsorbed carbon monoxide intermediate

Abstract Kinetics of the Pt-catalyzed oxidation of formaldehyde are shown to be similar to CO oxidation kinetics. The data are consistent with a mechanism of H 2 CO oxidation involing dissociative adsorption as CO(a) and H(a) followed by surface reaction with O(a) to produce CO 2 (g) and H 2 O(g).
Quasi-Stationary Waves in the Southern Hemisphere: An Examination of Their Simulation by the NCAR Climate System Model, with and without an Interactive Ocean*

Abstract The three primary quasi-stationary waves in the geopotential height field of the Southern Hemisphere, as simulated by the National Center for Atmospheric Research (NCAR) Climate System Model (CSM1) and the Community Climate Model, version 3 (CCM3), are examined and compared with the NCAR–National Centers for Environmental Prediction reanalyses. Fourier analysis is used to decompose the geopotential heights into its zonal harmonic components. Both models are able to simulate the mean and zonal asymmetry of the geopotential heights; however, the CSM1 simulates the interannual variability considerably better than the CCM3. The amplitude and phase of wave 1 are well simulated by the models, particularly in the subantarctic region. The models are also able to reproduce the interannual variation in phase and amplitude of wave 1. The success of the simulation is attributed to the models’ ability to simulate well the important features of the geopotential height and temperature distributions. The models ...
Emergent Literacy: Ways to Foster These Skills in Preschool Children from Low-Socioeconomic Backgrounds

Emergent literacy skills are important for children's academic achievement. Many preschool children from low-socioeconomic backgrounds have limited access to experiences that allow them to acquire emergent literacy skills such as letter knowledge, concepts of print, and phonological awareness. This article describes purposeful and age-appropriate instructional strategies that can be used by parents, teachers, and health care providers to ensure that preschool children from such backgrounds receive adequate literacy experiences. These instructional techniques may also be an effective tool for reducing the achievement gap in children from disadvantaged backgrounds.
Nutritional and hormonal factors concerned with the regulation of liver protein synthesis during acute centrifugation stress.

Glucocorticoids and growth hormone factors concerned with regulation of liver protein synthesis during acute centrifugation stress
Thickness, Phase Retardation, Birefringence, and Reflectance of the Retinal Nerve Fiber Layer in Normal and Glaucomatous Non-Human Primates

Purpose. We identified candidate optical coherence tomography (OCT) markers for early glaucoma diagnosis. Time variation of retinal nerve fiber layer (RNFL) thickness, phase retardation, birefringence, and reflectance using polarization sensitive optical coherence tomography (PS-OCT) were measured in three non-human primates with induced glaucoma in one eye. We characterized time variation of RNFL thickness, phase retardation, birefringence, and reflectance with elevated intraocular pressure (IOP).
The neuroendocrine basis of lactation-induced suppression of GnRH: Role of kisspeptin and leptin

Lactation is an important physiological model of the integration of energy balance and reproduction, as it involves activation of potent appetitive neuropeptide systems coupled to a profound inhibition of pulsatile GnRH/LH secretion. There are multiple systems that contribute to the chronic hyperphagia of lactation: 1) suppression of the metabolic hormones, leptin and insulin, 2) activation of hypothalamic orexigenic neuropeptide systems NPY, AGRP, orexin (OX) and melanin concentrating hormone (MCH), 3) special induction of NPY expression in the dorsomedial hypothalamus, and 4) suppression of anorexigenic systems POMC and CART. These changes ensure adequate energy intake to meet the metabolic needs of milk production. There is significant overlap in all of the systems that regulate food intake with the regulation of GnRH, suggesting there could be several redundant factors acting to suppress GnRH/LH during lactation. In addition to an overall increase in inhibitory tone acting directly on GnRH cell bodies that is brought about by increases in orexigenic systems, there are also effects at the ARH to disrupt Kiss1/neurokinin B/dynorphin neuronal function through inhibition of Kiss1 and NKB. These changes could lead to an increase in inhibitory auto-regulation of the Kiss1 neurons and a possible disruption of pulsatile GnRH release. While the low levels of leptin and insulin contribute to the changes in ARH appetitive systems, they do not appear to contribute to the suppression of ARH Kiss1 or NKB. The inhibition of Kiss1 may be the key factor in the suppression of GnRH during lactation, although the mechanisms responsible for its inhibition are unknown.
Progress With Gain Measurements In Li-Like Ions At 15.4 Nm (A1XI) And 12.9 Nm (SiXII)

The sequence of Li-like ions represents an attractive avenue to progress to laser action at soft X-ray wavelengths shorter than those of current X-ray lasers1,2 (see also Refs. 3-6). We are exploring the possibilities for laser action at 15.4 nm in Li-like A1XI and 12.9 nm in Li-like SiXII in a magnetically confined recombining plasma. A ti 1 kJ CO2 laser is focussed onto an aluminum or silicon target assembly and the resulting plasma confined in a solenoidal magnetic field of up to 90 kG. This approach is similar to our previous work on hydrogen-like carbon, CVI, which led to lasing action on the n = 3 to m = 2 transition at 18.2 nm. For lithium-like ions we measure a maximum gain-length (gL) on the 4f-3d transition, of gL Rs 3-4 at 15.4 nm and gL % 1-2 at 12.9 nm. The 18.2 nm laser has been applied to microscopy and first results from a soft X-ray laser microscope are presented.
Multiple item capacitated random yield systems

Two main contributors to the uncertainty of production systems are capacity and random yield; therefore, strategies are needed that incorporate both random yield and the increased effect due to capacity restrictions. This paper utilizes dynamic programming and linear programming transformation to provides a method to specify an optimal decision for a given inventory state. In doing so, it can be empirically shown that the structure of the optimal policy is not an order-up-to policy. Using this method, one only needs to solve a small subproblem, which using LP transformation can be done using commercially available LP solvers without concern for solution time. These results may improve the decision-making capabilities of real-time complex environments since the emphasis is on developing policy rules that are easy to implement in manufacturing applications, as well as service industries such as airlines, healthcare and education. Additionally, the results may be used as a means of evaluating (bounding) existing approximation methods.
Respiratory Viral Infections in Adults With and Without Chronic Obstructive Pulmonary Disease

A longitudinal cohort study of older adults with chronic obstructive pulmonary disease (COPD) who were stratified by FEV(1) at enrollment was done to define the etiology, frequency, severity, and medical-care impact of respiratory tract viral infections (RTVIs). Controls consisted of a group of subjects of comparable age with the patients. RTVIs were documented in 44% of observed acute respiratory illnesses in control subjects and in 27% of COPD subjects, who were followed for mean periods of 35 and 26 mo, respectively. In this heavily influenza-vaccinated cohort ( approximately 90% vaccinated each year), picornaviruses, parainfluenza viruses, and coronaviruses were most commonly identified. Mean time to return to clinical baseline was approximately 2 wk in each group. Control and COPD subjects with mild airways obstruction (baseline FEV(1) >/= 50% predicted) had few emergency-center visits or hospitalizations. Approximately half of COPD subjects with moderate/severe COPD (baseline FEV(1) < 50% predicted) had at least one emergency-center visit and/or hospitalization for acute respiratory illness. RTVIs were documented in 23% of hospitalizations and in 45% of patients admitted between December and March. RTVIs have a major impact on utilization of health care resources for COPD patients with moderate/severe airways obstruction.
Association of common genetic variants with diabetes and metabolic syndrome related traits in the Arizona insulin resistance registry: A focus on Mexican American families in the southwest

Background/Aims The increased occurrence of type 2 diabetes and its clinical correlates is a global public health issue, and there are continued efforts to find its genetic determinant across ethnically diverse populations. The aims of this study were to determine the heritability of diabetes and metabolic syndrome phenotypes in the Arizona Insulin Resistance (AIR) registry and to perform an association analysis of common single nucleotide polymorphisms (SNPs) identified by GWAS with these traits. All study participants were Mexican Americans from the AIR registry.
Navigating between Scylla and Charybdis: Mitochondria are both precedented and novel targets for drug development

Biotechnology companies frequently struggle to convince potential partners or investors that the company's research is cutting-edge, but not so novel as to be an unattractive risk. MitoKor is a biotechnology company that focuses on the development of drugs that act on mitochondrial targets. From a review of the scientific literature, it is clear that a number of drugs act on mitochondrial pathways although that site of action was usually not recognized or understood during early-stage development. At the same time, only a small fraction of all mitochondrial proteins have been identified. Therefore, it appears that mitochondria are a source of both novel and precedented drug targets. With the rapid pace of scientific research, it will be a continuing challenge for biotechnology companies to navigate between being too novel and not being novel enough. Drug Dev. Res. 57:75–82, 2002. © 2002 Wiley-Liss, Inc.
Nd isotopic ages of crust formation and metamorphism in the Precambrian of eastern and southern Mexico

Sm-Nd ages for garnets in the three Precambrian exposures of eastern and southern Mexico demonstrate that they belong to the Grenville tectonothermal event. The Sm-Nd garnet ages of 0.95 Ga for the Oaxacan Complex and 0.90 Ga for the Huiznopala Gneiss, Molango and the Novillo Gneiss, Ciudad Victoria, are postdated 75 Ma by Rb-Sr ages on biotites. Both sets of data document a cooling history following Grenville metamorphism at or before 1.0 Ga ago. Our garnet data are consistent with a blocking temperature for Sm-Nd in that mineral around 600° C suggested by Humphries and Cliff (1982).
The Limits of Rainbow Nation Multiculturalism in the New South Africa: Spatial Configuration in Zakes Mda's Ways of Dying and Jonathan Morgan's Finding Mr. Madini

This essay explores the changing politics of place, ownership, and access to public space in the New South Africa. In the transition to a postapartheid South Africa, a robust theory of multiculturalism—Rainbow Nation Ideol- ogy-was employed to bring people together. But how does that relate to the redistribution of actual nation-space, in the sense of material urban space? Through the literary exegesis of two seminal texts, this essay attempts to address how and why Rainbow Nation Ideology is effective in the abstract sense of establishing democratic parity for South Africa's multicultural population but fails to address socioeconomic disparity.
Serfs: Dynamically-bound parameterized components

Parameterization is an effective technique for decoupling design decisions in software. Several languages such as C++ and Ada (and Java and C# more recently) offer language constructs for building parameterized software. Using template or generic constructs, one can postpone committing to specific design choices until the software system is ready for deployment. However, in cases where such choices are influenced by the execution environment, deployment time may not be late enough. Moreover, in the context of software systems that have to satisfy high availability constraints, or are long-running, changes in design choices may be warranted even after deployment. In this paper, we present a design pattern-based methodology for building parameterized components that support dynamic binding of parameters. Moreover, the methodology also supports dynamic re-binding of parameters in the event that such online change is required.
Ultrahigh vacuum instrument that combines variable-temperature scanning tunneling microscopy with Fourier transform infrared reflection-absorption spectroscopy for studies of chemical reactions at surfaces

We describe the construction of an ultrahigh vacuum chamber that incorporates variable-temperature scanning tunneling microscopy (STM), Fourier transform infrared reflection-absorption spectroscopy (FT-IRAS), Auger electron spectroscopy, low-energy electron diffraction, and temperature programmed desorption, for studying structure and reactivity at surfaces. The chamber and manipulator design enables in situ sample preparation and analysis, and rapid access to several surface-analytical techniques by rotation only. This eliminates sample inconsistencies due to ex situ preparation or the necessity to run parallel experiments. Inclusion of FT-IRAS allows us to characterize surface species and identify adsorbates during studies using STM.
Reconstitution of Glucosylceramide Flip-Flop across Endoplasmic Reticulum IMPLICATIONS FOR MECHANISM OF GLYCOSPHINGOLIPID BIOSYNTHESIS

Most glycosphingolipids are synthesized by the sequential addition of monosaccharides to glucosylceramide (GlcCer) in the lumen of the Golgi apparatus. Because GlcCer is synthesized on the cytoplasmic face of Golgi membranes, it must be flipped to the non-cytoplasmic face by a lipid flippase in order to nucleate glycosphingolipid synthesis. Halter et al. (Halter, D., Neumann, S., van Dijk, S. M., Wolthoorn, J., de Maziere, A. M., Vieira, O. V., Mattjus, P., Klumperman, J., van Meer, G., and Sprong, H. (2007) Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis. J. Cell Biol. 179, 101-115) proposed that this essential flipping step is accomplished via a complex trafficking itinerary; GlcCer is moved from the cytoplasmic face of the Golgi to the endoplasmic reticulum (ER) by FAPP2, a cytoplasmic lipid transfer protein, flipped across the ER membrane, then delivered to the lumen of the Golgi complex by vesicular transport. We now report biochemical reconstitution studies to analyze GlcCer flipping at the ER. Using proteoliposomes reconstituted from Triton X-100-solubilized rat liver ER membrane proteins, we demonstrate rapid (t(½) < 20 s), ATP-independent flip-flop of N-(6-((7-nitro-2-1,3-benzoxadiazol-4-yl)amino)hexanoyl)-D-glucosyl-β1-1'-sphingosine, a fluorescent GlcCer analog. Further studies involving protein modification, biochemical fractionation, and analyses of flip-flop in proteoliposomes reconstituted with ER membrane proteins from yeast indicate that GlcCer translocation is facilitated by well characterized ER phospholipid flippases that remain to be identified at the molecular level. By reason of their abundance and membrane bending activity, we considered that the ER reticulons and the related Yop1 protein could function as phospholipid-GlcCer flippases. Direct tests showed that these proteins have no flippase activity.
Sensitivity of Uncinula necator to quinoxyfen: evaluation of isolates selected using a discriminatory dose screen

Quinoxyfen is a protectant fungicide that provides excellent control of many powdery mildew diseases. Prior to the launch of quinoxyfen in vines in 1998, a leaf disc sporulation assay was developed to assess the sensitivity of Uncinula necator (Schw) Burr to quinoxyfen. The distribution of EC(50) values from 56 monoconidial U. necator isolates collected from six countries between 1993 and 1996 was found to range from less than 0.03 to 2.6 mg litre(-1). Although this range of EC(50) values was quite broad, the inability to establish a minimum inhibitory concentration (MIC) for the majority of these isolates, including some of the most sensitive isolates, was unexpected and suggested that the leaf disc sporulation assay may not reflect the true activity of quinoxyfen in the field. In 2002, following the detection of isolates resistant to quinoxyfen in Blumeria graminis Speer f. sp. tritici Marchal, a discriminatory dose screen was developed to test large populations of U. necator for rare individuals with significantly decreased sensitivity to quinoxyfen. The individual isolates selected by this method were tested with the leaf disc sporulation assay. Although a significant proportion were found to have EC(50) values within the original distribution, a number of isolates with apparent reduced sensitivity to quinoxyfen were also detected. However, further examination of a subset of these isolates in a more quantitative germination/germ tube elongation inhibition assay suggested that the magnitude of the reduction in sensitivity for some of these isolates was much less than predicted by the sporulation assay. Thus, for an exclusively protectant fungicide such as quinoxyfen, a leaf disc sporulation assay may overestimate the frequency of isolates with significantly reduced sensitivity and the threat of decreased performance due to resistance.
Disparate determinants of summer and winter diet selection of a generalist herbivore, Ochotona princeps

The North American pika, Ochotona princeps, is a generalist herbivore that simultaneously selects two distinct diets: one consumed immediately (summer diet), the other harvested, transported, and stored for later consumption (winter diet). I investigated factors influencing diet selection at two sites on the West Knoll of Niwot Ridge, Boulder County, Colorado during 1991 and 1992. The composition of summer and winter diets differed significantly from each other as well as from the relative abundance of food items in the environment. Thus, pikas were not foraging randomly for either diet. To explore winter and summer diet selection, I tested two existing hypotheses: (1) that plant morphology restricts the winter diet breadth to plants that are easily harvested and large, and thereby maximizes the amount collected per foraging effort, or (2) to compensate for nutrients lost during storage, pikas bias their winter diet with high-nutrient species. I also tested the hypothesis that plant secondary compounds may be higher in the winter diet either because they function as preservatives or because pikas delay consumption of these species until the toxins degrade. For individual dietary items, I measured energy, nitrogen, water, fiber, total phenolic, condensed tannin, and astringency contents. There was little evidence to suggest that morphology excluded plants from the winter diet. Plant size was not a good predictor of abundance in the winter diet. Even after harvesting costs had been experimentally removed, cushion plants were still not included in the winter diet. There was weak support for an effect of nutrients on winter diet selection; in three of four cases, the winter diet was significantly lower in water and higher in total energy content as predicted by the nutrient compensation hypothesis. However, other nutrients exhibited no consistent pattern. Nutrients were not reliable predictors of the winter diet in multiple regression analyses. There was strong support for the hypothesis of manipulation of secondary compounds. The winter diet was significantly higher in total phenolics and astringency. Total phenolics were consistent predictors of the winter diet in multiple regression analyses. The winter diets of six additional pika populations contained plant species high in secondary compounds. The results suggest that pikas preferentially select plants with high levels of secondary compounds for their winter diet, possibly because the presence of such compounds promotes preservation of the cache. This behavior may also enable the exploitation of an otherwise unusable food resource, i.e., toxic plants.
Vapor−Liquid Equilibria of Acetone, Diisopropyl Ether, Ethanol, and Methyl Ethyl Ketone with Hydrocarbon Mixtures at 101.3 kPa

Isobaric vapor−liquid equilibria (VLE) data were measured at 101.3 kPa on four oxygenates (acetone, diisopropyl ether, ethanol, and methyl ethyl ketone) separately with hydrocarbon mixtures. Acetone, ethanol, and methyl ethyl ketone were mixed with a five-component hydrocarbon mixture and diisopropyl ether was mixed with a four-component hydrocarbon mixture. Calculations of nonideality of the vapor phase were made with the Soave−Redlich−Kwong equation of state. The vaporization equilibrium ratio of oxygenate in the hydrocarbon mixture was derived. Analysis of the experimental VLE data exhibits a minimum boiling temperature for the systems containing acetone, ethanol, and methyl ethyl ketone. The experimental data have been correlated with the mole fraction of oxygenate using the Redlich−Kister-type and Wisniak−Tamir equations.
Technological newness: An empirical study in the process industries

Abstract Technological change in product development is a crucial issue in the management of technology. The entire sweep of technological changes over the past hundred of years is, in essence, the sum of thousands of individual product development projects in thousands of firms. Yet the degree of technological change in individual development projects has not been extensively studied. This paper presents a four-dimensional characterization of technological newness for product development projects in the process industries in which product development is closely tied to process innovation. The characterization uses four dimensions of change that are required in the development of new products: chemistry, production equipment, fabrication technology and process control. Based on the framework of technological newness, the paper presents data collected on the degree of process change in a set of 20 product development projects conducted by a large manufacturer of advanced polymers. The data provide a clear demonstration of the value of the measurement framework, showing a strong relationship between the characterization of change and the project performance.