cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 36: Virtual screening with deep learning using cancer cell line dose-response data

Current high-throughput ligand and structural virtual screening methods typically rely on the identification of a specific functional target for the screen; however, the relationship between cancer genetic phenotype and the specific functional target is not fully understood at the onset of drug development. Cancer cell line (CCL) screening panels are continually used to study the relationship between cellular genetic and ligand structure. We propose combining the speed of machine learning-based virtual screening techniques with the greater than four million in vitro cancer cell line data points generated from the NCI-60, GDSC, and CTRP cancer cell line screens. Using deep neural networks, we train a regression neural network on an integrated dataset of CCL to predict area under the dose-response curve (AUC). Molecules are characterized using the Mordred descriptor package and with a message-passing network on the structure of the molecule, and cell lines are represented by LINCS100 RNA-seq and SNP quantification data. We present two validation styles using our model on random unseen training drugs and by unseen scaffolds. On unseen drugs, the enrichment factor is 42% for the top 1% predictions and BEDROC score is 0.25, based on binning active compounds as the bottom 2% of the overall AUC distribution from the NCI-60. Using the model as a screening tool in inference mode, we scored 1 million compounds from Enamine REAL lead-like compounds on all NCI60 and CCLE cell lines, though the entire screening results will be forthcoming (>450M compounds screened). Initial results show compounds screened by the model have a higher rate of bioactivity just based on the PubChem listings. We verify the robustness of the virtual screen by presenting common functional groups across highly scored drugs and finding stability across small perturbations both to the featurization and molecular structure. For molecules listed in PubChem, the top 10% of predicted compounds had 10x the bioactivity ranking than the bottom 10% of predictions from our model. We present a new high-throughput method for cancer drug virtual screening using CCL dose response. Our method utilizes aggregated data from in vitro CCL panels to train the dose-response model and is a multiclass model across all common CCLs. While we believe this technique is valuable for the community as a tool for integrating experimental cancer cell line data into existing virtual screening infrastructure, we acknowledge verification with in vitro testing outside the model validation data needs to be addressed in future work. Citation Format: Austin Clyde, Arvind Ramanathan, Rick Stevens. Virtual screening with deep learning using cancer cell line dose-response data [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 36.
Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice.

Purpose Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy plays a central role in the management of neovascular age-related macular degeneration (nAMD), diabetic retinal disease (DRD), and retinal venous occlusive disease (RVO). Within clinical trials, rates of systemic serious adverse events (SAEs) after anti-VEGF treatment have been low. However, the comparative systemic safety profile of common anti-VEGF agents remains incompletely understood. The goal of this study was to compare the systemic safety of intravitreal bevacizumab, ranibizumab, and aflibercept in real-world practice. Design Retrospective cohort study. Participants Using a large U.S. administrative claims database of commercially insured and Medicare Advantage enrollees, we identified adult cohorts receiving initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018. We included patients with 1 year of insurance coverage before initial treatment. Methods We compared predefined systemic outcomes between anti-VEGF agents occurring within 180 days of treatment initiation using propensity score–weighted Cox proportional hazards models. Patients were censored upon treatment with a different anti-VEGF medication or termination of health plan coverage. Main Outcome Measures Primary outcomes were acute myocardial infarction (MI), acute cerebrovascular disease (CVD), major bleeding, and all-cause hospitalization. Results A total of 87 844 patients received initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018 (69 007 bevacizumab; 10 895 ranibizumab; 7942 aflibercept). Postinjection 180-day event rates per 100 patients for MI, CVD, major bleeding, and all-cause hospitalization were similar for bevacizumab (0.64, 0.59, 0.34, and 10.41, respectively), ranibizumab (0.62, 0.53, 0.40, and 9.44, respectively), and aflibercept (0.63, 0.60, 0.20, and 9.88, respectively). No differences were identified for the risk of MI, CVD, major bleeding, or all-cause hospitalization when comparing the risk-adjusted effect of treatment initiation with bevacizumab versus ranibizumab (hazard ratio [HR], 0.96 [95% confidence interval {CI}, 0.74–1.25]; HR, 1.04 [95% CI, 0.78–1.38]; HR, 0.85 [95% CI, 0.61–1.19]; HR, 1.03 [95% CI, 0.96–1.10], all P > 0.05), bevacizumab versus aflibercept (HR, 0.95 [95% CI, 0.68–1.33], HR, 0.99 [95% CI, 0.71–1.38], HR, 1.02 [95% CI, 0.60–1.74], HR, 1.01 [95% CI, 0.93–1.10], all P > 0.05), or aflibercept versus ranibizumab (HR, 0.91 [95% CI, 0.62–1.35], HR, 1.12 [95% CI, 0.74–1.69], HR, 0.96 [95% CI, 0.53–1.73], HR, 1.02 [95% CI, 0.92–1.13], all P > 0.05). Conclusions We observed no differences in the risk of acute MI, CVD, major bleeding, or all-cause hospitalization after treatment initiation with intravitreal bevacizumab, ranibizumab, or aflibercept during routine clinical practice.
Welfarism and Axiomatic Bargaining Theory

Welfarism is a property of a social choice rule (SCR). Let X be a set of social alternatives, / a finite set of cardinality η of agents, and U a set of possible utility functions for the agents, defined on X. A SCR / is a correspondence from Un into X ; it associates with each profile u a set of socially acceptable alternatives. Define the utility possibilities set associated with the profile u and set X as:
Identifying Problematic Item Characteristics With Small Samples Using Mokken Scale Analysis

Researchers frequently use Mokken scale analysis (MSA), which is a nonparametric approach to item response theory, when they have relatively small samples of examinees. Researchers have provided so...
Tone behavior of the double loop /spl Sigma//spl Delta/ modulator with unstable filter dynamics

In this paper we analyze the tone behavior of the double loop /spl Sigma//spl Delta/ modulator with unstable filter dynamics. We show that some unstable limit cycles have an attractor region in their neighborhood which results in tones in the spectrum corresponding to the fundamental or harmonics of these limit cycles. We develop the tools to determine whether or not an unstable limit cycle has an attractor in its neighborhood and obtain a method to approximate the boundaries of these attractors. We then propose a novel /spl Sigma//spl Delta/ structure for tone removal. >
Growth of a community: ASBMB project to create resources to support the biochemistry and molecular biology community and education (348.1)

A consortium of federal and private foundations with biological scientific community resulted in the creation of the strategic document/plan “Vision and Change in Undergraduate Education, a Call to Action”. Principle findings of the plan include a need for core concepts and competencies, building communities for cultural change to develop educational scholars. In support of the key points of “Vision”, the National Science Foundation established the Research Coordination Networks-Undergraduate Biology Education program to support such collaborations. The ASBMB has been a participant in both programs and in 2010 was funded an NSF RCN-UBE to engage the BMB community to create core concepts in the field, generate a central resource to support the concepts and their assessment. The initial phase of the project involved starting the BMB community to ask key questions about core concepts and unpack the important components of each concept. Using surveys, small, regional and national meetings a series of core con...
Epidermal growth factor receptor binding is not a simple one-step process

The binding kinetics of 125I-labeled mouse epidermal growth factor (EGF) to receptors on human fibroblast cells in monolayer culture were measured at 4 degrees C. Initial binding rates as a function of hormone concentration allowed estimation of simple two-state on-off rate constants of 1.2 x 10(6) M-1 s-1 and 4.9 x 10(-3) s-1, respectively. These two-state parameters gave inadequate computer fits to long term kinetic and equilibrium-binding data, suggesting that an additional process(es) was occurring. Nonlinear equilibrium Scatchard plots and transient "pseudo-Scatchard" plots taken at pre-equilibrium times support the idea that at least one other process is occurring during receptor binding. 125I-EGF-receptor dissociation kinetic plots were biphasic, yielding rate constants of 1.5 x 10(-2) s-1 and 5.6 x 10(-5) s-1 with the ratio of the two components changing with the time of initial incubation with 125I-EGF. Application of a ternary complex model which assumed complexation of the bound receptor with a cell surface interaction molecule gave satisfactory fits to all data.
Characterization of structural and immunological properties of specific domains of Friend ecotropic and dual-tropic murine leukemia virus gp70s.

Abstract A detailed comparison of the gp70 proteins of cloned ecotropic Friend murine leukemia virus (FLV) and dual-tropic Friend mink focus-forming virus (FrMCF) was performed by analyzing the structural and immunological properties of amino- and carboxy-terminal domains of these molecules generated upon controlled trypsinization. The two gp70s gave characteristic fragmentation patterns; the amino-terminal fragments of FrMCF gp70 were smaller than the corresponding fragments of FLV and contained a trypsin site which resulted in a 19,000-dalton amino-terminal fragment not observed for FLV, whereas both molecules yielded an identically sized carboxy-terminal fragment. All amino-terminal fragments of both gp70 molecules contained an endo H-sensitive oligosaccharide chain; for FrMCF, a second endo H-sensitive carbohydrate was present as well at a carboxy-terminal site for approximately 50% of the molecules. Several aspects of the disulfide interactions of the two gp70s were conserved; in both cases the carboxy-terminal fragments were disulfide bonded to p15(E), there were no disulfide bonds between amino- and carboxy-terminal fragments, and the amino-terminal fragments exhibited a significant increase in mobility upon analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. Analysis of the immunoreactivity of the different domains of the proteins by immunoprecipitation of the fragments with antisera prepared against xenotropic murine leukemia virus and feline leukemia virus gp70s indicated major differences in antigenicity for the amino-terminal domains of FLV and FrMCF gp70, whereas the carboxy-terminal domains were immunologically conserved. Similar analyses with antibodies specific for p15(E) and Pr15(E) demonstrate that these components are conserved as well. These data provide direct evidence that p15(E) and the C-terminal gp70 domain of FrMCF gp70 are related to the corresponding regions of the ecotropic FLV parent and indicate that the acquisition of MCF-specific properties is due to the replacement of the ecotropic amino-terminal gp70 domain with sequences related to those of xenotropic gp70s.
Masculinity, Femininity and the Development of Sexual Orientation in Women

Abstract In an analysis that focuses exclusively on women, the authors argue that gender nonconformity is not the key to understanding women's sexual orientation. Instead, they assert, the associations among masculinity, femininity and women's sexual orientation are diverse and vary across time and place. To develop this perspective, this paper reviews research on biological processes, childhood gender nonconformity, and adult masculinity and femininity. It also draws on historical and cross-cultural accounts and considers the important but neglected role that financial self-sufficiency plays in the lives of women. The authors urge the adoption of a new paradigm recognizing that the development of women's sexual orientation can follow diverse developmental pathways shaped by multiple biological, social and cultural influences.
Successful treatment of an excimer laser-associated coronary artery perforation with the stack perfusion catheter

A 64-year-old woman underwent excimer laser angioplasty of the right coronary artery. The procedure was complicated by perforation, which was successfully managed without complication with a Stack perfusion catheter. This report describes successful nonsurgical treatment of laser-induced coronary perforation and makes recommendations for avoiding this complication in other patients.
Fundamental Chemical Processes in a Low-Density 27-MHz Helium ICP

A variable-pressure 27-MHz helium plasma was investigated in order to study the physical chemical nature of the inductive coupling and the microscopic atomic and molecular state variations which attend regular manipulations of plasma power and of helium pressure. Two modes of helium plasma excitation, the E- and H-plasma modes, are identified by widely differing capacities to effect ionization of other plasma species such as argon atoms. The switch from the helium E- to the H-plasma is abrupt and dependent on the gas pressure. The results presented suggest that it is the production of He+ and electrons and subsequent interactions in the plasma (electron recombination, collisions, etc.) which primarily determine the microscopic atomic and molecular behavior which we observe.
A neural circuit mechanism for regulating vocal variability during song learning in zebra finches

Motor skill learning is characterized by improved performance and reduced motor variability. The neural mechanisms that couple skill level and variability, however, are not known. The zebra finch, a songbird, presents a unique opportunity to address this question because production of learned song and induction of vocal variability are instantiated in distinct circuits that converge on a motor cortex analogue controlling vocal output. To probe the interplay between learning and variability, we made intracellular recordings from neurons in this area, characterizing how their inputs from the functionally distinct pathways change throughout song development. We found that inputs that drive stereotyped song-patterns are strengthened and pruned, while inputs that induce variability remain unchanged. A simple network model showed that strengthening and pruning of action-specific connections reduces the sensitivity of motor control circuits to variable input and neural ‘noise’. This identifies a simple and general mechanism for learning-related regulation of motor variability. DOI: http://dx.doi.org/10.7554/eLife.03697.001
A semisynthesis platform for investigating structure-function relationships in the N-terminal domain of the anthrax lethal factor

Many bacterial toxins act by covalently altering molecular targets within the cytosol of mammalian cells and therefore must transport their catalytic moieties across a membrane. The Protective-Antigen (PA) moiety of anthrax toxin forms multimeric pores that transport the two enzymatic moieties, the Lethal Factor (LF) and the Edema Factor, across the endosomal membrane to the cytosol. The homologous PA-binding domains of these enzymes contain N-terminal segments of highly charged amino acids that are believed to enter the pore and initiate N- to C-terminal translocation. Here we describe a semisynthesis platform that allows chemical control of this segment in LFN, the PA-binding domain of LF. Semisynthetic LFN was prepared in milligram quantities by native chemical ligation of synthetic LFN14−28αthioester with recombinant N29C-LFN29−263 and compared with two variants containing alterations in residues 14−28 of the N-terminal region. The properties of the variants in blocking ion conductance through the PA ...
Complication of pellagra in anorexia nervosa

A 16 year old girl presented to the emergency department with a low body mass index and skin changes.⇑ …
How hyphae grow: Morphogenesis explained?

Apical growth of fungal hyphae represents a relatively simple instance of cellular morphogenesis. Thanks to the polarized transport and exocytosis of precursor vesicles, new cell wall and plasma membrane are continuously deposited at the hyphal apex; the question is how the characteristic shape of tube and tapered tip comes about. Recent experiments lend support to a model whose central feature is a mobile vesicle supply center corresponding to the Spitzenkorper (apical body) visible in growing hyphae. Shapes predicted by the model agree remarkably well with those of actual hyphae. Nevertheless, critical examination of the model's premises suggests that it requires extension so as to incorporate both a driving force for expansion and a gradient of cell wall plasticity. I propose that a mobile vesicle supply center may be one, but only one, of a range of physiological devices employed by tip-growing organisms to localize the exocytosis of precursor vesicles. Apical growth should ensue whenever the loci of exocytosis advance vectorially, and nascent cell wall expands in a graded manner.
Mesomorphism in the 4,4′-Dialkoxy-trans-Stilbenes

Abstract In order to ascertain the effect of linkage groups (X[dbnd]Y) in mesomorphic substances of the general formula a homologus series of stilbenes has been prepared, where R[dbnd]Cn, H2n+1O—, X[dbnd]Y[dbnd]CH. The lower members of the series (1 ≤ n ≤ 10) are monotropic nematic, while the higher members (12 ≤ n ≤ 16) are monotropic smectic substances. The mesophase-isotropic transition temperatures are higher than those reported for the related nitrones (X[dbnd]CH, Y[dbnd]N → O) and Schiff Bases (X[dbnd]CH, Y[dbnd]N). Also the entropies of the nematic-isotropic transitions, as measured by differential scanning calorimetry, are nearly the same in the stilbenes and the nitrones. These results suggest that the permanenet dipole associated with the linkage group plays a relatively unimportant role in enhancing the intermolecular attractions which are responsible for mesomorphic alignment.
High sensitivity quantitative lipidomics analysis of fatty acids in biological samples by gas chromatography–mass spectrometry ☆

Historically considered to be simple membrane components serving as structural elements and energy storing entities, fatty acids are now increasingly recognized as potent signaling molecules involved in many metabolic processes. Quantitative determination of fatty acids and exploration of fatty acid profiles have become common place in lipid analysis. We present here a reliable and sensitive method for comprehensive analysis of free fatty acids and fatty acid composition of complex lipids in biological material. The separation and quantitation of fatty acids are achieved by capillary gas chromatography. The analytical method uses pentafluorobenzyl bromide derivatization and negative chemical ionization gas chromatography-mass spectrometry. The chromatographic procedure provides base line separation between saturated and unsaturated fatty acids of different chain lengths as well as between most positional isomers. Fatty acids are extracted in the presence of isotope-labeled internal standards for high quantitation accuracy. Mass spectrometer conditions are optimized for broad detection capacity and sensitivity capable of measuring trace amounts of fatty acids in complex biological samples. .
Disassembly sequencing problem: a case study of a cell phone

Selection of an optimal disassembly sequence is essential for the efficient processing of a product at the end of its life. Disassembly sequences are listings of disassembly actions (such as the separation of an assembly into two or more subassemblies, or removing one or more connections between components). Disassembly takes place in remanufacturing, recycling, and disposal with a disassembly line being the best choice for automation. In this paper, the disassembly sequencing problem is solved for a cell phone case on a disassembly line, seeking a sequence which is feasible, minimizes the number of workstations (and hence idle times), provides for early removal of high demand/value parts, provides the removal of parts that lead to the access of greatest number of still-installed parts, and early removal of hazardous parts as well as for the grouping of parts for removal having identical part removal directions. Since finding the optimal sequence is computationally intensive due to factorial growth, a heuristic method is used taking into account various disassembly-specific matters. Using the experimentally determined precedence relationships and task times of a real-world cell phone, a MATLAB program is designed and a sequencing solution is generated. Finally, Design for Disassembly (DFD) improvements are recommended with respect to environmentally conscious manufacturing.
Control System and Task Environment Effects on Ethical Judgment: An Exploratory Study of Industrial Salespeople

The objective of this research was to determine the effects of a firm's control system and dimensions of the work task environment upon ethical judgments made by salespeople. Industrial field salespeople are likely to encounter ethical conflicts on a daily basis in their dealings with customers, competitors, and their own management. How they resolve such conflicts is believed to be a function of both individual characteristics and factors in the situation. This study focuses on situational factors in the form of organization design variables, particularly control system and task environment. The firm's control system includes its method of monitoring, supervising and compensating salespeople. The study develops fourteen ethics-related selling scenarios and assesses, via projective questioning, how 446 salespeople would react to them. Findings indicate that organization design does influence the behavior a salesperson considers appropriate to cope with ethical conflicts. In particular, salespeople operating under a more bureaucratic, input-based control system advocate more ethical behavior than do salespeople operating under a more output-based, laissez-faire control system. Also, salespeople who perceive the market to be competitive recommend less ethical behavior. However, the proportion of salary versus commission in the salesperson's compensation system does not have an effect on response. Differences are also discovered with respect to the salesperson's seniority, rank, and certain features of the task environment.
Nonresonant Spectral Hole Burning in a Spin Glass

Large-amplitude low-frequency magnetic fields are found to burn spectral holes in the response of a $5%$ Au:Fe spin glass. There is negligible overlap between the degrees of freedom influenced by the highest and lowest frequencies. For sufficiently large fields, selected parts of the sample can be heated above the transition while the rest of the sample remains a spin glass. The return to equilibrium after heating indicates that the slow degrees of freedom are coupled to the thermal bath, but not strongly to each other. All prominent features are modeled by a distribution of independent domains, with the same relaxation time for local response and recovery.
Fortification of Cornbread with Lysine

Abstract LEARNING OUTCOME: To develop a lysine fortified cornbread acceptable to five year old children. Foods of plant origin do not provide complete proteins that promote growth in children. The limiting amino acid in flour and corn is lysine. The addition of lysine to a diet of corn and wheat products provides a source of complete protein. Lactalbumin, whey protein concentrate, is available in a high lysine formulation (11.8g./100g.). The purpose of this study was to produce an acceptable lysine fortified cornbread that would provide 25% of the daily recommended amount of lysine for a five year old child. The bread was tested for acceptance using sensory evaluation and a simplified hedonic "smiley" scale and objectively rated by photographic means. Children enrolled in the Center for Child Studies at Southeast Missouri State University (n=19), mean age 4.68 years, tasted the control and lysine fortified cornbread and colored either a smiley or frowny face to indicate like or dislike. Data were analyzed using SPSS ver. x. No significant differences were found. Of the 19 children participating, 13 "liked" the fortified bread. The same number of children "liked" the control indicating that the negative responses were likely to reflect a dislike for cornbread rather than a dislike for the fortified product. These results suggested that whey fortification in cornbread may be acceptable and provide an improved source of dietary protein
Can Artificial Soil be Used in the Vegetative Vigor Test for US Pesticide Registration

Current testing guidelines for pesticide registration for the protection of nontarget plants calls for the use of sterilized, standardized soil consisting of primarily sandy loam, loamy sand, loamy clay, or clay loam that contains up to 3% organic matter. Low organic matter soils can be difficult to manage in a greenhouse setting because when soils dry, they contract, causing impeded water infiltration, or when overwatered, poor drainage increases the chances of anaerobic conditions. The purpose of this study was to determine if the results for the vegetative vigor test differed when using either natural or artificial soils. The herbicide sulfometuron methyl was applied 14 d after emergence at 0.1 and 0.0032 of the suggested field application rate. Six plant species were tested, 4 of the common test species, Zea mays (corn), Glycine max (soybean), Avena sativa (oat), and Lactuca sativa (lettuce), and 2 native plants of the Willamette Valley, Oregon prairie, Bromus carinatus (California brome) and Ranunculus occidentalis (western buttercup). Herbicide application rate was the most significant factor in the experiment regardless of soil type. The different soils generally produced different results, even though the 2 native soils, one from Oregon and the other from Maryland, are both acceptable soils for the pesticide registration tests. The plants grown on artificial soil produced results generally between the Oregon and Maryland soil results. This study indicates that artificial soils may produce results similar to or more sensitive than soils currently used in the vegetative vigor test.
Functional Reconstitution of Endothelial Nitric Oxide Synthase Reveals the Importance of Serine 1179 in Endothelium-Dependent Vasomotion

Phosphorylation of endothelial nitric oxide synthase (eNOS) at serine 1179 can activate the enzyme, leading to NO release. Because eNOS is important in regulating vascular tone, we investigated whether phosphorylation of this residue is involved in vasomotion. Adenoviral transduction of endothelial cells (ECs) with the phosphomimetic S1179DeNOS markedly increased basal and vascular endothelial cell growth factor (VEGF)-stimulated NO release compared with cells transduced with wild-type virus. Conversely, adenoviral transduction of ECs with the non-phosphorylatable S1179AeNOS suppressed basal and stimulated NO release. Using a novel method for luminal delivery of adenovirus, transduction of the endothelium of carotid arteries from eNOS knockout mice with S1179DeNOS completely restored NO-mediated dilatation to acetylcholine (ACh), whereas vasomotor responses in arteries transduced with S1179AeNOS were significantly attenuated. Basal NO release was also significantly reduced in arteries transduced with S1179AeNOS, compared with S1179DeNOS. Thus, our data directly demonstrate that phosphorylation of eNOS at serine 1179 is an important regulator of basal and stimulated NO release in ECs and in intact blood vessels.
Microstructural and tribological characterization of laser surface engineered VC coating on tool/die steel

A successful effort has been made to deposit vanadium carbide on AISI H13 steel using Nd:YAG laser. A search for an ideal coating and equally suitable coating method for various applications will always be an interesting and challenging area in surface engineering. In the present study, a continuous, adherent, crack-porosity-free coating—composite in nature—has been obtained, which can serve as a protective tool for various surfaces. To explore the properties of this coating in greater detail, it has been evaluated for chemical, structural, mechanical, and tribological properties. It shows very high hardness and excellent wear resistance as compared to substrate H13 steel.
Metrology for micro-optics at NIST with μXCALIBIR

Microlenses play a key role in photonic devices for the applications such as communications, medical imaging, wavefront detection, machine vision and others. Microlenses can be either refractive or diffractive with apertures ranging from few tens of µm to about a mm. Lenses can be made as discrete lenses but for may applications lens arrays are fabricated. Figure metrology for micro-lenses is likely to pose unique challenges. When compared to “macro-” optical elements, the aperture of microlenses is no longer very much larger than the wavelength of source light. Diffraction effects can thus no longer be neglected. For example, the focus shift may lead to a substantial systematic error in a radius-of-curvature measurement of a microlens.
The use of differential thermal analysis for the examination of glasses

Differential thermal analysis (DTA) has been applied to the examination of a variety of glasses and glass-glass reactions. The method is described and results that were obtained which illustrate the usefulness of the technique are shown.
Distribution of enkephalin, substance P, tyrosine hydroxylase, and 5-hydroxytryptamine immunoreactivity in the septal region of the rat

Immunocytochemical methods were used to define the distribution of enkephalin (ENK), substance P (SP), tyrosine hydroxylase (TH), and serotonin (5-hydroxytryptamine: 5HT) in the rat septum. A dense plexus of axons containing enkephalin-like immunoreactivity is found in the intermediate lateral septal nucleus. This is surrounded laterally by SP-containing cell bodies and axons and medially by ENK-containing cell bodies. Both SP- and ENK-immunoreactive axons form pericellular and peridendritic terminal arbors around lateral septal neurons. TH-positive axons are distributed throughout the septum and form dense pericellular terminal baskets around scattered neurons in the medial half of the intermediate lateral septal nucleus and in the extreme lateral septum. Very few SP and TH immunoreactive axons are present in the ENK immunoreactive plexus zone. 5HT-immunoreactive axons are most dense at the lateral edge of the ventral and intermediate lateral septal nuclei but form pericellular terminal arbors only in the dorsal lateral septal nucleus, in the septofimbrial nucleus, and in the dorsal cap of the medial septal nucleus. These results indicate that the dorsal and intermediate lateral septal nuclei include three histochemically distinct laminated subfields: (1) an ENK immunoreactive axonal plexus within the lateral aspect of the intermediate lateral septal nucleus, (2) a more medial region of scattered ENK immunoreactive perikarya and similarly scattered TH immunoreactive pericellular baskets, and (3) a dorsolateral zone occupied by SP neurons and 5HT-containing pericellular baskets. Thus, the data suggest that SP- and ENK-containing neuronal populations in the lateral septum receive different monoaminergic inputs. Further, the somewhat exclusive laminated pericellular termination of peptide- and catecholamine-containing axons in the lateral septum predicts very different functional and pharmacological properties among zones.
On the similarity of dual operators

Abstract Let k be a field with an involution σ and 〈 , 〉 : V × W → k a non-degenerate sesquilinear form, where V , W are n -dimensional k -spaces. Assume that Λ ∈ End ( V ) and Λ ∗ ∈ End ( W ) are dual operators. We show that if Λ and Λ ∗ are similar, then Λ ∗ = ϕ Λ ϕ - 1 , where ϕ : V → W is Hermitian.
Microdetermination of iron in ferrocene derivatives

Summary A convenient method, not subject to the limitations of the ashing technique, is presented for the determination of iron in ferrocene derivatives. The method is based upon oxidation of the organic compound with nitric acid—hydrogen peroxide and determination of the ferric—thiocyanate complex spectrophotomet-rically.
The Empress Frederick and female education in the late nineteenth century: Germany, England and Italy

The long-time Prussian/German Crown Princess Victoria (1840–1901), known after her husband’s death as the Empress Frederick, played an important role as patroness of and advocate for many forms of academic and vocational education for girls and women. This article examines her work for various institutions in Berlin as well as her homeland. It also introduces a hitherto ignored link to the philanthropist Julie Schwabe, who brought Victoria into contact with the kindergarten movement, including not only the Pestalozzi-Froebel House in Berlin but also the Istituto Froebeliano in Naples and the Froebel Educational Institution in London.
Genetics and the origin of species: the continuing synthesis a symposium in honor of Richard G. Harrison

This is a special issue of Genetica that has its origins in a symposium held in honor of Richard G. Harrison at Ithaca, New York on July 22–23. Former students of Rick Harrison organized the symposium and most of the speakers were former students, as well. The quality and breadth of the talks were a testament to Rick’s influence as a thinker, synthesizer, and mentor and it is only appropriate to reflect on Rick’s contributions to the fields of evolutionary ecology, systematics, and genetics in this preface to the symposium articles.
Contribution of villus and intervillus epithelium to intestinal transmural potential difference and response to theophylline and sugar

Abstract A chamber design is described which permits isolation of villus or intervillus epithelium from proximal segments of Amphiuma intestine and measurement of the transepithelial potential difference (ψms) and short-circuit current (Isc) produced by each. In media containing Cl− and 10 mequiv./l HCO3− the villus generated a basal ψms of 0.8 mV (serosa negative) and Isc of 12 μA/cm2 while the intervillus ψms and Isc were not different from zero. Acetazolamide altered the villus ψms by 1.2 mV; the intervillus ψms by only 0.3 mV. Transepithelial gradients of HCO3− appeared to generate diffusion potentials across the intervillus but not the villus epithelium. The actively transported sugar galactose elevated ψms by 0.6 ± 0.1 mV in the intervillus epithelium and by 1.5 ± 0.2 mV in the villus epithelium for a response ratio ( 0.6 1.5 ) = 0.4 . The response ratio for valine was 0.3. In contrast, the response ratios for theophylline (0.7) and cyclic AMP (0.7) were significantly higher. These observations indicate that the entire epithelium is responsive to theophylline and cyclic AMP while Na+-dependent solute transport and the basal electrogenic ion transport processes are primarily functions of the cells lining the intestinal villus.
Mimosine Arrests Cells in G1 by Enhancing the Levels of p27Kip1

Abstract The plant amino acid mimosine, an effective inhibitor of DNA replication, has been demonstrated to arrest cell cycle progression in late G1. To understand further the molecular mechanism by which mimosine affects the cell cycle, we treated quiescent cells with serum in the presence of 800 μM mimosine. The cells did not enter S phase and were completely arrested in G1 phase. Although neither the mitogenic induction of the G1 cyclins nor the protein levels of cdk2 or cdk4 were affected, serum-dependent activation of cdk2 was blocked. This corresponded to elevated levels of the cdk inhibitor p27 Kip1 . This was not mediated through inhibition of degradation but rather involved increased synthesis of both p27 Kip1 mRNA and protein. Mimosine did not appear to affect mitogen-dependent signals that normally lead to p27 Kip1 downregulation since the inhibitor was induced to even greater levels in quiescent, unstimulated cells. In the presence of mimosine, actinomycin D treatment for 2 h prevented the increase of p27 Kip1 mRNA, but p27 Kip1 protein levels were still enhanced under these conditions. We propose that mimosine blocks the cell cycle in late G1 phase by upregulation of p27 Kip1 protein levels through transcriptional and posttranscriptional regulatory mechanisms.
Preventing postoperative pneumonia

While pneumonia is a common postoperative complication, there is a paucity of literature on pneumonia prevention outside of the intensive care unit.Wren and colleagues designed and implemented a wardbased pneumonia prevention program at the Veterans Affairs Palo Alto Health Care System in 2007. They previously reported an initial 81% decrease in the incidenceofward-acquiredpneumonia1 andnow report a significant long-term decrease when compared both with preintervention rates and the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).2 Although encouraging, these findings should be interpreted with caution. The preintervention rate of pneumonia was 0.78% in the Veterans Affairs Palo Alto Health Care System and 2.56% in ACS-NSQIP—a difference of 328% that is already of statistical significance. This remarkably low rateof pneumonia calls into question the adequacyof detection and reportingof pneumonia on their ward and alsomakes their finding of a significant differencebetween theirpostinterventionandACS-NSQIP rate of somewhat less consequence. A second concern is that the authors’ previous article reported that the overall rate of postoperative non– ventilator-associated pneumonia did not change with implementation of their program. Although the number of ward cases decreased from 13 to 3, the number of non– ventilator-associated pneumonia intensive care unit cases increased from 4 to 17, and therefore, the reported decrease could be due to redistribution in the location of patients. A third concern is that the authors did not evaluate changes in patient care or surgical technique that could have altered the incidence of postoperative pneumonia. A systematic review of strategies to reduce postoperative pulmonary complications3 found that choice of neuraxial blockade over general anesthesia led to a significant reduction in the rate of postoperative pneumonia (odds ratio = 0.61; 95% CI, 0.48-0.76), as did selective nasogastric decompression (odds ratio = 0.49; P < .001). Moreover, the authors’ program was implemented and evaluated over a period in which there was an ongoing shift from open to laparoscopic or robotic surgical techniques, which has been shown to significantly decrease the rates of postoperative pneumonia, particularly in colorectal and prostate operations.4,5 Without collecting and analyzing such data, it is impossible to know if any of them contributed to their findings. Despite these concerns, the authors should be commended for the development and implementation of a quality improvementmeasureaimedatdecreasing the rateofpostoperative pneumonia in a Veterans Affairs population. The 8 interventionsused in their programarenot particularly costly or time-consuming and serve to increase awareness and education of all health care professionals caring for postoperative patients.
Is Substance Abuse Treatment Providing Services to the Right Population

This study examined the relationship between treatment retention, and drug severity level in a therapeutic community setting for drug and alcohol treatment. Treatment retention is significant because length of time in treatment has been shown to correlate with success after treatment that impacts everyone. The design of this study was exploratory, descriptive, and cross-sectional. Data were collected in 2000 from a convenience sample of 18 to 25 year-old, primarily low-income and minority addicts who were currently in a therapeutic community in New Jersey, USA. The participants were then tracked for 90 days as to their status in the program and staff completed a motivation measure. Results indicated that severity of addiction was significant to treatment retention.
Gene transfer by adenovirus in smooth muscle cells.

Abstract We report adenovirus-mediated gene transfer into airway smooth muscle cells in cultured cells and organ-cultured tracheal segments. Incubation of cultured rat tracheal myocytes with virus (5 × 10 8 pfu/ml) for 6 h resulted in β-galactosidase expression in 94.8 ± 2.5% of cells ( n = 4). Following incubation of thin (less than 200 μm diameter) equine trachealis muscle segments with virus in organ culture (5 × 10 8 –5 × 10 10 pfu/ml) the average expression of the Lac Z gene was approximately 19 ± 10% ( n = 9). Expression was markedly improved, however, in segments from neonatal rats (13–21 days). In two experiments in which the mucosa and serosa were removed, nearly all cells expressed β-galactosidase, whereas in a third experiment in which the tissue was not dissected, about 40% of cells were stained. Viral infection had no effect on tension development of strips following organ culture. In vitro gene transfer may provide a useful method to alter protein expression and examine the effect of this alteration on excitation/contraction coupling in smooth muscle.
Single-mode Waveguide Horn-Grating Demultiplexer Circuit

Single-mode integrated optic waveguide demultiplexer structures were fabricated consisting of a 4-pm-wide input channel waveguide, an adiabatic beam expansion horn 130 μm at its output, a planar waveguide region, and several 3-μm period grating structures embedded in the planar waveguide region. The angular orientation of the gratings was adjusted to varying at specific wavelengths. The planar waveguide, the channel waveguide, the horn, and the grating structures were simultaneously formed by dilute silver nitrate ion exchange on an aluminum masked slide. High diffraction efficiencies were observed in good agreement with the theoretical model for the horn-grating interaction at 0.6328-, 0.789- and 0.82-μm wavelengths. This is the first reported operation of a single-mode demultiplexer structure with simultaneously fabricated input waveguide, beam expansion, and recollimation horms and multiple diffraction gratings.
The influence of the stigma of obesity on overweight individuals

OBJECTIVE: To investigate the internalization of anti-fat bias among overweight individuals across a variety of attitudes and stereotypes. DESIGN: Two studies were conducted using the Implicit Association Test (IAT), a performance-based measure of bias, to examine beliefs among overweight individuals about ‘fat people’ vs ‘thin people’. Study two also contained explicit measures of attitudes about obese people. SUBJECTS: Study 1 participants were 68 overweight patients at a treatment research clinic (60 women, 8 men; mean Body Mass Index (BMI) of 37.1±3.9 kg/m2). Study 2 involved 48 overweight participants (33 women, 15 men) with a BMI of 34.5±4.0 kg/m2. RESULTS: Participants exhibited significant anti-fat bias on the IAT across several attributes and stereotypes. They also endorsed the explicit belief that fat people are lazier than thin people. CONCLUSION: Unlike other minority group members, overweight individuals do not appear to hold more favorable attitudes toward ingroup members. This ingroup devaluation has implications for changing the stigma of obesity and for understanding the psychosocial and even medical impact of obesity on those affected.
On the stark difference in satellite distributions around the Milky Way and Andromeda

We compare spherically-averaged radial number counts of bright (> 10^5 Lsun) dwarf satellite galaxies within 400 kpc of the Milky Way (MW) and M31 and find that the MW satellites are much more centrally concentrated. Remarkably, the two satellite systems are almost identical within the central 100 kpc, while M31 satellites outnumber MW satellites by about a factor of four at deprojected distances spanning 100 - 400 kpc. We compare the observed distributions to those predicted for LCDM suhbalos using a suite of 44 high-resolution ~10^12 halo zoom simulations, 22 of which are in pairs like the MW and M31. We find that the radial distribution of satellites around M31 is fairly typical of those predicted for subhalos, while the Milky Way's distribution is more centrally concentrated that any of our simulated LCDM halos. One possible explanation is that our census is bright (> 10^5 Lsun) MW dwarf galaxies is significantly incomplete beyond ~ 100 kpc of the Sun. If there were ~8 - 20 more bright dwarfs orbiting undetected at 100 - 400 kpc, then the Milky Way's radial distribution would fall within the range expected from subhalo distributions and alos look very much like the known M31 system. We use our simulations to demonstrate that there is enough area left unexplored by the Sloan Digital Sky Survey and its extensions that the discovery of ~10 new bright dwarfs is not implausible given the expected range of angular anisotropy of subhalos in the sky.
A Triflate Hydrodeoxygenation Route to Resveratrol from Syringaldehyde

When a starting material is being contemplated for the synthesis of an active pharmaceutical ingredient or a building block for polymers, natural products are the green alternatives to petroleum fe...
Complications of bone metastases : Surgical management

BACKGROUND. Patients with metastatic disease to the bone present a management challenge. Of the complications encountered in these patients, the predominant types that require surgical intervention are pathologic or impending fractures and neurologic compromise secondary to cord compression from spinal metastases. A multimodality approach is helpful in caring for these patients, and addressing complications related to bony metastatic disease with timely and appropriate intervention is an important step in optimizing care and quality of life. METHODS. This article incorporates information from multiple sources and presents recent reviews of the experience at the Memorial Sloan-Kettering Cancer Center with acetabular reconstruction for metastatic lesions, and with the use of the posterolateral transpedicular approach to address metastatic disease in the spine. RESULTS. Of 55 patients who underwent reconstruction of the acetabulum for metastatic disease, although there was a 25% incidence of local disease progression, there was only a 9% incidence of late fixation failure. Of the 41 who were evaluable at 3 months, 83% continued to experience significant pain relief, and 50% of nonambulatory patients regained walking ability secondary to the procedure. Of the patients with more than 2 years of follow-up, 86% maintained pain relief and 71% maintained their ability to ambulate and function in their community. The preliminary series of 25 patients managed with a posterolateral transpedicular approach to address metastatic disease in the spine showed excellent tumor control, pain relief, and neurologic preservation with the technique. Particular benefit was obtained for patients with extensive epidural disease in which an anterior approach was contraindicated. CONCLUSIONS. Although a multimodality approach to the treatment of patients with metastatic disease to bone combining appropriate surgical intervention with systemic therapy and radiation can entail a major operative procedure, the overall benefits to a patient's quality of life outweigh the risks in most cases. Clinician awareness of the various therapeutic options and their indications, and aggressive advocacy of quality of life for these patients, can improve the care delivered to people with metastatic disease.