cssi/SciSciGPT-SciSciNet huggingface dataset:
Eicosanoids in Cancer: New Roles in Immunoregulation

Eicosanoids represent a family of active biolipids derived from arachidonic acid primarily through the action of cytosolic phospholipase A2-α. Three major downstream pathways have been defined: the cyclooxygenase (COX) pathway which produces prostaglandins and thromboxanes; the 5-lipoxygenase pathway (5-LO), which produces leukotrienes, lipoxins and hydroxyeicosatetraenoic acids, and the cytochrome P450 pathway which produces epoxygenated fatty acids. In general, these lipid mediators are released and act in an autocrine or paracrine fashion through binding to cell surface receptors. The pattern of eicosanoid production is cell specific, and is determined by cell-specific expression of downstream synthases. Increased eicosanoid production is associated with inflammation and a panel of specific inhibitors have been developed designated non-steroidal anti-inflammatory drugs. In cancer, eicosanoids are produced both by tumor cells as well as cells of the tumor microenvironment. Earlier studies demonstrated that prostaglandin E2, produced through the action of COX-2, promoted cancer cell proliferation and metastasis in multiple cancers. This resulted in the development of COX-2 inhibitors as potential therapeutic agents. However, cardiac toxicities associated with these agents limited their use as therapeutic agents. The advent of immunotherapy, especially the use of immune checkpoint inhibitors has revolutionized cancer treatment in multiple malignancies. However, the majority of patients do not respond to these agents as monotherapy, leading to intense investigation of other pathways mediating immunosuppression in order to develop rational combination therapies. Recent data have indicated that PGE2 has immunosuppressive activity, leading to renewed interest in targeting this pathway. However, little is known regarding the role of other eicosanoids in modulating the tumor microenvironment, and regulating anti-tumor immunity. This article reviews the role of eicosanoids in cancer, with a focus on their role in modulating the tumor microenvironment. While the role of PGE2 will be discussed, data implicating other eicosanoids, especially products produced through the lipoxygenase and cytochrome P450 pathway will be examined. The existence of small molecular inhibitors and activators of eicosanoid pathways such as specific receptor blockers make them attractive candidates for therapeutic trials, especially in combination with novel immunotherapies such as immune checkpoint inhibitors.
A Simulation of the Age Structure of Crabeater Seals in a Fluctuating Environment

A population model of crabeater seals was constructed to assess the sensitivity of the age struckture of crabeater seals to environmental fluctuations. The model incorporates density dependence in agespecific reproductive and survival schedules, with reproduction and juvenile survival being most sensitive to changing population size or carrying capacity. Environmental fluctuations were simulated by varying the populations’s carrying capacity in four ways: (1) random fluctuations; (2) random walk; (3) sinusoidal oscillations with minor stochastic variation; and (4) recurrent episodes of good years with variable periodicity. High carrying capacity produced strong cohorts from pups of that year and yearlings. However, the magnitude of these strong cohorts was only moderately correlated with the magnitude of the carrying capacity in the year of birth. Reasons for this include the reduced juvenile survival following population growth in good years, and the effects of carrying capacity in previous years that determined population size. These simulations indicate that fluctuations in the environment for crabeater seals can be transmitted to the age structure, although some “noise” is inherent in the age structure signals.
Prosthodontic Considerations in Implant Failure

Summary Due to the tremendous success of fixed implant restorations in the edentulous arch, confidence for similar levels of success in the partially edentulous patient was initially high. We finally have enough experience with this patient population to realize that although the success in the partially edentulous patient has been good, it has not been at the level originally anticipated. In evaluating the complications and failures that have occurred in the partially edentulous patient, we have been able to understand better the biomechanical differences between the edentulous implant restoration and the partially edentulous implant restoration. The potentially damaging bending overloads are well tolerated in the edentulous patient because of the tremendous tripod effect often created by the nature of the arch. The resulting cross-arch stabilization allows the damaging lateral forces to be transformed into acceptable axial forces. We currently have biomechanical guidelines to allow us to establish better support dynamics for our implant restorations, and along with more conservative occlusal schemes we can minimize the bending overloads in most partially edentulous patients as well. Treatment planning guidelines for the partially edentulous patient have evolved over the past several years, and we can expect more realistically to see success rates in the partially edentulous patient reach the high levels seen for more than 30 years in the edentulous patient.
Cancel Columbus: Patient Zero of the White Supremacist Plague

White supremacy begins and ends with Columbus. Cancel Columbus. Cancel white supremacy. Imagine a world in which human beings treat human beings like human beings Why is that so hard to imagine?
Sex, Drugs, and Love Among the Middle Aged: A Case Study of a Serodiscordant Heterosexual Couple Coping with HIV

ABSTRACT HIV infection attributable to injection is growing, as is the incidence among heterosexual persons. Some of the people affected are over 50, and we can anticipate a growing number of older people with substance use and HIV as primary concerns. Therefore, we need to know more about the intersections of age, addictions, and HIV. This article uses narrative analysis to examine a research interview with an African-American woman and her African-American HIV-infected male partner in order to gain insight about how a middle-aged serodiscordant drug-affected couple might struggle and succeed in the face of HIV. Implications for social work, policy and research are provided.
Controlling the actuation properties of MXene paper electrodes upon cation intercalation

Abstract Atomic force microscopy was used to monitor the macroscopic deformation in a delaminated Ti3C2 paper electrode in situ, during charge/discharge in a variety of aqueous electrolytes to examine the effect of the cation intercalation on the electrochemical behavior and mechanical response. The results show a strong dependence of the electrode deformation on cation size and charge. The electrode undergoes a large contraction during Li+, Na+ or Mg2+ intercalation, differentiating the Ti3C2 paper from conventional electrodes where redox intercalation of ions (e.g. Li+) into the bulk phase (e.g. graphite, silicon) results in volumetric expansion. This feature may explain the excellent rate performance and cyclability reported for MXenes. We also demonstrated that the variation of the electromechanical contraction can be easily adjusted by electrolyte exchange, and shows interesting characteristics for the design of actuators based on 2D metal carbides.
Laboratory Animal Act: A Legislative Proposal

In one recent experiment, mongrel dogs were anesthetizednafter which thirty-five percent of their body was burned to thenthird degree by the application of a two hundred degree centigradenhot plate to their skin.' In 1983, researchers at the NewnJersey Medical School placed electrodes in the hippocampusnportion of the brains of five female cats. The brain was stimulatednwith electrical current to determine whether or not therenwas an increase in the...
Symptom complaints and health care seeking behavior in subjects with bowel dysfunction

Abstract A significant proportion of the population (14%–22%) appears to have symptoms compatible with the irritable bowel syndrome, yet only a small number seek medical aid. To explore why some people with bowel dysfunction go to the doctor and others do not, we surveyed 566 healthy subjects. Eighty-six (15%) had bowel dysfunction compatible with irritable bowel syndrome, but the majority of those affected (53 subjects or 62%) had never been to a doctor for these complaints. Although those who consulted physicians for bowel symptoms were more likely to report abdominal pain than those who did not, pain was not sufficient to explain doctor visits. Subjects with bowel dysfunction also reported more nongastrointestinal symptoms, and those with bowel dysfunction who visited physicians were more likely to see physicians for their nongastrointestinal symptoms. The reported higher prevalence of psychopathology among the patient population with irritable bowel syndrome may be due to behavioral influences that lead to health care seeking.
Reinventing the Library for Online Education by Frederick Stielow

In the rapidly changing environment of libraries and librarians, Stielow's book engages one in a discussion of the past, the present, and the future of libraries and their relationship with higher ...
Electromagnetic Determination of Carotid Blood Flow in the Anesthetized Rat

The paper describes the design and performance of the smallest iron core electromagnetic flow transducer built so far. The design is miniaturized as to the total volume of the device as well as to the size of the artery it accommodates. The use of this transducer for recording of blood flow in the smallest species of animal employed until now in blood flow research is described. Illustrations of pharmacological observations in anesthetized rats are presented.
Gene Regulation by the LiaSR Two- Component System in Streptococcus mutans

The LiaSR two-component signal transduction system regulates cellular responses to several environmental stresses, including those that induce cell envelope damages. Downstream regulons of the LiaSR system have been implicated in tolerance to acid, antibiotics and detergents. In the dental pathogen Streptococcus mutans, the LiaSR system is necessary for tolerance against acid, antibiotics, and cell wall damaging stresses during growth in the oral cavity. To understand the molecular mechanisms by which LiaSR regulates gene expression, we created a mutant LiaR in which the conserved aspartic acid residue (the phosphorylation site), was changed to alanine residue (D58A). As expected, the LiaR-D58A variant was unable to acquire the phosphate group and bind to target promoters. We also noted that the predicted LiaR-binding motif upstream of the lia operon does not appear to be well conserved. Consistent with this observation, we found that LiaR was unable to bind to the promoter region of lia; however, we showed that LiaR was able to bind to the promoters of SMU.753, SMU.2084 and SMU.1727. Based on sequence analysis and DNA binding studies we proposed a new 25-bp conserved motif essential for LiaR binding. Introducing alterations at fully conserved positions in the 25-bp motif affected LiaR binding, and the binding was dependent on the combination of positions that were altered. By scanning the S. mutans genome for the occurrence of the newly defined LiaR binding motif, we identified the promoter of hrcA (encoding a key regulator of the heat shock response) that contains a LiaR binding motif, and we showed that hrcA is negatively regulated by the LiaSR system. Taken together our results suggest a putative role of the LiaSR system in heat shock responses of S. mutans.
TITANOMAGNETITE PROPERTIES AND MICROSTRUCTURES

Ulvospinel (Fe2TiO4) and titanomagnetites (TM) (pseudo-binary (1-x)Fe3O4xFe2TiO4 system, where, e. g. TM95 corresponds to x = 0.95) were made using a solid-state synthesis technique. For single phase titanomagnetites (x>0.75), our measured lattice constants extends the previous work of Wechesler to Ti-rich solid solutions, and extrapolates to a value of 8.531 A for single phase ulvospinel, agreeing closely to the literature value of 8.534 A. The lattice constants as a function of composition (x>0.75) were fit to a straight line with the equation y = 0.09x + 8.441. Grain sizes of single phase TM pellets of as-quenched and annealed samples were determined, showing that the grain size of the annealed samples grew noticeably after 100 hrs in Ar flow at 450 °C. For TM75, the grains grew from 11.7 μm to 15.4 μm. The ratios of grain sizes vary over the composition range, from 4% to 31%, suggesting coarsening driven by diffusional growth. In the samples that initially contained wustite as a second phase, there are grains with a lath microstructure with well-defined angles, indicating preferred orientations. Small amounts of Feor Ti-cation rich phases were observed to decorate the grain boundaries after long annealing. TiO2 formed on grain boundaries of TM75 annealed sample.
Representations of double affine lie algebras

We study a family of indecomposable integrable modules for the double affine algebra, the so-called Weyl modules. These modules have non-zero level with respect to one of the central elements and zero level with respect to the other. We give a condition for the modules to be irreducible, and use the idea of fusion product of modules to prove that they are generically reducible.
The Fragility of Goodness: Tragedy: fragility and ambition

They do not understand that it is by being at variance with itself that it coheres with itself: a backward-stretching harmony, as of a bow or a lyre…One must realize that conflict is common to all, and justice is strife, and all things come to pass according to strife and necessity. Heraclitus, DK b51 , 80 Here we come up against a remarkable and characteristic phenomenon in philosophical investigation: the difficulty – I might say – is not that of finding the solution but rather that of recognizing as the solution something that looks as if it were only a preliminary to it. ‘We have already said everything. – Not anything that follows from this, no, this itself is the solution!’ This is connected, I believe, with our wrongly expecting an explanation, whereas the solution of the difficulty is a description, if we give it the right place in our considerations. If we dwell upon it, and do not try to get beyond it. The difficulty here is: to stop. Wittgenstein, Zettel 314
Genetic counselling in the era of genomic medicine

Birth defects and familial diseases have caused concern and anxiety throughout mankind's existence. Plentiful historical and contemporary examples involve the stigmatisation of affected individuals and families. Many cultures have practices and taboos that have arisen from the desire to explain and prevent such disorders. Modern science brings a growing wealth of knowledge and techniques to the diagnosis, treatment and prevention of these disorders. However, a severe birth defect or an inherited genetic disorder still creates a heavy emotional, social and financial burden not only for those directly affected, but also for their families. And while modern research has made large strides towards identifying many disease‐causing alleles, patients' fears and anxieties about their future and the future of their children remain. This is not limited to classical inherited disorders. As researchers uncover the genetic components of multi‐factorial diseases, many more people will be found to have mutations that put them and probably their children at risk. The diagnosis of a genetic disorder in a newborn child, the identification of a mutation conferring an elevated risk of cancer, a positive result from a prenatal genetic screen for Down syndrome—all these scenarios confront patients with complex information to be understood and assimilated, and with an array of conflicting emotions. They require difficult decisions that involve many technical, ethical and highly personal questions (Weil, 2000). Genetic counselling can help in this process by offering various services within a clinical setting. These professionals assist patients in addressing the scientific and emotional issues that arise in such situations and help them make informed decisions based on their own values and individual circumstances (Walker, 1998). Genetic counselling, along with many other aspects of medicine and health care, must keep pace with radical new developments in biomedical research. Building on the Human Genome Project, scientists are advancing …
Solid-state crystal growth of refractory metals by arc-zone melting

Abstract Crystal growth by the arc-zone melting technique has been used over the past 25 years to prepare single crystals of the refractory metals and their alloys. During arc-zone melting only the upper surface of the metal is melted yet the entire cross section of the rod becomes single crystalline. The mechanism for growth of single crystals by this technique is not understood and a process parameter study was conducted to determine the operating mechanisms of crystal growth. It was found that crystal growth occurs in the solid state and is a result of large scale grain boundary migration. A minimum power input to the arc was required to prepare crystals and this was related to minimum temperature necessary for boundary migration. A series of quenching experiments indicates that boundary migration is driven by abnormal grain growth processes and is independent of the initial microstructure of the metal. The length and size of crystals prepared are determined by the number and frequency of boundary intersections with the advancing molten pool. There was no preferred orientation observed for the crystals prepared.
Climate change and waterborne disease risk in the Great Lakes region of the U.S.

Extremes of the hydrologic cycle will accompany global warming, causing precipitation intensity to increase, particularly in middle and high latitudes. During the twentieth century, the frequency of major storms has already increased, and the total precipitation increase over this time period has primarily come from the greater number of heavy events. The Great Lakes region is projected to experience a rise these extreme precipitation events. For southern Wisconsin, the precipitation rate of the 10 wettest days was simulated using a suite of seven global climate models from the UN Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report. For each ranking, the precipitation rate of these very heavy events increases in the future. Overall, the models project that extreme precipitation events will become 10% to 40% stronger in southern Wisconsin, resulting in greater potential for flooding, and for the waterborne diseases that often accompany high discharge into Lake Michigan. Using 6.4 cm (2.5 in) of daily precipitation as the threshold for initiating combined sewer overflow into Lake Michigan, the frequency of these events is expected to rise by 50% to 120% by the end of this century. The combination of future thermal and hydrologic changes may affect the usability of recreational beaches. Chicago beach closures are dependent on the magnitude of recent precipitation (within the past 24 hours), lake temperature, and lake stage. Projected increases in heavy rainfall, warmer lake waters, and lowered lake levels would all be expected to contribute to beach contamination in the future. The Great Lakes serve as a drinking water source for more than 40 million people. Ongoing studies and past events illustrate a strong connection between rain events and the amount of pollutants entering the Great Lakes. Extreme precipitation under global warming projections may overwhelm the combined sewer systems and lead to overflow events that can threaten both human health and recreation in the region. (Am J Prev Med 2008;35(5):451-458) © 2008 American Journal of Preventive Medicine
Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1). Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.
Role of protein C in childhood cerebrovascular occlusive accidents.

A group of 23 children with cerebrovascular occlusion of unknown oetiology were re-evaluated 6 months-2 years later. Plasma protein C levels were determined with the coagulation method and were low in 10 cases. The role of this deficiency and the necessity of this test in cerebrovascular occlusion is discussed.
Combustion Joining of Refractory Materials

This paper overviews heterogeneous exothermic reactive systems as they apply to the joining of materials. Techniques that are investigated fall under two general schemes: so-called Volume Combustion Synthesis (VCS) and Self-Propagating High-Temperature Synthesis (SHS). Within the VCS scheme, applications that are considered include Reactive Joining (RJ), Reactive Resistance Welding (RRW), and Spark Plasma Sintering (SPS). Under the SHS scheme, Combustion Foil Joining (CFJ) and Conventional SHS (CCJ) are discussed. Analysis of the relevant works show significant potential, particularly for the RJ, RRW, and CFJ approaches, in the joining of a variety of materials which are difficult, or impossible, to bond using conventional techniques. More specifically, it is shown that these methods can be successfully applied to the joining of: (i) dissimilar materials such as ceramics and metals and (ii) refractory materials, such as graphite, carbon-carbon composites, W, Ta, Nb, etc.
Sparse Matrix Computations on Reconfigurable Hardware

Using a high-level-language to hardware-description-language compiler and some novel architectures and algorithms to map two well-known double-precision floating-point sparse matrix iterative-linear-equation solvers - the Jacobi and conjugate gradient methods - onto a reconfigurable computer achieves more than a twofold speedup over software
Empirical ocean color algorithms for estimating particulate organic carbon in the Southern Ocean

[1] We have examined empirical algorithms for estimating surface concentration of particulate organic carbon (POC) from remotely sensed ocean color in the Southern Ocean using field data of POC, spectral remote-sensing reflectance, Rrs(λ), and the inherent optical properties (IOPs) of seawater collected during a number of cruises. Several algorithm formulations have been considered, including direct relationships between POC and the blue-to-green band ratios of reflectance and a single-wavelength two-step algorithm that consists of relationships linking reflectance to the backscattering coefficient and POC to the particulate backscattering coefficient at 555 nm. The best error statistics among the algorithms tested were obtained for the power function fit POC (in mg m−3) = 189.29 [Rrs(443)/Rrs(555)]−0.87. This band ratio algorithm is based on 85 pairs of field data and shows a small mean bias of about 3%, the normalized root mean square error of 27%, and the determination coefficient of 0.93. These error statistics as well as the analysis of matchup comparisons of satellite-derived POC and in situ POC determinations support the prospect for reasonably good performance of this algorithm in the Southern Ocean. The two-step empirical algorithm operating at 555 nm shows inferior error statistics of the regression fits and matchup comparisons compared with the band ratio algorithm. The analysis of our data set also indicates that a general trend of variation in the blue-to-green reflectance band ratio over the examined range of POC values is driven primarily by the green-to-blue ratio of particulate absorption coefficient.
Psychopharmacologic investigations in healthy elderly volunteers: MMPI depression scale.

The Depression Scale of the Minnesota Multiphasic Personality Inventory (MMPI) was used as a screening test for healthy volunteers in a psychopharmacologic research study. Data were collected on 43 men and 46 women under age 35 versus 33 men and 43 women over age 65 (plus a subsequent group of 40 men over age 65), and comparisons were made with more extensive data from the Mayo Clinic. The evidence indicates that elderly subjects differ strikingly from young subjects in their responses to items in the MMPI self-ratings of depression. Revised information on normative responses is needed. At present there are too many problems of interpretation when the Depression Scale items are applied to t.he elderly.
Facile activation of hydrogen by an unsaturated platinum-osmium cluster complex.

The electronically unsaturated platinum−osmium complex Pt2Os3(CO)10(PtBu3)2, 3, has been obtained from the reaction of Os3(CO)10(NCMe)2 with Pt(PtBu3)2. Compound 3 adds hydrogen at 0 °C to yield the dihydrido complex Pt2Os3(CO)10(PtBu3)2(μ-H)2, 4 (93% yield) within 10 min and subsequently the tetrahydrido complex Pt2Os3(CO)10(PtBu3)2(μ-H)4, 5, in 70% yield within 60 min. Compound 3 contains a trigonal bipyramidal cluster of five metal atoms having the two platinum atoms in the apical sites. With the addition of each equivalent of hydrogen, the trigonal bipyramidal cluster opens by series of Pt−Os bond cleavages that result in sequential shifts of the Pt groups to edges of the Os3 triangle. The hydrogen addition process can be reversed partially at 25 °C by purging solutions of 5 with nitrogen.
Tribology of Si-Based Ceramics: Wear Mechanisms

The wear mechanisms of Si-based ceramics are examined in terms of speed and load. The results are presented in wear maps which reveal different regimes of wear. This paper examines the effects of normal force and shear force on Si-based ceramic wear in the different wear regimes. In the mild wear regime, the wear processes are dominated by microabrasion and subsurface cracks. The severe wear regime is dominated by microfracture and tensile cracks on the surface. At still higher loads, surface cracks and gross fracture occur. The presence and the effects of third-body particles on the wear mechanisms are also discussed. Presented at the 50th Annual Meeting in Chicago, Illinois May 14–19, 1995
Three‐dimensional simulation of microchip encapsulation process

A finite element simulation of moving boundaries in a three-dimensional inertia-free, incompressible flow is presented. A control volume scheme with a fixed finite element mesh is employed to predict fluid front advancement. Fluid front advancement and pressure variation in a flow domain similar to the mold cavity used for microchip encapsulation are predicted. The predicted fluid front advancement and pressure variation are in good agreement with the corresponding experimental results. As the difference in the thicknesses of mold cavities above and below the microchip is changed, the weld line location and pressure variation during mold filling are found to change significantly.
Precise cell patterning using cytophobic self-assembled monolayer deposited on top of semi-transparent gold

This paper reports a simple and effective method for cell patterning by using a self-assembled monolayer (SAM)-treated glass surface which is surrounded by semi-transparent gold coated with another type of SAM. Specifically, a hydrophobic SAM, derived from 1-hexadecanethiol (HDT), was coated on the gold surface to prevent cell growth, and a hydrophilic SAM, derived from 3-trimethoxysilyl propyl-diethylenetriamine (DETA), was coated on the exposed glass surface to promote cell growth. The capabilities of this technique are as follows: 1) single-cell resolution, 2) easy alignment of the cell patterns to the structures already existing on the substrate, 3) visualization and verification of the predefined cytophobic/cytophilic pattern prior to cell growth, and 4) convenient monitoring cell growth at the same location for an extended long term period of time. Whereas a number of earlier techniques have demonstrated the single cell resolution, or visualization and verification of the cytophobic/cytophilic patterns prior to cell growth, we believe that our technique is unique in possessing all of these beneficial qualities at the same time. The distinguishing characteristic of our technique is, however, that the use of semi-transparent Cr/Au film allows for convenient brightfield pattern visualization and offers an advantage over previously developed methods which require fluorescent imaging. We have successfully demonstrated the patterning of four different kinds of cells using this technique: immortalized mouse hypothalamic neurons (GT1-7), mouse osteoblast cells (MC3T3), mouse fibroblast cells (NIH3T3) and primary rat hippocampal neurons. This study was performed with a specific ultimate application—the creation of a multi electrode array (MEA) with predefined localization of cell bodies on top of the electrodes, as well as predefined patterns for cell extensions to grow in between the electrodes. With that goal in mind, we have also determined critical parameters for patterning of each of these cell types, such as the minimum size of a cell-adherent island for exclusively anchoring one cell or two cells, as well as the width of the cytophilic pathway between two islands that enables cell extensions to grow, while preventing the anchoring of the cell bodies. Additionally, we have provided statistical analysis of the occupancy for various sizes and shape of cell-anchoring islands. As demonstrated here, we have developed a novel and reliable cell patterning technique, which can be utilized in various applications, such as biosensors or tissue engineering.
Spielraum: play, chance and creativity across disciplines

Creativity and technology share linguistic roots in "art, craft, making and method". But a more compelling substrate, increasingly evident in gaming culture, links the two. In the notion of Spielraum-- room-for-play-- a common ground of emergent possibility may be discerned. This interactive space of memory, thought, affect and sensory perception allows the mind to wander creatively, i.e. purposefully and at the same time playfully. Integrating non-methods of play and chance (two variants of spiel) with goal-directed activity, this paper proposes, is an important way to foster creative problem solving across disciplines.
Investigation of the Ca 2+ -dependent interaction of trifluoperazine with S100a: A 19 F NMR and circular dichroism study

S100a is a heterodimeric, acidic calcium-binding protein that interacts with calmodulin antagonists in a Ca2+-dependent manner. In order to study the behavior of the hydrophobic domain on S100a when bound to Ca2+, its interaction with trifluoperazine (TFP) was investigated using16F nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy. The dissociation constant (K d) values of TFP, as estimated from the chemical shifts of19F NMR, were 191 and 29 μm in the absence and presence of Ca2+, respectively, and were similar to those previously reported for S100b. However, the TFP linewidth in the presence of Ca2+-bound S100a was 65 Hz greater than in the presence of Ca2+-bound S100b. This suggests a slower TFP exchange rate for S100a than for S100b. Thus, the TFP linewidths observed for each isoform may reflect differences in structural and modulatory properties of the Ca2+-dependent hydrophobic domains on S100a and S100b. Additionally, the presence of magnesium had no effect on the observed Ca2+-induced TFP spectral changes in S100a solutions. Circular dichroism studies indicate that Ca2+ induces a small transition from α-helix to random coil in S100a; in contrast, the opposite transition is reported for calmodulin (Hennesseyet al., 1987). However, TFP did not significantly alter the secondary structure of Ca2+-bound S100a; this observation is similar to the effect of TFP on Ca2+-bound calmodulin and troponin C (Shimizu and Hatano, 1984; Gariepy and Hodges, 1983). It is, therefore, proposed that TFP binds to a hydrophobic domain on S100a in a fashion similar to other calcium-modulated proteins.
PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting

Hyperactivation of phosphatidylinositol 3-kinase (PI3K) signalling cascades is one of the most common events in human cancers. This Review discusses recent advances in our knowledge of the roles of distinct PI3K isoforms in normal and oncogenic signalling, and the current state and future potential of targeting this pathway in the clinic.
Square the crop circle

If they want to make progress, researchers of genetically modified crops must give some ground to their opponents, says Matthew C. Nisbet
Signaling Network Crosstalk in Human Pluripotent Cells: A Smad2/3-Regulated Switch that Controls the Balance between Self-Renewal and Differentiation

A general mechanism for how intracellular signaling pathways in human pluripotent cells are coordinated and how they maintain self-renewal remain to be elucidated. In this report, we describe a signaling mechanism where PI3K/Akt activity maintains self-renewal by restraining prodifferentiation signaling through suppression of the Raf/Mek/Erk and canonical Wnt signaling pathways. When active, PI3K/Akt establishes conditions where Activin A/Smad2,3 performs a pro-self-renewal function by activating target genes, including Nanog. When PI3K/Akt signaling is low, Wnt effectors are activated and function in conjunction with Smad2,3 to promote differentiation. The switch in Smad2,3 activity after inactivation of PI3K/Akt requires the activation of canonical Wnt signaling by Erk, which targets Gsk3β. In sum, we define a signaling framework that converges on Smad2,3 and determines its ability to regulate the balance between alternative cell states. This signaling paradigm has far-reaching implications for cell fate decisions during early embryonic development.
Modeling T Cell-Antigen Presenting Cell Interactions

We present and analyze a model for the interaction of naive T cells with antigen presenting cells (APCs) that results in T-cell activation. We use this model to examine delayed type hypersensitivity (DTH) reactions. We show that responses can be of two types; either the antigen is completely eliminated or the immune system fails to eliminate the antigen and chronic infection results. Both outcomes are characteristic of diseases in which delayed type hypersensitivity is the primary defense mechanism. We compare the effectiveness of two types of APCs macrophages and dendritic cells, in the generation of DTH responses. We conclude that dendritic cells are more suited to the task of stimulating naive T cells than are macrophages, as has recently been argued by Steinman and coworkers.
Sequence and Mapping of Galectin-5, a β-Galactoside-binding Lectin, Found in Rat Erythrocytes

A monomeric rat β-galactoside-binding lectin previously purified from extracts of rat lung has been localized to erythrocytes, and the cDNA encoding it has been isolated from a rat reticulocyte cDNA library. The deduced amino acid sequence of the cDNA predicts a protein with a Mr of 16,199, with no evidence of a signal peptide. The deduced sequence is identical to the sequences of seven proteolytic peptides derived from the purified lectin. Peptide analysis by mass spectrometry indicates that the N-terminal methionine is cleaved and that serine 2 is acetylated. The lectin shares all the strictly conserved amino acid residues of other members of the mammalian galectin family and is designated galectin-5 (GenBankTM accession number L36862). Galectin-5 is a weak agglutinin of rat erythrocytes, despite its monomeric structure. The gene encoding galectin-5 (LGALS5) has been mapped in mouse to chromosome 11, ∼50 centimorgans from the centromere and 1.8 ± 1.8 centimorgans from the polymorphic marker D11Mit34n, a region syntenic with human chromosome 17q11.
Provision of Morning Care to Nursing Home Residents With Dementia: Opportunity for Improvement?

Significant contact between nursing staff and nursing home residents with dementia occurs during assistance with activities of daily living during morning care; however, the content and process of morning care have received little attention in the scientific literature. To better understand the morning care process and its role in generation of pain symptoms, 51 videotaped episodes of morning care involving 17 nursing home residents from 3 long-term care facilities were coded and analyzed; each resident had a diagnosis of dementia and concern about possible pain during assistance with activities of daily living. The typical morning care episode involved performance of multiple activities of daily living during a short period of time, during which pain stimulation and expression occurred frequently. Much could be done to make morning care more an activity to be enjoyed rather than a task to be completed.
American Indians, civilized performance and the question of rights

AbstractBetween the middle of the 19th century and the beginning of the 20th, public arguments about the eligibility of American Indians for citizenship, and about the obligations of white Americans toward Indian populations, shifted from a focus on the rights of the Indian minority to a focus on the rights of the white majority. Similarly, discussions of the criteria for Indian citizenship also shifted, from a concern with the moral duty of the majority to ensure the human rights of the minority to a consideration of whether any claims to rights must be respected on moral grounds alone. The writings of Lydia Maria Child and Lyman Abbott on the 'Indian question' illustrate the ways in which Child's paternalistic family model of entitlement is replaced by a later model that emphasizes culture over morality, behavior over rights.
Some Inference Problems for Matrix Variate Elliptically Contoured Distributions

In this paper, maximum likelihood estimators for a broad class of matrix variate elliptically contoured distributions have been derived. Optimality properties of estimators in the multivariate regression models are studied when the error term has a matrix variate elliptically contoured distribution. Least-square estimators are also obtained for the multivariate random effect regression model when the underlying distribution is elliptically contoured.
Occurrence of secondary magnetite within biodegraded oil

Samples of solid bitumen from the Thornton Quarry (Illinois) and the Cynthia Quarry (Mississippi) were found to be strongly magnetic and to have rock magnetic properties suggesting that the magnetizable grains present are magnetite. Studies of magnetic isolates revealed that magnetite is present primarily as spherical crystal aggregates that appear identical to magnetite spherules isolated from re-magnetized Paleozoic carbonate units from other localities. Organic geochemical analyses of the solid bitumen suggest an origin by microbial attack on what once was liquid crude oil. The occurrence of secondary magnetite as inclusions within solid bitumen suggests a relationship between crude oil biodegradation and development of that mineral in our samples. We infer that secondary magnetite in other geologic environments may be related to the presence of hydrocarbons. The discovery of a natural association of secondary magnetite and hydrocarbons has important implications for paleomagnetism and for petroleum exploration.
On solutions of the integral form of the second-order boundary-layer equations

Abstract Approximate solutions to the second-order boundary-layer equations for incompressible flow are considered. A simplified form of the integral momentum equation for two-dimensional and axisymmetric flow is presented. Solutions to the problem of shear flow over a flat plate are obtained for five different polynomial approximations to the second-order boundary-layer velocity profile. It is found that the results obtained depend rather erratically on the polynomial degree employed.
Ergodic theory of one-dimensional dynamics

During the past fifty years a clearer understanding of one-dimensional dynamics has emerged. This paper summarizes the main results of the probabilistic theory of one-dimensional dynamics and shows the behavior to be surprisingly rich and a good starting point for the general theory of dynamics.
Rates of Best Rational Approximation of Analytic Functions

Let E be a compact set in the extended complex plane C and let f be holomorphic on E. Denote by @r"n the distance from f to the class of all rational functions of order at most n, measured with respect to the uniform norm on E. We obtain results characterizing the relationship between estimates of liminf"n"->"[email protected]^1^/^n"n and limsup"n"->"[email protected]^1^/^n"n.
Electron tunneling into amorphous germanium

A detailed study was undertaken of electron tunneling into amorphous Ge. At low temperature, $T\ensuremath{\lesssim}100$ K, the high-field conductivity of the $a\ensuremath{-}\mathrm{G}\mathrm{e}$ film is similar to the tunneling conductance. For $a\ensuremath{-}\mathrm{G}\mathrm{e}$ thicknesses $t\ensuremath{\lesssim}500$ \AA{} the conductance of $a\ensuremath{-}\mathrm{G}\mathrm{e}$ blends smoothly with the tunneling conductance. This makes separation of tunneling conductance from the bulk $a\ensuremath{-}\mathrm{G}\mathrm{e}$ conductance difficult at low temperatures for junctions with thick $a\ensuremath{-}\mathrm{G}\mathrm{e}$ layers. The relation $\ensuremath{\sigma}={\ensuremath{\sigma}}_{0}\mathrm{exp}[\ensuremath{-}{(\frac{{T}_{1}}{T})}^{\frac{1}{4}}]$ holds well for these junctions at zero bias for temperatures not showing bulk $a\ensuremath{-}\mathrm{G}\mathrm{e}$ effects. In junctions with sufficiently thin $a\ensuremath{-}\mathrm{G}\mathrm{e}$ layers, $t\ensuremath{\approx}100$ \AA{}, the bulk $a\ensuremath{-}\mathrm{G}\mathrm{e}$ does not seriously modify the conductance away from zero bias. A series of junctions formed on the same oxide with $t\ensuremath{\le}80$ \AA{} of $a\ensuremath{-}\mathrm{G}\mathrm{e}$ show an exponential drop in conductance with increasing $t$ leveling off at temperature-dependent values. This is interpreted as incomplete surface coverage. This interpretation is independent of the details of the tunneling mechanism into $a\ensuremath{-}\mathrm{G}\mathrm{e}$, but does place an upper limit on the possible tunneling range, varying from 28 \AA{} at 300 K to 50 \AA{} at 4.2 K. Tunneling thus only probes the surface layers of $a\ensuremath{-}\mathrm{G}\mathrm{e}$ and does not reflect the bulk properties. Capacitance studies of the junctions indicate the presence of a high density of interface states, ${N}_{s}\ensuremath{\ge}2.5\ifmmode\times\else\texttimes\fi{}{10}^{14}$ ${\mathrm{eV}}^{\ensuremath{-}1}$ ${\mathrm{cm}}^{\ensuremath{-}2}$. Superconductive tunneling confirms that tunneling is the dominant conduction mode for these junctions.
Methionine-80-sulfoxide cytochrome c: preparation, purification and electron-transfer capabilities

In order to explore the electron-transferring properties of methionine-80-sulfoxide cytochrome c, the pure, chromatographically homogeneous methionine-80-sulfoxide cytochrome c was previously published procedure (Ivanetich, K.M., Bradshaw, J.J. and Kaminsky, L.S. (1976) Biochemistry 15, 1144-1153) was found to produce a mixture of products. In the pure derivative, visible spectroscopy indicates that the 695 nm band indicative of the Met-80-Fe coordination is missing, amino acid analysis indicates that only one methionine is modified to the sulfoxide, and the E0' is found to be 240 mV vs. N.H.E. For succinate cytochrome c reductase activity, the Km for modified cytochrome was about one-ninth that of the native protein, while the maximum turnover number of the reductase with the modified protein was only about 54% of that with native protein. In contrast, the activity with cytochrome oxidase measured polarographically using ascorbate and TMPD under two different buffer/pH conditions, gave Km values that were very similar for both the native and modified cytochromes c, but the maximum turnover numbers of the oxidase with the modified protein were less than 40% of native in either buffer. It is concluded that the Met-80-sulfoxide cytochrome c in the reduced form is able to maintain substantially its heme crevice structure and thus maintain Km values similar to those of native protein. However, the low maximum turnover numbers for oxidase activity with the modified protein in the reduced state indicate that electron transfer itself has been significantly decreased, probably because the parity of acid/base and electrostatic interactions of Met-80 sulfur with the Fe in the two redox states has been disrupted.
Particle contamination control in the EXTRION 220

Abstract The design philosophy of the EXTRION 220, a serial implanter, with regard to particle contamination is discussed. The implanter is a hybrid electrostatic/mechanical scan system offering unique performance characteristics. Particle control has heen studied under stringent test conditions. The evolution of the particle control hardware is explained. Data documenting particle contamination levels is presented.