cssi/SciSciGPT-SciSciNet huggingface dataset:
The role of TNF-TNFR2 interactions in generation of CTL responses and clearance of hepatic adenovirus infection.

Deficiency or inhibition of tumor ne- crosis factor (TNF) significantly prolongs hepatic expression of recombinant adenoviral vectors. To explore mechanisms responsible for this observa- tion, the present studies examined the effects of TNF versus TNF receptor 1 (TNFR1) or TNFR2 deficiency on the course of antiviral-immune re- sponses to a replication-deficient, -galactosidase- encoding recombinant adenovirus (AdCMV-lacZ). Clearance of AdCMV-lacZ was significantly delayed in TNF-deficient mice. Less pronounced but signif- icant delays in AdCMV-lacZ clearance were ob- served in TNFR2-deficient but not TNFR1-defi- cient mice. Numbers of interferon- expressing intrahepatic lymphocytes (IHL) were similar in Ad- CMV-lacZ-infected, TNF-deficient, TNFR1-defi- cient, TNFR2-deficient, and control mice. How- ever, IHL isolated from AdCMV-lacZ-infected, TNF-deficient or AdCMV-lacZ-infected, TNFR2- deficient mice exhibited decreased levels of FasL expression and adenovirus-specific cytolytic T lym- phocyte (CTL) activity. Similar defects in allo-spe- cific killing of Fas-sensitive hepatocyte targets by TNF-deficient or TNFR2-deficient but not TNFR1- deficient CTL were also noted. No defects in gen- eration of allo-specific cytotoxicity directed against perforin-sensitive target cells were noted in TNF-, TNFR1-, or TNFR2-deficient lymphocytes. These findings indicate that TNF/TNFR2 interactions fa- cilitate generation of FasL-dependent CTL effector pathways that play an important role in in vivo antiviral-immune responses in the liver. J. Leukoc. Biol. 74: 000-000; 2003.
Silicon integrated microsensor incorporating a metal-doped phthalocyanine organic semiconductor used to selectively detect nitrogen dioxide and an organophosphorus compound

A novel gas-sensitive microsensor, whose design is based upon the interdigitated-gate-electrode field-effect transistor was realized by integrating it with ia selectively-deposited, chemically-active, electron-beam evaporated copper phthalocyanine (CuPc) thin film. When isothermally operated at 150 degrees C, the microsensor can selectively and reversibly detect parts-per-billion (ppb) concentration levels of two environmentally-sensitive pollutants, nitrogen dioxide (NO2) and diisopropyl methylphosphonate (DIMP). Although the CuPc thin film chemically and electrically interacts with NO2 and DIMP, just as it will likely interact with other electrically- active gases, or combinations thereof, the selectivity feature of the microsensor was established by operating it with a 5-V peak amplitude, 2-microsecond(s) duration, 1000 Hz repetition frequency pulse, and then analyzing its time- and frequency-domain responses. As a direct consequence of this analysis, the envelopes associated with the normalized- difference Fourier transform magnitude frequency spectra reveal features which unambiguously distinguish the NO2 and DIMP challenge gas responses. Furthermore, the area beneath each response envelope may correspondingly be interpreted as a metric for the microsensor's sensitivity to a specific challenge gas concentration. Scanning electron microscopy was used to characterize the CuPc thin film's morphology. Additionally, infrared spectroscopy was employed to verify the (alpha) - and (beta) -phases of the sublimed CuPc thin films and to study the NO2- and DIMP-CuPc interactions.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Density-Dependent Harvest Modeling for the Eastern Wild Turkey

Many current wild turkey (Meleagris gallopavo) harvest models assume density-independent population dynamics. We developed an alternative model incorporating both nonlinear density-dependence and stochastic density-independent effects on wild turkey populations. We examined model sensitivity to parameter changes in 5% increments and determined mean spring and fall harvests and their variability in the short term (3 yr) and long term (10 yr) from proportional harvesting under these conditions. In the long term, population growth rates were most sensitive to poult:female ratios and the form of density dependence. The nonlinear density-dependent effect produced a population that maximized yield at 40% carrying capacity. The model indicated that a spring or fall proportional harvest could be maximized for fall harvest rates between 0% and 13% of the population, assuming a 15% spring male harvest and 5% spring illegal female kill. Combined spring and fall harvests could be maximized at a 9% fall harvest, under the same assumptions. Variability in population growth and harvest rates increased uncertainty in spring and fall harvests and the probability of overharvesting annual yield, with growth rate variation having the strongest effect. Model simulations suggested fall harvest rates should be conservative (≤9%) for most management strategies.
Mini-Sudokus and Groups

Using a little group theory and ideas about equivalence relations, this article shows that there are only two essentially different 4 by 4 Sudoku grids. This can be compared with the 5,472,730,538 ...
Dissipation of soil fumigants from soil following repeated applications

BACKGROUND The dissipation of pesticides in soil and the occurrence of accelerated degradation following repeated applications are well-known phenomena with many pesticides, but much less so with soil fumigants. The fate of various soil fumigants was studied in different agricultural soils following repeated applications of chloropicrin. RESULTS Fumigant dissipation reflected by Σconcentration × time (ΣC × T) and half-life values varied widely among the tested soils. Methyl iodide (MI) had the slowest dissipation rate compared with other fumigants in all tested soils. Elimination of biotic agents by soil sterilization prior to MI application did not affect MI concentration in Oxnard soil. Clay content and fumigant dose (ΣC × T values) of chloropicrin, 1,3-dichloropropene and MI were significantly correlated. No significant correlations were found between soil properties and ΣC × T values following metam sodium and methyl bromide (MBr) application. CONCLUSION The fate of the tested soil fumigants is highly dependent on and specific to the fumigant, previous fumigant application and soil type. This study suggests that biotic factors are more essential in the dissipation of metam sodium and MBr than abiotic factors. By contrast, MI dissipation from the tested soils is affected more by abiotic factors than by biotic activities. © 2013 Society of Chemical Industry.
Quantitative changes in protein synthesis during oogenesis in Xenopus laevis.

Abstract Protein synthesis rates in Xenopus laevis oocytes from stage 1 through stage 6 were measured. In addition, the translational efficiencies, total RNA contents, and percentages of ribosomes in polysomes in growing oocytes at several stages were determined. Stage 1 oocytes synthesize protein at a mean rate of 0.18 ng hr−1 while stage 6 oocytes make protein at a rate of 22.8 ng hr−1. Polysomes from growing and full-grown oocytes sedimented in a sucrose gradient with a peak value of 300 S, corresponding to a weight-average packing density of 10 ribosomes per mRNA. Ribosome transit times of endogenous mRNAs were essentially unchanged at all stages examined. While the oocyte's total ribosomal RNA content was observed to increase about 115-fold during oogenesis, the percentage of ribosomes in polysomes remained constant at approximately 2%. Taken together, the data suggest that the 127-fold increase in protein synthesis which occurs during Xenopus oogenesis involves the progressive recruitment onto polysomes of mRNA from the maternal stockpile.
Cellular immune responses, chemokine, and cytokine profiles in turkey poults following infection with the intestinal parasite Eimeria adenoeides

ABSTRACT Cellular immune responses, chemokine, and cytokine profiles were investigated in 20-d-old turkey poults following an oral infection with 12.5 × 103 oocysts of Eimeria adenoeides, a protozoan parasite of the genus Eimeria that develops in the ceca. Large numbers of oocysts were produced in the feces of infected birds from d 5 after infection followed by a rapid decline by d 7. Local immune activities were characterized by observing the extent of leukocyte infiltration in the ceca by histology, measuring subsets of the lymphocyte population by immunohistochemistry, and determining the relative expression of cytokines by real-time, reverse-transcription PCR. Inflammation, assessed by scoring the extent of cellular infiltration of leukocytes in sections of ceca, was significantly higher in infected poults compared with uninfected poults on d 4, 7, 9, and 11 following infection. The percent area occupied by CD4+ and CD8+ cells in the ceca was significantly greater on d 9 and 11 (CD4+) and d 11 (CD8+) in infected poults compared with uninfected controls. The relative expression of the chemokine CXCLi2 and the cytokines interleukin (IL) 1β, interferon (IFN) γ, IL13, and IL10 was investigated in tissue samples taken from the ceca. Increased expression of CXCLi2 occurred on d 4 and 7. Increased expression of IL10 and IFNγ occurred on d 4 and of IL1β and IL13 occurred on d 7 postinfection. The increased leukocyte infiltration in the ceca, alterations in the lymphocyte subpopulations, and changes in expression of chemokines and cytokines are an indication of the cell-mediated immune mechanisms occurring in the host as a result of exposure to E. adenoeides.
The Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Induced 5-Lipoxygenase-Leukotriene B4 Cascade Plays Key Roles in KSHV Latency, Monocyte Recruitment, and Lipogenesis

Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). KS lesions are characterized by endothelial cells with multiple copies of the latent KSHV episomal genome, lytic replication in a low percentage of infiltrating monocytes, and inflammatory cytokines plus growth factors. We demonstrated that KSHV utilizes inflammatory cyclooxygenase 2/prostaglandin E2 to establish and maintain latency (Sharma-Walia, N., A. G. Paul, V. Bottero, S. Sadagopan, M. V. Veettil, N. Kerur, and B. Chandran, PLoS Pathog 6:e1000777, 2010 [doi:10.1371/journal.ppat.1000777]). Here, we evaluated the role of 5-lipoxygenase (5LO) and its chemotactic metabolite leukotriene B4 (LTB4) in KSHV biology. Abundant staining of 5LO was detected in human KS tissue sections. We observed elevated levels of 5LO and high levels of secretion of LTB4 during primary KSHV infection of endothelial cells and in PEL B cells (BCBL-1 and BC-3 cells). Blocking the 5LO/LTB4 cascade inhibited viral latent ORF73, immunomodulatory K5, viral macrophage inflammatory protein 1 (MIP-1), and viral MIP-2 gene expression, without much effect on lytic switch ORF50, immediate early lytic K8, and viral interferon-regulatory factor 2 gene expression. 5LO inhibition significantly downregulated latent viral Cyclin and latency-associated nuclear antigen 2 levels in PEL cells. 5LO/LTB4 inhibition downregulated TH2-related cytokine secretion, elevated TH1-related cytokine secretion, and reduced human monocyte recruitment, adhesion, and transendothelial migration. 5LO/LTB4 inhibition reduced fatty acid synthase (FASN) promoter activity and its expression. Since FASN, a key enzyme required in lipogenesis, is important in KSHV latency, these findings collectively suggest that 5LO/LTB4 play important roles in KSHV biology and that effective inhibition of the 5LO/LTB4 pathway could potentially be used in treatment to control KS/PEL.
Pediatric craniocervical spiral CT

Spiral CT, which consists of rapid volumetric data acquisition and planar image display, was performed on 100 children undergoing examinations of the brain and head and neck for a variety of clinical indications. The technique was evaluated for image quality and impact on clinical practice. Images of the brain were generally of diagnostic quality in infants and young children but not in older children, due to their larger heads and present X-ray tube current limitations. The lower contrast resolution demands in imaging head and neck structures permitted acquisition of high quality images in all age groups. The rapidity of the technique allowed vascular phase imaging with one-sixth to one quarter the amount of contrast medium injected routinely, reduced the number of artifacts related to patient motion and occasionally permitted scanning of young patients without sedation. As a consequence, the spiral technique appears to have the potential for improving the efficiency and safety of diagnostic CT in investigation of the brain, head and neck in children.
Optical and electronic properties of SiGeC alloys grown on Si substrates

Abstract Metastable Si 1 − x − y Ge x C y alloys were grown by molecular beam epitaxy on (100) Si substrates. Solid elemental sources were used for the Si and Ge beams, and a resistively heated graphite filament was used for the C beam. Up to 3 at% of C was incorporated in the alloy layers. Optical transmission measurements showed that the absorption edge of thick layers increased to higher energies with increasing C fraction, and revealed the presence of SiC and GeC vibrational modes in the infrared. At low temperatures, the alloys showed significant photoluminescence. The bandgap energies of thick layers increased linearly with the C fraction and followed a linear dependence of the bandgap on composition. Measurements of the valence band density of states using X-ray photoelectron spectroscopy indicated that the valence band energy maximum increased with the C fraction relative to that of SiGe alloys of similar composition. Our results indicated that SiGeC alloys are promising materials for Si-based heterostructure devices.
Adaptive supervisory control under sensor unavailability

We present a supervisory control architecture with control redundancy. We assume an adaptive architecture for the problem of switching from one control module to another when sensors used for observing events in the plant fail or become unavailable. It is assumed that there is an actual controller and a number of virtual controllers. The actual controller is in real feedback loop with the plant whereas the virtual ones are in virtual feedback such that the coupled behavior of any of these control modules with plant conforms to what is called normality criterion in the context of partial observation. Every time that a failure occurs and the environment changes, the actual controller is replaced by one of these virtual ones. The selection is based on some optimality criterion and user defined constraints.
Primary phosphatic oolites from the Lower Cambrian of Spitsbergen

Thin sandstones and sandy lenses within the Lower Cambrian Topiggane Shale Member of the Tokammane Formation from Ny Friesland, Spitsbergen (Svalbard), consist of medium to fine sand-size quartz, glauconite, and sparse feldspars and stable heavy minerals which are coated by concentrically laminated phosphate. The general inverse proportionality of the thickness of the phosphatic coatings to the detrital grain size suggests an energy/mass control of the phosphatic coating growth process. Four lines of evidence support a primary origin for the phosphatic oolitic coatings: 1) The detrital grains would be unsupported without oolitic coatings but as oolites they are grain supported; 2) the microscopic details of the concentrically laminated oolitic coatings are exquisitely preserved implying lack of replacement; 3) the guest-host relationships of the phosphate to subsequent diagenesis, involving silica and dolomite, indicate an early formation for the phosphate; and 4) there is a total lack of relict carbonate or textural evidence suggesting a replacement origin for the phosphate. Syntaxial overgrowths on the detrital quartz grains fill pores between the phosphatic oolites and occasionally displace the oolitic coatings but do not replace them. Minor dolomitic cement in burrow structures is exclusively external to the phosphatic oolites and neither displaces nor replaces the phosphate. Underlying and overlying strata, both of which are interpreted as having formed in tidal environments, suggest that the Topiggane Shale was also deposited on the shallow marine, passive margin of the north American plate bordering the Iapetus (Proto-Atlantic) Ocean.
Small-molecule inhibitors of proteins involved in base excision repair potentiate the anti-tumorigenic effect of existing chemotherapeutics and irradiation

There has been a recent upsurge in the development of small-molecule inhibitors specific to DNA repair proteins or proteins peripherally involved in base excision repair and the DNA damage response. These specific, nominally toxic inhibitors are able to potentiate the effect of existing cancer cell treatments in a wide array of cancers. One of the largest obstacles to overcome in the treatment of cancer is incomplete killing with initial cancer treatments, leading to resistant cancer. The progression of our understanding of cancer and normal cell responses to DNA damage has allowed us to develop biomarkers that we can use to help us predict responses of cancers, more specifically target cancer cells and overcome resistance. Initial successes using these small-molecule DNA repair inhibitors in target-validation experiments and in the early stages of clinical trials indicate an important role for these inhibitors, and allow for the possibility of a future in which cancers are potentially treated in a highly specific, individual manner.
Measurement of the ratio B(D0'e)B(D0K-e+e)

Using the CLEO detector at the Cornell Electron Storage Ring, we have performed a direct measurement of the ratio of {ital D}{sup 0} semileptonic branching fractions into vector and pseudoscalar final states. We find {ital B}({ital D}{sup 0}{r arrow}{ital K}{sup *{minus}}{ital e+}{nu}{sub {ital e}})/{ital B}({ital D}{sup 0}{r arrow}{ital K}{sup {minus}}{ital e+}{nu}{sub {ital e}})=0.51{plus minus} 0.18{plus minus}0.06, in agreement with the ratio derived by the E691 experiment which compares {ital D}{sup +} and {ital D}{sup 0} final states. We also set an upper limit on the ratio {ital B}({ital D}{sup 0}{r arrow}{ital {bar K}}{sup *0}{pi}{sup {minus}}{ital e+}{nu}{sub {ital e}})/{ital B}({ital D}{sup 0}{r arrow}{ital K}{sup *{minus}}{ital e}{nu}{sub {ital e}}){lt}0.64 at 90% confidence level.
Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder

Objective: To evaluate relationships between HIV-associated neurocognitive disorder and metabolic variables in a subgroup of HIV+ participants examined in a prospective, observational, multicenter cohort study. Methods: In a cross-sectional substudy of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, 130 HIV+ participants provided fasting blood samples. Neurocognitive impairment (NCI) was defined by performance on neuropsychological tests adjusting for age, education, gender, and race/ethnicity. Global ratings and global deficit scores were determined. Demographics, biomarkers of HIV disease, metabolic variables, combination antiretroviral therapy (CART) history, other drug exposures, and self-reported diabetes were examined in multivariate models predicting NCI. Separate models were used for body mass index (BMI) alone (n = 90) and BMI and waist circumference (WC) together (n = 55). Results: NCI (global impairment rating ≥5) was diagnosed in 40%. In univariate analyses, age, longer duration of HIV infection, obesity, and WC, but not BMI, were associated with NCI. Self-reported diabetes was associated with NCI in the substudy and in those >55 in the entire CHARTER cohort. Multivariate logistic regression analyses demonstrated that central obesity (as measured by WC) increased the risk of NCI and that greater body mass may be protective if the deleterious effect of central obesity is accounted for. Conclusions: As in HIV-uninfected persons, central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of NCI in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients. Avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons.
Calcium and IP3 dynamics in cardiac myocytes: experimental and computational perspectives and approaches.

Calcium plays a crucial role in excitation-contraction coupling (ECC), but it is also a pivotal second messenger activating Ca2+-dependent transcription factors in a process termed excitation-transcription coupling (ETC). Evidence accumulated over the past decade indicates a pivotal role of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release in the regulation of cytosolic and nuclear Ca2+ signals. IP3 is generated by stimulation of plasma membrane receptors that couple to phospholipase C (PLC), liberating IP3 from phosphatidylinositol 4,5-bisphosphate (PIP2). An intriguing aspect of IP3 signaling is the presence of the entire PIP2-PLC-IP3 signaling cascade as well as the presence of IP3Rs at the inner and outer membranes of the nuclear envelope (NE) which functions as a Ca2+ store. The observation that the nucleus is surrounded by its own putative Ca2+ store raises the possibility that nuclear IP3-dependent Ca2+ release plays a critical role in ETC. This provides a potential mechanism of regulation that acts locally and autonomously from the global cytosolic Ca2+ signal underlying ECC. Moreover, there is evidence that: (i) the sarcoplasmic reticulum (SR) and NE are a single contiguous Ca2+ store; (ii) the nuclear pore complex is the major gateway for Ca2+ and macromolecules to pass between the cytosol and the nucleoplasm; (iii) the inner membrane of the NE hosts key Ca2+ handling proteins including the Na+/Ca2+ exchanger (NCX)/GM1 complex, ryanodine receptors (RyRs), nicotinic acid adenine dinucleotide phosphate receptors (NAADPRs), Na+/K+ ATPase and Na+/H+ exchanger. Thus, it appears that the nucleus represents a Ca2+ signaling domain equipped with its own ion channels and transporters that allow for complex local Ca2+ signals. Many experimental and modeling approaches have been used for the study of intracellular Ca2+ signaling but the key to understanding of the dual role of Ca2+ mediating ECC and ECT lays in quantitative differences of local [Ca2+
The effects of corticotropin releasing factor on the anterior pituitary function of stalk-sectioned cynomdlgus macaques: Dose response of cortisol secretion

The recent identification of ovine corticotropin releasing factor (CRF), a 41-amino acid peptide, provides a potential new approach to evaluate disorders of the hypothalamic-pituitary-vadrenal axis. We report here the effects of this new factor in the pituitary stalk-sectioned cynomolgus macaque. Given as an intravenous bolus, CRF stimulated cortisol secretion with an ED50 between 0 .1 and 1 μg⁄kg body weight. The peak cortisol response occurred after 15-30 min at low doses (0.5 - 1 μg⁄kg) and after 45-90 min at higher doses (2-40 μg⁄kg). This factor also stimulated the release of growth hormone and prolactin, but had no effect on TSH or LH secretion.
Parameterized SPICE subcircuits for multilevel interconnect modeling and simulation

The authors describe a parameterized interconnect model library generator that provides VLSI designers with a direct link between numerical method-based capacitance simulators and SPICE-like circuit simulators. As a result, interconnect parasitics are parameterized in a manner similar to the parameterization of transistors in SPICE. Therefore, the effort and time needed by circuit designers or EDA tools to prepare distributed multiline R, C SPICE decks for circuit simulations is drastically reduced. >
Interhemispheric neuroplasticity following limb deafferentation detected by resting-state functional connectivity magnetic resonance imaging (fcMRI) and functional magnetic resonance imaging (fMRI)

Functional connectivity magnetic resonance imaging (fcMRI) studies in rat brain show brain reorganization following peripheral nerve injury. Subacute neuroplasticity was observed 2 weeks following transection of the four major nerves of the brachial plexus. Direct stimulation of the intact radial nerve reveals a functional magnetic resonance imaging (fMRI) activation pattern in the forelimb regions of the sensory and motor cortices that is significantly different from that observed in normal rats. Results of this fMRI experiment were used to determine seed voxel regions for fcMRI analysis. Intrahemispheric connectivities in the sensorimotor forelimb representations in both hemispheres are largely unaffected by deafferentation, whereas substantial disruption of interhemispheric sensorimotor cortical connectivity occurs. In addition, significant intra- and interhemispheric changes in connectivities of thalamic nuclei were found. These are the central findings of the study. They could not have been obtained from fMRI studies alone-both fMRI and fcMRI are needed. The combination provides a general marker for brain plasticity. The rat visual system was studied in the same animals as a control. No neuroplastic changes in connectivities were found in the primary visual cortex upon forelimb deafferentation. Differences were noted in regions responsible for processing multisensory visual-motor information. This incidental discovery is considered to be significant. It may provide insight into phantom limb epiphenomena.
Nonlinear analysis of gait kinematics to track changes in oxygen consumption in prolonged load carriage walking: A pilot study

Linking human mechanical work to physiological work for the purpose of developing a model of physical fatigue is a complex problem that cannot be solved easily by conventional biomechanical analysis. The purpose of the study was to determine if two nonlinear analysis methods can address the fundamental issue of utilizing kinematic data to track oxygen consumption from a prolonged walking trial: we evaluated the effectiveness of dynamical systems and fractal analysis in this study. Further, we selected, oxygen consumption as a measure to represent the underlying physiological measure of fatigue. Three male US Army Soldier volunteers (means: 23.3 yr; 1.80 m; 77.3 kg) walked for 120 min at 1.34 m/s with a 40-kg load on a level treadmill. Gait kinematic data and oxygen consumption (VO2) data were collected over the 120-min period. For the fractal analysis, utilizing stride interval data, we calculated fractal dimension. For the dynamical systems analysis, kinematic angle time series were used to estimate phase space warping based features at uniform time intervals: smooth orthogonal decomposition (SOD) was used to extract slowly time-varying trends from these features. Estimated fractal dimensions showed no apparent trend or correlation with independently measured VO2. While inter-individual difference did exist in the VO2 data, dominant SOD time trends tracked and correlated with the VO2 for all volunteers. Thus, dynamical systems analysis using gait kinematics may be suitable to develop a model to predict physiologic fatigue based on biomechanical work. Published by Elsevier Ltd.
Amelioration of proteolipid protein 139-151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms.

Copolymer 1 [Cop1, glatiramer acetate, Copaxone, poly(Y,E,A,K)n] is widely used in the treatment of relapsing/remitting multiple sclerosis in which it reduces the frequency of relapses by ≈30%. In the present study, copolymers with modified amino acid compositions (based on the binding motif of myelin basic protein 85–99 to HLA-DR2) have been developed with the aim of suppressing multiple sclerosis more effectively. The enhanced efficacy of these copolymers in experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with proteolipid protein 139–151 was demonstrated by using three protocols: (i) simultaneous administration of autoantigen and copolymer (termed prevention), (ii) pretreatment with copolymers (vaccination), or (iii) administration of copolymers after disease onset (treatment). Strikingly, in the treatment protocol administration of soluble VWAK and FYAK after onset of disease led to stasis of its progression and suppression of histopathological evidence of EAE. The mechanisms by which these effects are achieved have been examined in several types of assays: binding of copolymers to I-As in competition with proteolipid protein 139–151 (blocking), cytokine production by T cells (T helper 2 polarization), and transfer of protection by CD3+ splenocytes or, notably, by copolymer-specific T cell lines (induction of regulatory T cells). The generation of these copolymer-specific regulatory T cells that secrete IL-4 and IL-10 and are independent of the immunizing autoantigen is very prominent among the multiple mechanisms that account for the observed suppressive effect of copolymers in EAE.
Monolayer cell culture of freshly isolated adipocytes using extracellular basement membrane components.

Cell biological techniques requiring cells attached to surfaces, such as monolayer cell culture, microspectrofluorometry, and confocal microscopy, have not been readily available for use on adipocytes because they float and tend to lyse when attached to charged non-biological surfaces. A new method for attaching freshly isolated rodent adipocytes to thermanox plastic surfaces using Matrigel (a defined mixture of extracellular matrix components that resembles the basal lamina surrounding adipocytes in vivo) is described. The method takes advantage of an unusual physical characteristic of Matrigel, i.e., that it is a liquid at cold temperatures and a hydrated gel at higher temperatures. To attach the isolated cells, chilled thermanox plastic coverslips were coated with a thin uniform layer of ice-cold Matrigel and inverted into warm floating adipocytes. Adipocytes floated up against the liquid Matrigel and became immediately attached when the Matrigel changed to a gel in response to the warmth of the cells and media. Cell volume measurements of the attached versus freshly isolated cells indicate no significant difference in the centroid cell volume of the attached cells. This indicates that the method does not select for small or large cells. Adipocytes maintained for 6 days in culture did not display any change in their size or differentiated microscopic appearance. The relative concentrations of major proteins in silver-stained SDS-PAGE gels and several differentiation state-dependent proteins, including ATP-citrate lyase, carbonic anhydrase III (CA III), adipocyte lipid binding protein (ALBP), and pyruvate carboxylase, were examined. No significant change was observed in the relative concentrations of these proteins when the matrigel-cultured adipocytes were compared to freshly isolated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelial MKK3 Is a Critical Mediator of Lethal Murine Endotoxemia and Acute Lung Injury

Sepsis is a leading cause of intensive care unit admissions, with high mortality and morbidity. Although outcomes have improved with better supportive care, specific therapies are limited. Endothelial activation and oxidant injury are key events in the pathogenesis of sepsis-induced lung injury. The signaling pathways leading to these events remain poorly defined. We sought to determine the role of MAPK kinase 3 (MKK3), a kinase of the p38 group, in the pathogenesis of sepsis. We used a murine i.p. LPS model of systemic inflammation to mimic sepsis. Lung injury parameters were assessed in lung tissue and bronchoalveolar lavage specimens. Primary lung endothelial cells were cultured and assessed for mediators of inflammation and injury, such as ICAM-1, AP-1, NF-κB, and mitochondrial reactive oxygen species. Our studies demonstrate that MKK3 deficiency confers virtually complete protection against organ injury after i.p. LPS. Specifically, MKK3−/− mice were protected against acute lung injury, as assessed by reduced inflammation, mitochondrial reactive oxygen species generation, endothelial injury, and ICAM-1 expression after LPS administration. Our results show that endothelial MKK3 is required for inflammatory cell recruitment to the lungs, mitochondrial oxidant-mediated AP-1, NF-κB activation, and ICAM-1 expression during LPS challenge. Collectively, these studies identify a novel role for MKK3 in lethal LPS responses and provide new therapeutic targets against sepsis and acute lung injury.
Duplication and Adaptive Evolution of a Key Centromeric Protein in Mimulus, a Genus with Female Meiotic Drive

The fundamental asymmetry of female meiosis creates an arena for genetic elements to compete for inclusion in the egg, promoting the selfish evolution of centromere variants that maximize their transmission to the future egg. Such "female meiotic drive" has been hypothesized to explain the paradoxically complex and rapidly evolving nature of centromeric DNA and proteins. Although theoretically widespread, few cases of active drive have been observed, thereby limiting the opportunities to directly assess the impact of centromeric drive on molecular variation at centromeres and binding proteins. Here, we characterize the molecular evolutionary patterns of CENH3, the centromere-defining histone variant, in Mimulus monkeyflowers, a genus with one of the few known cases of active centromere-associated female meiotic drive. First, we identify a novel duplication of CENH3 in diploid Mimulus, including in lineages with actively driving centromeres. Second, we demonstrate long-term adaptive evolution at several sites in the N-terminus of CENH3, a region with some meiosis-specific functions that putatively interacts with centromeric DNA. Finally, we infer that the paralogs evolve under different selective regimes; some sites in the N-terminus evolve under positive selection in the pro-orthologs or only one paralog (CENH3_B) and the paralogs exhibit significantly different patterns of polymorphism within populations. Our finding of long-term, adaptive evolution at CENH3 in the context of centromere-associated meiotic drive supports an antagonistic, coevolutionary battle for evolutionary dominance between centromeric DNA and binding proteins.
A spectrally accurate method for overlapping grid solution of incompressible Navier-Stokes equations

An overlapping mesh methodology that is spectrally accurate in space and up to third-order accurate in time is developed for solution of unsteady incompressible flow equations in three-dimensional domains. The ability to decompose a global domain into separate, but overlapping, subdomains eases mesh generation procedures and increases flexibility of modeling flows with complex geometries. The methodology employs implicit spectral element discretization of equations in each subdomain and explicit treatment of subdomain interfaces with spectrally-accurate spatial interpolation and high-order accurate temporal extrapolation, and requires few, if any, iterations, yet maintains the global accuracy and stability of the underlying flow solver. The overlapping mesh methodology is thoroughly validated using two-dimensional and three-dimensional benchmark problems in laminar and turbulent flows. The spatial and temporal convergence is documented and is in agreement with the nominal order of accuracy of the solver. The influence of long integration times, as well as inflow-outflow global boundary conditions on the performance of the overlapping grid solver is assessed. In a turbulent benchmark of fully-developed turbulent pipe flow, the turbulent statistics with the overlapping grids is validated against published available experimental and other computation data. Scaling tests are presented that show near linear strong scaling, even for moderately large processor counts. A novel overlapping grid method for incompressible flow equations is developed.The overlapping grid method is based on spectral-element discretization.The method maintains global spectral accuracy with polynomial refinement.An explicit interface extrapolation scheme for temporal coupling is proposed.The scheme allows for high-order temporal accuracy with only a few iterations.
An Example of the Interpretation of Meteorite Properties: The Origin of Ordinary Chondrites

The ordinary chondrites account for 79% of observed meteorite falls. The relative abundances of the three ordinary chondrite groups (H, L, and LL) are 42, 49, and 9%, respectively. Each group includes representatives of Van Schmus-Wood (1967) petrologic types 3–6; the distribution among these types is shown in Table II-4. Type 6 is the most abundant type in the L and LL groups, type 5 in the H group.
Reconsidering coprophagy as an indicator of negative welfare for captive chimpanzees

Abstract For captive chimpanzees, ‘abnormal’ behaviours include behaviours observed only in captivity (i.e. species-atypical behaviours) and those that are performed at higher rates in captivity compared to in the wild. Both types are used as metrics for evaluating captive primates’ welfare. However, categorizing all abnormal behaviours together ignores variation in their etiologies, which limits our ability to understand them and provide useful interventions. Coprophagy (deliberately eating faeces) is an intriguing abnormal behaviour because, unlike many abnormal behaviours, it is performed at higher rates among captive chimpanzees that were mother reared, compared to those that were human reared, and it has been proposed that it represents a socially learnt ‘cultural’ behaviour. Furthermore, coprophagy is observed among both wild and captive animals, although at higher rates in captivity. Typically, coprophagy is classed with other abnormal behaviours by those evaluating captive chimpanzee welfare, but such categorization has arisen from a top–down approach based on a priori assumptions. To apply a bottom–up approach, which would allow us to identify relations between behaviours in chimpanzees’ repertoire, in this study we ran a principal components analysis on the behaviours performed by 60 captive chimpanzees, to determine whether coprophagy should be classified with other abnormal behaviours. The principal components analysis revealed seven factors that we termed social, aggressive, playful, active, feed, abnormal and self-directed. Furthermore, the analysis revealed that coprophagy loaded onto the ‘social’ factor, which included positive social behaviours, and not onto the ‘abnormal’ factor, which included other abnormal behaviours. Supporting previous research, we also found that those chimpanzees that were mother-reared showed higher rates of coprophagy than those that were human reared; there was a significant positive correlation between time spent with conspecifics during the first four years of life and the rate of coprophagy performed by the subjects as adults ( r = 0.575, N = 60, P
Forecasting Power of Implied Volatility: Evidence from Individual Equities

Assuming use of the correct option pricing model and an efficient market, an option's implied volatility is the market's consensus forecast of future realized volatility over the remaining life of that option. We examine 460 of the S&P 500 firms to demonstrate that 1) implied volatility is a better forecaster of realized volatility than historic volatility or GARCH models and 2) the information content of implied volatility significantly decreases with liquidity. Since individual equity options are American style, we obtain implied volatility from calls and puts separately rather than only calls or pooled data.
Traumatic Brain Injury in Kenya

1. Benson Kinyanjui[1][1][⇑][2] 1. 1University of Kentucky, Lexington, USA 1. Benson Kinyanjui, Department of Early Childhood, Special Education, and Rehabilitation Counseling, University of Kentucky, 229 Taylor Education Building, Lexington, KY 40506, USA. Email: benson.kinyanjui{at}uky.edu Kenya has a disproportionately high rate of road traffic accidents each year, many of them resulting in traumatic brain injuries (TBIs). A review of articles written on issues pertaining to the medical treatment of people with TBI in the past 15 years in Kenya indicates a significantly high incidence of TBIs and a high mortality rate. This article reviews the available literature as a first step in exploring the status of rehabilitation of Kenyans with cognitive impairments and other disabilities resulting from TBIs. From this preliminary review, it is apparent that despite TBI being a pervasive public health problem in Kenya, it has not received due attention in the public and private sectors as evidenced by a serious lack of post-acute rehabilitation services for people with TBIs. Implications for this lack of services are discussed and recommendations are made for potential approaches to this problem. [1]: #aff-1 [2]: #corresp-1
Emerging From the Black Box: AMLE's Continuing Influences on Its Newest Past Editor

Having recently completed my term as AMLE editor, I find the experience's influence on me as an educator and scholar to be both highly intertwined and continuing to unfurl. I describe how the journ...
Portrait of a Consultant in Hard Times John Nolen, 1928–1937

John Nolen was one of the first planners to build a national consulting practice focused on new towns. However, his office began to struggle financially in the late 1920s. Despite a thirty-year record, Nolen had no paying private-sector clients after 1931 and finally had to downsize his office. He survived on New Deal contracts for a while. But eventually he could not obtain work even from the Resettlement Administration, where his former proteges were implementing his ideas. Modern new town ideas from Clarence Stein were ascendant. Seen as a relic, Nolen died without a single project pending in his portfolio.
Endoscopic repair of skull base defects presenting with pneumocephalus.

Objectif: Un pneumocephale persistant est souvent revelateur de la presence d'un defaut de la base du crâne (BC), associe a l'un des sinus paranasaux, defaut qui necessite un traitement afin d'eviter les complications. L'etude avait donc pour but d'evaluer le degre de reussite de la fermeture endoscopique de defauts de la BC, accompagnes d'un pneumocephale. Type d'etude: Il s'agit d'un examen retrospectif de dossiers medicaux. Lieu: L'etude a ete menee dans un centre universitaire de soins tertiaires, en rhinologie. Methode: Nous avons procede a un examen retrospectif, au bout de 5 ans, de dossiers de patients ayant presente un pneumocephale. Les symptomes revelateurs de l'anomalie, l'etiologie des defauts de la BC, les resultats des examens radiologiques, les techniques d'operation et le suivi ont fait l'objet d'evaluation. Principaux criteres d'evaluation: Le principal critere consistait en l'evaluation de la reussite de la reparation endoscopique des defauts de la BC accompagnes d'un pneumocephale. Ont egalement ete evalues les facteurs susceptibles d'avoir joue un role dans l'echec du traitement, dans les cas appropries. Resultats: Onze patients presentant un pneumocephale associe a 14 defauts de la BC ont subi 17 reparations endoscopiques. Dans 11 interventions chirurgicales, il y avait une fuite active de liquide cephalo-rachidien (LCR), mais, dans les 6 autres, il n'y avait que la presence d'un pneumocephale, sans fuite de LCR. Le siege du pneumocephale, d'apres les radiogrammes, variait d'extra-axial a diffus, dans le parenchyme cerebral. L'existence des defauts de la BC a ete revelee par la tomodensitometrie (TDM) a grain fin, la cisternographie par TDM et l'administration intrathecale de fluoresceine. Les defauts ont ete localises dans le sphenoide, la selle turcique, le toit de l'ethmoide et la table posterieure du sinus frontal. La reparation endoscopique seule a suffi chez 8 patients sur 11 (72%). Les facteurs susceptibles d'avoir joue un role dans l'echec du traitement comprenaient les tumeurs malignes, un traitement anterieur par rayonnement, une infection intracrânienne, la malnutrition et la maladie de Cushing. Conclusions: La reparation endoscopique de defauts de la BC pour un pneumocephale connait un taux eleve de reussite. La localisation des defauts de la BC, dans ces cas, est souvent confirmee par la cisternographie par TDM et l'administration intrathecale de fluoresceine.
A Democratic Pynchon: Counterculture, Counterforce and Participatory Democracy

Toward the end of The Crying of Lot 49, Oedipa Maas reflects on the America her involvement with Pierce Inverarity's will has revealed to her. Those on the margins, disenfranchised, include the kids in immobilized railroad cars listening to their mothers' pocket radios, the squatters living in makeshift lean-tos behind highway billboards and in junkyards, drifters speaking their American language "carefully, scholarly, as if they were in exile from somewhere else invisible yet congruent with the cheered land she lived in" (180). And Oedipa, as she wanders through the "hieroglyphic streets," finds herself likening it to "walking among matrices of a great digital computer, the zeroes and ones twinned above, hanging like balanced mobiles right and left" (181).
New developments in the management of chemotherapy-induced emesis: do they impact on existing guidelines?

Guidelines for the management of chemotherapy-induced emesis are necessary to help clinicians match the emetogenicity of antineoplastic agents with the abundance of antiemetic agents now available. Numerous guidelines for antiemetic therapy currently exist, but compliance with them is inconsistent, in part because optimal antiemetic protection is not yet possible, even with the best guidelines. For this reason, guidelines must be dynamic and evolve as knowledge increases. Revision of antiemetic guidelines should be prompted by changes in general principles of treatment, not changes in specific details. Recent recognition of the unique benefits of incorporating selective neurokinin- 1 receptor antagonists into regimens for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy, particularly in delayed emesis, justifies modification of existing antiemetic guidelines.
Protein-quinone interaction: in vitro induction of indirect antiglobulin reactions with methyldopa.

Methyldopa-treated gamma globulin can be demonstrated serologically on either the red cell surface or on latex beads by the indirect antiglobulin reaction. The development of a positive antiglobulin reaction was related to methyldopa concentration and the length and temperature of incubation of methyldopa with protein and could be partially inhibited by the addition of albumin to the incubation mixtures. After more prolonged incubation, antiglobulin positivity also developed with plasma-treated with methyldopa. 14C-methyldopa was covalently bound to gamma globulin. Aggregation of gamma globulin following treatment with methyldopa could be demonstrated by both sedimentation velocity and molecular weight determinations employing low-speed equilibrium centrifugation. Protein aggregation was a function of time, temperature, and methyldopa concentration. Detectability by the antiglobulin reaction, the darkening noted in solutions to which methyldopa or hydroquinone had been added, as well as the aggregation of protein was inhibited by a reducing agent which prevented formation of a quinone from the hydroquinone. Some of the immunologically atypical features of the sensitization of red cells by methyldopa or its structural analogues are explicable by the adherence, in vivo, of chemically modified, nonantibody gamma globulin which renders the red cell directly antiglobulin positive.