cssi/SciSciGPT-SciSciNet huggingface dataset:
Multiple pathways of N-kinase activation in PC12 cells.

: Past work established a cell-free assay for a nerve growth factor (NGF)-activated protein kinase activity (designated N-kinase) that utilizes tyrosine hydroxylase and histone H1 as substrates and that is distinct from a variety of well-characterized kinases. This study explores the specificity and mechanistic pathway(s) by which N-kinase activity is regulated in PC12 rat pheochromocytoma cells. N-kinase is rapidly activated in these cells by treatment with NGF, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), phorbol ester, or dibutyryl cyclic AMP. Our data indicate that the stimulated activity is the same for each agent by several criteria: It exhibits the same characteristic biphasic elution pattern by Mono S fast protein liquid chromatography (FPLC), except for the case of dibutyryl cyclic AMP in which one of the activity peaks is somewhat shifted; it shows the same elution pattern by FPLC on a Superose 12 column; it possesses identical substrate specificity; and, except in the case of dibutyryl cyclic AMP, it does not show additivity when each agent is added simultaneously with NGF. The multiple forms of N-kinase are interconvertible in that rechromatography on a Mono S column yields a single peak of activity. Also, when NGF and dibutyryl cyclic AMP are simultaneously presented to cells, the chromatographic profile resembles that with NGF alone. Activation occurs through several independent initial pathways. Down-regulation of protein kinase C by phorbol ester pretreatment prevents N-kinase activation by phorbol ester, but not by the other agents. A PC12 cell-derived line deficient in cyclic AMP-dependent protein kinase II activity exhibits N-kinase activation by all treatments except dibutyryl cyclic AMP. The properties of N-kinase suggests that it is similar or identical to the ribosomal S6 protein kinase described by Blenis and Erikson. Additional experiments revealed that N-kinase activity can be stimulated in several cell lines in addition to PC12 cells. These findings indicate that the N-kinase can be activated via multiple second-messenger pathways and that it could therefore potentially play a significant role in mediating shared intracellular responses to various extracellular signals.
METABOLISM OF SCANDIUM-46 IN MAN.

Abstract The metabolism, tissue distribution and biological turnover of radioactive chelated scandium were determined in man. When administered intravenously as the weak chelate Sc46 NTA (nitrilotriacetate), Sc46 disappeared very slowly from the vascular space; it was excreted principally via the intestine. When Sc46 was administered as the strong chelate of ethylene-diaminetetraacetic acid, EDTA, or of diethylenetriaminepentaacetic acid, DTPA, the plasma level of Sc46 decreased rapidly and urinary excretion was high, up to 82 percent of the dose being excreted in 24 hr. The concentration of Sc46 in various tissues determined 5,6 and 7 months after the administration of Sc46 NTA showed that uptake was highest in spleen. Evidence is presented which suggests that the high body retention of Sc46 NTA may be due to the formation of colloidal aggregates and to binding of scandium to proteins. The biological half-life of Sc46 NTA determined with the whole-body counter and computer analysis was 1300 days in one patient and 1557 days in another.
A VARIANT OF CARNOSINEMIA WITH NORMAL SERUM CARNOSINASE ACTIVITY IN AN INFANT

The six week old son of a first cousin marriage presented with hyperammonemia, transient acidosts, hepatosplenomegaly, failure to thrive, and seizures. Quantitative plasma and urine amino acids, including lysine clearance, were normal, orotic acid excretion was not increased, and no organic acid abnormalities were evident by GLC-mass spectroscopic analysis. Notably, during periods when the patient was placed on a diet containing 1 gm/kg/day protein intake, arginine supplementation (100 mgm/kg/day) consistently and significantly lowered plasma ammonia (on arginine, 82 μgm% ± 3, S.E.; off arginine, 113 ± 8; p < .01). The mean value for plasma ammonia during periods on a 2gm/kg/day protein diet without arginine (80 ± 17) was lower than on 1 gm/kg/day protein (p=0.1). Liver biopsy was examined by light and electron microscopy. Enzymes of the urea cycle were assayed by Dr. P. J. Snodgrass, revealing a partial deficiency of CPS (0.49 μmol/mg prot/hr; normal neonatal mean 1.13, range 0.81-1.41), assayed in the presence of excess N-acetylglutamate. Since arginine activates glutamate N-acetylase and N-acetylglutamate produced by this reaction is a cofactor for CPS, we postulate that arginine, supplied as such or through moderate amounts of dietary protein, lowered plasma ammonia in our patient by stimulating residual CPS activity.
Tactile sensory analysis for robotic applications

In this paper we discuss the role of tactile sensors in robotic manipulatory systems and present a number of techniques useful in processing tactile information acquired using passive as well as active sensing modes. Successful adaptation of touch in robotic manipulatory systems entails in both enhancing the tactile sensor technology, and developing techniques for efficient and accurate analysis of the tactile information. This paper attempts to emphasize the importance of adopting active tactile sensing scheme as against restricting to passive tactile sensing scheme. In an endeavor to demonstrate the utility of tactual perception for robotic systems, several experiments were carried out on tactile images of objects smaller as well as larger than the sensor size. The experimental results bring out the advantages of employing passive and active tactile sensing techniques to accomplish robotic manipulatory tasks. Further, based on the experimental results it becomes quite apparent that the use of Fourier descriptors over the use of complex moment invariants as shape descriptors is more advantageous for object recognition tasks using passively acquired images. A new least-square cross-correlation technique for generating composite images acquired through active exploration of objects larger than the sensor is also proposed. The implementation results clearly show that an ad hoc technique for generating composite images introduces more error than the technique proposed in this paper.
Investigation of Shiga-Like Toxin Subunit B using Coarse-Grained Modeling

We investigate the structural properties of the Shiga-like toxin (SLT1) subunit B in the bulk and bound to a lipid membrane using coarse-grained (CG) molecular dynamics simulations. SLT1 consist of a cytotoxic A subunit that shuts down protein synthesis and five B subunits forming a homo-pentamer responsible for ferrying the A subunit into the cell. With or without the A unit attached, the B5 complex binds to specific glycolipids on the cell membrane and leads to toxin uptake by cooperatively driving membrane invagination. Unfortunately, the size of the protein-lipid system needed to investigate SLT1 driven vesiculation makes all-atom simulations impractical. Instead, CG models hold promise, having previously succeeded in simulating such events, even though at a much lower resolution [1]. We use an intermediate resolution systematic CG model of proteins and lipids, which improves the efficiency of our simulations while providing the necessary specificity to relate the results directly to SLT1 [2,3]. To ensure that the monomer structure resembles all-atom simulations, we augment the protein model with an intra-monomer elastic network that is parameterized using a novel iterative process. In addition, we explore ways to best represent the bonds between binding sites on the monomers and glycolipids. With the completed model, we investigate the stability and fluctuation modes of the Shiga B subunit in the bulk and on a membrane. In addition, we investigate the effect of the protein on the lipid bilayer, specifically its local bending deformation and lipid diffusion around the protein.[1] B.J. Reynwar, G. Illya, V.A. Harmandaris, M.M. Muller, K. Kremer, and M. Deserno, Nature 447, 461-464 (2007)[2] T. Bereau and M. Deserno, J. Chem. Phys. 130, 235106 (2009)[3] Z. Wang and M. Deserno, J. Phys. Chem. B 114, 11207 (2010)
Neuromyelitis optica in an adolescent after bone marrow transplantation.

Abstract Background Central nervous system complications of bone marrow transplant are a common occurrence and the differential diagnosis is quite broad, including opportunistic infections, medications toxicities, graft versus host disease, and other autoimmune processes. Patient Description We summarize previously reported cases of autoimmune myelitis in post-transplant patients and discuss a 17-year-old boy who presented with seronegative neuromyelitis optica after a bone marrow transplant for acute myeloid leukemia. Our patient had a marked improvement in symptoms after plasmapheresis. Conclusion Including our patient, there have been at least eight cases of post-transplant autoimmune myelitis presented in the literature, and at least three of these are suspicious for neuromyelitis optica. Several of these patients had poor outcomes with persistent symptoms after the myelitis. Autoimmune processes such as neuromyelitis optica should be carefully considered in patients after transplant as aggressive treatment like early plasmapheresis may improve outcomes.
Electrical Characteristics and Reliability of 4H-SiC PiN Diodes Fabricated on In-House Grown and Commercial Epitaxial Films

4H-SiC pin diodes fabricated on epitaxial films grown in-house on various substrates along with devices fabricated on commercial epi-material are presented. Defects have been observed using electroluminescence imaging and are correlated with device electrical performance. Most diodes fabricated with in-house epi-layers up to 25µm thick show relatively stable forward biased operation, although stacking fault propagation has been confirmed in all samples using electroluminescence imaging. Significant stacking fault propagation induced in the vicinity of testing probes has been observed and resulting design considerations are discussed.
Pharmacological strategies in treatment-resistant depression

Treatment-resistant depression may be due to factors such as co-morbid psychiatric or medical illnesses, chronic psychosocial stresses, and medication nonadherence. Alternative treatment strategies such as optimization, switching to a different antidepressant, augmentation or combination with another antidepressant are strategies useful in such patients. The first strategy in treating resistant depression is to optimize monotherapy. A switch should be made to another agent if there is no response to treatment after an adequate duration. Augmentation and combination strategies are useful if there is sub-optimal response to the initial antidepressant. With several antidepressants (selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors and the newer antidepresssants) and various antidepressant augmentation and combination strategies available to clinicians, the outcome of treating patients with depression should improve.
Assessment of Myocardial Postreperfusion Viability by Intravenous Myocardial Contrast Echocardiography Analysis of the Intensity and Texture of Opacification

Background—Although defects on intracoronary myocardial contrast echocardiography (MCE) indicate loss of viability after reperfusion, opacified segments may also exhibit persistent dyssynergy. Therefore, we related the intensity and texture of opacification produced by an intravenous contrast agent to histological findings to determine the characteristics of necrotic tissue by postreperfusion MCE. Methods and Results—MCE was performed by intravenous injection of 0.15 mL/kg QW7437 in 14 dogs who underwent 3-hour coronary occlusion followed by 3-hour reperfusion. At baseline and 3 hours after reperfusion, midventricular short-axis images were digitized and segmented. Infarction fraction (IF) for each segment was determined by triphenyltetrazolium chloride stain. Of 224 segments, 140 showed no or small infarction and served as a control group. Of 84 segments with significant infarction (IF>30%), 52 exhibited a defect on MCE, and 32 exhibited no defect. Echo texture was quantified by computing entropy based o...
Mass Customization Optimization Via Social Network Product Architecture Representation

Mass customization has opened a new realm of product design optimization. These problems require optimization of multiple objectives and have a very vast possible solution space. This paper presents an approach to solve this class of problems using social network based product representations to obtain component level information and then applying Genetic Algorithms to optimize the problem. We consider the case of assembling a PC from 16 subcomponents to demonstrate our approach, and use an established multi-objective GA - Non-dominated Sorting Genetic Algorithm II to optimize the problem. The objectives considered are cost, expected product life required by the user and product performance. Our results reduce the possible solution set from a 109 order to a 102 order figure. The approach is intrinsically robust and produces correct results even when the constraints specified by the user have a small error.© 2006 ASME
Spontaneous breaking of CP in SU(5), natural flavor conservation, and the baryon asymmetry

We present an SU(5) model in which CP is spontaneously broken at the grand unification mass scale and which preserves all the features of the Weinberg model of CP nonconservation with natural flavor conservation. Therefore, a contrast to a model recently proposed by Branco, in the present model a net cosmological baryon asymmetry can be generated through the decays of superheavy Higgs bosons. The implications for CP-nonconserving effects in proton decay are also discussed.
Measurement of atmospheric composition by the ATMOS instrument from Table Mountain Observatory

Following its first flight on board the Space Shuttle 'Challenger' as part of the Spacelab 3 payload, the Atmospheric Trace Molecule Spectroscopy (ATMOS) instrument has been operated at the Jet Propulsion Laboratory's Table Mountain Observatory (TMO; 34.4 deg N, 117.7 deg W, 2.23 km altitude) in the San Gabriel Mountains of Southern California. With the delay in the resumption of regular Shuttle flights, ATMOS has acquired a large number of high-quality, high-resolution infrared solar absorption spectra, spanning a period between late-1985 and mid-1990. These spectra are being analyzed to derive the column abundances of several atmospheric species including O3, HCl, HF, and HNO3. Although limited in temporal coverage, the preliminary results for these gases are discussed here in the context of the requirement and contribution to be made by similar instruments in detecting long term changes in stratospheric composition.
Proximity-based trust-advisor using encounters

No trust tantamounts to no communication in DTN and mobile ad-Hoc networks. In this work we propose a novel encounter-based trust framework based on the principle of homophiliy. We propose 4 trust advisors and analyze their performance using WLAN traces. We find that our filters not only provide meaningful trust but also improve network performance in the presence of selfish nodes.
Di- and Tri-fluorinated Analogs of Methyl Eugenol: Attraction to and Metabolism in the Oriental Fruit Fly, Bactrocera Dorsalis (Hendel)

Oriental fruit fly, Bactrocera dorsalis (Hendel), males are attracted to the natural phenylpropanoid methyl eugenol (ME). They feed compulsively on ME and metabolize it to ring and side-chain hydroxylated compounds that have both pheromonal and allomonal properties. Previously, we demonstrated that mono-fluorination at the terminal carbon of the ME side-chain significantly reduced metabolic side-chain hydroxylation, while mono-fluorination of ME at position 4 of the aromatic ring blocked ring-hydroxylation but surprisingly enhanced side-chain hydroxylation. Here, we demonstrated that the introduction of fluorine atoms on both the ring and side-chain of ME blocks both positions that undergo enzymatic hydroxylation and, in particular, completely inhibits oxidative biotransformation of the allyl group. In laboratory experiments, B. dorsalis males initially were more attracted to both 1-fluoro-4,5-dimethoxy-2-(3,3-difluoro-2-propenyl)benzene (I) and 1-fluoro-4,5-dimethoxy-2-(3-fluoro-2-propenyl)benzene (II) than to ME. However, both I and II were taken up by flies at rates significantly less than that of ME. Flies fed with difluoroanalog II partially metabolized it to 5-fluoro-4-(3-fluoroprop-2-en-1-yl)-2-methoxyphenol (III), and flies fed with trifluoroanalog I produced 4-(3,3-difluoroprop-2-en-1-yl)-5-fluoro-2-methoxyphenol (V), but the rates of metabolism relative to rates of intakes were much lower compared to those of ME. Flies that consumed either the tri- or difluorinated analog showed higher post-feeding mortality than those that fed on methyl eugenol. In field trials, trifluoroanalog I was ∼90% less attractive to male B. dorsalis than ME, while difluoroanalog II was ∼50% less attractive. These results suggest that increasing fluorination can contribute to fly mortality, but the trade off with attractancy makes it unlikely that either a di or trifluorinated ME would be an improvement over ME for detection and/or eradication of this species.
A comparison of measured and self-reported weights in a 4-year follow-up of spouse involvement in obesity treatment**

Reports of weight losses sustained beyond 2 years are rare and investigators often have relied upon self-reported weights. In the present investigation, a 4-year follow-up contact was attempted with all 34 subjects who had previously completed a 10-week behavioral weight control program. Both self-reported and measured weights were obtained when possible. Although these two measures were significantly correlated, discrepancies were often substantial, especially given the usual effect size in obesity treatment research. Analyses indicated a significant effect for the method of obtaining weight and a nonsignificant effect for the treatment condition (attending sessions with or without spouse and contingency contracting with or without spouse). Since the 2-year results had supported the effects of spouse involvement, the current results suggest that these positive effects eventually attenuate with time.
Thymus Lineage Commitment: A Single Switch

In this issue of Immunity, He et al. (2008) establish the logic and circuitry that determine CD4-CD8 lineage specification. It all comes down to an eighty base pair silencer switch.
Educating children with special needs: An interorganizational perspective on policy implementation

Abstract Educating handicapped children is dependent upon the relations among organizational and agency implementors. In this paper, factors influencing successful policy implementation are examined relative to the implementation of Massachusetts Special Education Law, Chapter 766. Case exploration suggests several possible strategic points of intervention for other states faced with implementing a later, but similar law, The Education for All Handicapped Children Act (P.L. 94–142). Seen within the larger context of degree of change required by a policy and consensus on policy goals, recommendations at the guideline development, resource distribution, and oversight stages can affect such implementation problems as organizational capability, dispositional conflicts of key actors, and interorganizational communications. The paper supports early analysis and feasibility estimates of policy implementation to enhance the needed interorganizational coordination for the education of handicapped children in the least restrictive environment.
Replicate each, anyone?

In both the IPSA and APL2/NARS extensions of APL, the SLASH symbol always represents an operator. Some new users of APL2, having been taught in the past that SLASH is an ambiguous symbol which is a dyadic function when it immediately follows data, find that the result when SLASH occurs between data and another operator is incompatible with that interpretation. The situation did not arise in APL1 because derived functions could not be operands. The classification of SLASH as an operator can be traced to the description given in the book. A Programming Language, from which APL ultimately derives. It was done so that the closely related MASK operation could be specified with the same symbol. In this paper the syntactic differences between dyadic functions and aonadic operators with data operands are explicated using the APL2 concept of syntactic binding. Two straightforward language extensions are considered based on the notions of a depth property, which APL2 shares with STSC's NARS, and pairwise evaluation, which derives from syntactic binding. Together they allow either dyadic functions or monadic operators with data operands to be executed in three structural contexts, which, in the cases of REPLICATE and EXPAND, can be loosely described as the same mask for each of several arrays, a separate mask for each array, and the same array for each of several masks.
Spectral Simplification in Vibrational Spectroscopy Using Doubly Vibrationally Enhanced Infrared Four Wave Mixing

A new form of vibrational spectroscopy has recently been demonstrated using three coherent sources to generate nonlinear four wave mixing (FWM). It is an optical analogue of 2D NMR. The four transitions that occur in FWM include combinations of infrared absorption and Raman transitions and result in doubly vibrationally enhanced (DOVE) four wave mixing (FWM). In this paper, we use acetonitrile in different mixtures as a model system to demonstrate the spectral selectivity that allows DOVE methods to remove the spectral congestion from vibrational spectra of complex mixtures and to discriminate against a strong water background. The selectivity results from two multiplicative vibrational enhancements and the intra- and intermolecular interactions that cause mode coupling. Since DOVE features cannot occur in the absence of mode coupling, these methods isolate the spectral features that are associated with interactions. This method promises to have important applications for probing complex biological, chemi...
Measurement of Internal Income-Leisure Tradeoffs

I. Introduction, 373.—II. Internal income-leisure tradeoffs, 375.—III. General features of the results, 378.—IV. The case chosen for study: The southern textile industry, 381.—V. Empirical results, 383.—VI. Conclusion, 387.—Appendix A, 387.—Appendix B, 389.—Appendix C, 391.
Tetrasomy 8 as a primary chromosomal abnormality in a child with acute megakaryoblastic leukemia: a case report and review of the literature

Tetrasomy 8 is a relatively rare chromosomal abnormality in hematological disorders, and is mostly associated with myeloid malignancies and poor prognosis. In a number of cases, tetrasomy 8 has been reported as an accompanying anomaly with other chromosomal changes. In this report, we describe a 14-year-old girl with acute megakaryoblastic leukemia associated with tetrasomy 8 (primary) and trisomy 6, 19 and 20. She died 6 months after diagnosis, suggesting a relatively poor prognosis for AML with tetrasomy 8. To the best of our knowledge, this is the first report of a tetrasomy 8 abnormality associated with subtype FAB M7. Interestingly, this abnormality has not been previously reported in childhood AML patients.
Locally Produced Complement Fragments C5a and C3a Provide Both Costimulatory and Survival Signals to Naive CD4+ T Cells

Costimulatory signals are critical to T cell activation, but how their effects are mediated remains incompletely characterized. Here, we demonstrate that locally produced C5a and C3a anaphylatoxins interacting with their G protein-coupled receptors (GPCRs), C5aR and C3aR, on APCs and T cells both upstream and downstream of CD28 and CD40L signaling are integrally involved in T cell proliferation and differentiation. Disabling these interactions reduced MHC class II and costimulatory-molecule expression and dramatically diminished T cell responses. Importantly, impaired T cell activation by Cd80-/-Cd86-/- and Cd40-/- APCs was reconstituted by added C5a or C3a. C5aR and C3aR mediated their effects via PI-3 kinase-gamma-dependent AKT phosphorylation, providing a link between GPCR signaling, CD28 costimulation, and T cell survival. These local paracrine and autocrine interactions thus operate constitutively in naive T cells to maintain viability, and their amplification by cognate APC partners thus is critical to T cell costimulation.
Effect of coronary stenosis severity on variability of quantitative arteriography, and implications for interventional trials

Abstract Quantitative coronary arteriography is now routinely used in studies assessing arterial remodelling in response to interventions such as lipid lowering and percutaneous transluminal coronary angioplasty. Although this methodology provides both relative and absolute measurements that can be evaluated statistically as continuous variables, it is, however, often desirable or necessary to establish categorical responses to the interventions based on the variability inherent in the quantitative methods (i.e., it is often necessary to state whether individual patients, as opposed to entire groups, have “restenosed,” “progressed,” “regressed,” and so forth, and these categorical designations are based on critical limits of variability). 1,2 These limits are generally based on an analysis of a rather diverse range of lesion severity, and the question arises as to whether the variability of measuring changes in lesion or segment morphology is affected by the initial severity of the lesion being studied. It is conceivable that variability may be greater at 1 end than at the other end of the spectrum of lesion severity. If this is true, then the use of 1 critical value to designate whether a subject has responded in a certain way would be inappropriate, and this designation would be better achieved by using criteria that more directly reflect the measurement variability of lesions of a specified, initial severity. This report examines whether the variability of measuring morphologic parameters of stenoses is affected by the baseline severity of the lesion.
Financial Distress Costs and Delayed Calls of Convertible Bonds: An Empirical Analysis

Theoretical analysis implies that optimal call policy would be to call the bonds as soon as the conversion value equals the call price. Empirical studies, however, report that firms appear to systematically delay the call and the difference between the conversion value and the call price is large at the time of the call. This study examines convertible bond calls between 1977 and 1993, with a view to explain the large difference between the conversion value and the call-price at the time of the call. A large majority of the firms calling the bonds have cash-flow incentive to call the bonds in that the after-tax interest payments are higher than the dividends on the converted shares. The large difference between the conversion value and the call price is positively related to the risk characteristics of the firm. Evidence seems to support the view that risk aversion and fear of potential financial distress may explain the large difference at the time of call between the conversion value and the call price.
Assessment of Treatment Response and Recurrence in Esophageal Carcinoma Based on Tumor Length and Standardized Uptake Value on Positron Emission Tomography–Computed Tomography

Background Previous studies demonstrated that a decrease of the standardized uptake value between pretreatment and posttreatment positron emission tomography (PET) scans can predict histopathologic treatment response in patients with esophageal cancer. Methods Forty-seven patients who underwent PET–computed tomography (CT) scans before (scan 1) and after (scan 2) neoadjuvant chemoradiotherapy and during the follow-up period after surgery (scan 3) were included in this study. It was evaluated whether decrease of metabolic tumor length between scan 1 and scan 2 can predict histopathologic response to treatment. Moreover, the value of PET-CT was compared with PET in the assessment of tumor recurrence based on a visual analysis of scan 3. Reference standards for treatment response and recurrence were histopathology results. Results The reduction of tumor length between before and after chemoradiotherapy scans (between scan 1 and scan 2) was a better predictor of histopathologic response and of time to recurrence than the decrease in standardized uptake value. The most accurate differentiation was achieved when using a cut-off value of 33% reduction of the initial tumor length. Using this threshold to define metabolic response, the sensitivity was 91% (19 of 21) and the specificity was 92% (24 of 26) for predicting histopathologic treatment response. Based on a visual analysis, PET-CT was more accurate than PET in the differentiation of tumor recurrence from posttreatment tissue changes. Integrated PET-CT achieved a sensitivity of 91% (48 of 53) and a specificity of 81% (30 of 37) in identifying sites of tumor recurrence, compared with 83% (44 of 53) and 65% (24 of 37) with PET. Conclusions Decrease of tumor length was shown to be a better predictor of treatment response and disease-free survival than decrease of standardized uptake value. Furthermore, PET-CT is more accurate in the evaluation of recurrence than PET.
Analytical studies of pyrethrin formulations by gas chromatography. II. Isolation of the pyrethrins from water-based formulations.

Abstract The extraction of pyrethrins and synergists from water-base aerosol formulations is improved and simplified by the use of acetone in the extraction procedure. The procedure minimizes interferences from extraneous substances previously encountered in the subsequent analysis of the pyrethrins by gas chromatography.
Examining the social landscapes of alternative reproductive strategies.

Social environments are inherently dynamic, often changing depending on the frequency and outcomes of conspecific interactions ‐ they can be simultaneously the targets and agents of selection. Understanding how organisms settle in heterogeneous social environments and the effects this has on reproductive success is vital to our understanding of the selective forces at work in wild populations. From an intensive behavioural and ecological study of territoriality in the polymorphic white-throated sparrow (Zonotrichia albicollis), we demonstrate that males of the two morphs inhabit social niches that correspond to their respective alternative reproductive strategies. By integrating molecular ecology and Geographic Information Systems, we generated continuous, socio-spatial models of local conspecific density and cuckoldry risk. Our results suggest that the morphs segregate their territories based on socio-spatial variables, creating a heterogeneous social landscape that matches each behavioural phenotype with a favourable social environment. Specifically, the monogamous tan males tended to settle in low-density areas that were also low for cuckoldry risk, while the opposite was true for the promiscuous white males. This pattern of socio-spatial heterogeneity, combined with the social niche partitioning we observed, might act as a social niche polymorphism, and play an important role in maintenance of the alternative reproductive strategies of the white-throated sparrow. Socio-spatial factors, similar to those observed in the white-throated sparrow, may play important roles in the evolution of mating systems in other species, even those with more continuous or cryptic variation.
Portraiture and British Gothic Fiction: The Rise of Picture Identification 1764-1835

In this compelling, thoroughly imagined, and highly researched book, Kamilla Elliott makes a convincing case that the myriad pictures, and especially portraits, that mark Gothic fiction are no mere...
X-ray imaging with edge-on microchannel plate detector: first experimental results

Abstract A novel scanning slit X-ray imaging system based on an “edge-on” microchannel plate detector was developed and tested. Images were acquired at 50 kV(p) X-ray tube voltage with a limiting spatial resolution of 7 lp/mm. The pixel noise was measured to be 0.3 count/pixel/s for a 50×70 μm2 pixel size. This photon counting detector can be considered to be virtually noise free.
An Interview with Khaled Mattawa

Khaled Mattawa is a poet, essayist, and translator. He was born in Benghazi, Libya. In 1979 he immigrated to the United States. He has bachelor degrees in political science and economics from the University of Tennessee at Chattanooga, and an MA in English and an MFA in creative writing from Indiana University. He is the recipient of numerous honors including the PEN Ameri
Inhibition of mouse embryonic development by calmodulin antagonists

Two-cell mouse embryos were incubated in the presence of calmodulin inhibitors to determine their effect on embryonic development to the blastocyst stage. Calmodulin, a Ca2+-dependent regulatory protein, has been localized in the cytoplasm and has been implicated in regulation of many cellular events, such as mitosis. Several concentrations of either commercial or synthesized calmodulin inhibitors were tested. Several phenothiazine sulfoxide derivatives were more effective than the three naphthalene sulonic acid derivatives tested; 2-chloro-10-aminopropyl phenothiazine and 10-aminopropyl phenothiazine were the most potent phenothiazines to inhibit embryonic development at the two-cell stage. The interesting aspect of this study is that phenothiazine sulfoxide derivatives are not potent inhibitors of calmodulin, however, they were successful in inhibiting embryonic development. Potent inhibitors of calmodulin apparently did not penetrate the embryonic membranes because they had no effect.
The synthesis of 6-deoxyanthracyclinones: (±)α-citromycinone and (±)4-demethoxy-6-deoxydaunomycinone

Abstract Two synthetic approaches have been explored to prepare 6-deoxyanthracyclinones in general and α-citromycinone in particular. The first approach employed as starting materials 1,4,5-trimethoxynaphthalene and the Diels-Alder product from butadie regioselective carbon acylation of 4-hydroxy-l,5-dimethoxynaphthalene with the half-ester acid chloride of cis-4,5-dicarboxycyclohexene. The resulting product was converted to 7,10-dideoxy-α-citromycinone; however, even the C-7—OH group required for glycosylation could not be introduced satisfactorily into this product. The second strategy employed as the key step the coupling of a highly functionalized metallated quinol equivalent with the monoketal of a benzocyclobutenedione. This route gave (± )-α-citromycinone and (±)-4-demethoxy-6-deoxydaunomycinone in quantities suitable for biological testing.
Non-Targeted and Targeted Protein Movement through Plasmodesmata in Leaves in Different Developmental and Physiological States

Plant cells rely on plasmodesmata for intercellular transport of small signaling molecules as well as larger informational macromolecules such as proteins. A green fluorescent protein (GFP) reporter and low-pressure microprojectile bombardment were used to quantify the degree of symplastic continuity between cells of the leaf at different developmental stages and under different growth conditions. Plasmodesmata were observed to be closed to the transport of GFP or dilated to allow the traffic of GFP. In sink leaves, between 34% and 67% of the cells transport GFP (27 kD), and between 30% and 46% of the cells transport double GFP (54 kD). In leaves in transition transport was reduced; between 21% and 46% and between 2% and 9% of cells transport single and double GFP, respectively. Thus, leaf age dramatically affects the ability of cells to exchange proteins nonselectively. Further, the number of cells allowing GFP or double GFP movement was sensitive to growth conditions because greenhouse-grown plants exhibited higher diffusion rates than culture-grown plants. These studies reveal that leaf cell plasmodesmata are dynamic and do not have a set size exclusion limit. We also examined targeted movement of the movement protein of tobacco mosaic virus fused to GFP, P30::GFP. This 58-kD fusion protein localizes to plasmodesmata, consistently transits from up to 78% of transfected cells, and was not sensitive to developmental age or growth conditions. The relative number of cells containing dilated plasmodesmata varies between different species of tobacco, with Nicotiana clevelandii exhibiting greater diffusion of proteins than Nicotiana tabacum.
The β-Catenin Destruction Complex

The Wnt/β-catenin pathway is highly regulated to insure the correct temporal and spatial activation of its target genes. In the absence of a Wnt stimulus, the transcriptional coactivator β-catenin is degraded by a multiprotein “destruction complex” that includes the tumor suppressors Axin and adenomatous polyposis coli (APC), the Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A (PP2A), and the E3-ubiquitin ligase β-TrCP. The complex generates a β-TrCP recognition site by phosphorylation of a conserved Ser/Thr-rich sequence near the β-catenin amino terminus, a process that requires scaffolding of the kinases and β-catenin by Axin. Ubiquitinated β-catenin is degraded by the proteasome. The molecular mechanisms that underlie several aspects of destruction complex function are poorly understood, particularly the role of APC. Here we review the molecular mechanisms of destruction complex function and discuss several potential roles of APC in β-catenin destruction.
Childhood maltreatment is associated with a sex-dependent functional reorganization of a brain inhibitory control network

Childhood adversity represents a major risk factor for drug addiction and other mental disorders. However the specific mechanisms by which childhood adversity impacts human brain organization to confer greater vulnerability for negative outcomes in adulthood is largely unknown. As an impaired process in drug addiction, inhibitory control of behavior was investigated as a target of childhood maltreatment (abuse and neglect). Forty adults without Axis-I psychiatric disorders (21 female) completed a Childhood Trauma Questionnaire (CTQ) and underwent functional MRI (fMRI) while performing a stop-signal task. A group independent component analysis identified a putative brain inhibitory control network. Graph theoretical analyses and structural equation modeling investigated the impact of childhood maltreatment on the functional organization of this neural processing network. Graph theory outcomes revealed sex differences in the relationship between network functional connectivity and inhibitory control which were dependent on the severity of childhood maltreatment exposure. A network effective connectivity analysis indicated that a maltreatment dose-related negative modulation of dorsal anterior cingulate (dACC) activity by the left inferior frontal cortex (IFC) predicted better response inhibition and lesser attention deficit hyperactivity disorder (ADHD) symptoms in females, but poorer response inhibition and greater ADHD symptoms in males. Less inhibition of the right IFC by dACC in males with higher CTQ scores improved inhibitory control ability. The childhood maltreatment-related reorganization of a brain inhibitory control network provides sex-dependent mechanisms by which childhood adversity may confer greater risk for drug use and related disorders and by which adaptive brain responses protect individuals from this risk factor.
Pharmacologic Inhibition of mTOR Improves Lapatinib Sensitivity in HER2-Overexpressing Breast Cancer Cells with Primary Trastuzumab Resistance

Lapatinib, a dual EGFR/HER2 kinase inhibitor, is approved for use in patients with trastuzumab-refractory HER2- overexpressing breast cancer. Increased PI3K signaling has been associated with resistance to trastuzumab, although its role in lapatinib resistance remains unclear. The purpose of the current study was to determine if PI3K/mTOR activity affects lapatinib sensitivity. Reduced sensitivity to lapatinib was associated with an inability of lapatinib to inhibit Akt and p70S6K phosphorylation. Transfection of constitutively active Akt reduced lapatinib sensitivity, while kinase-dead Akt increased sensitivity. Knockdown of 4EBP1 also increased lapatinib sensitivity, in contrast to p70S6K knockdown, which did not affect response to lapatinib. Pharmacologic inhibition of mTOR using rapamycin or ridaforolimus increased lapatinib sensitivity and reduced phospho-Akt levels in cells that showed poor response to single-agent lapatinib, including those transfected with hyperactive Akt. Finally, combination mTOR inhibition plus lapatinib resulted in synergistic inhibition of proliferation, reduced anchorage-independent growth, and reduced in vivo tumor growth of HER2- overexpressing breast cancer cells that have primary trastuzumab resistance. Our data suggest that PI3K/mTOR inhibition is critical for achieving optimal response to lapatinib. Collectively, these experiments support evaluation of lapatinib in combination with pharmacologic mTOR inhibition as a potential strategy for inhibiting growth of HER2-overexpressing breast cancers that show resistance to trastuzumab and poor response to lapatinib.
Size matters: the (negative) allometry of copulatory duration in mammals

The amount of time taken to copulate varies enormously among mammals. Because copulation likely exposes animals to an increased risk of predation, and uses time and energy that could be spent on foraging, smaller mammals (which are vulnerable to more predators and have a shorter time-to-starvation than larger mammals) should spend less time copulating than do larger mammals. Furthermore, if extended copulation reflects competition among males, then the duration of mating (after correction for body size) should be greater in mammals in which females mate with more than one male. We tested these predictions using comparative data from 113 mammalian species in 85 genera, 40 families, and 14 orders, while controlling for the effect of phylogeny. We found: (1) the relationship between duration of copulation and body size to be negative, not positive; (2) no relationship with inferred multiple mating by females (based upon relative testes mass). We suggest that small mammals may find the sustained maneuvering and body positioning of copulation easier than do large mammals. This hypothesis is supported by an apparently isometric relationship between duration of copulation and ratio of power to mass. © 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 87, 185–193.
Adenovirus-mediated Antisense Urokinase-Type Plasminogen Activator Receptor Gene Transfer Reduces Tumor Cell Invasion and Metastasis in Non-Small Cell Lung Cancer Cell Lines

The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the proteolytic cascade involved in the metastasis of lung and other cancers. We report that the reduction in uPAR levels produced by an antisense strategy using an adenovirus construct (Ad-uPAR) in H1299 cells, an invasive human lung cancer cell line that produces high levels of uPAR, resulted in a decrease of uPAR levels to 80-90% of those seen in cells infected with mock or adenovirus (Ad)-cytomegalovirus vector controls. In addition, increasing the multiplicity of infection from 25 to 200 caused a corresponding decrease in the level of uPAR protein within 5 days of treatment, as shown by Western blot analysis. Furthermore, the in vitro translation of total RNA levels of Ad-uPAR-infected H1299 cells in a rabbit reticulocyte lysate system caused a 50-70% decrease in uPAR immunoprecipitate in Ad-uPAR-infected cells relative to the levels in cells of mock and vector controls. The Matrigel invasion assay showed the invasion of H1299 cells and A549 cells infected with Ad-uPAR to be decreased by 70% relative to mock- and vector-infected controls. Infection of tumor cells with Ad-uPAR before implantation significantly reduced the incidence of lung metastasis by 85% as compared with the control virus-infected cells injected into nude mice through the tail vein. Our collective results show that the uPAR system is a potential target of treatment for lung cancers.
Correction to "Conditions for asymptotic stability of the discrete minimum-variance linear estimator"

This note presents bounds on the discrete Riccati equation, correcting an error in proving the stability of discrete-time minimum variance estimators.
The influence of fetal number on maternal concentrations of progesterone and testosterone in the mouse.

AbstractMice selected for large litters were used to study the relationship between fetal number and maternal progesterone and testosterone concentration. Experimental adjustment of conceptus number demonstrated that the presence of one fetus was sufficient to elevate maternal progesterone concentration above that found in females from which all conceptuses were removed. When one of more fetuses occupied the uterus, maternal progesterone concentration did not increase with increasing conceptus number. In contrast, maternal testosterone concentration was positively correlated with the number of fetal-placental units.
Nonlinear theory of modulated standing waves; domain walls, kinks and breathers

A nonlinear theory of modulated standing waves is developed in one dimension. The existence of various localized solutions is elucidated. These include: domain walls , which characterize the transition between regions of different wave number, kinks , which describe a shift in the phase of the oscillation, and lower cut-off breathers . All of these states correspond to a spontaneous breaking of translational invariance, while the domain wall in addition represents a broken parity. Except for the breathers, the modulational equations that describe these states take a form that differs from the sine-Gordon, nonlinear Schrodinger, Toda lattice and Korteweg de Vries equations. In addition to the hamiltonian limit, the case of damped parametrically driven motion is also discussed.
Quantification of choline- and ethanolamine-containing metabolites in human prostate tissues using 1H HR-MAS total correlation spectroscopy

A fast and quantitative 2D high-resolution magic angle spinning (HR-MAS) total correlation spectroscopy (TOCSY) experiment was developed to resolve and quantify the choline- and ethanolamine-containing metabolites in human prostate tissues in ≈1 hr prior to pathologic analysis. At a 40-ms mixing time, magnetization transfer efficiency constants were empirically determined in solution and used to calculate metabolite concentrations in tissue. Phosphocholine (PC) was observed in 11/15 (73%) cancer tissues but only 6/32 (19%) benign tissues. PC was significantly higher (0.39 ± 0.40 mmol/kg vs. 0.02 ± 0.07 mmol/kg, z = 3.5), while ethanolamine (Eth) was significantly lower in cancer versus benign prostate tissues (1.0 ± 0.8 mmol/kg vs. 2.3 ± 1.9 mmol/kg, z = 3.3). Glycerophosphocholine (GPC) (0.57± 0.87 mmol/kg vs. 0.29± 0.26 mmol/kg, z = 1.2), phosphoethanolamine (PE) (4.4± 2.2 mmol/kg vs. 3.4± 2.6 mmol/kg, z = 1.4), and glycerophosphoethanolamine (GPE) (0.54± 0.82 mmol/kg vs. 0.15± 0.15 mmol/kg, z = 1.8) were higher in cancer versus benign prostate tissues. The ratios of PC/GPC (3.5± 4.5 vs. 0.32± 1.4, z = 2.6), PC/PE (0.08± 0.08 vs. 0.01± 0.03, z = 3.5), PE/Eth (16± 22 vs. 2.2± 2.0, z = 2.4), and GPE/Eth (0.41± 0.51 vs. 0.06± 0.06, z = 2.6) were also significantly higher in cancer versus benign tissues. All samples were pathologically interpretable following HR-MAS analysis; however, degradation experiments showed that PC, GPC, PE, and GPE decreased 7.7± 2.2%, while Cho+mI and Eth increased 18% in 1 hr at 1°C and a 2250 Hz spin rate.