cssi/SciSciGPT-SciSciNet huggingface dataset:
Transport and metabolism of N-δ-chloroacetyl-l-ornithine by Saccharomyces cerevisiae

Abstract The general amino acid transport system of Saccharomyces cerevisiae functions in the uptake of neutral, basic, and acidic amino acids (M. Grenson, C. Hou, and M. Crabeel, 1970, J. Bacteriol. 103, 770–777; J. Rytka, 1975, J. Bacteriol.121, 562–570; C. Darte and M. Grenson, 1975, Biochem. Biophys. Res. Commun.67, 1028–1033). We have previously demonstrated that this transport system can be inhibited by the amino acid, N-δ-chloroacetyl- l -ornithine (NCAO) (F. S., Larimore and R.J. Roon, 1978, Biochemistry17, 431–436). In the present study radiolabeled NCAO was synthesized and its transport and metabolism studied. Under initial rate conditions: (a) NCAO was transported by the general amino acid transport system with a Km of 52 μ m , a V of 32 nmol/min/mg cells, and a pH optimum of 5.0; (b) the V for NCAO transport in gap mutants, which lack the general amino acid transport system, was approximately 1% of that observed with wild-type cells; (c) the V for NCAO in cells deprived of glucose was less than 5% of that observed when glucose was present. NCAO was transiently concentrated more than 1000-fold by yeast cells when glucose served as an energy source. The internal pool of NCAO was metabolized by the yeast cells and the products were excreted. When 100 μ m [14C]NCAO was incubated with a yeast cell suspension for 8 h, more than 95% of the compound was converted into two ninhydrin-negative excretory products. The effect of NCAO on the growth of yeast cells was determined. Wild-type strains did not grow when 1 m m NCAO was present in the medium. The growth of gap mutants was not inhibited by 1 m m NCAO.
Endocannabinoids in cognition and dependence

Cannabis use is associated with a wide range of pharmacological effects, some of which have potential therapeutic benefit while others result in negative outcomes. Acute cannabinoid intoxication has been well documented to produce deficits in cognitive functioning with concomitant changes in glutamatergic, GABAergic, and cholinergic neurochemical systems in the hippocampus, each of which has been implicated in memory. Additionally, cannabis-dependent individuals abstaining from this drug can undergo a constellation of mild withdrawal effects. The use of the CB1 cannabinoid receptor antagonist SR141716A and transgenic mice lacking the CB1 receptor are critical tools for investigating the role of the endocannabinoid system in cognition, drug dependence, and other physiological processes. Converging evidence in which performance in a variety of memory tasks is enhanced following either SR141716A treatment or in CB1 receptor knockout mice indicates that this system may play an important role in modulating cognition. There are also indications that this system may function to modulate opioid dependence. The purpose of this review is to describe recent advances that have furthered our understanding of the roles that the endocannabinoid system play on both cognition and drug dependence.
DNA methyltransferase-3–dependent nonrandom template segregation in differentiating embryonic stem cells

Asymmetry of cell fate is one fundamental property of stem cells, in which one daughter cell self-renews, whereas the other differentiates. Evidence of nonrandom template segregation (NRTS) of chromosomes during asymmetric cell divisions in phylogenetically divergent organisms, such as plants, fungi, and mammals, has already been shown. However, before this current work, asymmetric inheritance of chromatids has never been demonstrated in differentiating embryonic stem cells (ESCs), and its molecular mechanism has remained unknown. Our results unambiguously demonstrate NRTS in asymmetrically dividing, differentiating human and mouse ESCs. Moreover, we show that NRTS is dependent on DNA methylation and on Dnmt3 (DNA methyltransferase-3), indicating a molecular mechanism that regulates this phenomenon. Furthermore, our data support the hypothesis that retention of chromatids with the “old” template DNA preserves the epigenetic memory of cell fate, whereas localization of “new” DNA strands and de novo DNA methyltransferase to the lineage-destined daughter cell facilitates epigenetic adaptation to a new cell fate.
Intraspecific Variation in Growth of Marsh Macrophytes in Response to Salinity and Soil Type: Implications for Wetland Restoration

Genetic diversity within plant populations can influence plant community structure along environmental gradients. In wetland habitats, salinity and soil type are factors that can vary along gradients and therefore affect plant growth. To test for intraspecific growth variation in response to these factors, a greenhouse study was conducted using common plants that occur in northern Gulf of Mexico brackish and salt marshes. Individual plants of Distichlis spicata, Phragmites australis, Schoenoplectus californicus, and Schoenoplectus robustus were collected from several locations along the coast in Louisiana, USA. Plant identity, based on collection location, was used as a measure of intraspecific variability. Prepared soil mixtures were organic, silt, or clay, and salinity treatments were 0 or 18 psu. Significant intraspecific variation in stem number, total stem height, or biomass was found in all species. Within species, response to soil type varied, but increased salinity significantly decreased growth in all individuals. Findings indicate that inclusion of multiple genets within species is an important consideration for marsh restoration projects that include vegetation plantings. This strategy will facilitate establishment of plant communities that have the flexibility to adapt to changing environmental conditions and, therefore, are capable of persisting over time.
Postprocedure radiologist's interpretation of ERCP x-ray films: a prospective outcomes study.

Objective To prospectively determine if the current practice of radiologists' interpretation of post-ERCP spot images sent by endoscopists resulted in discrepancies in interpretation, affected subsequent management of patients, and resulted in additional costs. Methods A prospective analysis of 145 consecutive patients who underwent ERCP over the course of 4 months was performed. A separate endoscopist, not involved in the patient's care, reviewed the radiologist's report of the ERCP x-ray films to determine whether there was either concordance or discordance with the procedural findings. All patients' clinical courses were prospectively followed for a minimum of 6 months to determine whether clinical decision-making was affected by the radiologists' interpretation of the x-ray films. Secondarily, the cost of the current practice of postprocedure interpretation of ECRP radiographs was measured. Setting This study took place at University Hospitals of Cleveland, which is a tertiary care facility. Results In total, there were 61 (47%) discordant interpretations of 130 cholangiograms and 27 (38%) discordant interpretations of 72 pancreatograms, with an overall discordance between an endoscopist and a radiologist in 80 (55%) of the 145 cases. Clinical management was subsequently affected in 3 (2.1%) cases, all of which involved a discordant reading. In each of the 3 cases, further testing validated the gastroenterologist's initial findings at the time of the procedure. Radiologists were reimbursed $5395 for interpretation of ERCP x-ray films. Extrapolated over the course of a year, the reimbursement at this single tertiary care hospital would be greater than $16,000. Additional testing based on discordant reports resulted in $2510 of reimbursement for 3 patients. Limitation The limitation of this study is that it reflects data from only one academic institution. Conclusions Radiologists' interpretation of postprocedure ERCP films were inadequate, with a 47% discordance rate among cholangiograms and a 38% discordance rate among pancreatograms. The routine practice of postprocedure ERCP x-ray film interpretation by radiologists altered clinical practice in 2.1% of cases; subsequent care did not confirm radiologists' findings and imparted increased risk to the patients. This practice proved to be a misallocation of resources and should not be continued.
Wild-Type TP53 Inhibits G2-Phase Checkpoint Abrogation and Radiosensitization Induced by PD0166285, a WEE1 Kinase Inhibitor

Abstract Wild-Type TP53 Inhibits G2-Phase Checkpoint Abrogation and Radiosensitization Induced by PD0166285, a WEE1 Kinase Inhibitor. Radiat. Res. 157, 322 – 330 (2002). The WEE1 protein kinase carries out the inhibitory phosphorylation of CDC2 on tyrosine 15 (Tyr15), which is required for activation of the G2-phase checkpoint in response to DNA damage. PD0166285 is a newly identified WEE1 inhibitor and is a potential selective G2-phase checkpoint abrogator. To determine the role of TP53 in PD0166285-induced G2-phase checkpoint abrogation, human H1299 lung carcinoma cells expressing a temperature-sensitive TP53 were used. Upon exposure to γ radiation, cells cultured under nonpermissive conditions (TP53 mutant conformation) underwent G2-phase arrest. However, under permissive conditions (TP53 wild-type conformation), PD0166285 greatly inhibited the accumulation of cells in G2 phase. This abrogation was accompanied by a nearly complete blockage of Tyr15 phosphorylation of CDC2, an increased activity of CDC2...
Dynamic Shape Analysis Using Spectral Graph Properties

Dynamically allocated data structures pervade imperative and object-oriented programs. Automated analysis and testing of such programs requires reasoning about their data structures. The structures often have complex structural properties, such as a cyclicity of the object graph rooted at a given pointer. Such properties pose a challenge for automated reasoning. Shape analysis is a class of techniques that address reasoning about such programs. Traditionally, shape analysis is performed using static analysis of the program code. More recently, dynamic techniques for shape analysis have been developed, which inspect program states to identify properties of data structures. This paper presents a novel dynamic technique, which adapts well-studied results from graph theory to determine the shape of the program's key data structures. Specifically, spectral graph theory, a field that studies the properties of a graph in relation to the properties of matrices based on the graph, e.g., eigen values of its adjacency matrix, provides the foundational ideas. Experimental results using a suite of data structures demonstrate the potential the technique holds in identifying data structure properties and detecting likely erroneous program states.
Proteomic Profiling of Accessory Structures from the Mouse Sperm Flagellum

The flagellum of a mammalian spermatozoon consists of an axoneme surrounded in distinct regions by accessory structures known as the fibrous sheath, outer dense fibers, and the mitochondrial sheath. Although the characterization of individual proteins has provided clues about the roles of these accessory structures, a more complete understanding of flagellar function requires the identification of all the polypeptides in these assemblies. Epididymal mouse sperm were treated with SDS to dislodge sperm heads and to extract the axoneme and membranous elements. The remaining flagellar accessory structures were purified by sucrose gradient centrifugation. Analysis of proteins from these structures by two-dimensional gel electrophoresis and colloidal Coomassie Blue staining showed a highly reproducible pattern of >200 spots. Individual spots were picked, digested with trypsin, and identified by mass spectrometry and peptide microsequencing. Approximately 50 individual proteins were identified that could be assigned to five general categories: 1) proteins previously reported to localize to the accessory structures, e.g. ODF2 in the outer dense fibers, the sperm-specific glyceraldehyde-3-phosphate dehydrogenase in the fibrous sheath, and glutathione peroxidase in the mitochondrial sheath, validating this proteomic approach; 2) proteins that had not been shown to localize to any accessory structure but would be predicted to be present, e.g. glycolytic enzymes; 3) proteins known to be part of the flagellum but not localized to a specific site, e.g. adenylate kinase; 4) proteins not expected to be part of the accessory structures based on their previously reported locations, e.g. tektins; and 5) unknown proteins for which no information is available to make a determination as to location. The unexpected presence of the tektins in the accessory structures of the flagellum was confirmed by both immunoblot and immunofluorescence analysis. This proteomic analysis identified a number of unexpected and novel proteins in the accessory structures of the mammalian flagellum.
The nosology of schizophrenia: a co-operative study.

The purpose of the Stanley R. Dean Research Award, established in 1962, is to give public emphasis to the importance of basic research in achieving an understanding of schizophrenia and to recognize individual scientists who have made important contributions in this area. While he was full-time at the Mental Health Research Institute, the author, who received the third annual award, was Principal Investigator of the Schizophrenia and Psychopharmacology Joint Research Project. This was an extensive 7-year multidisciplinary program of basic research conducted under the joint auspices of The University of Michigan and Ypsilanti State Hospital. In the 1964 Stanley R. Dean Award Lecture, which follows, Dr. Gerard describes the work of the Project and some of the findings which have emerged.
Male Veterans' Perceptions of Midlife Career Transition and Life Satisfaction: A Study of Military Men Transitioning to the Teaching Profession

Members of Troops to Teachers (N = 102 male veterans) were surveyed regarding their career transition experiences and life satisfaction. Primary themes related to career transition included preparation for transition, investment vs. sacrifice, and rewards of new career. Primary themes related to life satisfaction included helping and serving others, accomplishment, and contentment vs. struggle.
A RAPID AND SIMPLE METHOD FOR THE DETECTION OF PROSTATE-SPECIFIC ANTIGEN mRNA IN ARCHIVAL TISSUE SPECIMENS USING A REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION ASSAY

Abstract Objectives Polymerase chain reaction (PCR) amplification of DNA from archival, fixed tissue sources is now performed routinely. In this report, we describe a reproducible technique for mRNA amplification from archival tissues. Methods Archival, fixed tissue was treated with a modification of a rapid, acid guanidinium technique. The RNA yielded was reverse transcribed and subjected to 40 cycles of two-step PCR, using a panel of primers designed to encompass relatively short (less than 250 bp) cDNA fragments. PCR products were analyzed by agarose gel electrophoresis followed by ethidium bromide staining. Results Using fixed, paraffin-embedded specimens of human prostate, we have demonstrated a reproducible pattern of reverse transcription (RT)-PCR products using several different primer sets. Our data suggest that RNA degradation proceeds to fragments approximately 250 bp or shorter in length but that many of these fragments survive intact over extended periods of time and are of suitable quality to serve as a template for RT and subsequent PCR amplification. Conclusions We describe a technique that will allow the retrospective analysis of archival tissues for gene expression. These methods are generally applicable to a wide variety of systems. Such a method will make it possible to perform retrospective studies of gene expression in the archival tissues of patients whose eventual clinical course is already known, greatly shortening the time needed for genetic outcome studies in slowly growing tumors, such as prostate cancer.
Microsclerotia of Metarhizium brunneum F52 Applied in Hydromulch for Control of Asian Longhorned Beetles (Coleoptera: Cerambycidae)

ABSTRACT The entomopathogenic fungus Metarhizium brunneum (Petch) strain F52 (Hypocreales: Clavicipitaceae) is able to produce environmentally persistent microsclerotia (hyphal aggregates). Microsclerotia of strain F52 produced as granules and incorporated into hydromulch (hydro-seeding straw, water, and a natural glue) provides a novel mycoinsecticide that could be sprayed onto urban, forest, or orchard trees. We tested this formulation against adult Asian longhorned beetles (Anoplophora glabripennis (Motschulsky)) using three substrates (moistened bark, dry bark, absorbent bench liner) sprayed with a low rate (9 microsclerotia granules/cm2) of hydromulch. Median survival times of beetles continuously exposed to sprayed moist bark or absorbent liner were 17.5 and 19.5 d, respectively. Beetles exposed to sprayed dry bark, which had a lower measured water activity, lived significantly longer. When moist bark pieces were sprayed with increased rates of microsclerotia granules in hydromulch, 50% died by 12.5...
Nerve conduction studies and sensibility testing in carpal tunnel syndrome

This paper compares the results of detailed sensibility testing with nerve conduction studies done in patients with carpal tunnel syndrome. Forty-three patients with 74 symptomatic hands were examined. Median and ulnar distal sensory and motor latencies were obtained bilaterally. Sensibility testing included assessment of perception of vibratory stimuli, classic two-point discrimination, and moving two-point discrimination. Comparison of the results were made in the overall group of patients, and patients were also grouped according to the severity of symptoms. In the 74 hands, nerve conduction studies were abnormal in 81 % and sensory examination was abnormal in 66%, for an overall combined abnormality rate of 92%. In the most severely involved hands, both nerve conduction and sensory testing were abnormal in approximately 80%. However, in the least severely involved group, nerve conduction studies were abnormal in 80%, while sensory examination was abnormal in only 10%.
Automatic boundary extraction of ultrasonic breast lesions

Breast cancer is the second leading cause of mortality in women. Automatically detecting tumors and extracting lesion boundaries in sonograms is difficult due to the specular and noisy nature of these images. Algorithms that claim to automatically classify ultrasonic breast lesions, rely on manual delineation of the tumor boundaries. This is however a slow and cumbersome task. In this work, we combine texture, intensity, gradient and a deformable model along with empirically determined domain specific knowledge to automatically find lesion margins in ultrasound images with no human intervention. The system has successfully extracted tumor boundaries in over 30 breast sonograms.
Decentralized nearly optimal control of a class of interconnected nonlinear discrete-time systems by using online Hamilton-Bellman-Jacobi formulation

In this paper, the direct neural dynamic programming technique is utilized to solve the Hamilton Jacobi-Bellman (HJB) equation online and forward-in-time for the decentralized nearly optimal control of nonlinear interconnected discrete-time systems in affine form with unknown internal subsystem and interconnection dynamics. Only the state vector of the local subsystem is considered measurable. The decentralized optimal controller design for each subsystem consists of an action neural network (NN) that is aimed to provide a nearly optimal control signal, and a critic NN which approximates the cost function. The NN weights are tuned online for both the NNs. It is shown that all subsystems signals are uniformly ultimately bounded (UUB) and that the subsystem inputs approach their corresponding nearly optimal control inputs with bounded error.
Survival of Escherichia coli O157:H7 in soil and on lettuce after soil fumigation.

Long-term survival of Escherichia coli O157:H7 in soil and in the rhizosphere of many crops after fumigation is relatively unknown. One of the critical concerns with food safety is the transfer of ...
Molecular imaging for detection of sensitivity and resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer

Advancing knowledge of non-small cell lung cancer (NSCLC) has provided new treatment options based on the specific gene alterations found in individual tumors. The presence of activating mutations in the epidermal growth factor receptor (EGFR) in NSCLC is strongly associated with a high sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and is also a criterion used to identify candidates for first-line therapy with these drugs among patients with advanced disease. However, acquired resistance to EGFR TKIs invariably emerges over time due in part to secondary mutations in EGFR or redundant lateral signaling. Molecular imaging, allowing the visualization of cellular processes and their modulation by both conventional anticancer drugs and molecularly targeted agents, may be effectively used in NSCLC patients during treatment with EGFR TKIs. In particular, positron emission tomography with 18F-FDG and 18F-FLT has been performed in both preclinical and clinical settings to distinguish treatment-sensitive from treatment-resistant NSCLCs. Here we provide a short overview of the mechanisms underlying sensitivity and resistance of NSCLCs to EGFR TKIs and then focus on the contribution that molecular imaging can make to the development of tailored therapy in NSCLC patients.
Congenital nasal pyriform aperture stenosis: Feeding evaluation and management

Abstract Purpose We identified four patients with congenital nasal pyriform aperture stenosis (CNPAS) with feeding and respiratory difficulties. While feeding difficulties have been described in infants with other causes of nasal obstruction (e.g., choanal atresia), little attention has been focused on feeding in infants with CNPAS. Findings All four patients were treated with nasal steroids and nasal saline and two underwent surgical repair of the CNPAS at 2 months of age. Except for gastroesophageal reflux in one patient, upper gastrointestinal tract (UGI) contrast studies were normal in all patients. Three patients underwent bedside swallow evaluations, two of whom participated in videoflouroscopic swallow studies (VFSS) because of limited oral intake or respiratory problems during feeding. These three patients presented with intact oral-motor coordination at rest and during non-nutritive sucking, and nasal whistling, nasal congestion, or breathing difficulties/desaturations with oral feeding. On VFSS, one infant had trace aspiration with thin and thick liquids. Three patients required supplemental feeding during the first year of life. All three patients with normal brain MRIs were successful oral feeders by 16 months of age, the fourth is undergoing feeding therapy at 24 months of age. Summary Feeding problems are common in infants with CNPAS and supplemental feedings may be needed even after management of airway difficulties. Infants with CNPAS should undergo comprehensive feeding/swallowing evaluations which may include bedside swallow evaluations and VFSSs. The prognosis for transitioning to total oral feedings is good and related to the extent of the airway obstruction and presence of other comorbidities.
High Resolution Electron Microscopy for Structure and Mapping

Electron microscopes are very valuable to the human genome project. Brookhaven’s Scanning Transmission Electron Microscope (STEM) is unique in many respects. It is like the National Synchrotron Light Source (NSLS) or the High Flux Beam Reactor (HFBR) at Brookhaven, but on a much smaller scale. The STEM uses electrons that are focussed through the sample, and detected. It is a scanning microscope because it scans the beam much like a television set. This is in contrast to most electron microscopes that are fixed beam, flood the sample with electrons, and then use a lens after the sample that reimages the material at higher magnification. There are some advantages of scanning, which I will describe.
Regulation of skeletal muscle perfusion during exercise

For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.
Helium isotope variations in Juan de Fuca ridge basalts

We have measured ³He/4He ratios and He and Ne concentrations on a suite of 24 basalt glasses from the neovolcanic zone of the Juan de Fuca Ridge (JdFR) from 44.6°N near the Blanco Transform up to 48.0°N on the Endeavour Segment. The helium isotope ratios exhibit a clear geographic variation, with relatively constant values of 7.8 RA along the southern JdFR increasing to a maximum of 8.8 RA at 46.9°N on the Cobb Segment, and then dropping to values of ∼8.0 RA at the Cobb Offset. Ratios along the Endeavour Segment further north are somewhat higher, averaging ∼8.2 RA. Basalts dredged from Axial Seamount have ³He/4He = 7.9–8.4 RA, indicating that the seamount does not have a geochemical or isotopic signature distinct from other portions of the JdFR. This confirms that while Axial Seamount is the locus of excess magma generation, it is devoid of any hotspot or ocean island basalt geochemical signature. For the whole sample set, ³He/4He ratios show a negative correlation with 87Sr/86Sr. We attribute the geographical variations in ³He/4He to broad-scale heterogeneity in the mantle source region beneath the JdFR. Beginning at Axial Seamount and further north, ³He/4He shows a positive correlation with Fe8.0, suggesting that melting dynamics in the underlying mantle may exert some control on the helium isotope ratios along part of our survey area.
Scanning Long-wave Optical Test System: a new ground optical surface slope test system

The scanning long-wave optical test system (SLOTS) is under development at the University of Arizona to provide rapid and accurate measurements of aspherical optical surfaces during the grinding stage. It is based on the success of the software configurable optical test system (SCOTS) which uses visible light to measure surface slopes. Working at long wave infrared (LWIR, 7-14 um), SLOTS measures ground optical surface slopes by viewing the specular reflection of a scanning hot wire. A thermal imaging camera collects data while motorized stages scan the wire through the field. Current experiments show that the system can achieve a high precision at micro-radian level with fairly low cost equipment. The measured surface map is comparable with interferometer for slow optics. This IR system could be applied early in the grinding stage of fabrication of large telescope mirrors to minimize the surface shape error imparted during processing. This advantage combined with the simplicity of the optical system (no null optics, no high power carbon dioxide laser) would improve the efficiency and shorten the processing time.
Fine structural correlates of the choroid plexus of the lateral cerebral ventricle of the human fetal brain

The germinal matrix neuroepithelium and the choroidal fissure of the fetal choroid plexus commonly possess microvessels that are often poorly developed. There may be a reduction of type IV collagen that surrounds these fragile microvessels. During the first and second trimester of neural development, these microvessels are friable and can undergo intraventricular hemorrhage under a number of circumstances. Early subtle changes in the integrity of germinal matrix epithelium are not easily visualized by ultrasound. The current investigation employing scanning electron microscopy clearly defines subtle hemorrhagic events and tearing of the germinal matrix neuroepithelium in the brains of human fetuses. A 23-week-old fetus survived for 11 days but died from other causes. The choroid plexus of this fetus was compared with the choroid plexus and germinal matrix epithelium of a 22-week-old fetus that was the product of an elective termination due to severe anhydramnios of unknown origin and a 19-week-old male fetus from an elective termination. All tissues were autopsy material not requiring institutional review board approval.
Regulation of m2 Muscarinic Receptor Gene Expression by Platelet-Derived Growth Factor: Involvement of Extracellular Signal-Regulated Protein Kinases in the Down-Regulation Process

To study the role of mitogen-activated protein kinase in the regulation of M2 receptors, we studied the effect of platelet-derived growth factor (PDGF) on M2 receptor gene expression. PDGF (4 ng/ml) caused a time-dependent decrease in M2 receptor number and in m2 receptor mRNA levels in HEL 299 cells. The PDGF-induced loss in m2 mRNA required de novo protein synthesis and occurred through a decrease in the rate of transcription of the m2 receptor gene. The down-regulation of M2receptors was not accompanied by an uncoupling of the remaining receptors, indicating a large receptor reserve in these cells. Preincubations with the phosphatidylinositol 3-kinase inhibitor wortmannin, the protein kinase C inhibitor GF 109203X and the cAMP-dependent protein kinase inhibitor H-8 did not attenuate PDGF-induced down-regulation, indicating a lack of involvement of these enzymes in the down-regulation process. Activation of the extracellular signal-regulated protein kinase (ERK) 1 and 2 proteins was measured by an “in gel” phosphorylation assay. Carbachol did not activate ERK1 or 2, whereas PDGF and 4β-phorbol 13,14-dibutyrate resulted in a large increase in ERK1 and 2 activity along with a decrease in m2 mRNA. Preincubation with PD 098059, an inhibitor of mitogen-activated protein kinase kinase, inhibited PDGF- and 4β-phorbol 13,14-dibutyrate-mediated activation of ERK 1 and 2 in a concentration-dependent manner. The inhibitory action of PD 098059 was reflected at the mRNA level attenuating both PDGF- and 4β-phorbol 13,14-dibutyrate-mediated decreases in m2 mRNA. These results suggest a role of ERK1 and 2 in the regulation of muscarinic m2 receptor gene expression.
Bankruptcy and Federal Crop Insurance

In the area of insurance law, there are several commentators who have written on the relationship between insurance law and that of bankruptcy law. But there is a gap in the literature relating to bankruptcy law and the law of federal crop insurance specifically. This article is intended to examine the nexus between bankruptcy law and the federal crop insurance program by analyzing some of the key issues which have appeared in litigated cases. From issues relating to replacement liens on crops, allegations of misrepresentations and its effects on a bankruptcy proceeding, setoffs, adequate protection of security interests, statutes of limitations, whether crop insurance proceeds are part of the bankruptcy estate, to preemption issues, the law of bankruptcy and the law of federal crop insurance intersect in a variety of interesting contexts.
Addition of Cleaved Tail Fragments during Lipid Oxidation Stabilizes Membrane Permeability Behavior

Lipid oxidation has been linked to plasma membrane damage leading to cell death. In previous work, we examined the effect of oxidation on bilayer permeability by replacing defined amounts of an unsaturated lipid species with the corresponding phospholipid product that would result from oxidative tail scission of that species. This study adds the cleaved tail fragment, better mimicking the chemical results of oxidation. Permeability of PEG12-NBD, a small, uncharged molecule, was measured for vesicles with oxidation concentration corresponding to between 0 and 18 mol % of total lipid content. Permeability was measured using a microfluidic trap to capture the vesicles and spinning disk confocal microscopy (SDCM) to measure the transport of fluorescent PEG12-NBD at the equatorial plane. The thicknesses of lipid bilayers containing oxidized species were estimated by measuring capacitance of a black lipid membrane while simultaneously measuring bilayer area. We found that relative to chemically modeled oxidized bilayers without tail fragments, bilayers containing cleaved tail groups were less permeable for the same degree of oxidation. Curiously, membrane capacitance measurements indicated that the addition of tail fragments to chemically modeled oxidized bilayers also thinned these bilayers relative to samples with no tail fragments; in other words, the more permeable membranes were thicker. Above 12.5% chemically modeled oxidation, compositions both with and without the cleaved tail groups showed pore formation. This work highlights the complexity of the relationship between chemically modeled lipid bilayer oxidation and cell membrane properties.
Comparing The Machiavellianism Of Todays Indonesian College Students With U. S. College Students Of Today And The 1960s

The tactics and strategies that were suggested by Niccolo Machiavelli in The Prince (1513) have become synonymous with manipulative and unethical practices. Machiavellis writing to the politician has been used to describe business leaders as well. The business literature indicates that Machiavellian tactics do not guarantee success. The research we report examined the Machiavellian tendencies of college students in Indonesia and compare those results to the literature including the original U.S. student sample of the 1960s and the Harmon and Webster student sample published in 2002.
Antiferromagnetic Exchange Constants Between Mn2+ Ions in II-VI Semimagnetic Semiconductors

Mn 2+ ion spins in II–VI compound semimagnetic semiconductors (SMS) such as Cd 1−x Mn Te interact with one another through an antiferromagnetic exchange which is responsible for many interesting properties of Mn-alloyed II–VI SMS. In particular, this interaction leads to unique magnetization (M) behavior of SMS as a function of applied magnetic field (B). The nearest-neighbor (NN) Mn 2+ −MN 2+ interaction has been shown to yield a series of five steps in M vs. B curves above about 10 T, providing a direct determination of the NN exchange constant J NN . A detailed analysis of the magnetization steps has yielded values for the next NN exchange constant J NNN . The magnetization steps also yield information on the distribution of Mn 2+ ions. Inelastic neutron scattering and Raman scattering provide alternative methods for the direct determination of the exchange constants.
New Directions in the Political Economy of Agriculture

Recent tendencies in the literature on the sociology and political economy of agriculture in advanced industrial societies are analyzed with respect to their adequacy for guiding future research and their implications for sociology at large. We argue that the emergent tradition of agrarian political economy, while it has been productive in many respects, has tended to have two limitations. First, agriculture has typically been reified by being conceptualized as a distinct and autonomous sector when, in fact, modern agriculture is increasingly characterized by a decline in its sectoral and national identities. Second, major contending theories, despite their apparent differences, have been rooted in common deductivist approaches that fail to recognize the contingent character of agricultural organization. Two theoretical strategies with particular promise for transcending these limitations are then discussed.
Life Insurance Companies and Pension Funds

Two of the largest types of financial institutions are neither banks nor direct depository institutions. Many times, neither of these will immediately come to mind if the layman is asked to name a large sophisticated financial intermediary. The reason for this lapse is that both institutions devote themselves to a different type of savings and investment function than do banks or building associations. Life insurance companies and pension funds cater to another sort of financial need than do banks that serve as depositories for current needs. Both invest for the individual on a future basis; seeking to protect his future needs for wealth and protection rather than serve more immediate concerns covered by depository institutions.
Numerical Methods Order One ODEs

This chapter discusses numerical methods for first order ODEs and includes a careful derivation of the error estimates for Euler’s method. It includes a review of function approximation tools. It reviews Runge–Kutta methods as well and discusses the MatLab implementation of both methods.
Ab Initio Study of the Electronic Properties and Thermodynamic Stability of Supported and Functionalized Two-Dimensional Sn Films

Using density-functional theory (DFT), we study the growth of pristine and functionalized tin monolayers (Sn-MLs) on three different substrates, CdTe, InSb, and Si(111), and the impact these substrates have on the topological insulating properties of the electronic band structure. The presence of the substrate leads to strain and electronic charge transfer, which cause significant changes in the stability and electronic properties of the supported Sn-ML. Growth of pristine Sn-MLs on Si(111) leads to metallic behavior resembling that of the high-buckled Sn-ML phase; pristine Sn-MLs grown on InSb do not maintain a gap throughout the entire Brillouin zone; and pristine Sn-MLs grown on CdTe are unlikely to exhibit an experimentally observable gap. Provided the charge transfer from the substrate can be compensated, halogen-functionalized Sn-MLs grown on CdTe and InSb are topological insulators, albeit with a reduced band gap compared to their free-standing counterparts (from 0.34 eV for Sn-ML-I to 0.17 eV for InSb-Sn-ML-I). We employ ab initio thermodynamics calculations to study the thermodynamic stability of the halogenated InSb-Sn-MLs and CdTe-Sn-MLs surfaces for a temperature range of 100--1000 K under two extreme environments: ultrahigh vacuum (used in most of the laboratory characterization techniques) and rich-halogen conditions (10% vol. halogen environment). Our results indicate that it is possible to obtain stable topologically insulating Sn-MLs grown epitaxially on lattice-matched substrates.
A little cooperation helps murine cytomegalovirus (MCMV) go a long way: MCMV co-infection rescues a chemokine salivary gland defect

Cytomegaloviruses (CMVs) produce chemokines (vCXCLs) that have both sequence and functional homology to host chemokines. Assessment of vCXCL-1's role in CMV infection is limited to in vitro and in silico analysis due to CMVs species specificity. In this study, we used the murine CMV (MCMV) mouse model to evaluate the function of vCXCL-1 in vivo. Recombinant MCMVs expressing chimpanzee CMV vCXCL-1 (vCXCL-1CCMV) or host chemokine, mCXCL1, underwent primary dissemination to the popliteal lymph node, spleen and lung similar to the parental MCMV. However, neither of the recombinants expressing chemokines was recovered from the salivary gland (SG) at any time post-infection although viral DNA was detected. This implies that the virus does not grow in the SG or the overexpressed chemokine induces an immune response that leads to suppressed growth. Pointing to immune suppression of virus replication, recombinant viruses were isolated from the SG following infection of immune-ablated mice [i.e. SCID (severe combined immunodeficiency), NSG (non-obese diabetic SCID gamma) or cyclophosphamide treated]. Depletion of neutrophils or NK cells does not rescue the recovery of chemokine-expressing recombinants in the SG. Surprisingly we found that co-infection of parental virus and chemokine-expressing virus leads to the recovery of the recombinants in the SG. We suggest that parental virus reduces the levels of chemokine expression leading to a decrease in inflammatory monocytes and subsequent SG growth. Therefore, aberrant expression of the chemokines induces cells of the innate and adaptive immune system that curtail the growth and dissemination of the recombinants in the SG.
Synaptic Mechanisms of Feature Coding in the Visual Cortex of Awake Mice

The synaptic mechanisms of feature coding in the visual cortex are poorly understood, particularly in awake animals. The ratio between excitation (E) and inhibition (I) might be constant across stimulus space, controlling only the gain and timing of neuronal responses, or it might change, directly contributing to feature coding. Whole-cell recordings in L2/3 of awake mice revealed that the E/I ratio systematically declines with increasing stimulus contrast or size. Suppressing somatostatin (SOM) neurons enhanced the E and I underlying size tuning, explaining SOM neurons' role in surround suppression. These data imply that contrast and size tuning result from a combination of a changing E/I ratio and the tuning of total synaptic input. Furthermore, they provide experimental support in awake animals for the "Stabilized Supralinear Network," a model that explains diverse cortical phenomena, and suggest that a decreasing E/I ratio with increasing cortical drive could contribute to many different cortical computations.
Sex differences in sleep-disordered breathing after stroke: results from the BASIC project.

Abstract Objective/Background Sleep-disordered breathing (SDB), an independent risk factor for stroke, is associated with worse post-stroke outcomes. Differences in the relationship between SDB and stroke may exist for women versus men. In this population-based study, we compared the prevalence of both pre- and post-stroke SDB by sex. We also explored whether menopausal status is related to post-stroke SDB. Patients/Methods We performed a cross-sectional study of subjects enrolled in the Brain Attack Surveillance in Corpus Christi (BASIC) project. Each subject (n = 1815) underwent a baseline interview including the Berlin Questionnaire to assess pre-stroke SDB risk and, if relevant, questions regarding menopausal status. Subjects were offered overnight SDB screening with a validated portable respiratory device (n = 832 with complete data). Log Poisson and linear regression models were used to assess the differences in SDB between men and women with adjustment for demographics, stroke risk factors, stroke severity, and other potential confounders. Results Women were less likely than men to be at high risk for pre-stroke SDB (56.6% versus 61.9%) (prevalence ratio [PR] 0.87 for women; 95% confidence interval [CI], 0.81–0.95). A lower proportion of women than men (50.8% versus 70.2%) had post-stroke SDB by respiratory monitoring (PR 0.71; 95% CI, 0.63–0.80). SDB severity was higher for men than for women (mean difference in respiratory event index [REI] 6.5; 95% CI, 4.3–8.7). No significant association existed between post-stroke SDB and either menopausal status or age at menopause. Conclusions After acute ischemic stroke, SDB was more prevalent and more severe in men than in women.
Quantification and ontology

Quineans have taken the basic expression of ontological commitment to be an assertion of the form '∃ x φ', assimilated to theEnglish 'there is something that is a φ'. Here I take the existential quantifier to be introduced, not as an abbreviation for an expression of English, but via Tarskian semantics. I argue, contrary to the standard view, that Tarskian semantics in fact suggests a quite different picture: one in which quantification is of a substitutional type apparently first proposed by Geach. The ontological burden is borne by constant symbols, and truth is defined separately from reference.
Microcredit and Inverted Banking

The main objective of microcredit schemes is to provide sustainable microfinance with economic development goals. If credit lending institutions can operate profitably and efficiently by targeting lending priorities for the asset-poor in order to elevate the economic status of such borrowers (often to remain above applicable poverty line) and without dependence on any significant financial subsidies, then the microfinance scheme may be deemed to operate as a sustainable microfinance.
Results of in vitro fertilization attempts in women 40 years of age and older: the Norfolk experience

Twenty-nine patients 40years of age or older were stimulated with gonadotropins, starting on day 3 of the cycle, in a total of 64cycles (January 1983 to June 1985) for multiple follicular development for in vitro fertilization. Most patients' infertility was due to tubal disease (n=8) or pelvic endometriosis (n=14). The mean number of preovulatory and immature oocytes recovered per laparoscopy was 2.53±1.73 and 1.57±1.58, respectively. There were no statistically significant differences between the number of preovulatory and immature oocytes harvested, fertilized, or transferred in this group and the number in patients younger than 40years of age. No statistically significant differences were observed between peripheral estradiol and progesterone levels in patients 40years of age or older and levels in patients 39years of age or younger. There were 15 pregnancies in this group of patients, for a pregnancy rate of 23.4% per stimulated cycle, 27.7% per laparoscopy, and 29.4% per transfer. The ongoing pregnancy rate (12%) was lower, and the total abortion rate (60%) was higher, in patients 40years of age or older in comparison with patients 39years of age or younger. Patients 40years of age or older should be counseled regarding the high abortion rate in this group.
Melanoma treatment costs: a systematic review of the literature, 1990-2011.

Context Melanoma is the most deadly form of skin cancer and an important public health concern. Given the substantial health burden associated with melanoma, it is important to examine the economic costs associated with its treatment. The purpose of the current study was to systematically review the literature on the direct medical care costs of melanoma. Evidence acquisition A systematic review was performed using multiple databases including MEDLINE, Embase, CINAHL, and Econlit. Nineteen articles on the direct medical costs of melanoma were identified. Evidence synthesis Detailed information on the study population, study country/setting, study perspective, costing approach, disease severity (stage), and key study results were abstracted. The overall costs of melanoma were examined as well as per-patient costs, costs by phase of care, stage of diagnosis, and setting/type of care. Among studies examining all stages of melanoma, annual treatment costs ranged from $44.9 million among Medicare patients with existing cases to $932.5 million among newly diagnosed cases across all age groups. Conclusions Melanoma leads to substantial direct medical care costs, with estimates varying widely because of the heterogeneity across studies in terms of the study setting, populations studied, costing approach, and study methods. Melanoma treatment costs varied by phase of care and stage at diagnoses; costs were highest among patients diagnosed with late-stage disease and in the initial and terminal phases of care. Aggregate treatment costs were generally highest in the outpatient/office-based setting; per-patient/per-case treatment costs were highest in the hospital inpatient setting. Given the substantial costs of treating melanoma, public health strategies should include efforts to enhance both primary prevention (reduction of ultraviolet light exposure) and secondary prevention (earlier detection) of melanoma.