cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-term vector integration site analysis following retroviral mediated gene transfer to hematopoietic stem cells for the treatment of HIV infection

We previously reported the efficacy of nonmyeloablative allogeneic transplantation in 2 HIV positive recipients, one of whom received retrovirus transduced hematopoietic stem cells to confer resistance to HIV. Here we report an assessment of retroviral integration sites (RISs) recovered out to 3 years post-transplantation. We identified 213 unique RISs from the patient's peripheral blood samples by linear amplification-mediated PCR (LAM-PCR). While vector integration patterns were similar to that previously reported, only 3.76% of RISs were common among early (up to 3 months) and late samples (beyond 1 year). Additionally, common integration sites were enriched among late samples (14.9% vs. 36.8%, respectively). Three RISs were found near or within known oncogenes, but 2 were limited to early timepoints. Interestingly, an integration site near the MDS1 gene was detected in long-term follow-up samples; however, the overall contribution of MDS1 integrated clone remained stably low during follow-up.
MATING SYSTEM AND DISTRIBUTION OF GENETIC VARIATION IN GYMNOCARPIUM DRYOPTERIS SSP. DISJUNCTUM

Levels and distribution of genetic variation were analyzed in 15 populations of the homosporous fern Gymnocarpium dryopteris ssp. disjunctum to evaluate the mating system and the genetic structure of this taxon. Estimated rates of intragametophytic selfing were 0.000 in all populations, signifying that all sporophytes examined arose via intergametophytic matings. Furthermore, values of F, the fixation index, ranged from -0.171 to 0.038, indicating that all populations approach Hardy-Weinberg equilibrium. Therefore, not only is intragametophytic selfing rare in G. dryopteris ssp. disjunctum, but intergametophytic selfing is also uncommon. Factors promoting outcrossing in G. dryopteris ssp. disjunctum include an antheridiogen system, an ontogenetic sequence that favors intergametophytic matings, and high levels of genetic load. Analysis of F-statistics indicated statistically significant genetic differentiation among populations despite a mean genetic identity of 0.973 and high levels of interpopulational gene flow (Nm = 3.41 to 4.09). These patterns may reflect levels of gene flow that prevent significant interpopulational divergence while permitting slight genetic differentiation among populations.
Preface to special issue: lightweight and practical formal methods in the design and analysis of safety-critical systems

The papers included in this special issue of Mathematical Structures in Computer Science were selected from a larger set we solicited from leading research groups on both sides of the Atlantic. They cover a wide spectrum of tutorials, recent results and surveys in the area of lightweight and practical formal methods in the design and analysis of safety-critical systems. All the papers we received were submitted to a rigorous process of review and revision, based on which we made our final selection.
Freeze fracture evidence for lateral phase separations in the plasmalemma of chilling-injured avocado fruit

Unripe avocado fruit (Persea americana Mill. cv Hass) were held at 6 °C either in air or in an atmosphere with 100 PPM ethylene and were assessed for chilling injury after one and two weeks. Injury did not occur in any fruit after one week. After two weeks, the fruit in air were still uninjured, but the fruit subjected to ethylene exhibited chilling injury. When the uninjured fruit (both air-treated for one and two weeks and ethylene-treated for one week) were allowed to warm to room temperature before freezing for freeze fracture electron microscopy, replicas revealed membranes with a randomly dispersed pattern of intramembranous particles (IMPs). However, when these uninjured fruit were frozen for freeze fracture without warming, particle-free domains were visible in the plasmalemma. The membranes of the ethylene-treated, chilling-injured (2 weeks) fruit, on the other hand, contained particle-depleted regions in the plasmalemma of fruit frozen not only from 6 °C but also in those allowed to warm to room temperature before freezing for freeze fracture. These particle depleted microdomains were not seen in fruit kept continuously at room temperature (20 °C), even in the presence of high levels of endogenous ethylene which is produced during normal ripening. We suggest these particle-depleted microdomains formed in the fruit frozen for freeze fracture from low temperatures and in the chilling-injured fruit to be due to lateral phase separations of the membrane components, possibly due to an increase in the viscosity of some membrane lipids, leading to the formation of microdomains of gel phase lipid in the plane of the membrane. These phase separations appear to be initially reversible by raising the temperature, however, this reversibility is apparently lost after injury has occurred. With regard to the cause of chilling injury in avocados, we suggest that some secondary effect is involved due to the long term presence of gel phase lipids in the membrane.
A Wind Tunnel as a Senior/Capstone Design Project: Laboratory Enhancement and Assessment of Student Learning

Senior-level engineering students spend their final year designing and constructing challenging engineering-based capstone design projects in groups of two or more. The main objective of the senior...
Does Three-Dimensional External Beam Partial Breast Irradiation Spare Lung Tissue Compared With Standard Whole Breast Irradiation?

Purpose To determine whether three-dimensional conformal partial breast irradiation (3D-PBI) spares lung tissue compared with whole breast irradiation (WBI) and to include the biologically equivalent dose (BED) to account for differences in fractionation. Methods and Materials Radiotherapy treatment plans were devised for WBI and 3D-PBI for 25 consecutive patients randomized on the NSABP B-39/RTOG 0413 protocol at Mayo Clinic in Jacksonville, Florida. WBI plans were for 50 Gy in 25 fractions, and 3D-PBI plans were for 38.5 Gy in 10 fractions. Volume of ipsilateral lung receiving 2.5, 5, 10, and 20 Gy was recorded for each plan. The linear quadratic equation was used to calculate the corresponding dose delivered in 10 fractions and volume of ipsilateral lung receiving these doses was recorded for PBI plans. Ipsilateral mean lung dose was recorded for each plan and converted to BED. Results There was a significant decrease in volume of lung receiving 20 Gy with PBI (median, 4.4% vs. 7.5%; p p = 0.02). Mean lung dose was lower for PBI (median, 3.46 Gy vs. 4.57 Gy; p = 0.005), although this difference lost significance after conversion to BED (median, 3.86 Gy 3 vs 4.85 Gy 3 , p = 0.07). PBI plans exposed more lung to 2.5 and 5 Gy. Conclusions 3D-PBI exposes greater volumes of lung tissue to low doses of radiation and spares the amount of lung receiving higher doses when compared with WBI.
Melanoma associated with tumour necrosis factor‐α inhibitors: a Research on Adverse Drug events And Reports (RADAR) project

Summary Background Tumour necrosis factor-α inhibitors (TNFαIs) are used for treatment of inflammatory disorders. There is evidence linking these agents with occurrence of malignancies. For four out of five TNFαIs the Food and Drug Administration (FDA) label states, ‘melanoma has been reported in patients treated with these agents’. Objectives To determine whether a statistically significant association exists between administration of TNFαIs and development of malignant melanoma. Methods We searched the FDA Adverse Event Reporting System (FAERS) database for terms related to melanoma and TNFαIs for detection of safety signals. We also searched a large urban academic electronic medical record (EMR) database for which we calculated the relative risk (RR) of melanoma in subjects exposed to TNFαIs vs. nonexposed subjects. Results There were 972 reports of melanoma associated with a TNFαI identified in the FAERS database, with 69 reports among individuals using more than one TNFαI. A safety signal was detected for infliximab, golimumab, etanercept and adalimumab, but not certolizumab pegol. For TNFαIs as a class of drugs, a safety signal was detectable in the FAERS database, and RR was significant in the EMR database. For the EMR cohort, 6045 patients were exposed to TNFαIs and 35 cases of melanoma were detected. Significance for RR was detected for adalimumab (RR 1·8, P = 0·02) and etanercept (RR 2·35, P = 0·0004 < 0·001). Conclusions We identified a significant association between exposure to TNFαIs and malignant melanoma in two different analyses. Our findings add to existing evidence linking these agents with the occurrence of malignant melanoma. Additional investigations are required to explore this association further along with the risk of melanoma with TNFαI therapy.
Evidence for a solar distortion rotating with a period of 12.2 days.

Most of the day-to-day fluctuation (originally believed to be error) in the Princeton solar oblateness observations is well described as the signal due to a ∼10 km distortion of the solar photosphere rotating rigidly with a period of 12.22±0.12 days (sidereal). This ‘solar-rotator’ signal is well-defined by the observations and seems clearly significant statistically. Owing to the apparent precession of the solar spin-axis on the sky, the signal is not strictly periodic and has a wave-form that evolves with time in a predictable way. The previously discussed enigmatic periodicity of the oblateness residuals, for which no non-solar sources were found, is eliminated when the solar-rotator signal is subtracted. The residual errors are then found to be normally distributed and uncorrelated. Including the solar-rotator signal in the least-square fit increases the implied static oblateness by 16% to Δr = 45.8±3.3 millisec (equatorial excess radius). Both the static oblateness signal and the solar-rotator signal might be interpreted phenomenonologically as ‘brightness’ signals due to a rigidly rotating non-uniform distribution of temperature in the upper photosphere. However, such a description encounters physical difficulties when the requirements of energy and momentum balance are considered. Including the excess static oblateness yields a distortion in the form of an ellipoid whose major axis is tilted 85° from the solar axis. Possible conflicts with other recent observations are discussed.
Assessment of Respirable Crystalline Silica Analysis Using Proficiency Analytical Testing Results from 2003–2013

Analysis of Proficiency Analytical Testing (PAT) results between 2003 and 2013 suggest that the variation in respirable crystalline silica analysis is much smaller today than it was in the period 1990–1998, partly because of a change in sample production procedure and because the colorimetric method has been phased out, although quality improvements in the x-ray diffraction (XRD) or infrared (IR) methods may have also played a role. There is no practical difference between laboratories using XRD or IR methods or between laboratories which are accredited or those which are not. Reference laboratory means (assigned values) are not different from the means of all participants across the current range of mass loading, although there is a small difference in variance in the ratios of all participants to reference laboratory means based on method because the reference laboratories are much more likely to use XRD than are the others. Matrix interference does not lead to biases or substantially larger variances f...
Marked variation in the size of genomic plasmids among members of a family of related Epstein-Barr viruses

Abstract Epstein-Barr virus (EBV) genomes in the P3J-HR-1 (HR-1) Burkitt lymphoma cell line rearrange at a high rate. Previously described deletions and rearrangements in HR-1 cells have been found at sites of EBV replication in vivo, suggesting that DNA rearrangement may be an integral aspect of EBV biology and pathogenesis. We examined the structure of linear EBV genomes in subcultures of HR-1 cells using contour-clamped homogenous electric field gel electrophoresis. We developed a second pulsed electrophoretic technique to separate intracellular circular EBV plasmids. The standard, linear HR-1 EBV genome was approximately 155 kilobases in length. Linear molecules of less than unit length, presumably defective genomes, were seen in numerous subcultures. Linear intracellular genomes greater than 155 kilobases were also detected, but only linear genomes of 155 kilobases or less were packaged into virions. The size of circular EBV plasmids also varied greatly among HR-1 subcultures, some of which contained two plasmids of different size. The progeny of the unusual circular plasmids could be either standard or nonstandard linear genomes. No aberrant linear or circular form was detected in a subculture carrying the previously described het fragments. Pulsed-gel electrophoresis has provided two additional characteristics of mutant EBVs: abnormal linear and circular genome configurations.
Variation in Nutrient Data Obtained by Three Commonly used Dietary Analysis Programs

Abstract LEARNING OUTCOME: The objective of this study was to determine whether there was variation in nutrient analysis of participant intakes when computed by three nutrition computer software programs. Two 24-hour recalls were obtained from each of sixty-seven elderly volunteers. The mean age for 20 males was 75 years (range 61–89) and 74.7 years (range 61–87) for 47 females. The participants were white with the exception of one black. Declared food items for each participant were entered into three dietary analysis programs to determine nutrient values of the dietary intakes. The software programs used were: Computrition; Food Processor Plus, version 6.0; and Nutritionist IV, version 3.5. Nutrient analysis of the nutrients common to all three programs were compared. Included were: protein, carbohydrate, fiber, fat, cholesterol, vitamins A, B1, B2, B3, B6, B12, C, folate, calcium, iron, phosphorus, potassium, sodium, zinc, and total calories. Percent variation of nutrient data from the three programs was determined using analysis of variance. Variations of nutrient analyses among the three programs were not significant for protein, carbohydrate, rat, cholesterol, vitamins B1, B2, B3, B6, B12, C, folate, calcium, iron, phosphorus, potassium, sodium, zinc, and total calories. There was a significant difference for analysis of vitamin A (P=.007) and fiber (P=.0001). These three specific nutrient analysis programs were chosen as they are popularly used in many hospital dietary departments and health and fitness facilities. Since study results showed only minimal variation in most of the nutrients calculated, professionals could use any of these programs with assurance that the patient/client will be given comparable information. However, the exceptions of vitamin A and fiber should be noted if precise data is required for either of these nutrients. Study findings can serve as guidelines for choosing an appropriate program to more accurately reflect the client's intake.
Superelastic electron scattering by polarized excited sodium

Absolute differential cross sections for superelastic scattering have been measured for the sodium resonant transition in the incident electron energy range 3\char21{}20 eV. Results are obtained with no calibration being needed and are related to time-reversed inelastic scattering with unpolarized particles. Comparisons with distorted-wave, close-coupling, and convergent-close-coupling calculations are presented.
Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65

RPE65, a membrane-associated protein in the retinal pigment epithelium, is the isomerohydrolase essential for regenerating 11-cis retinal, the chromophore for visual pigments. RPE65 mutations are associated with inherited retinal dystrophies. Here we report that single point mutations of RPE65, Y144D and P363T, identified in patients with Leber's congenital amaurosis (LCA), significantly decreased the stability of RPE65. Moreover, these mutations altered subcellular localization of RPE65 and abolished its isomerohydrolase activity. These observations suggest that the decreased protein stability and altered subcellular localization of RPE65 may represent a mechanism for these mutations to lead to vision loss in LCA patients.
The Soul of Medicine

This article considers contributions that the medical humanities have made to biomedical ethics. Philosophy has contributed methods of ethical justification to case analysis and has given birth to the New Professionalism movement. Taking biography as its paradigmatic resource, this movement has refocused medical education on the formation of physicians who not only have certain responsibilities to their patients, but also a regard for the role of the medical profession in working toward social justice. However, reliance on biography is now giving way to a renewed emphasis on autobiography, as educators seek to support medical students through the personal and spiritual journey that confrontation with death, disease, and injustice naturally entails. Reflective methods and techniques characterize this emerging era as educators and students try to preserve and reinvigorate the soul of medicine.
Characterization and optimization of pyroelectric X-ray sources using Monte Carlo spectral models

Abstract Pyroelectric X-ray sources produce emission through bulk heating of a ferroelectric crystal. In this study, a least-square based systematic curve fitting of X-ray emission to predicted models is used to generate an equivalent monoenergetic incident electron energy to simplify further X-ray source optimization. The measured X-ray spectrum of a 1 cm3 lithium tantalite crystal cycled over 140 K are shown to be approximated by those of an 85 keV monoenergetic electron beam. Using monoenergetic electron sources, common configurations for transmission and directional X-ray sources are simulated using electron targets comprised of gold, silver, copper, molybdenum and tungsten. X-ray production efficiency depends on target material selection, incident electron energy, and target thickness for both transmission and reflection geometries. At 20 keV, silver produced 69.7% more flux was in comparison to copper, the least efficient target material at this energy. Conversely, at 85 keV copper outperformed silver, the least efficient target material at this energy, by 21.6%. Pyroelectric X-ray sources can be improved for flux and energy tuning through the use of modeling and target design. Continued development of pyroelectric X-ray sources can lead to wide scale implementation for industrial X-ray fluorescence and medical therapeutic applications.
IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS VI. THE CROSS-REACTION BETWEEN TYPE XIV ANTIPNEUMOCOCCAL HORSE SERUM AND PURIFIED BLOOD GROUP A, B, AND O SUBSTANCES FROM HOG AND HUMAN SOURCES

Purified blood group A, B, and O substances from hog and human sources precipitate with Type XIV antipneumococcal horse serum and provide an explanation for the observation that Type XIV antibody agglutinates human erythrocytes of all four major blood groups. Individual preparations of A substance or O substance from either species vary in their capacity to precipitate Type XIV antibody although the hog A substances did not differ in potency toward anti-A. Similarly, no correlation between A activity and reactivity with Type XIV antibody could be found among the human A substances.
Influence of dextran sulfate and NaCl on the flocculation of oil-in-water emulsions stabilized by a nonionic surfactant

The creaming stability and viscosity of 10 wt % soybean oil-in-water emulsions stabilized by Tween 20 were monitored as a function of 500 kDa dextran sulfate (DS) concentration (0−5 wt %) and NaCl ...
Characterization of fast pyrolysis bio-oils produced from pretreated pine wood.

The pretreatment of biomass prior to the fast pyrolysis process has been shown to alter the structure and chemical composition of biomass feed stocks leading to a change in the mechanism of biomass thermal decomposition. Pretreatment of feed stocks prior to fast pyrolysis provides an opportunity to produce bio-oils with varied chemical composition and physical properties. This provides the potential to vary bio-oil chemical and physical properties for specific applications. To determine the influence of biomass pretreatments on bio-oil produced during fast pyrolysis, we applied six chemical pretreatments: dilute phosphoric acid, dilute sulfuric acid, sodium hydroxide, calcium hydroxide, ammonium hydroxide, and hydrogen peroxide. Bio-oils were produced from untreated and pretreated 10-year old pine wood feed stocks in an auger reactor at 450 °C. The bio-oils’ physical properties of pH, water content, acid value, density, viscosity, and heating value were measured. Mean molecular weights and polydispersity were determined by gel permeation chromatography. Chemical characteristics of the bio-oils were determined by gas chromatography–mass spectrometry and Fourier transform infrared techniques. Results showed that the physical and chemical characteristics of the bio-oils produced from pretreated pine wood feed stocks were influenced by the biomass pretreatments applied. These physical and chemical changes are compared and discussed in detail in the paper.
Focus on molecules: the GABAC receptor.

γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the retina and CNS, exerts its effects by activating three pharmacologically distinct types of GABA receptor (GABAR), each of which is expressed on retinal neurons. The GABACR is a member of the Cys-loop superfamily of ligand-gated ion channels that include the nicotinic acetylcholine, glycine and 5-HT3 receptors. The pentomeric structure of native GABAC receptors is composed of GABA ρ subunits, and three of which (ρ1 – ρ3) have been cloned from mammalian retinal cDNA libraries (NCBI accession number for human GABA ρ1, ρ2, and ρ3 subunit: NM_002042, NM_002043, and NM_001105580, respectively). In humans, the ρ1 and ρ2 subunits are located on chromosome 6q15; the ρ3 subunit is on chromosome 3q11. Each of the subunits is capable of forming a GABA-sensitive homooligomeric receptor when expressed in Xenopus oocytes, and co-assembly with the γ subunit of the GABAAR results in the formation of a receptor with functional properties that closely mimic the behavior of GABACR on bipolar cells (Qian and Ripps, 1999).
Prephenate dehydrogenase from Pseudomonas aeruginosa is a regulated component of the channel-shuttle mechanism controlling tyrosine—Phenylalanine synthesis

Abstract Prephenate dehydrogenase of Pseudomonas aeruginosa is unstable in crude extracts or following its partial purification by gel-filtration. However, when ion-exchange chromatography (DEAE-cellulose) is the initial purification step, a stable enzyme preparation is recovered. The enzyme, having a molecular weight of approximately 150,000, has a K m for prephenate of 0.05 m m , and is inhibited competitively (with respect to prephenate) by l -tyrosine. Feedback inhibition has not been found previously. It is concluded that the entry of prephenate into the tyrosine pathway is regulated largely by l -phenylalanine acting upon a bifunctional enzyme complex bearing activities for chorismate mutase and prephenate dehydratase. Overproduction of l -tyrosine in vivo is probably prevented by feedback inhibition of prephenate dehydrogenase.
Diagenetic controls on the structural evolution of siliceous sediments in the golconda allochthon, Nevada, U.S.A.

Abstract A model is proposed that links the diagenesis of siliceous sedimentary rocks with deformation to explain the heterogeneous structural fabric of radiolarian cherts in the upper Paleozoic Golconda allochthon of Nevada, U.S.A. Numerous thrust faults slice the cherts into packets, each with a unique set of internal structures. Fold geometries, boudin profiles, pressure-solution features, etc. vary from packet-to-packet and layer-to-layer. Analogous variations in the diagenetically mixed siliceous sediments of the Miocene Monterey Formation. California, suggest the cherts of the Golconda allochthon were similarly mixed when they were deformed. Radiolarian sediments composed of biogenic silica (opal-A) developed ductile structures and pressure-solution features because of their high porosity, weak lithification and the high solubility of disordered silica. Lowporosity, strongly-lithified, relatively-insoluble quartz cherts, the final product of silica diagenesis, deformed in a brittle fashion and developed fewer pressure-solution features. Diagenetically intermediate CT-cherts and CT-porcelanites exhibited transitional behavior. Mixed diagenetic zones produced structures with layer-by-layer changes in structural style. The dehydration of opal-A and opal-CT helped create the excess pore fluid pressures responsible for thrust faults, hydraulic fractures, dilation breccias and elastic intrusions. The presence of ductile structures and numerous pressure solution features in the oldest cherts of the Havallah sequence suggests that these cherts were deformed while diagenetically immature, possibly within a long-lived upper Paleozoic accretionary prism.
Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain

Selective activation of the peripheral cannabinoid receptor 1 (CB1R) has been shown to suppress neuropathic pain symptoms in rodents. However, relatively little is known about changes in CB1R and its endogenous ligands during development or maintenance of neuropathic pain. Using immunohistochemistry, Western blot, real-time reverse transcription polymerase chain reaction, as well as liquid chromatography/mass spectrometry, we studied the changes in CB1Rs and endocannabinoids N-arachidonoylethanolamine/anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat lumbar (L4 and L5) dorsal root ganglia (DRG) after neuropathic pain induction (L5 spinal nerve ligation: SNL). Immunohistochemistry revealed that in control rats, CB1R is expressed in the majority (76-83%) of nociceptive neurons as indicated by co-labeling with isolectin B4 (IB4) or antibodies recognizing transient receptor potential vanilloid (TRPV1), calcitonin gene related peptide (CGRP), and the NR2C/2D subunits of the N-methyl-D-aspartate receptor. After L5 SNL, CB1R mRNA and protein increases in the ipsilateral uninjured L4 DRG whereas the percentages of CB1R immunoreactive (CB1R-ir) neurons remain unchanged in L4 and L5 DRG. However, for these CB1R-ir neurons, we observe significant increases in percentage of TRPV1-ir cells in ipsilateral L4 DRG, and decreases in percentage of IB4- and CGRP-co-labeled cells in ipsilateral L5 DRG. Levels of both AEA and 2-AG increase significantly only in the ipsilateral L5 DRG. These results are consistent with the preserved analgesic effects of cannabinoids in neuropathic pain and provide a rational framework for the development of peripherally acting endocannabinoid-based therapeutic interventions for neuropathic pain.
Nitrogenase. I. Repression and derepression of the iron-molybdenum and iron proteins of nitrogenase in Azotobacter vinelandii.

Abstract Evidence is presented that the dilution effect on nitrogenase from Azotobacter vinelandii can be overcome by the addition of an optimal amount of Component I (iron-molybdenum protein) or Component II (iron protein); and this optimized activity parallels the activity obtained by applying the dilution-factor correction. The synthesis of both of the nitrogenase components, after exhaustion of ammonia from the medium, seems to be coordinate. The degradation of both of the nitrogenase components after repression was found to be coordinate and neither component was found to be in excess at any time after repression. For the initial one-half generation the nitrogenase activity falls at approximately the same rate as the increase in cell mass, suggesting simple dilution. After this point, however, activity falls more rapidly and more than 95 % of the activity is lost in two generations.
Crossover and scaling in SU(3) lattice gauge theories with Susskind fermions

Abstract The phase diagram of SU(3) lattice gauge theories with Susskind fermions is investigated by Monte Carlo methods. For three flavors in the continuum a significant shift in the location of the peak in the specific heat is found, as compared to the pure gauge case. These results suggest that the crossover region moves to smaller β when fermion polarization effects are included.
Apoptosis induced in neuronal cultures by either the phosphatase inhibitor okadaic acid or the kinase inhibitor staurosporine is attenuated by isoquinolinesulfonamides H-7, H-8, and H-9.

Protein phosphorylation is kept in balance by an orchestrated action of kinases and phosphatases; when this balance is lost, neuronal apoptosis may occur. Okadaic acid (OKA), a marine toxin that inhibits specifically protein phosphatases 1 and 2A (EC 3.1.3.16), and staurosporine, an inhibitor of protein kinase C (PKC; EC 2.7.1.37), induced apoptosis in primary cultures of rat cerebellar granule neurons. We assayed apoptosis by the DNA gel electrophoresis, by the in situ TUNEL assay, and by morphological appearance following propidium iodide staining. Cell viability was assessed by the Trypan blue assay. Both OKA- and staurosporine-induced neuronal apoptosis were prevented by a macromolecular synthesis inhibitor actinomycin D and by a group of isoquinolinesulfonamide kinase inhibitors (H-7, 1-[5-isoquinolinesulfonyl]-2-methylpiperazine; H-8, N-?2-[methylamino]ethyl?-5-isoquinolinesulfonamide; H-9, N-(2-aminoethyl)-5-isoquinolinesulfonamide, but not by inhibitors of PKC, cyclic-GMP- and cyclic-AMP-dependent kinases, calcium/calmodulin-dependent kinases, tyrosine kinases, or by antioxidants. We postulate that a common mechanism, possibly an increased protein phosphorylation, is responsible for apoptosis triggered by an inhibition of phosphatases 1 and 2A and PKC. Elucidating the isoquinolinesulfonamide-sensitive mechanism may help us find new therapies for neurodegenerative diseases that involve apoptosis.
Transmission Electron Microscopy of Pzt Thin-Films Prepared by A Sol-Gel Technique

The microstructure of lead zirconate titanate (PZT) thin films prepared by a sol-gel technique was investigated using transmission electron microscopy (TEM) and transmission electron diffraction. We investigated the microstructure of three sets of thin films with different chemical compositions: PZT 53/47 films with no excess PbO; with excess PbO; and PZT 65/35 with no excess PbO. All samples were fired for 30 minutes at temperatures ranging from 400C to 700C. Incorporation of excess PbO in the 53/47 film fired at 450C resulted in polycrystalline perovskite grains with an average grain size of less than 0.1 μm. Grain boundaries are decorated by 5-10 nm diameter precipitates possibly caused by the segregation of remnant pyrochlore or excess PbO. The films have high values of dielectric constant (up to 2500) when fired at 700C. PZT 65/35 fired at 700C consists of two distinct phases: a fine-grained matrix of pyrochlore, and 10-μm diameter rosettes of perovskite. The correlations between the compositions, the microstructure of the films, and their processing conditions on the one hand, and ferroelectric properties on the other are discussed.
Community-wide health risk assessment using geographically resolved demographic data: a synthetic population approach.

Background Evaluating environmental health risks in communities requires models characterizing geographic and demographic patterns of exposure to multiple stressors. These exposure models can be constructed from multivariable regression analyses using individual-level predictors (microdata), but these microdata are not typically available with sufficient geographic resolution for community risk analyses given privacy concerns. Methods We developed synthetic geographically-resolved microdata for a low-income community (New Bedford, Massachusetts) facing multiple environmental stressors. We first applied probabilistic reweighting using simulated annealing to data from the 2006–2010 American Community Survey, combining 9,135 microdata samples from the New Bedford area with census tract-level constraints for individual and household characteristics. We then evaluated the synthetic microdata using goodness-of-fit tests and by examining spatial patterns of microdata fields not used as constraints. As a demonstration, we developed a multivariable regression model predicting smoking behavior as a function of individual-level microdata fields using New Bedford-specific data from the 2006–2010 Behavioral Risk Factor Surveillance System, linking this model with the synthetic microdata to predict demographic and geographic smoking patterns in New Bedford. Results Our simulation produced microdata representing all 94,944 individuals living in New Bedford in 2006–2010. Variables in the synthetic population matched the constraints well at the census tract level (e.g., ancestry, gender, age, education, household income) and reproduced the census-derived spatial patterns of non-constraint microdata. Smoking in New Bedford was significantly associated with numerous demographic variables found in the microdata, with estimated tract-level smoking rates varying from 20% (95% CI: 17%, 22%) to 37% (95% CI: 30%, 45%). Conclusions We used simulation methods to create geographically-resolved individual-level microdata that can be used in community-wide exposure and risk assessment studies. This approach provides insights regarding community-scale exposure and vulnerability patterns, valuable in settings where policy can be informed by characterization of multi-stressor exposures and health risks at high resolution.
Effect of protoporphyrin on hemoglobin synthesis.

Abstract 1. 1. The synthesis of hemoglobin was studied in a system in vitro which contained ribosomes, pH-5 enzymes, and the supernatant solution prepared from rabbit reticulocytes. 2. 2. When protoporhyrin IX was added to this “cell-free” system, the release into solution of protein labeled with [14C]leucine was increased 2- to 3-fold. 3. 3. The same effect was observed whether the protoporhyrin IX was added initially or after the reaction mixture had been incubated for 10 min. 4. 4. The increase in the radioactivity of the soluble protein was maximal when the concentration of protoporphyrin IX was 32 μM. 5. 5. These studies suggest that the mechanism for the release of hemoglobin from the ribosomes may be associated with the synthesis of heme from protoporphyrin IX and iron.
Light-induced calcium fluxes from outer segment layer of vertebrate retinas.

Light affects the membrane potential of a vertebrate retinal rod or cone cell by transiently reducing its ‘dark current’, an inward flow of Na+ through the plasma membrane covering the light-absorbing outer segment1,2. In rods most photons are absorbed by photopigment molecules in intracellular disk membranes that are physically separate from the plasma membrane2–5. Photochemical events in the disks probably control the Na+ conductance of the plasma membrane through a chain of events that ultimately change the level of a diffusable substance in the cytoplasm of the outer segment. By combining reversibly with Na+ carriers or channels in the plasma membrane, this ‘internal transmitter’ substance would modulate the dark current and thus the rod's membrane potential6. There is evidence that the internal transmitter is free Ca2+ (refs 7–10). Ca2+ buffer EGTA has a desensitizing effect on rods, consistent with a free cyto-plasmic Ca2+ concentration of about 1 µM in darkness and release of 500–1,000 additional calcium ions for each absorbed photon10. However, there is insufficient proof that Ca2+ is released into the cytoplasm of rod outer segments by light and removed again in darkness. Reports that light reduces the total Ca2+ in outer segments have varied widely in their details11–15. Small amounts of Ca2+, ∼1 mol per mol of photoisomerized rhodopsin, are released by strongly illuminated isolated rod disks16, but this is not enough to explain the large size of single photon responses10,17. We have studied net movements of 2+ in the receptor layer of albino rat retinas during the responses of the rods to light with the aim of detecting release of internal 2+ by a rise in its extrusion into the interstitial space.
A saline intrusion into Seneca Lake, New York1

A warm, saline plume sinks, upon entering Seneca Lake, to just above the thermocline, 15 to 25 m deep. At that depth, based on vertical soundings of temperature and conductivity, the plume spreads radially, maintaining a distinct identity for 150–200 m. Temperature measurements alone suggest that the plume retains its identity to a distance of 1 km from its origin.
Motivational Influences on Cognitive Performance in Children: Focus Over Fit.

Cognitive psychologists have begun to address how motivational factors influence adults' performance on cognitive tasks. However, little research has examined how different motivational factors interact with one another to affect behavior across the life span. In the current study, the authors examined how children perform on a classification task when placed in a regulatory fit or mismatch. Nine-year-old children performed a classification task in which they either gained or lost points for each response. Additionally, children were given either a global promotion focus (trying to earn a gift card) or a prevention focus (trying to avoid losing a gift card). Previous work indicates that adults in this task tend to perform better when there is a match (or fit) between the incentive to gain, or avoid losing, a global reward, and the more local task reward structure to either maximize points gained or minimize points lost on a trial-by-trial basis. Unlike adults, 9-year-olds perform better in the promotion c...
Effect of naloxone treatment on luteinizing hormone and testosterone concentrations in boars with high and low libido.

SUMMARY The objective was to determine the effects of the opioid peptide receptor antagonist, naloxone on circulating concentrations of luteinizing hormone (LH) and testosterone in boars characterized as having high (n=8) or low libido (n=8) based on the willingness to mount an artificial sow and allow semen collection. On the day of the experiment, blood was sampled every 15 min for 4 h before and 4 h after i.v. injection of naloxone (1 mg/kg body weight). After naloxone treatment, a libido status by time interaction was detected and concentrations of LH within 15 min after treatment were greater (p
The X-Ray Pattern of Sericin and Silk Wax from Bombyx mori

Several x-ray reflections occurring in raw silk and in some preparations of sericin, and previ ously thought to be characteristic of sericin, are shown to arise from silk wax. The wax is asso ciated with the sericin fraction most strongly attached to the fibroin and it is present within the silk gland prior to spinning.
Dependence of substance CT number on scanning technique and position within scanner

A body tissue will vary in its CT value from one study to another not only because of changes in its physiology, but also because of technical factors related to the scanning procedure itself. Changing the mAs of a scan and/or position of a substance within the CT scanner was shown by the use of a phantom study to give a small relative but readily measurable change in the CT value of the substance. Thus, small relative changes in CT numbers should be regarded with caution when comparing one substance or area with another or one study with another.
Experimental increase in accommodative potential after neodymium:yttrium–aluminum–garnet laser photodisruption of paired cadaver lenses ☆

Abstract Purpose Loss of lens elasticity is one of several proposed mechanisms responsible for the decline in accommodation with age and is the most accepted explanation for presbyopia. We wish to confirm the lens elasticity premise and attempt to experimentally reverse the age-dependent loss of accommodative potential as measured by polar strain. Design Experimental human autopsy eye study. Participants and controls Thirty-six cadaver lenses were tested to determine the age-dependent polar strain. Eleven lens pairs were then tested with one lens treated with neodymium:yttrium–aluminum–garnet (Nd:YAG) laser and the other left untreated before rotation as an age control. Testing Using a custom-made rotational apparatus (described by Fisher, 1971), freshly excised cadaver lenses ( t test. Main outcome measures Polar strain (decrease in axial thickness with rotation) of the lens. Results An age-dependent decrease in polar strain was observed that paralleled the findings of Fisher. Both measured and projected polar strain were greater in the lased than unlased lens, and this difference was highly significant by paired t test ( P = 0.001 and P = 0.004, respectively). Conclusions Age-dependent loss of lens elasticity (polar strain) can be experimentally reversed (increased) by selective intralenticular photodisruption.
Cryptic promoter activity in the DNA sequence corresponding to the pim-1 5′-UTR

The serine/threonine kinase pim-1 mRNA contains a long and G/C rich 5'-untranslated region (5'-UTR). Previous work suggested that the pim-1 5'-UTR harbors an internal ribosomal entry site (IRES) allowing for internal initiation of translation. However, several previously reported eukaryotic IRES elements actually contain cryptic promoter activity. To test whether an IRES or a cryptic promoter is present in the pim-1 5'-UTR, the 5'-UTR was re-examined using stringent test procedures. Our results show the presence of strong promoter activity in the DNA sequence corresponding to the pim-1 5'-UTR. Both promoterless dicistronic test and northern blot analysis show transcripts being derived from the cryptic promoter in the pim-1 5'-UTR sequence. This cryptic promoter is active in all cell types tested, including Cos-7, NIH3T3, HEK293, Jurkat and K562 cells. When a dicistronic mRNA containing the pim-1 5'-UTR was translated in vitro or in vivo, no IRES activity could be detected. However, the control IRESs from both human rhinovirus and encephalomyocarditis virus exhibited strong IRES activities. In addition, both the RNase protection assay and the 5'-RACE assay detected endogenous pim-1 transcripts with shorter 5'-UTRs. Our data strongly suggest that the IRES activity reported earlier for the pim-1 5'-UTR sequence is due to cryptic promoter activity.
Flexible endosopic management of Zenker's diverticulum: characteristics and outcomes of 52 cases at a tertiary referral center

Summary Zenker's diverticulum causes substantial morbidity among affected elderly patients. In the United States, rigid endoscopic cricopharyngeal myotomy is the mainstay of management and the flexible endoscopic technique is reserved for those not deemed candidates for rigid endoscopy due to an inability to extend the neck and/or medical comorbidities. Short- and long-term outcomes following flexible endoscopic cricopharyngeal myotomy in the United States are limited. We reviewed the patient characteristics and outcomes of 58 consecutive flexible endoscopic cricopharyngeal myotomies performed at Mayo Clinic, Rochester, between March 2006 and November 2013. There were 58 procedures performed on 52 unique patients. The median age was 77 years, and 48% of patients were female. More than one third of patients had either failed previous rigid therapy or were deemed inoperable by the referring surgeon. Size of the diverticulum ranged from 1 cm to 5 cm with a mean of 2.8 cm. Most procedures (67%) were performed under general anesthesia. Initial procedural success was achieved in all patients. Of the patients, 77% reported complete symptom resolution at mean follow-up time of 26 months. Of the procedures, 71% were not associated with any adverse event, but esophageal microperforation occurred during 11 procedures (19%). Of these, nine resolved with conservative management, one required an endoscopic stent, and one developed a neck abscess that required drainage. Our data show in a group of elderly patients with preexisting comorbidities flexible endoscopy therapy for Zenker's diverticulum is feasible. Initial symptomatic improvement was universal, and long-term response appears durable. The most common adverse event was esophageal microperforation, and the majority (82%) of these resolved with conservative management. Direct comparison with outcomes of rigid endoscopic or open surgical techniques has not been performed, but these data suggest that a randomized trial is warranted to assess the efficacy and safety of a flexible endoscopic technique.
Planetary wave breaking and nonlinear reflection : Seasonal cycle and interannual variability

Abstract Forty-six years of daily averaged NCEP–NCAR reanalysis data are used to identify the occurrence of planetary wave breaking (PWB) in the subtropical upper troposphere. As large-amplitude waves propagate into the subtropics where the zonal flow is weak, they may break. PWB is diagnosed by observing the large-scale meridional overturning of potential vorticity (PV) contours on isentropic surfaces near the subtropical tropopause. PWB occurs most often during summer, and almost exclusively over the subtropical ocean basins in the Northern Hemisphere. The seasonal evolution of the zonal flow (and the associated latitudinal PV gradient) regulates the location and frequency of PWB. Significant interannual variability in PWB is associated with well-known modes of climate variability. One of the most interesting dynamical consequences of PWB is the possibility of nonlinear reflection poleward out of the wave-breaking region. Modeling studies have found nonlinear reflection following PWB. Observations show ...
Core–Satellite Strategies: Combining Stability and Opportunity in an ETF Portfolio

So-called core-satellite strategies have gained popularity among asset managers seeking to combine strict risk control with opportunities to create alpha through active management. Traditionally core satellite portfolios consist of a passively managed core around which the satellites—usually actively managed vehicles—“revolve.” The rationale behind this is that the core of the portfolio should be consistent with investors’ long-term aims, enabling them to catch asset class risk premiums in efficient markets in a controlled and cost-effective way. The satellites are meant to generate alpha in inefficient market segments.
Enhanced Hepatic apoA-I Secretion and Peripheral Efflux of Cholesterol and Phospholipid in CD36 Null Mice

CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL) but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36−/−) mice. Feeding CD36−/− mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36−/− mice and cholesterol uptake from HDL or LDL by isolated CD36−/− hepatocytes was unaltered. However, CD36−/− hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36−/− macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36−/− cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.