cssi/SciSciGPT-SciSciNet huggingface dataset:
Nuclear envelope and lamin B2 function in the central nervous system

The nuclear envelope (NE) embraces the genome with a rich tapestry of outer and inner membrane proteins, some of which mechanically link the cytoskeleton to the nucleoskeleton (1). The nucleoskeleton includes the nuclear intermediate filaments, formed by independent networks of A- and B-type lamins. Humans have one gene (LMNA) encoding A-type lamins and two genes encoding B-type lamins (LMNB1 and LMNB2) (2). Fascinating links to human physiology have emerged as mutations in LMNA were found to cause a spectrum of disorders, generally termed “laminopathies.” Most known laminopathies affect one or more specific “load-bearing” tissues, with clinical phenotypes that include muscular dystrophy, cardiomyopathy, skin or bone defects, or widespread connective tissue defects that lead to segmental progeroid (“accelerated aging”) syndromes (3). Certain mutations in LMNA can even cause lipodystrophy and diabetes, or Charcot-Marie-Tooth axonal neuropathy. However, the central nervous system was conspicuously and puzzlingly unaffected, even in LMNA knockout mice. A new report in a recent issue of PNAS (4) fills this major gap in knowledge by showing that lamin B2 knockout mice have grossly abnormal development of the cerebral cortex and cerebellum. Lamins A, B1, and B2 show complex and differential patterns of expression in developing neurogenic regions of the rat brain (5). Lamins B1 and B2 are each expressed at the highest levels in different neuronal cell types, suggesting both overlapping and potentially unique roles during brain development (5). Neuronal functions for B-type lamins were first seen in Drosophila, which has one A-type lamin and one B-type lamin; mutating the B-type lamin disrupted the developmentally regulated migration of nuclei within photoreceptor cells (6). Mice deficient in lamin B1 die soon after birth with multiple phenotypes including lung and bone defects (7). The new study by Coffinier et al. (4) shows that lamin B2 knockout mice have severe defects in the layering of neurons in the cerebral cortex and cerebellum. This phenotype, known as lissencephaly, is due to defective migration of nuclei within developing lamin B2-deficient mouse neurons. Thus, lamin B2 is a crucial nucleoskeletal component of the nuclear migration machinery in mammals, along with the NE-spanning LINC complexes formed by SUN-domain proteins and Syne/Nesprin proteins (8, 9). Lamin B2 now provides the molecular “platform” needed for researchers to identify the other NE and intranuclear proteins that interact functionally with lamin B2 during nuclear migration, and map new genes relevant to lissencephaly.
The economic significance of the Gulf of Mexico related to population, income, employment, minerals, fisheries and shipping

The Gulf of Mexico is a major economic asset to the 11 states in the United States and Mexico that surround its shores. The potential impact of a post-embargo Cuba (in terms of US involvement), and an historic May 1995 agreement among officials of five US states (Florida, Alabama, Mississippi, Louisiana, and Texas) and six Mexican states (Tamaulipas, Veracruz, Campeche, Tabasco, Yucatan, and Quintana Roo) which called for stronger cooperation to deepen relations for the 50 million inhabitants of the Gulf of Mexico makes recent economic interest of political jurisdictions surrounding the Gulf of Mexico readily apparent. This agreement called for immediate intensification of relations affecting investment, tourism, agriculture, fishing, health and environment, education and culture, infrastructure, communication, financing, trade and development. A number of these issues are geographic in nature, while some are tied not only to geography, but to the use of the body of water which links them. They are water dependent.
Glass as a waste form for the immobilization of plutonium

Several alternatives for disposal of surplus plutonium are being considered. One method is incorporating Pu into glass and in this paper we discuss the development and corrosion behavior of an alkali-tin-silicate glass and update results in testing Pu doped Defense Waste Processing Facility (DWPF) reference glasses. The alkali-tin-silicate glass was engineered to accommodate a high Pu loading and to be durable under conditions likely to accelerate glass reaction. The glass dissolves about 7 wt% Pu together with the neutron absorber Gd, and under test conditions expected to accelerate the glass reaction with water, is resistant to corrosion. The Pu and the Gd are released from the glass at nearly the same rate in static corrosion tests in water, and are not segregated into surface alteration phases when the glass is reacted in water vapor. Similar results for the behavior of Pu and Gd are found for the DWPF reference glasses, although the long-term rate of reaction for the reference glasses is more rapid than for the alkali-tin-silicate glass.
Spatial autocorrelation analysis of small-scale genetic structure in a clonal soft coral with limited larval dispersal

The philopatric larval dispesal and small effective population sizes characteristic of many clonal species should promote the development of significant small-scale genetic structure within populations as a result of isolation-by-distance. We used spatial autocorrelation statistics to detect genetic structure, arising from both clonal reproduction and philopatric dispersal of sexual propagules, for five allozyme loci within populations of the soft coral Alcyonium sp. In a population on Tatoosh Island, Washington, USA, sampled in 1991/1992, we found significant positive spatial autocorrelation at all loci among individuals separated by <40 cm, reflecting the presence of significant smallscale genetic structure due to associations among clonemates. For 4 of 5 loci, however, we detected no significant spatial autocorrelation among the different clones within this population over distances of 1 to 40 m. Analysis of soft-coral populations from six additional, topographically diverse sites in the north-east Pacific also did not reveal significant spatial autocorrelation among clones at any loci. This general lack of spatial autocorrelation of genotypes among clones suggests that significant small-scale genetic structure has not arisen in populations of Alcyonium sp. as a consequence of isolation-by-distance.
17-Beta-estradiol induces transformation and tumorigenesis in human breast epithelial cells

Breast cancer is a malignancy whose dependence on estrogen exposure has long been recognized even though the mechanisms whereby estrogens cause cancer are not clearly understood. This work was performed to determine whether 17beta-estradiol (E2), the predominant circulating ovarian steroid, is carcinogenic in human breast epithelial cells and whether nonreceptor mechanisms are involved in the initiation of breast cancer. For this purpose, the effect of four 24 h alternate periods of 70 nM E2 treatment of the estrogen receptor alpha (ER-alpha) negative MCF-10F cell line on the in vitro expression of neoplastic transformation was evaluated. E2 treatment induced the expression of anchorage-independent growth, loss of ductulogenesis in collagen, invasiveness in Matrigel, and loss of 9p11-13. Only invasive cells that exhibited a 4p15.3-16 deletion were tumorigenic. Tumors were poorly differentiated ER-alpha and progesterone receptor-negative adenocarcinomas that expressed keratins, EMA, and E-cadherin. Tumors and tumor-derived cell lines exhibited loss of chromosome 4, deletions in chromosomes 3p12.3-13, 8p11.1-21, 9p21-qter, and 18q, and gains in 1p, and 5q15-qter. The induction of complete transformation of MCF-10F cells in vitro confirms the carcinogenicity of E2, supporting the concept that this hormone could act as an initiator of breast cancer in women. This model provides a unique system for understanding the genomic changes that intervene for leading normal cells to tumorigenesis and for testing the functional role of specific genomic events taking place during neoplastic transformation.
Fast scanning in AFM using non-raster sampling and time-optimal trajectories

Standard approaches to high-speed AFM rely on moving the tip faster along the raster-scan pattern. Recent work has developed a non-raster scheme for string-like samples such as biopolymers that reduces imaging time by reducing the total number of measurements. This local raster-scan algorithm steers the tip in a sinusoidal path along the sample, acquiring only data near the sample of interest. It has been shown that for a particular class of samples, an order-of-magnitude reduction in imaging time is possible. In this paper we build upon that approach but consider time-lapse imaging. In this scenario, the prior knowledge from previous images can be used to setup a time-optimal control problem between successive crossing points along the string-like sample. Using recent results in time-optimal control, we solve this problem and illustrate that it can, in principle at least, yield at least an additional order of magnitude improvement in the imaging rate.
Function and structure of Drosophila glycans

Through the application of classic organismal genetic strategies, such as mutagenesis and interaction screens, Drosophila melanogaster provides opportunities to understand glycan function. For instance, screens for Drosophila genes that establish dorsal-ventral polarity in the embryo or that influence cellular differentiation through signal modulation have identified putative glycan modifying enzymes. Other genetic and molecular approaches have demonstrated the existence of phylogenetically conserved and novel oligosaccharide processing activities and carbohydrate binding proteins. While the structural characterization of Drosophila oligosaccharide diversity has lagged behind the elucidation of glycan function, landmarks are becoming apparent in the carbohydrate terrain. For instance, O-linked GlcNAc and mucins, spatially and temporally regulated N-linked oligosaccharide expression, glycosphingolipids, heparan sulfate, chondroitin sulfate and polysialic acid have all been described. A major challenge for Drosophila glycobiology is to expand the oligosaccharide structural database while endeavoring to link glycan characterization to functional analysis. The completion of the Drosophila genome sequencing project will yield a broad portfolio of glycosyltransferases, glycan modifying enzymes and lectins requiring characterization. To this end, the great range of genetic tools that allow the controlled spatial and temporal expression of transgenes in Drosophila will permit unprecedented manipulation of glycosylation in a whole organism.
Stabilizing fine sand by adding clay: Laboratory wind tunnel study*

Summary Because of the need to develop inexpensive technology to stabilize highly erodible soils and arrest migrating sand dunes, this research was undertaken. Our objective was to evaluate the effectiveness of adding clay to very sandy soil to reduce wind erosion susceptibility. The study was conducted in a laboratory wind tunnel facility. In the first part of the study, various amounts of bentonite and kaolinite clay were added to a fine sand. The mixtures were wetted with simulated rain, and resulting aggregates were tested for mechanical stability. The aggregates' resistance to crushing increased greatly with increasing clay content. Because the bentonite was several times more effective than kaolinite, bentonite was used in the second part of the study. Trays were filled with various concentrations of bentonite-sand mixtures, wetted with simulated rain, dried, and tested in the wind tunnel with and without abrader at a free stream wind speed of 14 m s -1. Without abrader (wind only), the soil loss increased with clay concentration. With an abrader of sand introduced into ISSN 0933-3630 @1990 by CATENA VERLAG, D-3302 Cremlingen-Destedt, W. Germany 0933-3630/90/5011851/US$ 2.00 + 0.25 the wind tunnel upwind of the test section, cumulative soil loss from the tray with the untreated sample was 20 and 30 times more than that from the trays treated with 10 or 20 g bentonite per kg of sand. Wind erosion susceptibility of sandy soil was reduced greatly by adding small amounts of bentonite clay in this laboratory study.
Quartz Crystal Microbalance as a Sensor to Characterize Macromolecular Assembly Dynamics

The quartz crystal microbalance sensor has a resonant frequency 𝑓 and a quality factor 𝑄 which can be used to probe the properties of nanometer thick film loads. A recent review by Arnau (2008) has discussed many of the considerations necessary to accurately probe for these properties. To avoid needless duplication but to still provide an adequate background for the new user, we briefly outline the basic measurement methodologies and analytical techniques that were covered in the review. Details will be provided on some specific perspectives of the authors. For example, the special precautions necessary when dealing with soft films (polymeric and biological) under liquid are overviewed. To illustrate applications of the QCM technique, simple bilayer and vesicle behaviors are discussed, along with the structural transformation resulting from protein adsorption onto an intact vesicle adlayer. The amphipathic 𝛼-helical (AH) peptide interaction is given as a particular example. Lastly, we summarize a top-down approach to functionalize a surface with a cell membrane and to study its interaction with proteins.
An ephemeral pheromone of female house mice: degradation by oxidation

Abstract At least two pheromones exist in female house mouse urine that elicit 70-kHz ultrasonic mating vocalizations from males: (1) a potent albeit ephemeral pheromone found in freshly voided urine which disappears within 15-18 h and (2) a more persistent, but less potent pheromone that remains for at least 30 days. Three experiments examined whether male responsiveness to the ephemeral pheromone and its loss in aged urine were due to volatility or oxidation. Experiment 1 demonstrated that both sexually experienced and inexperienced males must physically contact fresh urine before vocalizing. Experiment 2 indicated that storing freshly voided urine in an air-tight syringe does not attenuate the loss of the ephemeral pheromone. Experiment 3 demonstrated that the loss of activity of the ephemeral pheromone can be prevented with either β-mercaptoethanol or dithiotreitol. Thus, the ephemeral pheromone is non-volatile and appears to be degraded by oxidation.
Measurements and Interpretations of Sliding Wear Damage in Metals

Research on sliding friction and wear of metals has involved studies of subsurface microstructural deformation. This paper considers the difficulties of measuring deformation and analyzing the implications of such studies on several bases: (1) defining the physical extent of sliding-induced deformation, (2) making appropriate measurements of deformation for complex tribological conditions, and (3) correlating microstructural wear damage with the measurable friction forces on sliding contacts. Data for unlubricated block-on-ring tests of Cu and 1020 steel on 4619 steel are used to demonstrate limitations and correlations possible with metallographic studies in tribology.
Prescribing patterns of physicians

Abstract The widespread use of many new and powerful drugs and the increasing recognition of adverse effects has stimulated interest in the manner in which physicians prescribe drugs. The three main sources of information about the prescribing patterns of physicians are marketing research data, studies of general practice and monitoring of prescribing in hospitals. These sources show that prescribing patterns vary greatly among physicians according to their place and type of practice and the community in which they prescribe. The need for further research into the prescribing practices of physicians is stressed and a possible approach to these studies is outlined. Improved information systems for the monitoring of drug consumption is prerequisite to more detailed investigations into physicians' prescribing patterns.
Systematic review of laryngeal reinnervation techniques

Abstract Objective To systematically review outcomes of reinnervation techniques for the management of unilateral vocal fold paralysis (UVFP). Data Sources Medline and Cochrane databases for English-language studies published between 1966 and 2009 on the surgical management of UVFP. Review Methods Studies were excluded if they reported on bilateral vocal fold paralysis, used nonhuman subjects, or did not assess clinical outcomes. Outcomes of interest were visual analysis, acoustic analysis, perceptual analysis, and electromyography. Results Of 686 initial studies, 14 studies encompassing 329 patients were eligible for analysis. All studies had a case-series design. Of reported patients, 60.2 percent were men, with mean age of 51 years (range, 12-79 years). The most common reinnervation technique was ansa cervicalis-to-recurrent laryngeal nerve (RLN), which was most commonly performed after thyroidectomy (43.5%). Other techniques with reportable outcomes included primary RLN anastomosis, ansa-to-RLN combined with cricothyroid muscle-nerve-muscle pedicle, ansa-to-thyroarytenoid neural implantation, ansa-to-thyroarytenoid neuromuscular pedicle, and hypoglossal-to-RLN. Median postsurgical follow-up was 12 months, and mean time to first signs of reinnervation was 4.5 months (SD 2.9 months). Visual analysis of glottic gap showed the greatest mean improvement with ansa-to-RLN, from 2.25 (SD 0.886) to 0.75 (SD 0.886) mm ( P P Conclusion Reinnervation is effective in the management of UVFP, although the specific method may be dictated by anatomical limitations. Prospective studies utilizing uniform and consistent outcome parameters are necessary.
Implicit Shape Kernel for Discriminative Learning of the Hough Transform Detector

The Hough transform provides an efficient way to detect objects. Various methods have been proposed to achieve discriminative learning of the Hough transform, but they have usually focused on learning discriminative weights to the local features, which reflect whether the features are matched on the object or the background. In this paper, we propose a novel approach to put the whole Hough transform into a maximum margin framework, including both the weights for the local features and their locations. This is achieved through the kernel methods of the SVM. We propose a kernel that can be used to learn a SVM classifier that determines the presence of the object in a subimage. The kernel is designed such that during testing, the standard Hough transform process can be used to obtain the exact decision scores of the SVM at every location and scale of a test image. The experiment results show that our approach significantly improves the detection performance over previous methods of learning the Hough transform.
Feature-scale simulation of resist-patterned electrodeposition

A numerical simulation of resist-patterned or "through-mask" electroplating has been performed to investigate shape evolution at the scale of small lithographic features. Shape evolution and step coverage have a significant influence on the shapes of such microelectronic structures as conductor lines, vias, and magnetic pole pieces. The simulation and associated analysis are based on a model for the rate distribution of the electrodeposition reaction that includes the depletion of the depositing metal ions and the inhibiting action of leveling agents. A stagnant boundary layer is assumed to be present, and the diffusion theory of leveling with a one-parameter description of kinetic inhibition is employed. The results show that when the geometry of a feature cavity makes possible the occurrence of concentration-field effects (such as radial diffusion), an uneven metal-ion flux should cause nonuniform growth at high fractions of the limiting current, and leveling agents should exert an opposing effect, even causing a strong reverse nonuniformity in some cases.
Green-nano approach to nanostructured polypyrrole

Bulk quantities of polypyrrole nanofibers and nanospheres can be synthesized with a facile, one-step “green-nano” chemical oxidative polymerization approach, by simply using different reaction media.
Exercise, blood lactate and food intake.

Erhohte Lactatmengen im Plasma konnen wahrend korperlicher Anstrengung die Freisetzung eines Stoffes verursachen, welcher, ahnlich wie Insulin, im mittleren Hypothalamus wirkt. Dieser Stoff konnte auch an der Auslosung der Hypophagie, welche nach korperlicher Anstrengung auftritt, beteiligt sein.
ON ASYMPTOTIC STABILITY OF GROUND STATES OF NLS

We prove in dimension n = 3 an asymptotic stability result for ground states of the Nonlinear Schrodinger Equation which contain one internal mode.
Rotational Levels of Shallow Acceptor States: The Undulation Spectra of N in GaP

We report the first direct evidence of rotational levels of vibronic states in solids. These levels are associated with the ground states of shallow acceptors and provide the basis of a detailed understanding of the fine structure or "undulations" in emission spectra derived from bound excitons in GaP. This explanation is contrasted with one proposed recently by Hopfield, Kukimoto, and Dean.
Biological and Behavioral Correlates of Quiet Sleep Respiration Rates in Infants

Abstract MONTGOMERY-DOWNS, H. AND E. B. THOMAN. Biological and behavioral correlates of quiet sleep respiration rates in infants. PHYSIOL BEHAV 64 (5) 637–643, 1998.—The sleep and respiration of 88 infants were recorded for 24-h periods on the first 2 postnatal days and again at 6 months. The recordings were made with the Motility Monitoring System, which does not require instrumentation of the infants. Quiet sleep respiration rates (QSRR) increased over the first 2 days (mean = 42.2, SD = 1.0 and mean = 44.5, SD = 1.1, respectively), then decreased by 6 months (mean = 25.3, SD = 0.5); females showed lower QSRR on the first 2 days; infants delivered vaginally showed lower QSRR at 6 months; by 6 months QSRR was significantly higher during the day than at night; and significant individual differences across age and from day to nighttime were found at each age. Delivery mode, maternal age and education, and mental scores at 6 and 12 months were negatively related to QSRR at 6 months. Taken together, these data suggest a developmental advantage of slower QSRR and evidence for the role of the higher central nervous centers in the regulation of QSRR.
A Study of the Forces on an Oscillating Cylinder

Flow over a cylindrical structure is a problem of interest in different engineering fields, especially offshore structures like risers and spars, which are constantly subject to sea waves. In this study, numerical simulation of the flow over a fixed cylinder at a low Reynolds number was carried out using the Reynolds-averaged Navier-Stokes model. It is well known theoretically and experimentally that the lift is self excited and has a frequency equal to the vortex shedding frequency. Then the cylinder was forced to oscillate in the cross-stream direction with different frequencies and amplitudes. The flow structure, including the lift and drag, was examined within the so-called lock-in frequency range, where the lift frequency is entrained by the cylinder frequency. The frequency-response curves for the lift and drag and the phase between the hydrodynamic force and the cylinder were produced for different motion amplitudes. These curves change significantly as either the motion amplitude or frequency is varied. Two modes of response were identified associated with high lift and low lift; each one has different characteristics.Copyright © 2007 by ASME
Direct Observation of Tribochemically Assisted Wear on Diamond-Like Carbon Thin Films

Friction represents a major energy wastage, with typical estimates in the range of 2–5 % of the GDP of developed countries; 15 % of the energy losses in a new automobile engine are due to friction (Uchida et al. J. Cryst. Growth 114:565–568, 1991). While the macroscopic laws of friction have been known for centuries, the exact nanoscale processes taking place are less clear. It is established that friction involves small asperities sliding on a locally flat surface, but the exact mechanisms of slip as well as energy dissipation are still unclear and sometimes controversial. In many ways even less is known about chemical reactions occurring during sliding, what is called tribochemistry. We report here direct in situ observation at the nanoscale of tribochemically assisted wear for a tungsten tip sliding on diamond-like carbon films in wet hydrogen, nitrogen and compare these to similar experiments in vacuum. Differences in the wear directly indicate passivation of the films in hydrogen and accelerated wear in wet nitrogen. The results are surprisingly similar to what one would expect at the macroscale, indicating that in many respects there is little difference between the processes taking place across many length scales.
Primary aldosteronism due to bilateral nodular hyperplasia: CT demonstration.

Abstract Often the CT appearance of adrenal hyperplasia is indistinguishable from the normal appearing gland. We report a case of a 53-year-old man with focal adrenal hyperplasia demonstrated by CT. The CT examination is indistinguishable from bilateral adrenal adenomas.
Use of standardized source sets for enhanced EMI classification of buried heterogeneous objects

Most unexploded ordinance (UXO) are heterogeneous objects containing parts of different metals, e.g., head, body, tail and fins, copper banding, etc. Recently, low frequency electromagnetic induction (EMI) sensing, based on the EM diffusion phenomena, has shown considerable progress for the detection and discrimination of UXO. EMI responses are sensitive to the type of metal (conductivity and permeability), to the distance between the sensor and scatterer, and to the coupling effects between different parts of the object. Until now, the simple dipole models used to represent EMI response have neglected the coupling and close proximity effects seen for realistic objects. These factors can interact with the particulars of excitation and observation to produce substantially varied signature patterns for a given object. This means that a key requirement in discrimination/inversion processing is to calculate very fast but very realistic EMI responses for actual target types. This work presents a new discrimination technique based on the standardized excitation approximation (SEA). The SEA seeks to identify objects in terms of their characteristic responses to sets of well defined excitations that can be used to describe any primary (excitation) field. In the new SEA system presented here, the standardized excitations are those produced by a standardized source set (SSS), in particular, fictitious magnetic sources distributed mathematically over a surface surrounding a scatterer. Several numerical results are given to illustrate the efficiency and accuracy of the proposed new technique. Finally, the spatial distribution and frequency dependence of responding equivalent sources are analyzed to demonstrate the usefulness of SSS for target discrimination.
Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus

Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus. Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expression of 24 osteoarthritis-related and 4 obesity-related genes in meniscus was assessed by quantitative real-time PCR. The relationship between gene expression and patient age and BMI was analyzed using Spearman’s rank–order correlation. Hierarchical cluster dendrogram and heat map were generated to study inter-gene associations. Age was negatively correlated (P<0.05) with the expression of MMP-1 (r=−0.447), NFκB2 (r=−0.361), NFκBIA (r=−0.312), IκBA (r=−0.308), IL-8 (r=−0.305), ADAMTS-4 (r=−0.294), APLN (apelin) (r=−0.250) and IL-6 (r=−0.244). Similarly, BMI was negatively correlated with the expression of APLN (r=−0.328), ACAN (r=−0.268) and MMP-1 (r=−0.261). After adjusting for the correlation between age and BMI (r=0.310; P=0.008), the only independent effect of BMI on gene expression was for APLN (r=−0.272). However, age had an independent effect on the expression on ADAMTS-4 (r=−0.253), MMP-1 (r=−0.399), IL-8 (r=−0.327), COL1A1 (r=−0.287), NFκBIA (r=−0.278), NFκB2 (r=−0.312) and IκBA (r=−0.299). The gene correlation analysis identified four clusters of potentially relevant genes: transcription factors, matrix-degrading enzymes, cytokines and chemokines, and obesity genes. Age and BMI were negatively correlated with several osteoarthritis- and obesity-related genes. Although the bulk of these changes appeared to be driven by age, expression of APLN was related to BMI. Inter-gene correlation analysis implicated a common role for strongly correlated genes. Although age-related variations in gene expression appear to be more relevant than obesity-related differences for the role of the meniscus in osteoarthritis development, further investigation into the role of APLN in meniscus and joint health is warranted.
A single-stage polymerase-based protocol for the introduction of deletions and insertions without subcloning.

A single-stage polymerase-based procedure is described that allows extensive modifications of DNA. The version described here uses the QuikChange Site-Directed Mutagenesis System kit supplied by Stratagene. The original protocol is replaced by a single-stage method in which linear production of complementary strands is accomplished in separate single primer reactions. This has proved effective in introducting insertions and deletions into large gene/vector combinations without subcloning.
Tunable nonviral gene delivery nanoparticles optimized for in vitro transfection of hepatocytes and hepatoma cells

Purpose To demonstrate effective gene delivery to hepatocytes and selectivity toward hepatoma cells using high throughput screening of a library of biodegradable, non-toxic poly(beta-amino ester) (PBAE) nanoparticle (NP) delivery vehicles. Materials and Methods PBAEs were synthesized per established protocols. eGFP reporter DNA was used for in vitro transfection of rat hepatoma cells (MCA-RH7777) and hepatocytes (BRL-3A). NPs were formed by mixing DNA and PBAEs at varying ratios. Cells were cultured separately or in co-culture for high-throughput screening. For co-cultures, hepatoma cells were stably transfected with H2B-Cherry. Transfection efficacy was measured by microscopy and flow cytometry. H2B-Cherry signal was used to distinguish hepatoma from hepatocytes. eGFP expression is reported as percent of total cells that are GFP+ and average GFP intensity per cell. Positive controls for in vitro transfection included commercially available cationic lipids and polyethyleneimine. Reported results are mean±SEM. Results Hepatoma cells were transfected up to 98±0.4% efficacy with no non-specific cytotoxicity. Hepatocytes were transfected with as high as 73±0.4% efficacy with 10±4% non-specific toxicity. In contrast, all positive controls caused 30% to >80% toxicity in BRL-3As. Of the NPs tested, most showed significant specificity for hepatoma cells over hepatocytes when cultured separately (12 of 21 formulations with p Conclusion PBAE-NPs provide a tunable strategy for efficient, non-toxic gene delivery to either hepatocytes or hepatoma cells, with significant selectivity for the latter.
Determination of iron and copper in seawater at pH 1.7 with a new commercially available chelating resin, NTA Superflow

The use of a commercially available chelating resin with NTA-type functional groups for concentration of trace metals from seawater is described. Trace metal recoveries from this NTA Superflow chelating resin are pH dependent. At a pH of ≤2 only iron(III) and copper are quantitatively recovered from the resin. Iron(II) cannot be quantitatively recovered from this resin below a pH of 5. However, oxidation of acidified seawater samples (pH 1.7) with H2O2 prior to loading onto the resin has been demonstrated to allow quantitative recovery of total dissolved iron. Deferrioxamine and Rhodoturlic Acid, two commercially available siderophores were used to investigate the effect of strong Fe(III)-binding organic ligands on the ability to retain iron at different pH values. Acidification of seawater samples to pH 1.7 dissociates the iron complexed to these organic ligands, thereby allowing total dissolved iron and copper to be determined. Acidified samples from Monterey Bay were analyzed by a flow injection method coupled to ICP-SFMS detection using the NTA Superflow resin in the pre-concentration step. Results from this study show that when seawater samples are stored acidified (pH 1.7) over time, a portion of iron(III) is reduced to iron(II), thus necessitating the use of H2O2 to reoxidize the Fe(II) to Fe(III) prior to analysis. Total dissolved concentrations of iron and copper can be directly obtained on seawater samples at pH 1.7 with this method, eliminating the need to buffer the sample to a higher pH prior to column loading. This resin has the potential to be used in shipboard or in situ flow injection methods.
A statistical simulation model for mobile radio fading channels

Recently, a Clarke's model-based simulator was proposed for Rayleigh fading channels. However, that model, as shown in this paper, may encounter statistic deficiency. Therefore, an improved model is presented to remove the statistic deficiency. Furthermore, a new simulation model is proposed for Rician fading channels. This Rician fading simulator with finite number of sinusoids plus a zero-mean stochastic sinusoid as the specular (line-of-sight) component is different from all the existing Rician fading simulators, which have non-zero mean deterministic specular component. The statistical properties of the proposed Rayleigh and Rician fading channel models are analyzed in detail, which shows that these statistics either exactly match or quickly converge to the theoretically desired ones. Additionally and importantly, the probability density function of the Rician fading phase is not only independent from time but also uniformly distributed, which is fundamentally different from that of all the existing Rician fading models. The statistical properties of the new simulators are evaluated by numerical results, finding good agreement in all cases.
Casting Bread Upon the Water: Comments on Technology, Globalization, and Agriculture

The issues raised in this paper session-concerning technical change. globalization, and chronic low returns in agriculture-are of long-standing importance in our profession. The papers, like many policy discussions in our discipline, have focussed largely on the U.S. agricultural sector. In this comment I will make some remarks relative to the domestic situation, but would also like to branch out a bit to address the worldwide impact of changing technology and increasingly open markets. The "Farm Problem" in the United States From the 1930s through the 1960s, the "farm problem" was recognized as being that of constant excess capacity caused by technical change, a situation known to agricultural economists as Willard Cochrane's famous "treadmill." In the 1970s, swings in international demand introduced a new problem, increased price risk caused by a shifting demand curve. Many people attending this conference or reading this paper may be too young to have a clear recollection of the agricultural situation in the early 1970s. From the summer of 1972 to the fall of 1974, the average price of corn tripled and the price of wheat increased fourfold (Destler). Net farm income soared and acreage expanded, to the apocryphal "fence row to fence row" level. U.S. consumers, of course, were upset by the rising food prices,
Assortment Planning for Vertically Differentiated Products

We consider the problem of a retailer managing a category of vertically differentiated products. The retailer has to pay a fixed cost for each product included in the assortment and a variable cost per product sold. Quality levels, fixed, and variable costs are exogenously determined. Customers differ in their valuation of quality and choose the product (if any) that maximizes their utility. First, we consider a setting in which the selling prices are also fixed. We find that the optimal set of products to offer depends on the distribution of customer valuations and might include dominated products, that is, products which are less attractive than at least one other product, on every possible dimension. We develop an efficient algorithm to identify an optimal assortment. Second, we consider a setting in which the retailer also determines the selling prices. We show that in this case the optimal assortment does not include any dominated product and does not vary with the distribution of customer valuations when there is no fixed cost. We develop several efficient algorithms to identify an optimal assortment and optimally price the products. We also test the applicability of our methods with realistic data for two product categories.
Prednisolone Bioavailability in the Dog

With a fasted dog as an animal model, the bioavailability and pharmacokinetics of prednisolone were studied following rapid intravenous injection and oral dosing of a prednisolone sodium phosphate solution and also following oral doses of prednisolone as tablets and a slurry. Hydrolysis of the phosphate ester to prednisolone in the body is extremely rapid and complete, thus permitting accurate calculation of the distribution volume of prednisolone. Enteral absorption of prednisolone from a slurry is superior to that from prednisolone tablets and from a prednisolone sodium phosphate solution. Reduced absorption from tablets, compared to the slurry, is probably due to tablet disintegration characteristics; reduced absorption from the solution is probably due to poor membrane permeability of the ionized drug. Information obtained from a single animal may indicate the need for expanded studies in humans.
Lighting up the senses: FM1-43 loading of sensory cells through nonselective ion channels

We describe a novel mechanism for vital fluorescent dye entry into sensory cells and neurons: permeation through ion channels. In addition to the slow conventional uptake of styryl dyes by endocytosis, small styryl dyes such as FM1-43 rapidly and specifically label hair cells in the inner ear by entering through open mechanotransduction channels. This labeling can be blocked by pharmacological or mechanical closing of the channels. This phenomenon is not limited to hair cell transduction channels, because human embryonic kidney 293T cells expressing the vanilloid receptor (TRPV1) or a purinergic receptor (P2X2) rapidly take up FM1-43 when those receptor channels are opened and not when they are pharmacologically blocked. This channel permeation mechanism can also be used to label many sensory cell types in vivo. A single subcutaneous injection of FM1-43 (3 mg/kg body weight) in mice brightly labels hair cells, Merkel cells, muscle spindles, taste buds, enteric neurons, and primary sensory neurons within the cranial and dorsal root ganglia, persisting for several weeks. The pattern of labeling is specific; nonsensory cells and neurons remain unlabeled. The labeling of the sensory neurons requires dye entry through the sensory terminal, consistent with permeation through the sensory channels. This suggests that organic cationic dyes are able to pass through a number of different sensory channels. The bright and specific labeling with styryl dyes provides a novel way to study sensory cells and neurons in vivo and in vitro, and it offers new opportunities for visually assaying sensory channel function.
Revision of Fisher's Analysis of Mendel's Garden Pea Experiments

R. A. Fisher ([1936][1]) made the assertion that the data in Mendel's experiments with garden peas ([Mendel 1866][2]) were too close to expectation. One of the most striking examples seemed to be the six experiments with plant characters designed to test the theoretical 2:1 ratio of heterozygotes (
Sequence diversity and haplotype associations with phenotypic responses to crowding: GIGANTEA affects fruit set in Arabidopsis thaliana.

Identifying the molecular genetic basis of intraspecific variation in quantitative traits promises to provide novel insight into their evolutionary history as well as genetic mechanisms of adaptation. In an attempt to identify genes responsible for natural variation in competitive responses in Arabidopsis thaliana, we examined DNA sequence diversity at seven loci previously identified as members of the phytochrome B signalling network. For one gene, GIGANTEA (GI), we detected significant haplotype structure. To test for GI haplogroup–phenotype associations, we genotyped 161 A. thaliana accessions at GI and censused the same accessions for total fruit set and the expression of three phenotypic traits (days to flowering, petiole length, and inflorescence height) in a greenhouse experiment where plants were grown in crowded and uncrowded environments. We detected a significant association between GI and total fruit set that resulted in a 14% difference in average fruit set among GI haplogroups. Given that fruit set is an important component of fitness in this species and given the magnitude of the effect, the question arises as to how variation at this locus is maintained. Our observation of frequent and significant epistasis between GI and background single nucleotide polymorphisms (SNP), where the fitness ranking of the GI allele either reverses or does not differ depending on the allele at the interacting SNP, suggests that epistatic selection may actively maintain or at least slow the loss of variation at GI. This result is particularly noteworthy in the light of the ongoing debate regarding the genetic underpinnings of phenotypic evolution and recent observations that epistasis for phenotypic traits and components of fitness is common in A. thaliana.
Dorsal Premotor Neurons Encode the Relative Position of the Hand, Eye, and Goal during Reach Planning

When reaching to grasp an object, we often move our arm and orient our gaze together. How are these movements coordinated? To investigate this question, we studied neuronal activity in the dorsal premotor area (PMd) and the medial intraparietal area (area MIP) of two monkeys while systematically varying the starting position of the hand and eye during reaching. PMd neurons encoded the relative position of the target, hand, and eye. MIP neurons encoded target location with respect to the eye only. These results indicate that whereas MIP encodes target locations in an eye-centered reference frame, PMd uses a relative position code that specifies the differences in locations between all three variables. Such a relative position code may play an important role in coordinating hand and eye movements by computing their relative position.
Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery

The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). A cassette encoding siRNA targeted to a 3' untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.
Lineage-Specific Telomere Shortening and Unaltered Capacity for Telomerase Expression in Human T and B Lymphocytes with Age

Age effects on telomere length and telomerase expression in peripheral blood lymphocytes were analyzed from 121 normal individuals age newborn to 94 years and revealed several new findings. 1) Telomere shortening was observed in CD4+ and CD8+ T and B cells with age. However, the rate of telomere loss was significantly different in these populations, 35 +/- 8, 26 +/- 7, and 19 +/- 7 bp/year for CD4+ and CD8+ T and B cells, respectively. In addition, CD4+ T cells had the longest average telomeres at all ages, followed by B cells, with CD8+ T cell telomeres the shortest, suggesting that these lymphocyte populations may have different replicative histories in vivo. 2) Telomerase activity in freshly isolated T and B cells was indistinguishably low to undetectable at all ages but was markedly increased after Ag and costimulatory receptors mediated stimulation in vitro. Furthermore, age did not alter the magnitude of telomerase activity induced after stimulation of T or B lymphocytes through Ag and costimulatory receptors or in response to PMA plus ionomycin treatment. 3) The levels of telomerase activity induced by in vitro stimulation varied among individual donors but were highly correlated with the outcome of telomere length change in CD4+ T cells after Ag receptor-mediated activation. Together, these results indicate that rates of age-associated loss of telomere length in vivo in peripheral blood lymphocytes is specific to T and B cell subsets and that age does not significantly alter the capacity for telomerase induction in lymphocytes.
Monolithic dual-quantum-well 10 Gb/s Mach-Zehnder transmitter

A 10 Gb/s transmitter composed of a sampled-grating DBR (SGDBR) laser and Mach-Zehnder modulator was fabricated on a dual-quantum-well integration platform. The device exhibited error free operation and negative chirp
Colorectal cancer survival advantage in MUTYH-associated polyposis and Lynch syndrome families.

The cardinal features of colorectal cancer in patients with the MUTYH-associated polyposis syndrome, featured in this editorial, are of very recent discovery and remain under review as new clinical phenotypes for these patients are still being identified. Importantly, its phenotype results from homozygosity of the MUTYH gene and, therefore, is inherited in an autosomal recessive pattern. In a more intensively studied hereditary colorectal cancer syndrome, namely Lynch syndrome, the cardinal features have been shown to result from an autosomal dominantly inherited pattern and includes earlier average age of cancer onset, when compared with the general population (45 years for Lynch syndrome colorectal cancer and 64 years for patients with colorectal cancer in the general population), accelerated carcinogenesis, high risk for metachronous colorectal cancers, specific pathology features for Lynch syndrome colorectal cancers that are more often poorly differentiated and have an excess of Colorectal Cancer Survival Advantage in MUTYH-Associated Polyposis and Lynch Syndrome Families