cssi/SciSciGPT-SciSciNet huggingface dataset:
Double-smoothing for bias reduction in local linear regression

Abstract Local linear regression involves fitting a straight line segment over a small region whose midpoint is the target point x, and the local linear estimate at x is the estimated intercept of that straight line segment, with an asymptotic bias of order h 2 and variance of order ( nh ) - 1 (h is the bandwidth). In this paper, we propose a new estimator, the double-smoothing local linear estimator, which is constructed by integrally combining all fitted values at x of local lines in its neighborhood with another round of smoothing. The proposed estimator attempts to make use of all information obtained from fitting local lines. Without changing the order of variance, the new estimator can reduce the bias to an order of h 4 . The proposed estimator has better performance than local linear regression in situations with considerable bias effects; it also has less variability and more easily overcomes the sparse data problem than local cubic regression. At boundary points, the proposed estimator is comparable to local linear regression. Simulation studies are conducted and an ethanol example is used to compare the new approach with other competitive methods.
Transport near a vertical ice surface melting in saline water: experiments at low salinities

Time-exposure photographs of the buoyancy-driven flow adjacent to a submerged vertical ice surface melting in 10‰ saline water are presented for ambient water temperatures between 1 and 15°C. For ambient temperatures greater than 1·9°C, the thermal and saline components of the buoyancy force are at least partially opposed to each other. Since most past studies of ice melting in saline water have concentrated on oceanic salinities, little is known about the complicated flow behaviour which results from these opposed buoyancy effects at ambient water salinities between fresh water and oceanic salinities (35‰). The results presented here provide new insight concerning the subtle mechanisms which arise in such flows. Photographs of the entire flow field document the many different and complicated flow configurations that arise. At 10‰, as the ambient temperature is increased from 1 to 15°C, regimes of upward, bi-directional and split flow are observed. In the latter circumstance, the flow is laminar and bi-directional over part of the ice surface and turbulent over the rest of the surface. Bi-directional flow results from reversal of part of the upward wake above the top of the ice surface. Split flow appears to be a consequence of the transition to turbulence of either the inner or outer portion of the laminar bi-directional flow. Measured velocity profiles, surface heat-transfer rates and interface temperatures agree well with the analytical results reported in a previous study for conditions that result in conventional boundary-layer flow. These experimental results, together with those of previous studies, indicate the approximate extent of the different flow regimes that arise for a vertical ice surface melting in cold, low-salinity water.
Nonequilibrium inhomogeneous processes. An alternative mesoscopic description

Abstract It is demonstrated that there is an inconsistency between the master equation and its associated Fokker—Planck equation for the inhomogeneous process whose transition rates depend on the state variable. This inconsistency results from an unjustified assumption adopted since Planck in 1917. An alternative to the Planck's assumption leads to the development of the first general mesoscopic framework applicable to any nonequilibrium Markov process that can be inhomogeneous and with any transition length. It is shown that even under the limit of small transition lengths, none of the previous relevant suggestions is appropriate.
Tetraphyllin B and epitetraphyillin B sulphates: Novel cyanogenic glucosides from Passiflora caerulea and P. alato-caerulea

Abstract An epimeric mixture of tetraphyllin B-4-sulphate and epitetraphyllin B-4-sulphate was isolated from Passiflora caerulea and P. alato-caerulea .
EZH2 Codon 641 Mutations are Common in BCL2- Rearranged Germinal Center B Cell Lymphomas

Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic “hit” in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways.
A Stroke of Language

The author reflects on foreign-language learning by his EFL students as well as his own foreign-language learning. He concludes by musing on the possible and fantastical devastation on language-ability wrought by strokes.
Pilot‐Plant Scale Preparation of Human Serum Albumin

. Pilot-plant scale experiments using production scale fractionation equipment have been carried out to prepare human serum albumin according to a two-step simple method reported previously. Results have indicated that scale-up is feasible and the resultant albumin is of at least the same quality but with better yield when compared to that obtained by the conventional ethanol fractionation method. Filtration to replace centrifugation in one of the steps for liquid-solid separation was also attempted. It proved to be superior to centrifugation in terms of time and labor savings, but a small percentage of albumin was not recoverable. However, because of the simplicity and higher yield of this fractionation method the final albumin yield is still higher than that obtained by the conventional ethanol method even if the filtration step is introduced. Diafiltration and ultrafiltration are used for solvent removal and concentration, instead of lyophilization and reconstitution to prepare the final albumin solutions.
The “second” inaugural address of Lyndon Baines Johnson: A definitive text

(1967). The “second” inaugural address of Lyndon Baines Johnson: A definitive text. Speech Monographs: Vol. 34, No. 1, pp. 102-108.
High finesse integrated Brillouin-active fiber ring and loop mirror

Nonlinear fiber optics, in the form of stimulated Brillouin scattering (SBS), has now emerged as the essential means for the construction of active optical devices used for all-optic in-line switching, channel selection, amplification, oscillation in optical communications, optical logic elements in optical computation and sensing, and a host of other applications. This paper attempts to present a survey and some of our own research findings on the nature of stimulated Brillouin scattering in single mode optical fibers and its device applications. In theory, the backscattering nature of the phenomenon enables its application as channel selectors and switches and filters in optical transmission and communications. We have been engaged in the design and implementation of fiber configurations, such as rings and loop mirrors, with the purpose of lowering the threshold. We report on experimental schemes involving Brillouin ring with amplifier-in-the ring, and Brillouin-NALMs (nonlinear amplifying loop mirrors). These successful devices are being studied for application as optical logic and neuron elements, Brillouin-NALMs for optical switching, and highly versatile sensors.
Direct hepatic tumor injection in rats: Can it be used for analysis of MR imaging contrast agents?

With a recently described rat model technique for direct hepatic injection of tumor cells for imaging research, there were concerns that the injection itself might produce lesions detectable with magnetic resonance (MR) imaging, thereby producing false-positive results. To examine this possibility, the authors prospectively studied 14 Sprague-Dawley rats after direct hepatic injection of cells from a rat hepatoma cell line. The rats were imaged with a variety of pulse sequences before and after intravenous injection of the contrast agent manganese dipyridoxal diphosphate at a dose of 8 mumol/kg. No intrahepatic lesions could be detected with MR imaging during the first 6 days after direct hepatic injection of the tumor cells. Therefore, the direct injection technique should be accurate for evaluating various MR imaging sequences and contrast agents for early hepatic tumor detection.
Thapsigargin Selectively Rescues the Trafficking Defective LQT2 Channels G601S and F805C

Abstract Several mutations in the human ether-a-go-go-related K+ channel gene (HERG or KCNH2) cause long QT syndrome (LQT2) by reducing the intracellular transport (trafficking) of the channel protein to the cell surface. Drugs that bind to and block HERG channels (i.e. E4031) rescue the surface expression of some trafficking defective LQT2 mutations. Because these drugs potently block HERG current, their ability to correct congenital LQT is confounded by their risk of causing acquired LQT. We tested the hypothesis that pharmacological rescue can occur without HERG channel block. Thapsigargin (1 μm), a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor, rescued the surface expression of G601S, and it did so without blocking current. Thapsigargin-induced rescue and E4031-induced rescue caused complex glycosylation that was evident within 3 h of drug exposure. Disruption of the Golgi apparatus with brefeldin A prevented thapsigargin- and E4031-induced rescue of IG01S. Confocal imaging showed that G601S protein is predominantly “trapped” intracellularly and that both thapsigargin and E4031 promote its relocation to the surface membrane. We also studied two other trafficking defective LQT2 mutations. Thapsigargin rescued the C terminus mutation F805C but not N470D, whereas E4031 rescued N470D but not F805C. Other sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitors did not rescue G601S or F805C. This study 1) supports the hypothesis that the LQT2 trafficking defective phenotype can be reversed without blocking the channel; 2) demonstrates pharmacological rescue of a C terminus LQT2 mutation; and 3) shows that thapsigargin can correct trafficking defective phenotypes in more than one channel type and disease (i.e. LQT2 and cystic fibrosis).
Effects of opioid peptides and opiate alkaloids on insulin secretion in the rabbit.

In pentobarbital-anesthetized rabbits, iv injection of 9 nmol (31 μg) human β-endorphin (βh-endorphin)/kg BW caused a significant (P < 0.05) increase in serum glucose and a significant decline in serum insulin during the subsequent 60 min. When 9 nmol/kg BW βh-endorphin were injected simultaneously with 0.7 g glucose/kg BW, the clearance of serum glucose and the expected glucose-stimulated rise in serum insulin were both inhibited. The threshold dose for the insulinopenic effect of βh-endorphin in the anesthetized, glucose-loaded rabbit was 0.09 nmol/ kg BW. Threshold doses/kg BW were determined for six structurally related peptides found to possess insulinopenic activity: camel β-endorphin, 0.09 nmol; N-arg-βh-endorphin, 0.09 nmol; D-ala2-βh-endorphin, 0.09 nmol; leu5-βh-endorphin, 0.09 nmol; met-(O)5-βh-endorphin, 0.9 nmol; and βh-endorphin1-27,0.9 nmol. Threshold dose/kg BW for somatostatin was 9 nmol. The following compounds were inactive at 9 nmol/kg BW: N-acetyβh- endorphin; Nlacetyl-arg-(βh-endorph...
Antiviral therapy for influenza virus infections.

Abstract Every year, influenza viruses cause global epidemics that result in significant morbidity and mortality. Influenza infections can be serious in children, especially infants and toddlers. Four antiviral agents, amantadine, rimantadine, oseltamivir, and zanamivir, are available for the treatment or prophylaxis of influenza. Experience with the use of these antiviral drugs for influenza in children is limited. Given the small degree of therapeutic gain that is reported from clinical trials, considerations about cost effectiveness are important in deciding whether to use these agents in the treatment of suspected or proven influenza infections in healthy children. Copyright 2002, Elsevier Science (USA). All rights reserved.
SERIAL OPTICAL CONHERENCE TOMOGRAPHY FINDINGS FROM 6 TO 12 MONTHS AFTER IMPLANTATION OF ZILVER PTX STENTS FOR THE FEMOROPOPLITEAL LESIONS

Zilver PTX have shown to favorable outcomes. However, vascular response after Zilver PTX implantation remains unclear. Serial optical conherence tomography (OCT) was performed in 3 patients with 8 Zilver PTX for femoropopliteal lesions at 6 and 12 months follow-up. We analyzed neointimal thickness
Klinefelter's syndrome: report of a case studied by fluorohydrocortisone suppression of adrenal function.

KLINEFELTER'S syndrome now includes, according to the broadened concept of Heller and Nelson (1), all patients with azoospermia, small atrophic testes, clumped Leydig cells, hyalinized tubules, and increased urinary gonadotropins. The pathologic process involving the testes may be progressive, existing in different degrees at different times in a given individual. In addition to the originally described normally or subnormally virilized males (2), there is recognized a group of patients with varying degrees of eunuchoidism thought to depend on the age of the subject at onset of the disease. Gynecomastia and other physical abnormalities are variably present. In previous studies, a tendency to low 17-ketosteroid excretion has been observed, particularly in the more eunuchoid patients. The following case is presented because the data suggest that a substantial portion of this eunuchoid patient's 17-ketosteroid excretion was of gonadal origin. It is also of interest that urinary corticoid excretion was elevat...
Cobalt(II)-Catalyzed Intermolecular Benzylic C−H Amination with 2,2,2-Trichloroethoxycarbonyl Azide (TrocN3)

2,2,2-Trichloroethoxycarbonyl azide (TrocN3) is an effective nitrene source for cobalt(II)-catalyzed intermolecular nitrene insertion of C−H bonds. Among different metalloporphyrins studied, Co(II)(TPP) was shown to be a competent catalyst for the selective amination of various benzylic C−H bonds under mild conditions without the need of other reagents or additives, forming the desired Troc-protected amines in moderate to high yields with nitrogen gas as the only byproduct.
Advancing Stages of Group Development Theory: The Case of Institutionalized Older Persons

ABSTRACT Using content analysis to analyze process recordings, the developmental patterns of two groups of older institutionalized persons are presented. The similarities to and differences from the stages of group development described by Bennis and Shepard; Garland, Jones, and Kolodny; and Schiller are discussed. Findings suggest that vulnerability to institutional power and the resultant dependence on the social worker were critical variables influencing how the groups developed over time. Differential principles for applying stages of group development theory to practice are offered.
Variational Methods in Nuclear Collision Problems

Variational methods, similar to the Rayleigh-Ritz method for bound state calculations, are developed for the phase shifts and elements of the scattering matrix in nuclear collisions. Numerical applications to neutron-proton and neutron-deuteron scattering involving trial functions with undetermined coefficients are described. Another variational principle, for scattering amplitudes, is shown to lead to the Born approximations and a formula recently derived by Schwinger. It may also be used in conjunction with the method of undetermined coefficients.
The Validity of the Student Academic Support Scale: Associations with Social Support and Relational Closeness

This study validates the Student Academic Support Scale (SASS), a 15-item multidimensional measure assessing informational, esteem, motivational, and venting support. Confirmatory factor analysis (CFA) revealed good model fit and replicated prior CFA tests (Mazer & Thompson, 2011; Thompson & Mazer, 2009). Correlations between student academic support and traditional social support measures provided convergent validity evidence. A positive association between student academic support and relational closeness suggests that the SASS construct is related to other theoretically similar constructs, providing evidence for construct validity. Discriminant validity evidence was established, suggesting that the SASS is distinct from measures of traditional social support.
N6-(Δ2-isopentenyl)adenosine: Biosynthesis in vitro in transfer RNA by an enzyme purified from escherichia coli

Abstract An enzyme has been partially purified from E. coli which catalyzes in vitro the transfer of the Δ2-isopentenyl group from Δ2-isopentenyl- pyrophosphate to an adenosine residue in Mycoplasma sP. (Kid) tRNA. The product of the reaction has been identified as N6-(Δ2-isopentenyl)adenosine (iA), which is known to be absent in Kid tRNA. The enzyme has an approximate molecular weight of 55,000 daltons and is specific for tRNA.
Time-dependent changes in the effects of cholinesterase inhibitors on shuttle-box avoidance

Physostigmine and neostigmine were compared for their effects on shuttle-box avoidance acquisition and retention. Physostigmine impaired acquisition at doses lower than neostigmine. Avoidance performance 1, 7, or 14 days after acquisition was impaired by the administration of 0.4 mg/kg physostigmine or an equimolar dose of neostigmine. The effects of lower doses of physostigmine, but not of neostigmine, were dependent upon the time of original training relative to drug administration and retesting. The results suggest that the peripheral effects of higher doses of cholinesterase inhibitors impair avoidance performance. The effects of lower doses of physostigmine on acquisition and the time-dependent effects on subsequent performance are probably due to the central actions of this drug.
TLR4 activates the β-catenin pathway to cause intestinal neoplasia.

Colonic bacteria have been implicated in the development of colon cancer. We have previously demonstrated that toll-like receptor 4 (TLR4), the receptor for bacterial lipopolysaccharide (LPS), is over-expressed in humans with colitis-associated cancer. Genetic epidemiologic data support a role for TLR4 in sporadic colorectal cancer (CRC) as well, with over-expression favoring more aggressive disease. The goal of our study was to determine whether TLR4 played a role as a tumor promoter in sporadic colon cancer. Using immunofluorescence directed to TLR4, we found that a third of sporadic human colorectal cancers over-express this marker. To mechanistically investigate this observation, we used a mouse model that over-expresses TLR4 in the intestinal epithelium (villin-TLR4 mice). We found that these transgenic mice had increased epithelial proliferation as measured by BrdU labeling, longer colonic crypts and an expansion of Lgr5+ crypt cells at baseline. In addition, villin-TLR4 mice developed spontaneous duodenal dysplasia with age, a feature that is not seen in any wild-type (WT) mice. To model human sporadic CRC, we administered the genotoxic agent azoxymethane (AOM) to villin-TLR4 and WT mice. We found that villin-TLR4 mice showed an increased number of colonic tumors compared to WT mice as well as increased β-catenin activation in non-dysplastic areas. Biochemical studies in colonic epithelial cell lines revealed that TLR4 activates β-catenin in a PI3K-dependent manner, increasing phosphorylation of β-cateninSer552, a phenomenon associated with activation of the canonical Wnt pathway. Our results suggest that TLR4 can trigger a neoplastic program through activation of the Wnt/β-catenin pathway. Our studies highlight a previously unexplored link between innate immune signaling and activation of oncogenic pathways, which may be targeted to prevent or treat CRC.
The effect of the duration of progestin use on the occurrence of endometrial cancer in postmenopausal women

AbstractObjectiveWomen who have ever used estrogen replacement therapy (ERT), even at a low dose, have an increased incidence of endometrial cancer. The addition of a progestin to ERT reduces the incidence of endometrial cancer. The duration of progestin administration is more important than the dos
Breaking through the thresholds: an analysis for iterative reweighted ℓ 1 minimization via the Grassmann angle framework

It is now well understood that the l 1 minimization algorithm is able to recover sparse signals from incomplete measurements [2], [1], [3] and sharp recoverable sparsity thresholds have also been obtained for the l 1 minimization algorithm. However, even though iterative reweighted l 1 minimization algorithms or related algorithms have been empirically observed to boost the recoverable sparsity thresholds for certain types of signals, no rigorous theoretical results have been established to prove this fact. In this paper, we try to provide a theoretical foundation for analyzing the iterative reweighted l 1 algorithms. In particular, we show that for a nontrivial class of signals, the iterative reweighted l 1 minimization can indeed deliver recoverable sparsity thresholds larger than that given in [1], [3]. Our results are based on a high-dimensional geometrical analysis (Grassmann angle analysis) of the null-space characterization for l 1 minimization and weighted l 1 minimization algorithms.
Sphingosine-1-Phosphate Receptor-2 Function in Myeloid Cells Regulates Vascular Inflammation and Atherosclerosis

Objective— Sphingomyelin deposition and metabolism occurs in the atherosclerotic plaque, leading to the formation of sphingosine-1-phosphate (S1P), which activates G protein–coupled receptors to regulate vascular and immune cells. The role of S1P receptors in atherosclerosis has not been examined. Methods and Results— We tested the hypothesis that S1P receptor-2 (S1PR2) regulates atherosclerosis. Apoe −/− S1pr2 −/− mice showed greatly attenuated atherosclerosis compared with the Apoe −/− mice. Bone marrow transplant experiments indicate that S1PR2 function in the hematopoietic compartment is critical. S1PR2 is expressed in bone marrow–derived macrophages and in macrophage-like foam cells in atherosclerotic plaques. Reduced macrophage-like foam cells were found in the atherosclerotic plaques of Apoe −/− S1pr2 −/− mice, suggesting that S1PR2 retains macrophages in atherosclerotic plaques. Lipoprotein profiles, plasma lipids, and oxidized low-density lipoprotein uptake by bone marrow–derived macrophages were not altered by the S1pr2 genotype. In contrast, endotoxin-induced inflammatory cytokine (interleukin [IL]-1β, IL-18) levels in the serum of S1PR2 knockout mice were significantly reduced. Furthermore, treatment of wild-type mice with S1PR2 antagonist JTE-013 suppressed IL-1β and IL-18 levels in plasma. Conclusion— These data suggest that S1PR2 signaling in the plaque macrophage regulates macrophage retention and inflammatory cytokine secretion, thereby promoting atherosclerosis.
Modal variability in the Southeast Pacific Basin: Energetics of the 2009 event

Abstract We study the barotropic variability in the Southeast Pacific Basin, in particular focusing on the extreme event during the fourth quarter of 2009. A 3-year integration of a barotropic shallow-water model forced with wind stress anomalies generates localized variability that is similar in spatial extent and amplitude as the observed anomalous event. An eigenmode analysis of the same model shows the presence of several free modes in the Southeast Pacific, but projection of the modal patterns on the model output shows that their amplitudes are low. Instead, the mode is interpreted as an almost -free mode. The modal excitation accounts for a considerable fraction (23% on average) of the kinetic energy input by the wind stress in the Southeast Pacific Basin, increasing to 38% for the anomalous event in 2009. Surprisingly, a similar but weaker event during the third quarter of 2008 appears to have been more significant from an energetics point of view, with almost 50% of the energy being input into the mode. Key areas of energetic dissipation appear to be the Eltanin Fracture Zone, the crest of the East Pacific Rise, and the Chile Rise/East Pacific Rise intersection.
Pistachio nutshell foreign body of the oral cavity in two children

Abstract Pistachio nutshell foreign bodies have been documented in the literature, occurring most commonly in the bronchi. The objective of this study is to report on two cases of oral cavity lesions, which were subsequently found to be pistachio nutshell foreign bodies. The first patient is a 9-month-old male who presented with a hard palate mass measuring 1.5 cm. The patient was evaluated in the operating room, and found to have a submucosal pistachio nutshell foreign body. The second patient is a 17-month-old female who presented with a firm, fixed midline hard palate mass. The lesion was subsequently noted to dislodge from the palate, and was identified as a pistachio nutshell.
A nonstandard geometric quantization of the harmonic oscillator

In the standard geometric quantization of the harmonic oscillator in (R2,dp∧dx), using standard holomorphic coordinate z=x−ip induces a standard complex structure which Kahler polarizes the prequantum line bundle. Hence, the quantum Hilbert space maybe identified with holomorphic functions which are L2 integrable with respect to Gaussian measure, denoted by H. The corresponding quantized Hamiltonian is then given by ℏz(∂∕∂z). We propose using a different almost complex structure J (under some restrictions) compatible with dp∧dx and construct a quantum Hilbert space HJ containing nontrivial L2 sections and a quantized Hamiltonian QJ. The main result is that (HJ,QJ) is unitarily equivalent to (H,ℏz(∂∕∂z)).
Rapid sea level rise and ice sheet response to 8,200-year climate event

[1] The largest abrupt climatic reversal of the Holocene interglacial, the cooling event 8.6-8.2 thousand years ago (ka), was probably caused by catastrophic release of glacial Lake Agassiz-Ojibway, which slowed Atlantic meridional overturning circulation (AMOC) and cooled global climate. Geophysical surveys and sediment cores from Chesapeake Bay reveal the pattern of sea level rise during this event. Sea level rose ∼14 m between 9.5 to 7.5 ka, a pattern consistent with coral records and the ICE-5G glacio-isostatic adjustment model. There were two distinct periods at ∼8.9-8.8 and ∼8.2-7.6 ka when Chesapeake marshes were drown as sea level rose rapidly at least ∼12 mm yr -1 . The latter event occurred after the 8.6-8.2 ka cooling event, coincided with extreme warming and vigorous AMOC centered on 7.9 ka, and may have been due to Antarctic Ice Sheet decay.
Rapid modeling of animated faces from video

Generating realistic 3D human face models and facial animations has been a persistent challenge in computer graphics. We have developed a system that constructs textured 3Dface models from videos with minimal user interaction. Our system takes images andvideo sequences of a face with an ordinary video camera. After five manual clicks ontwo images to tell the system where the eye corners, nose top and mouth corners are, thesystem automatically generates a realistic looking 3D human head model and the constructed model can be animated immediately. A user with a PC and an ordinary camera can use our system to generate his/her face model in a few minutes. Copyright © 2001 John Wiley & Sons, Ltd.
Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA-1

Transcription factor GATA-1 is essential at multiple stages of hematopoiesis. Murine gene targeting and analysis of naturally occurring human mutations demonstrate that GATA-1 drives the maturation of committed erythroid precursors and megakaryocytes. Prior studies also suggest additional, poorly defined, roles for GATA-1 at earlier stages of erythromegakaryocytic differentiation. To investigate these functions further, we stimulated Gata1- murine embryonic stem-cell-derived hematopoietic cultures with thrombopoietin, a multistage cytokine. Initially, the cultures generated a wave of mutant megakaryocytes. However, these were rapidly overgrown by a unique population of thrombopoietin-dependent blasts that express immature markers and proliferate indefinitely. Importantly, on restoration of GATA-1 function, these cells differentiated into both erythroid and megakaryocytic lineages, suggesting that they represent bipotential progenitors. Identical cells are also present in vivo, as indicated by flow cytometry and culture analysis of fetal livers from Gata1- chimeric mice. Our findings indicate that loss of GATA-1 impairs the maturation of megakaryocyte-erythroid progenitors. This defines a new role for GATA-1 at a relatively early stage of hematopoiesis and provides potential insight into recent discoveries that human GATA1 mutations promote acute megakaryoblastic leukemia, a clonal malignancy with features of both erythroid and megakaryocyte maturation.
Considering Spatial Correlation in Mixed-Effects Regression and the Impact on Ground-Motion Models

Abstract Ground-motion models are commonly used in earthquake engineering to predict the probability distribution of the ground-motion intensity at a given site due to a particular earthquake event. These models are often built using regression on observed ground-motion intensities and are fitted using either the one-stage mixed-effects regression algorithm proposed by Abrahamson and Youngs (1992) or the two-stage algorithm of Joyner and Boore (1993). In their current forms, these algorithms ignore the spatial correlation between intraevent residuals. This paper emphasizes the theoretical importance of considering spatial correlation while fitting ground-motion models and proposes an extension to the Abrahamson and Youngs (1992) algorithm that allows the consideration of spatial correlation. By refitting the Campbell and Bozorgnia (2008) ground-motion model using the mixed-effects regression algorithm considering spatial correlation, it is apparent that the variance of the total residuals and the ground-motion model coefficients used for predicting the median ground-motion intensity are not significantly different from the published values even after the incorporation of spatial correlation. However, there is an increase in the variance of the intraevent residual and a significant decrease in the variance of the interevent residual. These changes have implications for risk assessments of spatially-distributed systems because a smaller interevent residual variance implies lesser likelihood of observing large ground-motion intensities at all sites in a region.
How Do Synaptic Coupling and Spatial Temporal Delay Influence Traveling Waves in Nonlinear Nonlocal Neuronal Networks

We are concerned with existence, uniqueness, and stability of the traveling wave of a nonlocal model equation which incorporates spatial temporal delay due to the finite propagation velocity of action potentials along axons. In particular, we investigate how wave shape, speed, and stability vary as the synaptic coupling and the model parameters change. The synaptic coupling may be of pure excitation, lateral inhibition, or lateral excitation. We introduce two concepts: the speed index function and the stability index function. One interesting point is that we can define the stability index function through the speed index function. By using this relationship, the stability of the traveling wave can be analyzed easily. These concepts (the speed index function and the stability index function) may play very important roles in rigorous mathematical analysis of traveling waves of nonlinear singularly perturbed systems of integral differential equations. The analysis and results on the speed, the speed index f...
Challenges and opportunities for virtualized security in the clouds

The virtualization technologies that underlie the cloud computing infrastructures pose challenges on enforcing security policy when we have a sense of ambiguity concerning the actual physical properties of the resources. On the other hand, the virtual machine managers provide us with better sandboxing, detailed monitoring capabilities and fine-grained access control on the resource usage. As we expect the whole world to virtualize over the next 5-10 years, the presentation will present a forward-looking view on the cloudy road ahead with a focus on the associated security topics.
Patient Discomfort Following Pectoral Defibrillator Implantation Using Conscious Sedation

BACKGROUND The miniaturization of implantable cardioverter defibrillators (ICDs) has made pectoral implantation possible. However, postoperative pain following the procedure has not been systematically studied. The aim of the current study was to prospectively assess patient discomfort and identify factors influencing pain perception during follow-up. METHODS Pain related to device implantation was quantified in 21 consecutive patients (age, 61 +/- 11 years; 17 men and 21 women; 16 of 21 had coronary artery disease; left ventricular ejection fraction, 32% +/- 15%) undergoing pectoral ICD implantation with conscious sedation (fentanyl 118 +/- 72 micrograms midazolam 14 +/- 9 mg). Patients completed the Visual Analogue Scale (VAS, 0-100) and the McGill Pain Questionnaire 24 hours and 1 month postoperatively. Regression analysis was used to define clinical and procedure related variables affecting patient discomfort and frequency of postoperative analgesic use. RESULTS The mean VAS score was 34 +/- 20 24 hours postoperatively. A single (4.8%) patient described postoperative pain as severe. Pain was reported to be moderate by 10 (47.6%) patients and mild by 10 (47.6%) patients. Intraoperative fentanyl requirement was a predictor of postoperative pain (R = 0.51, P = 0.036), and procedural duration was a strong predictor of postoperative analgesic use (R = 0.75, P < 0.001). Pain at 1 month decreased to a VAS score of 19 +/- 18 (P = 0.002 vs 24 hours) and was rated to be severe, moderate, and mild by 1, 3, and 17 patients, respectively. Late pain was related to a VAS score at 24 hours (R = 0.67, P = 0.004). CONCLUSIONS (1) Pectoral ICD implantation using conscious sedation is well tolerated. (2) Postoperative discomfort correlates with longer procedural times and larger intraoperative narcotic requirements.
Identifying materials limits of chemically amplified photoresists

Chemically amplified photoresists are likely to remain the primary imaging materials for the semiconductor industry. As feature sizes decrease to dimensions comparable to the characteristic size of the molecules in the photoresist, a significant challenge lies in identifying the ultimate resolution limit of these materials. To address this challenge, we investigated model photoresist materials with high resolution measurements to examine the effect of individual factors among interdependent process steps on line-edge roughness (LER). Using a bilayer film sample geometry, we measured the internal deprotection interface with nanometer resolution as a function of photoacid size, initial resist copolymer composition, and amine base quencher by neutron reflectivity and infrared spectroscopy. After development, we found that the resist chemistry and additives can play an important role in LER through its influence on acid diffusion. However, these model experiments suggest that there is a limit in LER even with an idealized exposure image contrast and decreases in the width of the reaction-diffusion front. However, there may be opportunities to further decrease LER during development by tuning the response of the photoresist to the developer solution.
Peptide sequencing: The utility of chemical ionization mass spectrometry

Chemical ionization mass spectrometry is used at low resolution to determine the sequences of permethylated acetyl peptides. The method has been tested with 45 peptides, between 2 and 5 residues long, including examples of all of the common amino acids except cysteine and N-terminal asparagine. The isobutane chemical ionization spectra contain three principal types of N-terminal sequence ion and one type of C-terminal sequence ion. The redundant information available from these four types of sequence ion increases the reliability of the sequence determination. In prospect, isobutane chemical ionization mass spectrometry seems to be a useful technique for peptide sequence determination, and may have advantages in some cases.
The intercultural communication cultural immersion experience: Preparing leaders for a global future

The dynamics of globalization mean we face a reality wherein leaders are called upon to communicate effectively in cultural situations unfamiliar to them. This situation brings new challenges for communication and leadership educators. Our article describes a cultural immersion experience called The Cagli Project, where communication and leadership students learn effective intercultural communication skills for leadership formation while studying in Italy. The philosophical and experiential aspects of the program are described along with leadership outcomes. The article ends with a discussion of the transferability of this model to alternative programs. Perhaps nothing has had a more profound effect on human communication and hence leadership in the past half century than the movement of people around the globe and the growing diversity of world society. Globalization is the mantra that seems to be driving much that is new in higher education today. It has its roots in the “global economy” and seems most relevant to the business disciplines, but there is a sub-text to globalization that resonates throughout all our institutions, and that is diversity (Caputo, 2011).
Single-Lead VDD Pacing System

A single pass ventricular lead with a dual chamber electrode system, designed for VDD pacing, was implanted in 17 patients (11 men, 6 women, aged 53 to 86 years, mean 74) for symptomatic bradycardia due to second-or third-degree AV block and normal sinus node function. Bipolar atrial electrodes, diagonally displaced along the lead axis and positioned within the right atrial cavity, are used to detect atrial activity that is then differentially processed within the pacemaker. P wave amplitude (amp) derived from a PSA-DAA device at implant was 1.38 +/- 0.28 mV. P wave signal amp derived from telemetered atrial electrograms was 1.29 +/- 0.22 mV at predischarge (n = 17), 1.31 +/- 0.24 mV at 3 months (n = 15), 1.30 +/- 0.24 mV at 6 months (n = 8), 1.51 +/- 0.34 mV at 9 months (n = 4), and 1.35 +/- 0.35 mV at 12 months (n = 2); and the far-field QRS signal measured at predischarge was of negligible voltage (0.17 +/- 0.07 mV). The susceptibility of the atrial sensor system to interference was noted with chest wall stimulation and only at higher sensitivities (0.1 to 0.3 mV) and not with isometric arm exercise. Intact VDD pacing function at rest and during exercise was established using Holter and periodic ECG monitoring. Postoperative complications included one lead displacement and one pocket hematoma. Three patients died postimplant of causes unrelated to pacemaker function. Advantages of the single-lead VDD pacing include: (1) elimination of second atrial sensing lead; (2) superior atrial sensing performance; (3) effective resistance to myopotential and far-field signal interference; and (4) stability of postimplant atrial signal amplitude.
Immune complexes in breast cancer patients as detected by Clq binding

Levels of Clq binding activity have been measured in the sera of patients with benign and malignant breast disease. Cancer patients showed significantly higher binding activity than patients with gross fibrocystic disease. Clq binding levels were not related to levels of carcinoembryonic antigen, or rheumatoid factor. The Clq reactive material was identified as being precipitable with Protein A, and predominantly eluted in gel filtration fractions with a molecular weight of approximately 1 x 10(6). These studies indicate that Clq binding level may be of use in the differential diagnosis of benign and malignant breast disease.
Second-look laparotomy after chemotherapy in the management of ovarian malignancy

Eighty-eight patients with ovarian malignancy underwent second-look laparotomy as part of their plan of management at Indiana University Hospital. Thirty-five patients (39.8%) were found to have no gross or microscopic evidence of persistent neoplasm, and an additional 16 (18.2%) had only microscopic tumor. Patients with initial Stage III or IV disease were less likely to have negative findings at laparotomy than were patients with Stage I or II disease. A complete initial cytoreductive operation (residual disease = 0 cm) correlated positively with negative findings at laparotomy. Endometrioid histologic findings were associated with a favorable condition at the second look, but tumor grade was associated with superior survival only for patients with grade 0 disease. Eight of 30 patients (26.7%) with invasive carcinoma and negative findings at second-look laparotomy have had tumor recurrence (2 to 63 months), and five of eight have died. Intraperitoneal chromic phosphorus salvage therapy for patients with microscopic disease was promising, with eight of 15 treated patients (53.3%) alive after therapy, with no evidence of disease from 16 to 56 months after the second look. Second-look laparotomy has been the major determinant of continued or alternative therapy for patients with ovarian malignancy. Second-look laparotomy has been incorporated into the standard management plan without a formal clinical trial. The need for a second look may be reduced by identifying patients who do not benefit from the procedure. Patients with persistent disease confirmed by noninvasive means can continue therapy without laparotomy. There is also a subgroup of patients with a favorable prognosis whose therapy could be safely discontinued without laparotomy.
Identification of the Penta-EF-hand Protein ALG-2 as a Ca2+-dependent Interactor of Mucolipin-1

Loss of function mutations in mucolipin-1 (MCOLN1) have been linked to mucolipidosis type IV (MLIV), a recessive lysosomal storage disease characterized by severe neurological and ophthalmological abnormalities. MCOLN1 is an ion channel that regulates membrane transport along the endolysosomal pathway. It has been suggested that MCOLN1 participates in several Ca2+-dependent processes, including fusion of lysosomes with the plasma membrane, fusion of late endosomes and autophagosomes with lysosomes, and lysosomal biogenesis. Here, we searched for proteins that interact with MCOLN1 in a Ca2+-dependent manner. We found that the penta-EF-hand protein ALG-2 binds to the NH-terminal cytosolic tail of MCOLN1. The interaction is direct, strictly dependent on Ca2+, and mediated by a patch of charged and hydrophobic residues located between MCOLN1 residues 37 and 49. We further show that MCOLN1 and ALG-2 co-localize to enlarged endosomes induced by overexpression of an ATPase-defective dominant-negative form of Vps4B (Vps4BE235Q). In agreement with the proposed role of MCOLN1 in the regulation of fusion/fission events, we found that overexpression of MCOLN1 caused accumulation of enlarged, aberrant endosomes that contain both early and late endosome markers. Interestingly, aggregation of abnormal endosomes was greatly reduced when the ALG-2-binding domain in MCOLN1 was mutated, suggesting that ALG-2 regulates MCOLN1 function. Overall, our data provide new insight into the molecular mechanisms that regulate MCOLN1 activity. We propose that ALG-2 acts as a Ca2+ sensor that modulates the function of MCOLN1 along the late endosomal-lysosomal pathway.
Fracture properties and behavior of transparent ceramics

For the past several decades, the Army has been interested in materials transparent to visible and infrared wavelengths for use in armor, IR windows and sensor windows. Future requirements for transparent armor are systems that can defeat greater threats without increased weight and thickness and minimal optical distortion. The Army Research Laboratory is developing transparent armor systems to increase the performance of new windows. Aluminum oxynitride spinel and single-crystal sapphire are two of the ceramic candidates for advanced transparent armor applications.
“Follow the Water”: Steve Squyres and the Mars Exploration Rovers ☆

Abstract Steve Squyres was responsible for assembling the team of scientists, engineers and instruments that formed the Mars Exploration Rovers (MER). Squyres developed a vision that small-scale observations made by a robotic geologist on Mars would be the key for resolving the mystery of water on Mars. Prior to the MER missions, planetary scientists were divided between groups holding that ancient fluvial-like surface features on Mars were formed by water and those holding that the erosive and depositional forces were tied to liquid and gaseous CO2. At issue was a fundamental understanding not only of early Martian geological processes and early solar luminosity, but also the possibility of life on Mars. To resolve these questions, Squyres and his team developed a new breed of rovers that were capable of identifying minerals and collecting textural observations. The resulting twin rovers, Opportunity and Spirit, have successfully resolved the single most important question about Mars that scientists have been debating for the past 30 years, providing compelling evidence for the action of water on the Martian surface. Squyres and the MER team have also initiated a new era in planetary exploration and inspired a new generation of students to become scientists and explorers. Steve Squyres and the MER team produced fundamental insights into the geology and climatology of Mars. These have resulted in major advances in our understanding of the potential for life on other planets and of life’s evolution on Earth. For the discovery and elucidation of water on Mars through the “robotic geologists” of the Mars Exploration Rovers, Steve Squyres was awarded the 2007 Benjamin Franklin Medal in Earth and Environmental Science.
Implementation of artificial neural networks with optics

Optical implementation of artificial neural nets (ANNs) with electronically addressable liquid crystal televisions (LCTVs) are presented. The major advantages of the proposed ANNs must be the low cost and the flexibility to operate. To test the performance, several artificial neural net models have been implemented in the LCTV ANNs. These models include the Hopfield, Interpattern Association, Hetero-association, and Unsupervised ANNs. System design considerations and experimental demonstrates are provided.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.