cssi/SciSciGPT-SciSciNet huggingface dataset:
Crossroads between membrane trafficking machinery and copper homeostasis in the nerve system

Imbalanced copper homeostasis and perturbation of membrane trafficking are two common symptoms that have been associated with the pathogenesis of neurodegenerative and neurodevelopmental diseases. Accumulating evidence from biophysical, cellular and in vivo studies suggest that membrane trafficking orchestrates both copper homeostasis and neural functions-however, a systematic review of how copper homeostasis and membrane trafficking interplays in neurons remains lacking. Here, we summarize current knowledge of the general trafficking itineraries for copper transporters and highlight several critical membrane trafficking regulators in maintaining copper homeostasis. We discuss how membrane trafficking regulators may alter copper transporter distribution in different membrane compartments to regulate intracellular copper homeostasis. Using Parkinson's disease and MEDNIK as examples, we further elaborate how misregulated trafficking regulators may interplay parallelly or synergistically with copper dyshomeostasis in devastating pathogenesis in neurodegenerative diseases. Finally, we explore multiple unsolved questions and highlight the existing challenges to understand how copper homeostasis is modulated through membrane trafficking.
Chapter 11 Lipoprotein lipase

Publisher Summary This chapter highlights lipoprotein lipase (LPL), an enzyme of the lipid transport system. The primary function of LPL in the lipid transport system is catalysis of the core triglyceride of circulating chylomicrons and very low-density lipoproteins (VLDL). LPL is synthesized in parenchymal cells, secreted, and bound to endothelial cell. The enzyme, thus, has its site of physiological action at capillary endothelial surfaces where circulating lipoprotein particles are bound and the triglyceride is hydrolyzed. LPL is necessary for the initial lipolysis of triglyceride to diglyceride, and apparently also for hydrolysis of diglyceride to monoglyceride. Three characteristics that distinguish LPL from other lipases include (1) LPL is characterized by an alkaline pH optimum, (2) inhibition by low concentrations of NaCl, and (3) the requirement for apolipoprotein C-II for maximal activity. The requirement for apolipoprotein C-II for optimal LPL activity is a well-established property of the enzyme. Apolipoprotein C-II is a 78 amino acid polypeptide present on chylomicrons, VLDL, and high-density lipoproteins (HDL). The portion of the C-II molecule that specifically activates LPL and another domain responsible for lipid binding have been determined with the use of chemically modified and synthetic apoprotein C-II fragments.
Saliency-based scene recognition based on growing competitive neural network

This paper proposes the saliency-based scene recognition model in which objects in saliency-based attended spots are sequentially encoded to be invariant with respect to position and size and their positions and sizes are encoded simultaneously. In this model, object recognition and its recall are performed based on the growing two-layered competitive spiking neural network with reciprocal connection between the layers. This neural network represents objects using latency-based temporal coding and grows in size and recognizability through learning and self-organization. Through simulation experiments of a robot equipped with a camera, it is shown that scene recognition is well performed by our model, in which objects are encoded in-variantly with respect to position and size and their positions and sizes are encoded suitably enough for scene recognition.
Protolith age of the Swakane Gneiss, North Cascades, Washington: Evidence of rapid underthrusting of sediments beneath an arc

[1] The metamorphic core of the North Cascades largely comprises island arc and oceanic terranes juxtaposed prior to circa 96 Ma magmatism. However, the tectonic affinity of the structurally deepest terrane, the 9–12 kbar Swakane Gneiss, is distinctly different from other terranes in the core; it is not intruded by arc-related plutons and contains abundant Precambrian zircons. New U-Pb analyses of detrital zircons from the Swakane Gneiss yield dates from 73 Ma to 1610 Ma with a dominant Late Cretaceous population. These data indicate that the Swakane protolith was deposited as late as 72.5 ± 0.6 Ma, the 206Pb/238U date of the youngest detrital grain. Following deposition, the gneiss was intruded by peraluminous leucogranite sheets that may represent partial melt derived from the gneiss at near- to postpeak P-T conditions. One sheet yielded a U-Pb crystallization age of 68.36 ± 0.07 Ma, which indicates that the gneiss was deeply buried within 5 Myr of deposition. Two possible mechanisms considered for this rapid burial (∼7 mm/yr) are overthrusting of a forearc or back arc basin by older crystalline rock or underthrusting of trench sediments during low-angle subduction. The model involving overthrusting of a forearc or back arc basin is most consistent with thermobarometric and isotopic data and the regional geologic setting of the Cascades core. Rapid burial of the Swakane protolith is coincident with burial of sediments that formed the Pelona, Orocopia and Rand schists of southern California; however, differences in peak metamorphic temperatures indicate that conditions of burial must have varied along the plate margin.
Virus analysis: techniques, tools, and research issues tutorial

The tutorial covers techniques, tools, and research issues in analyzing computer viruses. It provides participants the background needed to initiate research in reverse engineering computer viruses.
The complexation of lanthanides by aminocarboxylate ligands—II: Thermodynamic parameters

Abstract The values of the free energy, enthalpy and entropy of complexation are reported for a series of aminocarboxylate ligands. For all the systems, a region of “compensation” between ΔH 1 , and ΔS 1 exists between Nd(III) and Ho(III) which is related to dehydration effects. The entropies are a function of the number of ligand carboxylate groups coordinated. Correction of the enthalpy for the coordination of the carboxylate groups gives a residual enthalpy which is a linear function of the basicity of the nitrogen groups. In the HEDTA complexes, the data are consistent with outer sphere coordination of the alcohol group in the light lanthanides and with inner sphere coordination in the heavy members.
Growth hormone reduces chloride secretion in human colonic epithelial cells via EGF receptor and extracellular regulated kinase.

Abstract Background & Aims: Growth hormone (GH) has been shown to alleviate symptoms in patients with Crohn's disease. Chloride secretion is important in driving intestinal fluid secretion. We examined whether GH inhibits chloride secretion induced by carbachol (CCh, a calcium-dependent pathway), and the downstream effectors responsible. Methods: T 84 cells were pretreated with GH at various concentrations followed by CCh (100 μmol/L). Chloride secretion was assessed as changes in short circuit current (▵I sc ) in Ussing chambers. Tyrphostins AG1478 (an epidermal growth factor receptor [EGFr] inhibitor) and AG490 (a Janus kinase 2 [JAK2] inhibitor), SB203580 (a p38 inhibitor), and PD98059 (a MEK1 inhibitor) were used. Results: GH inhibited CCh-induced chloride secretion at up to 10 nmol/L, but higher concentrations were less effective. GH caused tyrosine phosphorylation of JAK2 and EGFr. AG490 suppressed activation of JAK2 and EGFr in response to GH. AG1478 prevented GH activation of EGFr and reversed its inhibitory effect on chloride secretion. GH also induced activation of both p38 and ERK1/2. AG490 reversed GH-induced tyrosine phosphorylation of both ERK1/2 and p38, but AG1478 reversed that of ERK1/2 only. PD98059, but not SB203580, reversed the inhibitory effect of GH on chloride secretion. Conclusions: GH inhibits CCh-induced chloride secretion via a JAK2-dependent mechanism involving transactivation of EGFr and consequent recruitment of ERK1/2. Although activated, p38 does not contribute to the inhibitory effect of GH on secretion. These data elucidate mechanisms of GH inhibition of chloride secretion in intestinal epithelia, which may be relevant to therapeutic benefits of GH in Crohn's disease or other diarrheal diseases.
Surface Diffusion and Concentration Polarization on Oxide-Supported Metal Electrocatalyst Particles

A common assumption for solid oxide fuel cells (SOFCs) is that the hydrogen–oxygen reaction that produces the electrical current is strictly localized at the triple phase boundary (TPB) between the metal catalyst particle, the zirconia support, and the gas atmosphere. Detailed analysis of oxygen spillover onto the catalyst surface indicates that the reactive area simply spreads over the surface as needed to support the current, leading to TPB widths of several hundred Angstroms. Lower adspecies surface diffusivities (due to catalyst crystallography), lower reactant partial pressures (due to electrode design), and higher current demands, generally shift the peak turnover number (TON) for H2O generation away from the TPB in practical SOFCs with cermet anodes. The diffusivity–coverage relationship (repulsive, neutral, or attractive adspecies interactions) affects the location of the TON peak on the catalyst surface in a non-monotonic manner, indicating that care should be taken when applying research data to models of practical SOFCs. The most detailed surface diffusion model investigated in this work indicates that the catalytic process is limited by oxygen surface diffusion on the metal particle.
Glutathione and glutathione S-transferases in a human plasma cell line resistant to melphalan

We report the development of a melphalan-resistant HS-Sultan human plasma cell line. The melphalan-resistant [MEL(R)] cell line was 16.7-fold more resistant to melphalan in vitro than the parent cell line [MEL(S)]. The wild type and MEL(R) HS-Sultan cell lines formed localized plasmacytomas when injected into nude mice. A dose-response effect of melphalan against the drug-sensitive plasmacytomas was present in vivo. A dose of 10 mg/kg of melphalan, which caused a 90% regression of MEL(S) plasmacytomas, had no effect on the MEL(R) plasmacytomas in vivo. In contrast to previous reports, there was no increase in the levels of glutathione (GSH) in the MEL(S) and MEL(R) plasmacytomas, suggesting that the association of elevated glutathione levels and melphalan resistance may not be common to all drug-resistant lines. In the MEL(R) plasmacytomas, there was a 1.5-fold induction of a pi type glutathione S-transferase (GST) as evidenced by isoelectric focusing (IEF) and Western blotting. This GST isoenzyme was purified and, although immunochemically similar to the pi type isoenzymes induced in other drug-resistant cell lines, was noted to have different functional characteristics. These data suggest that, depending on cell type and the drug studied, functionally different GST isoenzymes may be induced and they could be of importance in the development of drug resistance.
Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells

Selective gene transfer to tumor is critical in cancer gene therapy. We previously used ionizing radiation to improve adenovirus uptake in intrahepatic tumors but liver cytotoxicity associated with the viral administration still occurred. Here, we explore the potential of radiation for improving gene delivery by a virus-mimicking nanoparticle, transferrin (Tf)-cationic liposome-DNA complex (Tf-lipoplex). Transduction by Tf-lipoplex was highly efficient in various cell lines and further increased by radiation in a dose- and time-dependent manner. This radiation induction, which was associated with an increase in Tf-lipoplex uptake (3- to 4-folds in hepatocytes WB and lung cancer cells, LLC1), was absent when a Tf-deficient complex was used or abolished by the presence of free Tf, suggesting that Tf receptor (TfR) interaction is required for radiation induction. Radiation (10–20 Gy) markedly induced transgene (LacZ) expression in LLC1 xenografts (3.5- to 7.4-folds), correlating with increased plasmid content and TfR expression in irradiated tumors. Moreover, Tf-lipoplex-mediated gene expression was not observed in the liver or other normal tissues regardless of radiation treatment. We conclude that radiation improves Tf-lipoplex gene delivery selectively to tumor cells both in vitro and in vivo. Our findings may provide insight in developing ligand-specific lipoplex for molecularly targeted cancer gene therapy.
The expansion of human γδ T cells in response to Daudi cells requires the participation of CD4+ T cells

The Burkitt’s lymphoma cell line Daudi is a potent inducer of human γδ T-cell expansion. Using an in vitro culture system comprised of irradiated Daudi cells as stimulators and normal human lymphocytes as responders, the cellular determinants of this response were investigated. Three of four monoclonal antibodies (mAbs 1-1C4, L243, and 9.3F10) directed against disparate epitopes of human major histocompatibility complex (MHC) class II, as well as a mAb with specificity for CD4 (OKT4), inhibited the expansion of γδ T cells in response to Daudi cell stimulators. mAbs with a specificity for CD74 and CD8 were non-inhibitory. Lymphocyte depletion experiments demonstrated a critical role for the CD4+ T-cell subset in the expansion of γδ T cells. Other data pointed towards requirements for direct cell contact in this system, and the addition of exogenous recombinant interleukin (IL)-2, IL-4, and IL-12 failed to reconstitute γδ T-cell expansion in CD4+ lymphocyte-depleted cultures. These results complement previous findings in murine infectious disease and mycobacterial systems, providing a direct demonstration that CD4+ T cells play a role in γδ T-cell expansion through an interaction with human leucocyte antigen (HLA) class II on Daudi cells. The data point towards important functional links between the acquired and natural immune systems.
Regulation of small RNA stability: methylation and beyond

As central components of RNA silencing, small RNAs play diverse and important roles in many biological processes in eukaryotes. Aberrant reduction or elevation in the levels of small RNAs is associated with many developmental and physiological defects. The in vivo levels of small RNAs are precisely regulated through modulating the rates of their biogenesis and turnover. 2′-O-methylation on the 3′ terminal ribose is a major mechanism that increases the stability of small RNAs. The small RNA methyltransferase HUA ENHANCER1 (HEN1) and its homologs methylate microRNAs and small interfering RNAs (siRNAs) in plants, Piwi-interacting RNAs (piRNAs) in animals, and siRNAs in Drosophila. 3′ nucleotide addition, especially uridylation, and 3′-5′ exonucleolytic degradation are major mechanisms that turnover small RNAs. Other mechanisms impacting small RNA stability include complementary RNAs, cis-elements in small RNA sequences and RNA-binding proteins. Investigations are ongoing to further understand how small RNA stability impacts their accumulation in vivo in order to improve the utilization of RNA silencing in biotechnology and therapeutic applications.
Chiroshield: a Salisbury/Dallenbach shield alternative

The enhancement of impedance matching and the increased absorption afforded by the use of chiral materials are here combined with specified coated surfaces which act as screens or shields for use in radar cross-section management and control. These chiral shields offer attractive advantages with respect to broadband frequency response and reduced reflection when compared to their conventional counterparts.
Diffuse optical excitations in Mn 12 -acetate

We report transmittance and polarized reflectance measurements of crystalline ${\mathrm{Mn}}_{12}$-acetate over a wide frequency range (600--50 000 ${\mathrm{cm}}^{\ensuremath{-}1})$ to investigate the electronic structure of this prototypical molecular magnet. Overall, the spectral features are quite diffuse down to 10 K, although a number of Mn inner $\ensuremath{\rightarrow}$ outer and O $\stackrel{\ensuremath{\rightarrow}}{p}$ Mn d charge transfer excitations are observed and assigned. The two lowest energy excitations (at 13 500 and 15 900 ${\mathrm{cm}}^{\ensuremath{-}1})$ are polarized perpendicular to the easy magnetization (c) axis. Optical gaps are estimated at 8750 ${\mathrm{cm}}^{\ensuremath{-}1}$ (1.08 eV) and 14 000 ${\mathrm{cm}}^{\ensuremath{-}1}$ (1.75 eV), corresponding to minority and majority gaps, respectively.
Type I nitric oxide synthase (NOS) is the predominant NOS in rat small intestine. Regulation by platelet-activating factor.

Abstract Constitutive nitric oxide synthase (cNOS) may play an important protective role in the intestine, since our previous study has shown that the degree of bowel injury induced by platelet-activating factor (PAF), a potent inflammatory mediator, is inversely related to the cNOS content of the intestine. This study aims to examine the composition of the cNOS system in rat small intestine, and its regulation by PAF. We found that an approximately 120 kDa NOS I (neuronal NOS) is the predominant NOS in rat intestine, as evidenced by the following: (a) immunoblotting with specific antibodies detected a NOS I of approximately 120 kDa, but little NOS III; (b) the Ca 2+ -dependent, constitutive NOS (cNOS) activity of the rat intestine was removed by immunoprecipitation with the anti-NOS I, but not anti-NOS II or anti-NOS III antibodies; (c) RT–PCR revealed constitutive expression of NOS I in the intestinal tissue, but only a minute amount of NOS III. Immunofluorescent staining with anti-NOS I located NOS in the Auerbach plexus and nerve fibers in the muscle layer. We also found that this 120 kDa NOS I is rapidly (within 1 h) down-regulated in response to PAF administration. The protein level, enzyme activity as well as mRNA of nNOS were all decreased in the intestine.
Novel Approach for High Resolution Tem Studies of Ceramic-Ceramic Interfaces

Ceramic coatings on oxides can be studied by high resolution transmission electron microscopy (HRTEM), with minimal sample preparation, if the substrate consists of nonporous particles of simple geometric shape. Interfaces suitable for ‘end-on’ examination by HRTEM can be readily obtained without any necessity for ion-beam thinning. All the interface orientations that are thermodynamically stable are available for examination from a single sample. This technique is of general applicability and can be used for studies of metal-ceramic and ceramic-ceramic interfaces. We have examined the nature of boron nitride interfaces with oxides such as MgO, TiO2 and Al2O3 and find that BN appears to wet the oxide surface and form tough, adherent coatings. The hexagonal crystalline BN grows with the (0001) planes always being locally parallel to the oxide surface in every instance.
Cytochrome P450 Genes from the Sacred Lotus Genome

Cytochrome P450 monooxygenases (P450s) in the sacred lotus (Nelumbo nucifera) genome have been identified and named according to systematic P450 nomenclatures. Comparisons of these sequences with those in the papaya and grape CYPomes have indicated that gene blooms exist in the CYP89, CYP94, CYP96 and CYP714 families and that less dramatic expansions exist in the CYP71 and CYP72 families. Expansions in the CYP94 and CYP96 families may be associated with generation of the extremely hydrophobic leaf surfaces associated with the “lotus effect” in this water-adapted species, since these families are known to hydroxylate fatty acids and alkanes in the wax biosynthetic pathways of other plant species. Evolution of the CYP719 and CYP80 families may be associated with production of a number of benzylisoquinoline and aporphine alkaloids. Structures for anonaine and roemerine, two of the most abundant aporphine alkaloids in lotus leaves and seeds, contain methylenedioxy bridges that are known to be generated by members of the CYP719 family. With only one CYP719A22 gene existing in the lotus genome, it is likely that it is involved in making aporphine alkaloids. The fact that CYP719 has not previously been seen in angiosperm phylogeny below the order of Ranunculales suggests that its presence in lotus (in the Proteales) presents an evolutionary terminus prior to its loss in more recent eudicot species. With several CYP80 family genes existing in the lotus genome, there are multiple candidates for those involved in conducting benzylisoquinoline alkaloid synthesis.
Unpowered Approach and Landing Guidance with Normal Acceleration Limitations

F UTURE reusable launch vehicles (RLV) may greatly benefit from advanced guidance and control (AG&C) technologies. Hanson [1–3] has argued that AG&Cwill greatly improve safety and reliability by successfully returning an RLV that is plagued by aerosurface failures, poor vehicle performance, and larger-thanexpected flight dispersions. Advanced guidance methods have been developed for the ascent, entry, and landing phases of an RLV [3– 10]. Approach and landing (A&L) is a critical flight phase that brings the unpowered vehicle from the terminal area energy management (TAEM) phase to runway touchdown. The Space Shuttle A&L guidance scheme uses a two-phase (steep and shallow) reference flight path, which has proven to be effective for low lift-to-drag (L=D) vehicles [11]. Shuttle guidance also relies on a small set of fixed A&L reference profiles, and therefore it may not be well-suited for scenarios with large trajectory dispersions, poor vehicle performance, or actuator failures. Schierman et al. [9] and Kluever [10] have developed onboard trajectory-reshaping algorithms for the A&L phase of an RLV. Both algorithms recompute a new reference A&L path in the presence of winds, aerodynamic uncertainties, and extreme trajectory dispersions. This Note presents an A&L guidance scheme for an unpowered vehicle with diminished maneuverability in the vertical plane, namely, limited normal acceleration capabilities. An RLV with limited normal acceleration will have difficulty transitioning from the initial steep glide slope to a shallow flight path required for touchdown. The proposed guidance method computes a new reference trajectory such that load factor is minimized during the A&L phase. Trajectory planning is accomplished by performing a series of 1-D searches by iterating on a single guidance parameter and numerically propagating multiple paths to touchdown conditions. Numerical results are presented to demonstrate the effectiveness of the guidance method. System Models
RNA folding: A tale of two riboswitches

Riboswitches are so named because they switch gene expression on or off in response to binding of specific metabolites. Two evolutionarily and mechanistically divergent riboswitches that recognize the universal methyl donor S-adenosylmethionine are shown to undergo dynamic conformational sampling before ligand binding.
Epigenetic Inactivation of SFRP Genes and TP53 Alteration Act Jointly as Markers of Invasive Bladder Cancer

In the United States each year, almost 13,000 deaths are attributable to bladder cancer, with the majority of these deaths related to higher stage, muscle-invasive solid tumors. Epigenetic silencing of the secreted frizzled receptor proteins (SFRP), antagonists of the WNT pathway, leads to constitutive WNT signaling, altering cell morphology and motility. Identifying alterations in this pathway in bladder cancer may prove useful for defining the invasive phenotype and provide targets for guiding therapy. Using a population-based study of bladder cancer (n = 355), we examined epigenetic alterations, specifically gene promoter hypermethylation, of four SFRP genes in addition to immunohistochemical staining of TP53, which has been previously shown to be a predictor of invasive disease. We observed a significant linear trend (P 30-fold risk of invasive disease for patients with both altered SFRP gene methylation and intense TP53 staining (odds ratio, 32.1; P < 10(-13)). Overall patient survival was significantly poorer in patients with any SFRP genes methylated (P < 0.0003) and in proportional hazards modeling, patients with methylation of any SFRP gene had significantly poorer overall survival (hazard ratio, 1.78; P < 0.02) controlled for TP53 staining intensity and other survival-associated factors. Classifying tumors based on SFRP methylation status and TP53 protein staining intensity may be a clinically powerful predictor of invasive, deadly disease.
Measuring Sexual Identity Using Survey Questionnaires: How Valid Are Our Measures?

Patterns of poorer health are observed in numerous groups within the US population. The Healthy People 2020 initiative provides a national framework to improve the health of all people in the USA. One of the four overarching goals of Healthy People 2020 is to achieve healthy equity, eliminate disparities, and improve the health of all groups including, lesbian, gay, bisexual, and transgender (LGBT) people. To achieve this goal for LGBT populations requires that these groups be identified in national health surveys. Sexuality, however, is a complex phenomenon that incorporates numerous, even contradictory, meanings, attitudes, and types of experiences, creating a major challenge in developing a single measure that is both meaningful and comparable across various socio-cultural groups throughout the US population. Without quality data, the picture of LGBT health, as it is portrayed through official statistics, is distorted. We contend that the specific construct of sexual identity (i.e., how individuals identify and conceptualize their own selves) is a key construct necessary for tracking health disparities. In this paper, we assess the validity of sexual identity measures using qualitative data from cognitive interview studies as well as estimates produced from the National Survey of Family Growth and the National Health and Nutrition Examination Survey.
Mechanism of rapid desensitization of muscarinic K+ current in adult rat and guinea pig atrial cells

Acetylcholine (Ach) activates the muscarinic K+ current in atrial cells via the inhibitory GTP binding protein. After activation, the whole-cell K+ current decreases rapidly (rapid desensitization) to approximately half of the initial current within approximately 20 seconds. The mechanism of this rapid desensitization was investigated in adult rat and guinea pig atrial cells. Whole-cell voltage-clamp and patch-clamp techniques were used to study the K+ current. In voltage-clamped whole cells, ACh activated a K+ current that desensitized rapidly during the initial approximately 20 seconds followed by a slower decrease over several minutes. The rapid K+ current desensitization (a rapid decrease in channel open probability) was also observed at the single-channel level in cell-attached patches and was associated with a progressive shortening of the channel open time and prolongation of the closed time. These changes in channel current and kinetics were abolished by removal of the cytoplasm (by forming inside-out patches) and were partially inhibited by phosphatase inhibitors, suggesting an involvement of cytosolic phosphatase(s) in K+ current desensitization. In inside-out patches with ACh in the pipette and GTP in the bath, the open time of muscarinic K+ channels and channel open probability were increased by 1 mM Mg(2+)-ATP (but not by the nonhydrolyzable analogue, adenylylimidodiphosphate) and decreased by alkaline phosphatase. These results suggest that the rapid K+ current desensitization in adult rat or guinea pig atrial cells is produced by changes in the gating kinetics of the K+ channel, possibly mediated via membrane-associated protein kinase and cytosolic phosphatase(s).
Grain Sorghum Response to Fall Armyworm and Corn Earworm Infestation

In two plantings of grain sorghum, Sorghum bleolor (L.) Moench, we investigated the impact of whorl injury by natural infestations of fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), on subsequent panicle development and infestation. We also examined plant response to panicle infestation by corn earworm, Heliothis zea (Boddie) (Lepidoptera: Noctuidae). Treatments were applications of chlorpyrifos, methomyl, or Bacillus thuringiensis (Berliner) to the whorl, panicle, or both. Fall armyworm injury to the whorl caused light to moderate whorl injury in nontreated plots; injury was approximately 30% greater in the later planting, possibly reflecting differences in sorghum maturity. Fall armyworm damage delayed panicle development in the second planting by 2-4 d and may have prolonged anthesis. Fall armyworm injury did not measurably affect panicle oviposition by corn earworm. Whorl stage applications of chlorpyrifos apparently increased corn earworm survival on panicles, possibly because of toxicity to beneficials. Methomyl and chlorpyrifos were ovicidal for corn earworm, with up to 18-fold more noneclosed eggs recorded from treated than from nontreated panicles. Control of fall armyworm and corn earworm with chlorpyrifos increased yield in the second planting 106% relative to nontreated plots. Fall armyworm control with methomyl increased plant height 6.8% in the second planting relative to nontreated plots. Yield losses were significantly correlated with corn earworm density in the first planting and fall armyworm damage in the second.
Stochastic dynamics of a neural network with inhibitory and excitatory connections

We analyze the dynamics of a stochastic neural model. We show that an inhibitory neuron incorporated into a population of connected excitatory neurons, stabilizes the oscillations of the total activity.
Distribution of the ices exposed near the south pole of Mars using Thermal Emission Imaging System (THEMIS) temperature measurements

[1] Understanding the present and past water cycle on Mars requires an accurate knowledge of the distribution and amount of H2O available near the surface. In this article, we present a map of the distribution of the surface material exposed between 87°S and 70°S in the summer (e.g., CO2 and H2O ices, dust) based on temperature measurements made by Thermal Emission Imaging System (THEMIS). Our compositional map (100 m per pixel) is in good agreement with spectral mapping returned by Observatoire pour la mineralogie, l'Eau, la Glace et l'activite (OMEGA) and Compact Reconnaissance Imaging Spectrometer for Mars (CRISM). Exposed water ice covers a total surface area of approximately 40,000 km2. A large fraction of the water ice is exposed at the periphery of the CO2 cap. An approximately 25,000-km2 large patch centered at 83.5°S and 345°E is discovered and represents the largest exposure of water ice in the southern hemisphere. It is not located on the south polar layered deposits but on the surrounding mantled terrains. THEMIS VIS, MOC and HiRISE images indicate that the surface roughness of exposed water ice terrains is typically lower than that of the surrounding dust. Polygonal patterns are observed on the water ice but not exclusively. There is a strong correlation between the surface albedo, the composition of the exposed material, and the timing of the initial seasonal CO2 frost deposition and final removal. These exposed water ice outcrops are not stable in the present environment and lose a vertical layer of tens to hundreds of micrometer a year to the atmosphere. The spike of water vapor above the south pole during the southern summer occurs while the water ice is still covered by a layer of seasonal CO2 frost, indicating that the sublimation of the exposed water ice is not the main contributor of vapor for the southern atmosphere. As water ice is not stable, it may indicate the past location of part of the CO2 perennial cap that has been eroded.
Earlier recovery with beating-heart surgery: A comparison of 300 patients undergoing conventional versus off-pump coronary artery bypass graft surgery

Abstract Objective: To compare outcomes and cost of off-pump coronary artery bypass (OP-CAB) surgery versus cardiopulmonary bypass–assisted coronary artery bypass graft (CABG) surgery. Design: Retrospective review. Setting: A tertiary care university teaching hospital. Participants: Patients (n = 300) undergoing isolated CABG surgery performed by a single surgeon between July 1998 and February 2000. Interventions: Two groups of patients were compared: 150 consecutive patients undergoing OP-CAB surgery and a matched cohort of 150 consecutive patients undergoing conventional CABG surgery. Measurements and Main Results: The 2 groups were evenly matched in terms of age and incidence of diabetes, hypertension, peripheral vascular disease, left main disease, prior strokes, congestive heart failure, and recent infarctions. OP-CAB procedures required 3.3 grafts per patient versus 3.8 grafts per patient required for CABG surgery ( p = 0.02). Overall mortality was 2.0% (1.3% in the OP-CAB surgery group v 2.7 % in the CABG surgery group; p = NS). Extubation times (6.6 hours v 9.5 hours; p = 0.003), surgical intensive care unit length of stay (39 hours v 49 hours; p = 0.03), and hospital length of stay (6.1 days v 7.0 days; p = 0.04) were all significantly shorter for the OP-CAB surgery group. The combined aggregate endpoints of death and major morbidity were significantly less in the OP-CAB surgery group (5.3% v 12.7%; p = 0.02). Conclusion: OP-CAB surgery is associated with low morbidity and mortality and accelerated recovery compared with conventional CABG surgery. OP-CAB surgery may represent the ideal revascularization strategy for patients at high risk for undergoing cardiopulmonary bypass.
Putative anaerobic activity in aerated composts

It has been suggested that anaerobic microenvironments develop in aerobic composts, regardless of the aeration system used, and that anaerobic activity is responsible for odor generation and nitrogen losses. This study was designed to measure levels of microorganisms capable of anaerobic growth in two aerated composts: municipal solid waste, a relatively nutrient-rich compost, and pulp and paper-mill solid waste, which is relatively nutrient-poor. Anaerobic microorganisms were isolated from both composts at mesophilic and thermophilic temperatures. The majority of the anaerobic mesophiles were facultative anaerobes, whereas facultative, anaerobic thermophiles varied from 0 to 100%. Serially-diluted samples were spot-plated onto various media to preserve microbial consortia. Levels of aerobic and anaerobic exoenzyme production on spot-plates were similar on cell-wall, starch, and casein media. Although microbial levels on spread plates indicate that aerobes are present in much higher numbers than anaerobes (in 47 of 56 subsamples, 90% of the population were aerobes), microbial growth levels and exoenzyme production on spot-plates indicate that anaerobes may be responsible for a large portion (greater than or equal to 72%) of the metabolic activity in anaerobic microenvironments of aerobic composts.
Thymidine phosphorylase and 2-deoxyribose stimulate human endothelial cell migration by specific activation of the integrins α5β1 and αVβ3

Thymidine phosphorylase is an angiogenic factor that is frequently overexpressed in solid tumors, in rheumatoid arthritis, and in response to inflammatory cytokines. Our previous studies showed that cells expressing thymidine phosphorylase stimulated endothelial cell migration in vitro. This was a consequence of the intracellular metabolism of thymidine by thymidine phosphorylase and subsequent extracellular release of 2-deoxyribose. The mechanisms by which 2-deoxyribose might mediate thymidine phosphorylase-induced cell migration in vitro, however, are obscure. Here we show that both thymidine phosphorylase and 2-deoxyribose stimulated the formation of focal adhesions and the tyrosine 397 phosphorylation of focal adhesion kinase in human umbilical vein endothelial cells. Although similar actions occurred upon treatment with the angiogenic factor vascular endothelial growth factor (VEGF), thymidine phosphorylase differed from VEGF in that its effect on endothelial cell migration was blocked by antibodies to either integrin alpha 5 beta 1 or alpha v beta 3, whereas VEGF-induced endothelial cell migration was only blocked by the alpha v beta 3 antibody. Further, thymidine phosphorylase and 2-deoxyribose, but not VEGF, increased the association of both focal adhesion kinase and the focal adhesion-associated protein vinculin with integrin alpha 5 beta 1 and, in intact cells, increased the co-localization of focal adhesion kinase with alpha 5 beta 1. Thymidine phosphorylase and 2-deoxyribose-induced focal adhesion kinase phosphorylation was blocked by the antibodies to alpha 5 beta 1 and alpha v beta 3, directly linking the migration and signaling components of thymidine phosphorylase and 2-deoxyribose action. Cell surface expression of alpha 5 beta 1 was also increased by thymidine phosphorylase and 2-deoxyribose. These experiments are the first to demonstrate a direct effect of thymidine phosphorylase and 2-deoxyribose on signaling pathways associated with endothelial cell migration.
Quantum interference and relaxation in optically detected double resonance

Abstract A theory predicting an interference effect analogous to that observed in rotational spectroscopy is presented for the optical detection of double resonances in triplet states of organic molecules. Relaxation parameters that characterize the processes of thermal equilibration can be evaluated from the concomitant spectral lineshapes.
Comparable Growth of Virulent and Avirulent Mycobacterium tuberculosis in Human Macrophages In Vitro

The relative virulence and avirulence of Mycobacterium tuberculosis strains H37Rv and H37Ra were previously defined using animal infection models. To investigate host species' specificity of mycobacterial virulence, growth of the 2 M. tuberculosis strains in human monocyte-derived macrophages in vitro was studied. Mycobacterial growth was evaluated by acid-fast staining, electron microscopy, and colony-forming units (cfu) assay. As expected, the 2 strains demonstrated significantly different growth rates in mouse macrophages in vitro (53 h for H37Rv, 370 h for H37Ra). In marked contrast, in human macrophages the average division times of the strains were nearly equal (80 h for H37Rv and 76 h for H37Ra by cfu measurement, and 96 h for H37Rv and 104 h for H37Ra by acid-fast staining). These findings indicate that observations of mycobacterial virulence in murine systems may not necessarily translate to the human system, in which different mechanisms to control mycobacterial growth may be expressed.
Efficacy of a tailored tobacco control program on long-term use in a population of U.S. military troops.

The authors evaluated the effect of a brief tailored smoking control intervention delivered during basic military training on tobacco use in a population of military personnel (N = 33,215). Participants were randomized to either a tobacco use intervention (smoking cessation, smokeless tobacco use cessation, or prevention depending on tobacco use history) or a health education control condition. Results indicated that smokers who received intervention were 1.16 (95% confidence interval [CI] = 1.04, 1.30) times (7-day point prevalence) and 1.23 (95% CI = 1.07, 1.41) times (continuous abstinence) more likely to be abstinent than controls from smoking cigarettes at the 1-year follow-up (p <.01); the cessation rate difference was 1.60% (31.09% vs. 29.49%) and 1.73% (15.47% vs. 13.74%) for point prevalence and continuous abstinence, respectively. Additionally, smokeless tobacco users were 1.33 (95% CI = 1.08, 1.63) times more likely than controls (p <.01) to be continuously abstinent at follow-up, an overall cessation rate difference of 5.44% (33.72% vs. 28.28%). The smoking prevention program had no impact on smoking initiation. These results suggest potential for large-scale tobacco control efforts.
BCR/ABL Regulates Expression of the Cyclin-dependent Kinase Inhibitor p27Kip1 through the Phosphatidylinositol 3-Kinase/AKT Pathway

Deregulation of cell cycle checkpoints is an almost universal abnormality in human cancers and is most often due to loss-of-function mutations of tumor suppressor genes such as Rb, p53, or p16(INK4a). In this study, we demonstrate that BCR/ABL inhibits the expression of a key cell cycle inhibitor, p27(Kip1), by signaling through a pathway involving phosphatidylinositol 3-kinase (PI3K). p27(Kip1) is a widely expressed inhibitor of cdk2, an essential cell cycle kinase regulating entry into S phase. We demonstrate that the decrease of p27(Kip1) is directly due to BCR/ABL in hematopoietic cells by two different approaches. First, induction of BCR/ABL by a tetracycline-regulated promoter is associated with a reversible down-regulation of p27(Kip1). Second, inhibition of BCR/ABL kinase activity with the Abl tyrosine kinase inhibitor STI571 rapidly increases p27(Kip1) levels. The PI3K inhibitor LY-294002 blocks the ability of BCR/ABL to induce p27(Kip1) down-regulation and inhibits BCR/ABL-induced entry into S phase. The serine/threonine kinase AKT/protein kinase B is a known downstream target of PI3K. Transient expression of an activated mutant of AKT was found to decrease expression of p27(Kip1), even when PI3K was inhibited by LY-294002. The mechanism of p27(Kip1) regulation is primarily related to protein stability, since inhibition of proteasome activity increased p27(Kip1) levels in BCR/ABL-transformed cells, whereas very little change in p27 transcription was found. Overall, these data are consistent with a model in which BCR/ABL suppresses p27(Kip1) protein levels through PI3K/AKT, leading to accelerated entry into S phase. This activity is likely to explain in part previous studies showing that activation of PI3K was required for optimum transformation of hematopoietic cells by BCR/ABL in vitro and in vivo.
Small Non-Cleaved-Cell Lymphoma (Undifferentiated Lymphoma, Burkitt's Type) in American Adults: Results with Treatment Designed for Acute Lymphoblastic Leukemia

PURPOSE: Small non-cleaved-cell lymphoma (SNCL) "Burkitt's type," a rapidly growing lymphoma, has been rare among adults in the United States, but has greatly increased in incidence with the acquired immunodeficiency syndrome epidemic. This report details the results of treatment of adult SNCL with a series of protocols originally designed for the treatment of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Between July 1973 and May 1987, 29 adults with newly diagnosed SNCL were treated at Memorial Hospital with intensive chemotherapy originally designed for ALL: the cyclophosphamide L-2, L-10, L-17, and L-20 protocols. Nine patients had positive serologies for human immunodeficiency virus (HIV) infection. One patient with all measurable disease resected was not evaluable for response. RESULTS: Sixteen of 28 evaluable patients (57%) achieved a complete remission with treatment. With follow-up as long as 153 months (median, 47 months), 50% of all patients and 59% of patients with negative or unknown HIV serologies have survived and are probably cured. Patients with an initial serum lactic acid dehydrogenase (LDH) level of greater than 500 U/L had a significantly shortened survival as compared with those with a lower serum LDH. Other pretreatment patient characteristics associated with a shortened survival of borderline statistical significance were high National Cancer Institute stage (C, D) and bone marrow involvement. These results are similar to those for ALL and lymphoblastic lymphoma and are comparable to those for American SNCL in the literature. CONCLUSIONS: Approximately one half of adults with SNCL are curable with intensive chemotherapy. More intensive chemotherapy with hematopoietic growth factor and/or autologous bone marrow or peripheral stem cell support may increase curability.
GEOLOGY AND BOUGUER GRAVITY ANOMALIES OF THE GULF OF TONKIN AND VICINITY

Abstract Outcrops of rock types around the Gulf of Tonkin range in age from Cambrian to Recent. The basement complex of the Gulf of Tonkin consists of Carboniferous carbonates and Lower Paleozoic metamorphic rocks. The Gulf of Tonkin and vicinity are comprised of three tectonic units: 1. (1) the Caledonian South China-North Vietnam Foldbelt, 2. (2) the Variscan Southeastern Maritime Foldbelt and 3. (3) the Indosinian Foldbelt of Vietnam. The Gulf of Tonkin subsided after the Cretaceous period. Up to 5 km of Tertiary sediments has accumulated in the Gulf of Tonkin. A distinct Bouguer gravity anomaly of +10 mgal is present in the middle of the Gulf of Tonkin and is also associated with shallow depth to Moho. Recent discovery of natural gas and oil in the Gulf of Tonkin may indicate major oil and gas fields.
Salamander predation and vertical distributions of zooplankton

SUMMARY. 1. The impact of different predation regimes of zooplanktivorous larval tiger salamanders, Ambystoma tigrinum nebulosum, on the vertical temporal distributions of Daphnia pulex, Diaptomus nudus and larval Chaoborus flavicans was studied in limnetic enclosures in a pond in east-central Arizona. Zooplankton densities were monitored 1-2 h before sunset, at sunset, and 1-2 h after sunset at three depths (0-0.4, 1.0 and 2.0 m) in four salamander treatments (0, 20, 40 salamanders per enclosure, and unenclosed limnetic areas). 2. Densities and body size of Daphnia pulex were consistently greater in salamander-free enclosures than in other treatments. More Daphnia were generally nearer the surface (0-1.0 m) than along the bottom before and at sunset than after sunset in enclosures without salamanders. After sunset, Daphnia was by far most dense along the bottom. Densities were uniform among depths and sample times in treatments with salamanders. Salamanders moved throughout the water column. Frequencies of D. pulex spined morphs (with prominent dorsal crest) did not differ among salamander treatments. 3. Chaoborus densities were positively correlated with D. pulex distributions among depths and sample times in treatments. Spatio-temporal distributions of Chaoborus were influenced more by their daphnid prey than by risk of predation from larval salamanders. 4. Densities of Diaptomus nudus were highest in open water controls and lowest in enclosures without salamanders. Diaptomus was generally more dense between 0 and 1 m than at 2.0 m depths in all treatments, and vertical distributions were not dependent on salamander density.
Assessment of skewed exposure in case‐control studies with pooling

Pooling based strategies that combine samples from multiple participants for laboratory assays have been proposed for epidemiologic investigations of biomarkers to address issues including cost, efficiency, detection, and when minimal sample volume is available. A modification of the standard logistic regression model has been previously described to allow use with pooled data; however, this model makes assumptions regarding exposure distribution and logit-linearity of risk (i.e., constant odds ratio) that can be violated in practice. We were motivated by a nested case-control study of miscarriage and inflammatory factors with highly skewed distributions to develop a more flexible model for analysis of pooled data. Using characteristics of the gamma distribution and the relation between models of binary outcome conditional on exposure and of exposure conditional on outcome, we use a modified logistic regression to accommodate non-linearity due to unequal shape parameters in gamma distributed exposure for cases and controls. Using simulations, we compare our approach with existing methods for logistic regression for pooled data considering: 1. Constant and dose-dependent effects; 2. Gamma and log-normal distributed exposure; 3. Effect size, and; 4. The proportions of biospecimens pooled. We show that our approach allows estimation of odds ratios that vary with exposure level, yet has minimal loss of efficiency compared to existing approaches when exposure effects are dose-invariant. Our model performed similarly to a maximum likelihood estimation approach in terms of bias and efficiency, and provides an easily implemented approach for estimation with pooled biomarker data when effects may not be constant across exposure.