cssi/SciSciGPT-SciSciNet huggingface dataset:
Nucleotide Dependence of Rab Geranylgeranylation: Rab ESCORT PROTEIN INTERACTS PREFERENTIALLY WITH GDP-BOUND Rab *

Geranylgeranylation of Rab GTPases is an essential post-translational modification that enables Rabs to associate with intracellular membranes where they regulate exocytic and endocytic pathways. Geranylgeranylation is initiated by formation of a stable complex between newly synthesized Rab proteins and Rab escort protein (REP). The complex is recognized by Rab geranylgeranyl (GG) transferase, which transfers two GG groups to Rabs. The geranylgeranylated Rabs regulate vesicular movement by oscillating between an inactive GDP-bound form and an active GTP-bound form. In this study, I show that the kinetics of geranylgeranylation is influenced by the nucleotide status of nascent Rab. GDP-bound Rab is geranylgeranylated with 10–50-fold higher affinity than GTP-bound Rab (or GTP analog-bound Rab), as indicated by the apparent Km of the reaction. In vitro REP·Rab binding assays demonstrate that REP forms a stable complex only with the GDP-bound form of Rab but not the GTP-bound form, suggesting that the apparent Km effect in the prenylation reaction is due to a discrimination between the two different nucleotide-bound forms of Rab by REP. Inasmuch as Rabs are likely GTP-bound after synthesis and REP does not possess GTPase-activating protein activity, these results raise the possibility that a Rab GTPase-activating protein enhances the REP·Rab interaction prior to prenylation.
Femtosecond microscopy of an expanding 3 -size aluminum plasma excited at relativistic intensity

A λ2-size spot of an aluminum target excited at >1018W/cm2 is found to expand radially and vertically at nearly 108cm/s by imaging radial expansion with <1µm resolution and inferring vertical expansion from time-resolved resonance absorption.
Human Adenine Phosphoribosyltransferase PURIFICATION, SUBUNIT STRUCTURE, AND SUBSTRATE SPECIFICITY

Adenine phosphoribosyltransferase (APRT) catalyzes the magnesium dependent conversion of adenine to adenosine 5’-monophosphate (AMP) utilizing the high energy compound, 5-phosphoribosyl-lpyrophosphate (PP-ribose-P) as a cosubstrate. In humans this enzyme provides the only apparent pathway for conversion of dietary adenine into utilizable nucleotides. The finding of elevated levels of APRT activity in patients with the Lesch-Nyhan syndrome (Seegmiller, Rosenbloom and Kelley, 1967; Kelley, 1968) and the discovery of at least three families with a genetically determined partial deficiency of APRI activity in circulating erythrocytes (Kelley, et al., 1968; Kelley, Fox and Wyngaarden, 1970; Emmerson, et al., present symposium) stimulated our study of a highly purified preparation of human adenine phosphoribosyltransferase.
Clinical significance of fever in the systemic lupus erythematosus patient receiving steroid therapy.

Clinical significance of fever in the systemic lupus erythematosus patient receiving steroid therapy. Background Active systemic lupus erythematosus (SLE) can cause fever. Steroids (glucocorticoids) suppress SLE fever; however, the extent to which steroid therapy affects SLE fever not previously been rigorously studied. Methods Study A is a prospective study of recurrently active SLE patients ( N = 92, 60 renal SLE and 32 nonrenal SLE) who recorded daily oral evening temperatures while participating in a longitudinal study of risk factors for SLE flare. Study B is a retrospective study of consecutive febrile SLE patients ( N = 22) who received steroids initially because SLE was suspected. At final analysis 11 had SLE fever and 11 had infection fever. Results In study A during a mean follow-up of 13.2 ± 8.1 months, 51 of the 92 patients experienced 73 SLE flares. In only one patient was SLE fever associated with SLE flare. In the other 50 patients who flared, there was no significant trend to develop fever prior to or at the onset of SLE flare. Prednisone, median dose 10mg, was being received at 82% of the study visits at which an SLE flare was declared. In study B, prednisone 28mg (range 20 to 40mg) completely suppressed SLE fever, usually within 24 hours. In contrast, infection fever persisted despite prednisone 35 to 300mg/day. Of those with infection fever, three developed fatal sepsis when high-dose steroid therapy was continued. Conclusion In SLE patients receiving prednisone at maintenance doses or greater, SLE fever is rare. When fever does develop, it is usually due to infection. Continuing high steroid dose steroid therapy in those with infection fever may increase the risk of severe sepsis.
Using a blackboard architecture or expert system to identify obfuscated targets from symptoms

A variety of techniques exist for enhancing or inferring the existence and characteristics of an obscured or partially concealed target. Targets, however, may be completely blocked from view, presenting nothing to enhance and no image area to extend inferentially. Despite the difficulty, concealed (particularly intentionally) targets may be the most important to detect. This paper proposes a technique for using a Blackboard Architecture or Expert system to infer a target’s existence from symptoms (maneuvers of other units, water and soil deformation, etc.) and discusses the differences between the two approaches (Blackboard Architecture and expert system) for doing so.
The underwater sound field from vibratory pile driving.

Underwater noise from vibratory pile driving was observed using a vertical line array placed at range 16 m from the pile source (water depth 7.5 m), and using single hydrophones at range 417 m on one transect, and range 207 and 436 m on another transect running approximately parallel to a sloping shoreline. The dominant spectral features of the underwater noise are related to the frequency of the vibratory pile driving hammer (typically 15–35 Hz), producing spectral lines at intervals of this frequency. The mean-square pressure versus depth is subsequently studied in third-octave bands. Depth and frequency variations of this quantity observed at the vertical line array are well modeled by a field consisting of an incoherent sum of sources distributed over the water column. Adiabatic mode theory is used to propagate this field to greater ranges and model the observations made along the two depth-varying transects. The effect of shear in the seabed, although small, is also included. Bathymetric refraction on the transect parallel to the shoreline reduced mean-square pressure levels at the 436-m measurement site.
5’-adenosine monophosphate mediated cooling treatment enhances ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) stability in vivo

Gene mutations that produce misprocessed proteins are linked to many human disorders. Interestingly, some misprocessed proteins retained their biological function when stabilized by low temperature treatment of cultured cells in vitro. Here we investigate whether low temperature treatment in vivo can rescue misfolded proteins by applying 5’-AMP mediated whole body cooling to a Cystic Fibrosis (CF) mouse model carrying a mutant cystic fibrosis transmembrane conductance regulator (CFTR) with a deletion of the phenylalanine residue in position 508 (ΔF508-CFTR). Low temperature treatment of cultured cells was previously shown to be able to alleviate the processing defect of ΔF508-CFTR, enhancing its plasma membrane localization and its function in mediating chloride ion transport. Here, we report that whole body cooling enhanced the retention of ΔF508-CFTR in intestinal epithelial cells. Functional analysis based on β-adrenergic dependent salivary secretion and post-natal mortality rate revealed a moderate but significant improvement in treated compared with untreated CF mice. Our findings demonstrate that temperature sensitive processing of mutant proteins can be responsive to low temperature treatment in vivo.
Verifiable Escrowed Signature

We combine a publicly verifiable encryption technique and a Schnorr type signature scheme to achieve a verifiable escrowed signature scheme. The scheme allows a signer to convince a verifier the validity of a signature without letting him see the signature value. The unavailable but verifiable signature is encrypted under a public key of someone (e.g., a trusted third party) who stays off-line. The technique will have useful applications in such as fair exchange of contracts between two untrusted parties without using on-line help of a commonly trusted third party, and fair escrow cryptosystems using off-line escrow agents.
A Teaching Conference of One's Own: Inviting Faculty into the Scholarly Work of Teaching

This essay examines the value of creating a peer-reviewed conference on teaching at one's own campus. A conference created by faculty and for faculty is an effective way to address several challenges faced by many teaching centers, especially the challenge of involving a wide range of faculty in scholarly approaches to teaching. I cite experience and data from my center's work in this area over the past six years and contextualize it amidst the literature on the scholarship of teaching and learning.
From communal charity to national welfare: Jewish orphanages in Eastern Europe before and after World War I

This article examines Jewish institutions for the care of orphans in an attempt to understand several aspects of Jewish life in Eastern Europe: (1) attitudes towards orphans on the part of communal leaders, intellectuals, and political activists; (2) the transition of Jewish charitable and (in the modern period) philanthropic institutions from the pre‐modern communal charity of the early nineteenth century to modern “scientific philanthropy” at the fin de siecle to national welfare in the interwar period; (3) and, to a lesser extent, the experiences of orphans themselves, as far as is possible to ascertain from documents relating to the institutions that cared for them. Marginal figures such as orphans were of growing concern to the organised Jewish community in its increasingly complex encounter with modernity in the Russian Empire, and traditional patterns of charity, family life, and relations between socioeconomic classes were cast into doubt by new government policies and modern scientific attitudes ...
Detection of botulinum neurotoxin-A activity in food by peptide cleavage assay

The World Health Organization (WHO) and U.S. Centers for Disease Control and Prevention (CDC) have labeled botulinum toxins as a high priority biological agent that may be used in terrorist attacks against food supplies. Due to this threat there is an increased need to develop fast and effective methods to detect active botulinum neurotoxins (BoNTs). This study reports the successful use of an enzymatic assay employing an internally quenched fluorogenic peptide as a fast, simple and inexpensive alternative to the mouse bioassay. In less than 15 min the assay can detect 0.25 nM BoNT-A in liquid food samples. The detection level is far below the adult human lethal oral dose of 70 μg of toxin. Immunomagnetic beads coated with IgG monoclonal antibodies that target the toxin heavy chain can concentrate the toxin without neutralizing its enzymatic activity, overcoming matrix effects caused by endogenous protease inhibitors and peptidases. This fast and effective assay system could be used for large scale screening to detect BoNT-A.
Advances in the Treatment of Obstructive Sleep Apnea

This article focuses on the treatment of obstructive sleep apnea (OSA), using the most recent available data. The first choice of treatment for patients with moderate or severe obstructive sleep apnea is continuous positive airway pressure (CPAP), which was first described in 1981 (Sullivan et al. Lancet 1(8225):862-5, 1981) and works by splinting the airway open to facilitate proper airflow. For patients with mild OSA, other treatments may be considered including positional therapy, weight loss, or oral appliances. Oral appliances are continuing to become more mainstream, and may be a reasonable first-line treatment even for some patients with moderate OSA, such as those who cannot tolerate or do not want to use CPAP. Some evidence suggests that adherence to mandibular advancement devices (MADs), a type of oral appliance, may be superior to that of CPAP. Recent evidence has suggested that the MAD may be similar to CPAP in preventing cardiovascular mortality in OSA, though objective measurement of MAD adherence was not available in the study. Objective adherence monitors are now available for oral appliances and should prove valuable for clinicians. Pharmacotherapy has not been shown to be significantly effective in the treatment of OSA and should be considered as an adjunctive treatment class, though some emerging evidence may support pharmacotherapy for specific purposes, such as acetazolamide for high-altitude travelers and zonisamide for weight loss. Upper airway surgical intervention remains a second- or third-line treatment class for moderate to severe OSA, though multiple case series of maxillomandibular advancement (MMA) have shown considerable, statistically significant improvements in AHI. Weight loss should always be recommended for patients with OSA who are overweight or obese, as weight loss may result in improvement in OSA. Bariatric operations are effective for obesity and are reasonable considerations for obese patients, although a recent randomized controlled trial found that bariatric intervention failed to achieve superiority over conventional weight loss therapy in terms of apnea-hypopnea index (AHI) reduction.
PROTEIN COAGULATION AND ITS REVERSAL : GLOBIN.

1. The globin prepared from hemoglobin by the acid acetone method is denatured globin. 2. The denaturation and coagulation of globin by acid acetone are reversible. 3. Soluble globin can be obtained from the acid acetone globin even if the globin is first precipitated by trichloracetic acid or heated to 100 degrees C. 4. Hill and Holden's theory that they separated native globin from hemoglobin without any intermediate denaturation is not proven by their experiments.
Combating inter-cell interference in 802.11ac-based multi-user MIMO networks

In an 802.11ac-based MU-MIMO network comprised of multiple cells1, inter-cell interference allows only a single AP to serve its clients at the same time, significantly limiting the network capacity. In this work, we overcome this limitation by letting the APs and clients in interfering cells coordinately cancel the inter-cell interference using their antennas for beamforming. To achieve such coordinated interference cancellation in a practical way, we propose a novel two-step optimization. First, without requiring any channel knowledge, each AP and client optimizes the use of its antennas for either data communication or inter-cell interference cancellation, in order to maximize the total number of deliverable streams in the MU-MIMO network. Second, with only partial channel knowledge, each AP and client optimizes their beamforming weights after the optimal antenna usage has been identified in the first step. Our solution, CoaCa, integrates this two-step optimization into 802.11ac with small modifications and negligible overhead, allowing each AP and client to locally perform the two-step optimization. Our experimental evaluation indicates that for a MU-MIMO network with two cells, by cancelling the inter-cell interference CoaCa can convert the majority of the expected number of streams increase (50%-67%) into network capacity improvement (41%-52%).
Strain-life fatigue predictions for sintered steels with nonzero mean stress

Several approximate models have been utilized for fatigue life prediction. Some of these models are available for mean stress (or strain) correction on fatigue life, when nonzero mean stress (or strain) is applied. In this paper, the most commonly used empirical strain-life models for fatigue life predictions, for materials subjected to variable amplitude loads, are described. Experimental results of fatigue tests, where the specimens of sintered steels were subjected to partial random loads, are presented and compared with those results obtained theoretically by the models. The utilization of the various models and their influence on results are discussed.
Biochemical characterization of the kinase domain of the rice disease resistance receptor-like kinase XA21

The rice disease resistance gene, Xa21, encodes a receptor kinase-like protein consisting of leucine-rich repeats in the putative extracellular domain and a serine/threonine kinase in the putative intracellular domain. The putative XA21 kinase domain was expressed as maltose-binding and glutathione S-transferase fusion proteins in Escherichia coli. The fusion proteins are capable of autophosphorylation. Phosphoamino acid analysis of the glutathione S-transferase fusion protein indicates that only serine and threonine residues are phosphorylated. The relative phosphorylation rate of the XA21 kinase against increasing enzyme concentrations follows a first-order rather than second-order kinetics, indicating an intramolecular phosphorylation mechanism. Moreover, the active XA21 kinase cannot phosphorylate a kinase-deficient mutant of XA21 kinase. The enzymatic activity of the XA21 kinase in a buffer containing Mn(2+) is at least 15 times higher than that with Mg(2+). The K(m) and V(max) of XA21 kinase for ATP are 0.3 microm and 8.4 nmol/mg/min, respectively. Tryptic phosphopeptide mapping reveals that multiple sites on the XA21 kinase are phosphorylated. Finally, our data suggest that the region of XA21 kinase corresponding to the RD kinase activation domain is not phosphorylated, revealing a distinct mode of action compared with the tomato Pto serine/threonine kinase conferring disease resistance.
Robust Control of Nonlinear Systems Using Model-Error Control Synthesis

A new approach for the robust control of nonlinear systems is presented. This approach employs an optimal real-time nonlinear estimator to determine model error corrections to the control input using a one time-step ahead technique. Control compensation is achieved by using the estimated model error as a signal synthesis adaptive correction to the nominal control input so that maximum performance is achieved in the face of extreme model uncertainty and disturbance inputs. A significant advantage of this approach over other adaptive methods is that model parameters need not be updated online. Instead, the effects of these errors are used to update the actual control signal, which leads to a simple design strategy. The model-error control synthesis approach is used in conjunction with a variable structure controller to suppress the wing-rock motion of a slender delta wing. Simulation results indicate that the model-error control synthesis approach is extremely effective in providing closed-loop robustness in the face of significant model uncertainties and disturbance inputs. 1 Assistant Professor, Texas A&M University, Department of Aerospace Engineering, College Station, TX 77843-3141. Senior Member AIAA.
Ethical Incentives — Not Payment — For Organ Donation

The therapeutic promise of transplanting organs from cadaveric donors, as envisioned by the pioneers of transplantation,1 has never been realized because the demand for cadaveric organs has far exceeded the supply. The waiting list for organ transplants continues to grow, and in 2000, nearly 5000 patients were removed from the list because of death.2 Consequently, many patients with end-stage organ failure are no longer relying solely on the waiting list. Instead, they are turning to spouses, friends, or strangers as possible donors — a medically acceptable alternative because advances in immunosuppression have eliminated the requirement of a genetic match for . . .
Low Resolution Crystal Structure of Arenicola Erythrocruorin: Influence of Coiled Coils on the Architecture of a Megadalton Respiratory Protein

Abstract Annelid erythrocruorins are extracellular respiratory complexes assembled from 180 subunits into hexagonal bilayers. Cryo-electron microscopic experiments have identified two different architectural classes. In one, designated type I, the vertices of the two hexagonal layers are partially staggered, with one hexagonal layer rotated by about 16° relative to the other layer, whereas in the other class, termed type II, the vertices are essentially eclipsed. We report here the first crystal structure of a type II erythrocruorin, that from Arenicola marina , at 6.2 A resolution. The structure reveals the presence of long continuous triple-stranded coiled-coil “spokes” projecting towards the molecular center from each one-twelfth unit; interdigitation of these spokes provides the only contacts between the two hexagonal layers of the complex. This arrangement contrasts with that of a type I erythrocruorin from Lumbricus terrestris in which the spokes are broken into two triple-stranded coiled coils with a disjointed connection. The disjointed connection allows formation of a more compact structure in the type I architecture, with the two hexagonal layers closer together and additional extensive contacts between the layers. Comparison of sequences of the coiled-coil regions of various linker subunits shows that the linker subunits from type II erythrocruorins possess continuous heptad repeats, whereas a sequence gap places these repeats out of register in the type I linker subunits, consistent with a disjointed coiled-coil arrangement.
Limited transcriptional response of ovine microglia to prion accumulation.

The conversion of normal cellular prion protein to disease-associated prion protein (PrP Sc ) is a fundamental component of prion disease pathogenesis. The molecular mechanisms contributing to prion conversion and the impact of PrP Sc accumulation on cellular biology are not fully understood. To further define the molecular changes associated with PrP Sc accumulation in cultured cells, the transcriptional profile of PrP Sc -accumulating primary ovine microglia was compared to the profile of PrP Sc -lacking microglia using the Affymetrix Bovine Genome Array. The experimental design included three biological replicates, each with three technical replicates, and samples that were collected at the point of near maximal PrP Sc accumulation levels as measured by ELISA. The array analysis revealed only 19 upregulated genes and 30 downregulated genes in PrP Sc -accumulating microglia. The results support the hypothesis that chronic PrP Sc accumulation in cultured microglia results in a limited transcriptional response.
Grain‐Bridging Mechanisms in Monolithic Alumina and Spinel

The postfracture tensile (PFT) test procedure is implemented to study wake zone stresses in monolithic alumina, which contribute toward the cumulative component of toughening. This novel procedure allows for the direct evaluation of the critical wake zone stress and stress distribution as a function of crack face separation. These PFT results for the current alumina yield a maximum wake zone stress which compares favorably with the theoretical and experimental citations in the literature. We present the controlling relationship between the grain size distribution and fracture mode, and the PFT curve character as a means which may lead to microstructural design. Finally, the grain interlocking mechanism is quantitatively shown to be more effective in this noncubic material than in cubic magnesium aluminate spinel microstructures.
Alleviation of the Backus Effect in geomagnetic field modelling

Satellite magnetometry is plagued by the Backus effect which renders maps of the magnetic field derived from measurements of the total field intensity unreliable, especially near the geomagnetic equator. The only remedy is to use oriented, vector component data in addition to scalar intensity data, but this requires either accurate determination of the satellite attitude or the use of data from permanent magnetic observatories. The former adds considerably to the cost and complexity of satellite magnetometry; the latter suffers in practice from the poor geographical distribution of magnetic observatories. Here we re-examine the problem of attitude determination, and ask how well the attitude needs to be determined to alleviate the Backus effect. We show that the use of a more complete model of the errors in satellite vector component data allows the requirements on attitude determination to be relaxed significantly, so that lower-cost means of obtaining attitude determination, such as GPS, can be employed.
Cr and TaN absorber mask etch CD performance study for extreme-ultraviolet lithography

Extreme Ultraviolet Lithography (EUVL) is the leading candidate for the 45 nm node technology and beyond. A mask film structure and material selection become increasingly important for a success in the EUVL mask process development. Etch CD performance is considered in the material selection of an EUV mask absorber stack. This paper reports the study of etch CD performance and pattern loading effects in the plasma etch on two potential absorber materials of Cr and TaN. The etch process was experimentally setup on wafer samples and two different film etches were conducted in the same etch chamber. The CD data was collected on an SEM and was used for the CD performance analysis and comparison. In this study, it was found that the process etch CD bias in the TaN etch was significantly smaller than that in the Cr etch due to a fast etch rate of the TaN etch. The variation of the etch CD bias in the TaN etch was slightly higher than that in the Cr etch. The global pattern density changes had less impact to the Cr etch bias than the TaN etch bias.
A THERMODYNAMIC ANALYSIS OF THE PARTITIONING OF CHOLESTEROL AND RELATED COMPOUNDS BETWEEN TRIOLEOYLGLYCEROL AND EGG PHOSPHATIDYLCHOLINE BILAYERS

Abstract The free energy of transfer of a number of alcohols, including cholesterol, from a bulk isotropie lipid phase, trioleoylglycerol (TG), to an anisotropic lipid phase, egg phosphatidylcholine (PC), was determined. n-Alkane-1-ols partitioned preferentially into the bilayer phase; for example, the free energy of transfer of octanol-1 from TG to PC was about −1.0 kcal/mol. This preference declined with increasing number of carbons at a rate of 40 cal/mol of CH2. Cholesterol had a much stronger preference for the bilayer with a free energy of −1.3 kcal/mol, compared to an extrapolated value of −0.2 kcal/mol for a normal alkane-1-ol with the same number of carbon atoms. Thus, the excess free energy of −1.1 kcal/mol represents the favourable interaction of the cholesterol skeleton with the bilayer phase. This conclusion was confirmed by comparing cholesterol 3-hemisuccinate to oleic acid. Substituting TG for water as the standard state has eliminated the large hydrophobic effect and has permitted us to identify for the first time the subtle binding increment of the steroid ring system.
Complexity perplexity: a systematic review to describe the measurement of medication regimen complexity.

Introduction: Complex medication regimens are error prone and challenging for patients, which may impact medication adherence and safety. No universal method to assess the complexity of medication regimens (CMRx) exists. The authors aim to review literature for CMRx measurements to establish consistencies and, secondarily, describe CMRx impact on healthcare outcomes. Areas covered: A search of EMBASE and PubMed for studies analyzing at least two medications and complexity components, among those self-managing medications, was conducted. Out of 1204 abstracts, 38 studies were included in the final sample. The majority (74%) of studies used one of five validated CMRx scales; their components and scoring were compared. Expert opinion: Universal CMRx assessment is needed to identify and reduce complex regimens, and, thus, improve safety. The authors highlight commonalities among five scales to help build consensus. Common components (i.e., regimen factors) included dosing frequency, units per dose, and non-or...
Comparing and Combining Read Miss Clustering and Software Prefetching

A recent latency tolerance technique, read-miss clustering, restructures code to send demand-miss references in parallel to the underlying memory system. An alternative, widely-used latency tolerance technique is software prefetching, which initiates data fetches ahead of expected demand-miss references by a certain distance. Since both techniques seem to target the same types of latencies and use the same system resources, it is unclear which technique is superior or if both can be combined. This paper shows that these two techniques are actually mutually beneficial, each helping to overcome limitations of the other: We perform our study for uniprocessor and multiprocessor configurations, in simulation and on a real machine (the Convex Exemplar). Compared to prefetching alone (the state-of-the-art implemented in systems today), the combination of the two techniques reduces the execution time by an average of 21% across all cases studied in simulation, and by an average of 16% for 5 out of 10 cases on the Exemplar. The combination sees execution time reductions relative to clustering alone averaging 15% for 6 out of 11 cases in simulation and 20% for 6 out of 10 cases on the Exemplar.
Strategies for adaptive optimization with aggregation constraints using interior-point methods

Constraint-aggregation methods are used in engineering optimization problems to approximately impose a bound on a quantity of interest in a differentiable manner. In this paper, we present strategies to adaptively solve aggregation-constrained problems. These adaptive techniques achieve a tighter bound approximation while also reducing the computational cost of optimization. We focus on two aggregation techniques: Kreisselmeier-Steinhauser (KS) aggregation, and induced exponential aggregation. We demonstrate that the proposed adaptive technique achieves significant computational savings compared to fixed-aggregation methods for a series of stress-constrained mass-minimization problems.
Inhibition of NF-kappa B binding correlates with increased nuclear glucocorticoid receptor levels in acute alcohol-treated human monocytes.

BACKGROUND Acute alcohol treatment blocks inflammatory cytokines via inhibition of NF-kappaB in monocytes in the presence of ongoing IkappaBalpha degradation, suggesting regulation of NF-kappaB activation downstream of IkappaBalpha degradation. DNA binding of NF-kappaB has been suggested to be regulated by other nuclear regulatory factors, including the glucocorticoid receptor (GR). Here, we show for the first time that acute alcohol (25 mM) exposure modulates GR activation in monocytes. METHODS Human peripheral blood monocytes were treated with lipopolysaccharide (LPS) in the presence or absence of alcohol (25 mM) for 1 hour. Nuclear GR levels were estimated by Western blotting and NFkappaB activation was studied in the same extracts by gel shift analysis (EMSA). Cells were stimulated with 1 microM of Dex to be used as positive control for GR activation. GR/GRE binding was also determined in nuclear extracts by EMSA. IkappaBalpha mRNA known to be induced by GR/GRE activation was studied in total RNA extracts by the SuperArray method (SuperArray Inc., Bethesda, MD). RESULTS LPS is a potent inducer of GR nuclear translocation and GR binding to the glucocorticoid response element (GRE). Acute alcohol treatment both induced (p < 0.05) and augmented (p < 0.05) LPS-stimulated GR nuclear levels. However, alcohol inhibits LPS-induced (nonligand bound) GR/GRE binding activity in monocytes. This inhibition of GR transactivation by alcohol was further confirmed by decreased expression (40%) of a target gene, IkappaBalpha. Thus, alcohol treatment increases nonligand-bound nuclear GR, but inhibits its transactivation function. Ligand-induced GR/GRE binding was decreased in alcohol-treated monocytes. Inhibition of ligand-induced GR/GRE binding by alcohol exposure is likely due to cytoplasmic retention of the GR. CONCLUSIONS Our results show that acute alcohol exposure inhibits GR in monocytes by differently affecting ligand- and nonligand-induced GR nuclear translocation. These data also suggest that acute alcohol regulates GR activation in monocytes concomitant to inhibition of NF-kappaB activation.
Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism

Sleep disruption has detrimental effects on glucose metabolism through pathways that remain poorly defined. Although numerous studies have examined the consequences of sleep deprivation (SD) in the brain, few have directly tested its effects on peripheral organs. We examined several tissues in mice for induction of the unfolded protein response (UPR) following acute SD. In young animals, we found a robust induction of BiP in the pancreas, indicating an active UPR. At baseline, pancreata from aged animals exhibited a marked increase in a pro-apoptotic transcription factor, CHOP, that was amplified by SD, whereas BiP induction was not observed, suggesting a maladaptive response to cellular stress with age. Acute SD increased plasma glucose levels in both young and old animals. However, this change was not overtly related to stress in the pancreatic beta cells, as plasma insulin levels were not lower following acute SD. Accordingly, animals subjected to acute SD remained tolerant to a glucose challenge. In a chronic SD experiment, young mice were found to be sensitized to insulin and have improved glycemic control, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations. Our results show that both age and SD cooperate to induce the UPR in pancreatic tissue. While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, CHOP induction in pancreatic tissues suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells and that these effects may be exacerbated by normal aging.
The effects of boceprevir and telaprevir on the pharmacokinetics of maraviroc: an open-label, fixed-sequence study in healthy volunteers.

OBJECTIVE To evaluate the effects of boceprevir (BOC) and telaprevir (TVR) on the pharmacokinetics (PK) of maraviroc (MVC) in healthy volunteers. METHODS In this open-label, fixed-sequence study, 14 volunteers received MVC 150 mg twice daily alone for 5 days (period 1), followed by MVC + BOC 800 mg 3 times daily and MVC + TVR 750 mg 3 times daily, each for 10 days in periods 2 and 3, respectively, with a ≥10-day wash-out. PK was analyzed on day 5 of period 1 and day 10 of periods 2 and 3. Safety was also assessed. RESULTS Ratios of the adjusted geometric means (90% confidence intervals) for MVC area under the curve from predose to 12 hours, maximum plasma concentration, and plasma concentration at 12 hours were 3.02 (2.53 to 3.59), 3.33 (2.54 to 4.36), and 2.78 (2.40 to 3.23), respectively, for MVC + BOC versus MVC alone, and 9.49 (7.94 to 11.34), 7.81 (5.92 to 10.32), and 10.17 (8.73 to 11.85), respectively, for MVC + TVR versus MVC alone. PK profiles for MVC + BOC or TVR were consistent with historic values for BOC and TVR monotherapy. Adverse event incidence was higher with MVC + BOC and MVC + TVR versus MVC alone. Dysgeusia (50%) and pruritus (29%) occurred most commonly with MVC + BOC, and fatigue (46%) and headache (31%) with MVC + TVR. There were no serious adverse events. CONCLUSIONS MVC exposures were significantly increased with BOC or TVR, therefore MVC should be dosed at 150 mg twice daily when coadministered with these newly approved hepatitis C protease inhibitors. No dose adjustment for BOC or TVR is warranted with MVC. MVC + BOC or TVR was generally well tolerated with no unexpected safety findings.
Making by-products a main product of discussion: A challenge to accounting educators

Abstract Current textbook coverage of accounting for by- products is critically examined in the present article. Most texts suggest that, because amounts involved are relatively “immaterial,” any of several techniques is acceptable. For the most part, little reference to any underlying concepts, other than the concept of “materiality,” is included in textbook discussion of this topic. Educational theorists assert that learning is enhanced when students are able to anchor new information to material previously learned. The authors argue that it is both possible and desirable to tie the presentation of by-product accounting to (a) the FASB Concept Statements (specifically, to asset and revenue recognition concepts) and (b) other financial accounting practices to which students are traditionally exposed. The by-products illustration used in this article is but one example of how cost accounting topics can be tied to the mainstream of accounting thought. The authors encourage such applications in other cost accounting areas by accounting educators.
Intracellular alkaline phosphatase activity in cultured human cancer cells.

The effect of saponin treatment in demonstrating intracellular portion of alkaline phosphatase activity in human cancer cell lines was evaluated. Previous reports using standard lead-salt techniques visualized enzyme almost exclusively on the plasma membrane and sometimes in the lysosomes. However, by treating cells with saponin before or during the cytochemical incubation, intracellular alkaline phosphatase became demonstrable at the endoplasmic reticulum, Golgi apparatus, Golgi-derived vesicles and mitochondria as well as lysosomes and plasma membrane. These intracellular catalytic activities were significantly inhibited by the specific amino acid inhibitors characteristic for each cell line, and this suggested that intracellular alkaline phosphatase is the same isoenzyme as that present in the plasma membrane. The results of our current and previous studies therefore indicate that saponin reveals latent intracellular alkaline phosphatase activity by changing the membrane's physical state; thereby increasing the availability of both catalytic and antigenic sites of the enzyme to substrate and to antibody respectively.
RELATIONSHIP BETWEEN INTRACRANIAL ULTRASOUND (US) ABNORMALITIES AND VENTILATORY ASSISTANCE (VA) IN LOW BIRTH WEIGHT (LBW) INFANTS

RELATIONSHIP BETWEEN INTRACRANIAL ULTRASOUND (US) ABNORMALITIES AND VENTILATORY ASSISTANCE (VA) IN LOW BIRTH WEIGHT (LBW) INFANTS
Environmental Helicity and Its Effects on Development and Intensification of Tropical Cyclones

AbstractMuch attention has been given to the impact of environmental wind shear in the 850–200-hPa layer on tropical cyclones (TCs). However, even with the same magnitude of shear, helicity in this layer can vary significantly. A new parameter is presented, the tropical cyclone–relative environmental helicity (TCREH). Positive TCREH leads to a tilted storm that enhances local storm-scale helicity in regions of convection within the TC. This enhanced local-scale helicity potentially allows for more robust and longer-lasting convection, which is more effective at generating latent heat and subsequent TC intensification. TC vertical tilt is often attributed to wind shear. Different values of helicity modulate this tilt and certain tilt configurations are more favorable for development or intensification than others, suggesting that mean positive environmental helicity is more favorable for development and intensification than mean negative helicity. Idealized modeling simulations demonstrate the impact of en...
A checkable interface language for pointer-based structures

We present a technique for analysing structural constraints on data aggregates in high-level languages. Our technique includes a formal constraint language and a dataflow algorithm for automatically checking equality constraints. The constraint language is used to augment the type information on program interfaces. For example, one can specify that a procedure must return aggregates A and B where each element in aggregate A points to some element in aggregate B, and that parameter C will have the properties of a rooted tree both on input and output. Our dataflow algorithm tracks the constraints which must apply at each statement in order for the procedure to satisfy its interface, and detects invalid programs which fail to satisfy the constraints on their interfaces. We apply our technique to several examples.Our work is motivated by the requirements for expressive interface definition languages for distributed systems, and by the desire to mechanically check program modules against their interfaces. Our analysis techniques also yield information which may enable compilers and stub generators to produce better implementations.
Chemical composition of aqueous extracts of fly ash: Ionic speciation as a controlling factor

Abstract Concentrations of Na, K, Ca, Mg, SO4, and Si in eight successive extracts of a fly ash sample were determined. Calculation of elemental speciation in solution phase using the chemical equilibrium computer program: GEOCHEM indicated that Na and K were mainly in the free ionic forms whereas, concentrations of Ca2+ and Mg2+ constituted 58–92% of the total analytical concentrations. Concentrations of Ca and Mg ion pairs with OH‐ and SO2‐ 4 ions ranged from 8–42% of total concentrations. Computed saturation indices suggested that the precipitation‐dissolution reactions of ettringite, brucite, sepiolite, laumontite, and phillipsite may be controlling various ion activities in the extracts.
Instability in voluntary contributions based upon jointness in supply

The results of this analysis can be briefly summarized as follows. Voluntary provision of a public good may produce an unstable supply of this good in large group sizes. The primary characteristic responsible for this instability is jointness in supply. Non-exclusionary spillovers without jointness in supply do not produce a similar instability in the system.
Understanding net lost revenue adjustment mechanisms and their effects on utility finances

Abstract Net lost revenue adjustment (NLRA) mechanisms are the most prevalent policy used in the USA to permit utilities to recover lost revenue from demand-side management (DSM) programs. The tendency for net lost revenue to accumulate over time and for NLRA mechanisms to increase utility rates is a concern for regulators and utilities. Their concern is heightened by the competitive pressures facing energy utilities. This paper discusses the concept of lost revenue, describes the three different NLRA mechanisms used by states, and examines the effects of these mechanisms on utility finances. Our results indicate that all three NLRA mechanisms restore the net revenue lost through DSM program operation. We found that the prospective surcharge mechanism exposes the utility to less variation in cash flow as a result of net lost revenue. Increasing the accuracy of the net lost revenue forecast reduces the volatility in monthly cash flow. All three mechanisms result in higher rates and, when the amortization periods are similar, have similar effects on rates. The primary difference between the mechanisms is in the timing of these rate effects. We anticipate that NLRA mechanisms will change in response to customer and industry needs. Changes to NLRA mechanisms may include net lost revenue recovery caps, partial revenue recovery, and time limits for recovery.
An Analog Data Break Interface

This paper describes the interface used for online control of the Princeton-Pennsylvania Accelerator with a PDP-9. The paper is organized into four sections. The first section is concerned with the specifications for the equipment. The requirements are unique because of the cyclic nature of the synchrotron. Section two discusses various I/O techniques and the design compromises they require. The third section deals with the concept of an analog data break interface. The last section is a summary of existing and planned hardware.
Marriage and long-term survival after coronary artery bypass grafting.

OBJECTIVE To examine the effects of marital status and marital satisfaction on survival after coronary artery bypass grafting (CABG). METHODS Participants were 225 people who had CABG between 1987 and 1990. Marital status at the time of surgery and marital satisfaction 1 year after surgery were used to predict survival 15 years after surgery. RESULTS Married people were 2.5 times (p < .001) more likely to be alive 15 years after CABG than those who were not married. This finding was true for men and women, although the result for women was marginally significant adjusting for age. Those in high-satisfaction marriages were 3.2 times (p < .003) more likely to be alive 15 years after CABG compared with those reporting low marital satisfaction. Highly satisfied men were 2.7 times (p < .03) and highly satisfied women were 3.9 times (p < .15) more likely to be alive adjusting for age. Although the result was not significant for women, the effect size for marital satisfaction was actually larger for women than for men. CONCLUSIONS Being married, especially being in a highly satisfying marriage, offered a significant benefit to long-term survival after CABG. Why marital status and marital satisfaction have this effect on survival is surely mulitfactorial, most likely a combination of spousal support and survivor motivation to adopt a healthy lifestyle, along with the provision of emotional support to the survivor, which all could have the effect of modulating the physiologic mechanisms responsible for slowing the advancement of CVD.
Nanobiosensing Using Plasmonics Nanoprobes

This presentation describes the development and applications of the plasmonics and surface-enhanced Raman scattering (SERS) nanoprobes for biomedical diagnostics and ultra-high through put screening. Plasmonics refers to the research area of enhanced electromagneic properties of metallic nanostructures.
Thermal Conductivity in Solar Magnetoplasmas

The work of Ulmschneider (1970) on the effective thermal conductivity of partially ionized plasmas has been generalized to include the effects of magnetic fields. The contributions of electron, ion and neutral heat flows have been evaluated within the framework of the binary collision theory of Burgers (1960). In the temperature regime below 15000K and pressures of 106 dyn cm−2 excellent agreement is obtained with the results of Ulmschneider for the translational part of the non-magnetic thermal conductivity. For higher temperatures a systematic discrepancy of a factor of 2 arises due to the lower order approximation in the kinetic treatment of the electrons in Burgers' theory. It is shown that the neutral component dominates heat transport in a solar magnetoplasma even at temperatures as high as 15000K and that the magnetic modulations are of a secondary character. The application of the present theories to the sunspot models of Yun (1972) shows pronounced maxima in both electrical and thermal conductivities at the interface between umbra and penumbra.
Effect size estimates in chemical aversion treatments of alcoholism

This study found that aggregate studies on alcohol aversion therapy tended to support a moderate level of treatment impact that may have noteworthy practical import. Emetics appear to generate fairly consistent findings; a paralysis-inducing chemical may produce variable results.
Links between the police response and women's psychological outcomes following intimate partner violence.

Virtually no research considers the psychological impact of institutional support for survivors of intimate partner violence (IPV). This study sought to fill this gap by examining associations between one component of institutional support--the police response--and posttraumatic stress disorder (PTSD) symptom severity and posttrauma appraisals (i. e., anger, fear, and self-blame) in a diverse sample of female IPV survivors (N = 236). RESULTS indicated that a more negative police response, as operationalized by women's unmet expectations in relation to the police, was significantly associated with greater PTSD symptom severity in a very conservative test that involved controlling for personal resources and social support. Police response was not significantly associated with the tested posttrauma appraisals. Implications for policy and practice will be discussed. This study advances understanding of the psychological impact of the police response--one key component of institutional support.