cssi/SciSciGPT-SciSciNet huggingface dataset:
Reduced murine hind limb ischemia-reperfusion injury in toll-like receptor mutant mice is associated with decreased nets

Purpose Mechanism of ischemia-reperfusion (IR) injury in peripheral vascular disease is unknown. The pattern recognition receptors, Toll-like receptor (TLR) family of proteins, are key players in IR associated with stroke and myocardial infarction. Our aim was to: 1) create a murine model of hind limb injury to evaluate the role of TLR4 in IR, and 2) determine whether inactive TLR4 led to a decrease in the detection of neutrophil extracellular traps (NETs), which is known to be highly thrombogenic and may mediate microvascular injury. Materials and Methods A calibrated tension tourniquet was applied to unilateral hind limb of wild type (WT) and TLR4 knockout mice (TLR4m) for 1.5 hours to induce ischemia and then immediately removed to initiate reperfusion. At the end of 48 hours of reperfusion, mice were sacrificed and hind limb tissue as well as serum specimens were collected for analysis. For immunohistochemistry, mouse monoclonal anti-histone H2A/H2B/DNA complex antibody to detect NETs, rabbit polyclonal anti-H2A and rabbit polyclonal anti-myeloperoxidase were used. Muscle ATP levels were determined using ATP-lite luminescence assay. Nuclear NF-κB activity was determined using a Trans-AM™ NF-κB p65 transcription factor assay. IκBα expression was quantitated using Western blot analysis. ELISA assay was performed to compare levels of KC, MCP-1 and VEGF in the serum samples isolated from both the WT and TLR4m groups. Results IR injury in the hind limb of WT demonstrated significant levels of muscle fiber injury, decreased energy substrates, increased NF-κB activation and decreased I-κBα levels when compared to the TLR4 knockout mice samples. There was marked decrease in the level of neutrophil and monocyte infiltration in the TLR4 mutant mice, marked decrease in the levels of NETs detection. In situ nuclease treatment of wild-type tissue sections significantly diminished the level of NETs immunostaining demonstrating the specificity of our antibody to detect NETs and suggesting a potential role for nuclease treatment in IR injury. Conclusion These results suggest a pivotal role for TLR4 in mediating hind limb IR injury and suggest that NETs may potentially exacerbate the extent of muscle fiber injury.
Effect of multiscale model uncertainty on identification of optimal catalyst properties

Computer-based catalyst design has been a long standing dream of the chemistry community for replacing tedious and expensive experimental trial-and-error. While first-principle kinetic modeling emerges as a powerful tool for catalyst selection, it has mainly been limited to using a single catalyst descriptor, simplified chemical kinetic models, and assumptions that question the predictive capability of computational results in the absence of addressing the effect of error in kinetic parameters. Here, we introduce a new framework to address the effect of model uncertainty on optimal catalyst property identification. The framework is applied to the ammonia decomposition reaction for CO-free H2 production for fuel cells. It is shown that a range of materials, rather than a single material, should be experimentally screened. Among kinetic model parameters, the often neglected adsorbate–adsorbate interactions can have a profound effect on catalyst selection. The importance of lateral interactions is confirmed with recent experimental data.
Patching plus extended exposure and tacking of the common carotid cuff may reduce the late incidence of recurrent stenosis after carotid endarterectomy.

Objective The safety and durability of carotid endarterectomy (CEA) require attention to certain technical details that may evolve over time. The objective of this study was to determine whether routine patch angioplasty and precautions related to the common carotid cuff could reduce the risks for perioperative stroke, internal carotid artery (ICA) thrombosis, or recurrent carotid stenosis. Methods The senior author (N.H.) performed 1959 consecutive isolated CEAs at the Cleveland Clinic from 1976 to 2004. This series can be divided into three distinct eras with respect to patching and management of the proximal common carotid cuff: (1) primary arteriotomy closure with selective patching in only 38 of 653 CEAs (5.8%) from 1976 to 1983 (group 1); (2) routine patching without any special precautions related to the common carotid cuff in 568 CEAs from 1983 to 1990 (group 2); and (3) routine patching with extended exposure and tacking sutures to secure the carotid cuff in 738 CEAs from 1990 to 2004 (group 3). Results Although vein patching alone seemed to have less risk for perioperative stroke (1.2% vs 2.4%) or ICA thrombosis (0.6% vs 1.8%) than primary closure, these differences did not attain statistical significance. There also were no significant differences in the perioperative stroke and ICA thrombosis rates among the three eras in which changes occurred in patch use and in the management of the carotid cuff. After adjusting for the various lengths of follow-up in the study groups, however, group 3 had a significantly lower risk for recurrent 60% to 99% stenosis or ICA occlusion at >5 years after CEA (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.22; P P = .003) and advancing age (OR, 0.89 per year; 95% CI, 0.85-0.92 per year; P P = .009) and in patients who had undergone previous ipsilateral CEA (OR, 6.02; 95% CI, 1.63-22.2; P = .007). Conclusions Routine patching plus extended exposure and tacking of the common carotid cuff appear to significantly reduce the long-term incidence of recurrent 60% to 99% stenosis or ICA occlusion after CEA.
Cryptococcus neoformans: the model organism for yeast antifungal drug susceptibility testing.

We describe an approach to antifungal susceptibility testing of the yeast Cryptococcus neoformans that shows promise for predicting the mycological response in patients to treatment. Quantitative cultures of the cerebrospinal fluid provide a direct measure of the patient’s mycological response to treatment and have been used in multiple studies to identify the most promising antifungal drugs for subsequent testing in larger clinical studies. Using these quantitative measures of response, a modified macrobroth dilution assay system shows the potential for predicting the response of an individual patient to treatment with amphotericin B, fluconazole, or the combination of amphotericin B plus flucytosine. We describe this modified macrobroth dilution assay method, the statistical approach for assessing susceptibility, and the clinical decisions that can be guided by this in vitro antifungal drug susceptibility testing.
New foundations for a relational theory of theory-revision

AGM-theory, named after its founders Carlos Alchourron, Peter Gardenfors and David Makinson, is the leading contemporary paradigm in the theory of belief-revision. The theory is reformulated here so as to deal with the central relational notions ‘J is a contraction of K with respect to A’ and ‘J is a revision of K with respect to A’. The new theory is based on a principal-case analysis of the domains of definition of the three main kinds of theory-change (expansion, contraction and revision). The new theory is stated by means of introduction and elimination rules for the relational notions. In this new setting one can re-examine the relationship between contraction and revision, using the appropriate versions of the so-called Levi and Harper identities. Among the positive results are the following. One can derive the extensionality of contraction and revision, rather than merely postulating it. Moreover, one can demonstrate the existence of revision-functions satisfying a principle of monotonicity. The full set of AGM-postulates for revision-functions allow for completely bizarre revisions. This motivates a Principle of Minimal Bloating, which needs to be stated as a separate postulate for revision. Moreover, contractions obtained in the usual way from the bizarre revisions, by using the Harper identity, satisfy Recovery. This provides a new reason (in addition to several others already adduced in the literature) for thinking that the contraction postulate of Recovery fails to capture the Principle of Minimal Mutilation. So the search is still on for a proper explication of the notion of minimal mutilation, to do service in both the theory of contraction and the theory of revision. The new relational formulation of AGM-theory, based on principal-case analysis, shares with the original, functional form of AGM-theory the idealizing assumption that the belief-sets of rational agents are to be modelled as consistent, logically closed sets of sentences. The upshot of the results presented here is that the new relational theory does a better job of making important matters clear than does the original functional theory. A new setting has been provided within which one can profitably address two pressing questions for AGM-theory: (1) how is the notion of minimal mutilation (by both contractions and revisions) best analyzed? and (2) how is one to rule out unnecessary bloating by revisions?
Testing for phylogenetic signal in comparative data: behavioral traits are more labile.

Abstract The primary rationale for the use of phylogenetically based statistical methods is that phylogenetic signal, the tendency for related species to resemble each other, is ubiquitous. Whether this assertion is true for a given trait in a given lineage is an empirical question, but general tools for detecting and quantifying phylogenetic signal are inadequately developed. We present new methods for continuous-valued characters that can be implemented with either phylogenetically independent contrasts or generalized least-squares models. First, a simple randomization procedure allows one to test the null hypothesis of no pattern of similarity among relatives. The test demonstrates correct Type I error rate at a nominal α = 0.05 and good power (0.8) for simulated datasets with 20 or more species. Second, we derive a descriptive statistic, K, which allows valid comparisons of the amount of phylogenetic signal across traits and trees. Third, we provide two biologically motivated branch-length transformat...
Analysis of photon-mediated entanglement between distinguishable matter qubits

We theoretically evaluate establishing remote entanglement between distinguishable matter qubits through interference and detection of two emitted photons. The fidelity of the entanglement operation is analyzed as a function of the temporal- and frequency-mode matching between the photons emitted from each quantum memory. With a general analysis, we define limits on the absolute magnitudes of temporal- and frequency-mode mismatches in order to maintain entanglement fidelities greater than 99% with two-photon detection efficiencies greater than 90%. We apply our analysis to several selected systems of quantum memories. Results indicate that high fidelities may be achieved in each system using current experimental techniques, while maintaining acceptable rates ofentanglement. Thus,itmightbepossibletousetwo-photon-mediated entanglement operations between distinguishable quantum memories to establish a network for quantum communication and distributed quantum computation.
Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction.

A series of bupropion (1a) analogues (1b−1ff) were synthesized, and their in vitro and in vivo pharmacological properties evaluated with the goal of developing a 1a analogue that had better properties for treating addictions. Their in vitro pharmacological properties were examined by [3H]dopamine ([3H]DA), [3H]serotonin ([3H]5HT), and [3H]norepinephrine ([3H]NE) uptake inhibition studies, and by binding studies at the dopamine, serotonin, and norepinephrine transporters using [125I]RTI-55 in cloned transporters. Several analogues showed increased [3H]DA uptake inhibition with reduced or little change in [3H]5HT and [3H]NE uptake inhibition relative to bupropion. Thirty-five analogues were evaluated in a 1 h locomotor activity observation test and 32 in an 8 h locomotor activity observation test and compared to the locomotor activity of cocaine. Twenty-four analogues were evaluated for generalization to cocaine drug discrimination after i.p. administration, and twelve analogues were tested in a time course...
Strain differences in tolerance induction to human γ-globulin subclasses: Dependence on macrophages

Abstract BALB/c and DBA/2 mice differ with respect to ease of tolerance induction with HGG, BALB/c mice being the resistant strain. When tested for susceptibility to tolerance induction with individual IgG subclasses, both strains were easily rendered unresponsive with IgG 1 and IgG 2 and less so with IgG 4 . A strain difference appeared with IgG 3 , where only BALB/c mice showed complete resistance to tolerance induction. Mixtures of the IgG subclasses Showed that IgG 1 and IgG 2 accounted for most of the tolerance to whole HGG seen in both strains, while addition of IgG 3 to the mixture made DBA/2 completely tolerant but reversed the trend toward tolerance in the BALB/c mice. By rosette assay it was found that BALB/c macrophages had receptors for IgG 3 (and to a lesser extent for IgG 4 ). These results are consistent with the hypothesis that resistance to tolerance induction with HGG is dependent on the presence of a receptor on the macrophage for a minor IgG subclass.
Editorial: A Specific Question of Ethics

This PDF file contains the editorial “Editorial: A Specific Question of Ethics” for OE Vol. 34 Issue 12
Lack of MMTV Superantigen Presentation in MHC Class II-Deficient Mice

Abstract Mammary tumor viruses (MMTVs) as well as their endogenous counterparts encode superantigens which react with T cells expressing particular T cell receptor Vβ chains. Several lines of evidence indicated that MHC class II is required for the functional presentation of these superantigens. Here we provide direct proof that the function of superantigens is abrogated in the absence of MHC class II expression. No deletion of Mls-1-reactive T cells was observed in MHC class II-deficient mice, and splenocytes from these animals did not stimulate Mls-1-reactive T cell hybridsin vitro.Furthermore, the viral spread in MHC class II-deficient mice, maternally infected with MMTV(C3H), was severely reduced. While initial infection in the gut-associated lymphocytes was comparable between MHC class II-deficient and normal mice, the level of infection in the spleen and the mammary tissue was much lower in the deficient animals. Quantitation of proviral DNA in spleen revealed a direct correlation between the magnitude of superantigen stimulation and degree of infection. These experiments document the direct effect of superantigen stimulation on viral amplification.
Injury to the Ca2+ ATPase of the sarcoplasmic reticulum in anesthetized dogs contributes to myocardial reperfusion injury

Objective : Sarcoplasmic reticulum dysfunction may contribute to calcium (Ca2+) overload during myocardial reperfusion. The aim of this study was to investigate its role in reperfusion injury. Methods : Open chest dogs undergoing 15 min of left anterior descending coronary artery occlusion and 3 h of reperfusion were randomized to intracoronary infusions of 0.9% saline, vehicle, or the Ca2+ channel antagonist, nifedipine (50 μg/min from 2 minutes before to 5 minutes after reperfusion). After each experiment, transmural myocardial biopsies were removed from ischemic/reperfused and nonischemic myocardium in the beating state and analyzed for (i) sarcoplasmic reticulum protein content (Ca2+ ATPase, phospholamban, and calsequestrin) by immunoblotting and (ii) Ca2+ uptake by sarcoplasmic reticulum vesicles with and without 300 micromolar ryanodine or the Ca2+ ATPase activator, antiphospholamban (2D12) antibody. Results : Contractile function did not recover in controls and vehicle-treated dogs after ischemia and reperfusion (mean systolic shortening, −2±2%), but completely recovered in nifedipine-treated dogs (17±2%, p = NS vs. baseline, p <0.01 vs. control). Ventricular fibrillation occurred in 50% of controls and vehicle dogs and 0% of nifedipine-treated dogs ( p <0.01). Ca2+ uptake by the sarcoplasmic reticulum vesicles was severely reduced in ischemic/reperfused myocardium of controls and vehicle dogs ( p <0.01 vs. nonischemic). Ryanodine and the 2D12 antibody improved, but did not reverse the low Ca2+ uptake. Protein content was similar in ischemic/reperfused and nonischemic myocardium. In contrast, Ca2+ uptake and the responses to ryanodine and 2D12 antibody were normal in ischemic/reperfused myocardium from nifedipine-treated dogs. Conclusion : Dysfunction of the sarcoplasmic reticulum Ca2+ ATPase pump correlates with reperfusion injury. Reactivation of Ca2+ channels at reperfusion contributed to Ca2+ pump dysfunction. Ca2+ pump injury may be a critical event in myocardial reperfusion injury.
Mantle Plumes and Entrainment: Isotopic Evidence

Many oceanic island basalts show sublinear subparallel arrays in Sr-Nd-Pb isotopic space. The depleted upper mantle is rarely a mixing end-member of these arrays, as would be expected if mantle plumes originated at a 670-kilometer boundary layer and entrained upper mantle during ascent. Instead, the arrays are fan-shaped and appear to converge on a volume in isotopic space characterized by low (87)Sr/(86)Sr and high (143)Nd/(144)Nd, (206)Pb/(204)Pb, and (3)He/(4)He ratios. This new isotopic component may be the lower mantle, entrained into plumes originating from the core-mantle boundary layer.
Site of origin of a hyperglycemic substance liberated into the pancreato-duodenal blood by deserpidine injections.

The injection of deserpidine into the pancreato-duodenal artery of normal dogs is followed by a prompt rise in blood sugar concentration. This hypcrglycemia is not observed in previously depancreatized dogs. The results suggest that deserpidine causes the release of a hyperglycemic substance originating in the pancreas. The nature of this substance is unknown, although it appears to be different from the hyperglycemic material released bjr the injection of growth hormone.
A calcium-dependent chloride current in insulin-secreting βTC-3 cells

Ca2+-dependent conductances have been hypothesized to play a role in the bursting pattern of electrical activity of insulin-secreting β cells in response to high plasma glucose. A Maxi K+ channel has received the most attention, while a low-conductance Ca2+-activated K+ current has also been identified. We used an increasingly popular β cell model system, the βTC-3 cell line, and the perforated-patch technique to describe the properties of a novel Ca2+-dependent Cl–current [ICl(Ca)] in insulin-secreting pancreatic β cells. The reported ICl(Ca) could be activated under physiological Ca2+ concentrations and is the first of its kind to be described in pancreatic insulin-secreting cells. We found that long depolarizing steps above –20 mV elicited an outward current which showed slow inward relaxation upon repolarization to negative membrane potentials. Both the outward currents and the inward tails showed dependence on Ca2+ influx: their current/voltage (I/V) relations followed that of the ”L-like” Ca2+ current (ICa) present in these cells; they were blocked completely by the removal of external Ca2+ or application of Cd2+ at concentrations sufficient for complete block of ICa; and their magnitude increased with the depolarizing step duration. Moreover, the inward tail decayed monoexponentially with a time constant which at voltages negative to activation of ICa showed a weak linear voltage dependence, while at voltages positive to activation of ICa it followed the voltage dependence of ICa. This Ca2+-dependent current reversed at –21.5 mV and when the external Cl–concentration was reduced from 159 mM to 62 mM the reversal potential shifted by ≈+20 mV as predicted by the Nernst relation for a Cl–-selective current. Cl–channel blockers such as DIDS (100 μM) and niflumic acid (100 μM) blocked this current. We concluded that this current was a Ca2+-dependent Cl–current [ICl(Ca)]. From substitution of the external Cl–with various monovalent anions and from the reversal potentials we obtained the following permeability sequence for ICl(Ca): I–>NO3–>Br–>Cl–>Acetate–.
Rotor position estimation of PMSM by Sliding Mode EMF observer under improper speed

The paper discusses the problem of rotor position estimation for the nonsalient permanent magnet synchronous motor (PMSM) and presents a Sliding Mode (SM) EMF observer that is based on the machine's model in the stationary reference frame. The speed of the PMSM which is an input of the proposed sliding mode observer is obtained from a speed estimator. The paper assumes that the speed estimate is different from the real speed and shows that the gains of the SM observer can be designed such that the EMF estimates produced by the SM observer tend to the real EMFs. The observer is designed and analyzed in the framework of nonlinear control using Lyapunov's theory and is validated using simulations. The method proposed is relatively simple and can be used to estimate the rotor position of the PMSM in a sensorless drive.
Effect of Pretreatment with Alcohol on Subsequent Endocrine and Immune Responses in the Adult Male Rat

We have previously shown that daily injection of alcohol for 3 days induced a significant and long-lasting blunting of the hypothalamic-pituitary-adrenal (HPA) axis response to a subsequent treatment with this drug. The fact that, in contrast, the HPA axis response to footshocks was not altered by prior alcohol administration, suggested the presence of a phenomenon of selective neuroendocrine tolerance. To further test this hypothesis, we determined whether an initial alcohol challenge would alter the ACTH response to immune signals, such as interleukin-1beta (IL-1beta) and/or endotoxin (lipopolysaccharide; LPS). Because of the functional connection between the HPA axis and immune responses, we also determined whether the LPS-induced release of tumor necrosis factor-alpha and interleukin-6, as well as IgG and IgM responses to an antigenic challenge, would be influenced by previous exposure to alcohol. We show here that the intragastric injection of 3 g of alcohol/kg daily for 3 days did not significantly alter the ability of IL-1beta (400 ng/kg) or LPS (1 microg/kg), both injected intravenously 7 days later, to release ACTH. Drug pretreatment did not significantly alter the tumor necrosis factor-alpha response to the low dose of endotoxin used, whereas there was a tendency toward increased circulating interleukin-6 levels in alcohol-pretreated animals. Finally the IgG, but not IgM, response to the antigen phosphocholine-keyhole limpet hemocyanin was significantly (p < 0.05) augmented in rats administered alcohol 7 days before the antigenic challenge. Collectively, these results indicate that an initial exposure to alcohol does not induce long-term changes in the ability of an immune signal (IL-1beta or endotoxin) to activate the HPA axis. In contrast, a small but detectable enhancement of cytokine responses to LPS, and of the IgG response to phosphocholine-keyhole limpet hemocyanin, was observed.
Quantitation of in vitro cell adhesion to cementum, dentin and enamel.

The William's blister test for adhesion was used to determine the strength of epithelial and fibroblast cell attachments to cementum, dentin and enamel. Differences of air pressure required (cm H2O) to debond the samples from a cell monolayer were measured and recorded on a strip chart recorder (Fletcher et al. 1977). Gingival and skin-muscle cells detached at similar pressures from cementum, dentin and enamel. Higher pressures (of debond) were required with cells grown on a polystyrene surface.
Single-Subject design for locomotor activity

Rats were given daily 1-hr sessions in photocell cages until baseline locomotion stabilized. d-Amphetamine 0.5–2.0 mg/kg p.o. significantly increased locomotion. Chlorpromazine 2.5–20 mg/kg p.o. and pentobarbital 5.0–20 mg/kg p.o. significantly decreased locomotion. N = 4 per drug. Results demonstrate the appropriateness of using chronic single subjects to assess the effects of drugs on locomotion. An attempt to generate cumulative dose-effect curves in rats run once a week was less successful because of intrasubject variability. The method could also be used for multiple drug studies in lesioned or cannulated preparations.
Individual cognitive behavioral treatment and family therapy for physically abused children and their offending parents: a comparison of clinical outcomes

Few studies have evaluated short-term psychosocial treatments with physically abused school-aged children and their offending parents or families. This study compares the treatment outcomes of 55 cases that were randomly assigned to individual child and parent cognitive behavioral therapy (CBT) or family therapy (FT) with those who received routine community services (RCS). Measures of child, parent, and family dysfunction and adjustment were collected from both participants and supplemented with official social service records to evaluate the efficacy of treatment through 1-year follow-up. Compared with RCS, CBT and FT were associated with improvements in child-to-parent violence and child externalizing behavior, parental distress and abuse risk, and family conflict and cohesion. All three conditions reported several improvements across time. One parent participant each in CBT and FT and three in RCS were found to have engaged in another incident of physical maltreatment after treatment had begun. No dif...
Mark Twain in the Twenty-First Century

On 14-15 January 2002, Ken Burns brought his latest patriotic documentary, Mark Twain, to PBS, and what a pleasure it was, the great photographs, the great singular life, all that wit and humor. As one enjoyed The Civil War (1990), Baseball (1994), and Jazz (2001), each film declaring a triumph for our new post-Civil War nationality, one relished Mark Twain, which might be said to conclude that specific cycle of films in Burns's documentary project. The first night ended with Mark Twain writing and publishing the Adventures of Huckleberry Finn (1885). We got a good look at Quarry Farm in Elmira, New York, where Mark Twain wrote The Adventures of Tom Sawyer (1876) and Huckleberry Finn. There was the famous octagonal study, so beautifully placed on a promontory overlooking the broad expanse of the Chemung River valley, Mark Twain in it, leaning out, looking at us. We saw in different photographs the strong black face of Mary Ann Cord, cook, "Aunt Rachel" in "A True Story" (1874), and the strong black face of John T. Lewis, farm managerAfrican American persons around Mark Twain as he wrote Huckleberry Finn. We owe Auntie Cord and John Lewis a lot, Mark Twain insisted. Mark Twain had their stories. In "A True Story" Aunt Rachel rebukes "Misto C" for his blindness to the tragedy of her life. As Huck confronts the consequence of his race betrayal, the social hell reserved for nigger lovers in slaveholding Missouri, these richly humane African-American voices are speaking around Mark Twain, are in their African American conversation, are often speaking to him, addressing his "Southern" innocence. Mark Twain's importance in American literature, said Mark Twain, depends on Jim, on the African American factor in Mark Twain's literary production. It is a major point in the film, a restatement of that verity. Jim does not save Huck in Huckleberry Finn, losing him finally to Tom Sawyer, but he saves Mark Twain in the twentieth century and is floating him still in the twenty-first. Part One ends presenting Huck's letter to Miss Watson, a letter of betrayal, quite possibly the
Up-regulation of translation eukaryotic initiation factor 4E in nucleophosmin 1 haploinsufficient cells results in changes in CCAAT enhancer-binding protein α activity: implications in myelodysplastic syndrome and acute myeloid leukemia.

NPM1 is a ubiquitously expressed nucleolar phosphoprotein, the gene for which maps to chromosome 5q35 in close proximity to a commonly deleted region associated with (del)5q, a type of myelodysplastic syndrome (MDS). This region is also a frequent target of deletions in de novo and therapy-related MDS/acute myeloid leukemia. Previous studies have shown that Npm1+/− mice develop an MDS-like disease that transforms to acute myeloid leukemia over time. To better understand the mechanism by which NPM1 haploinsufficiency causes an MDS phenotype, we generated factor-dependent myeloid cell lines from the bone marrow of Npm1+/+ and Npm1+/− mice and demonstrated compromised neutrophil-specific gene expression in the MNPM1+/− cells. We attribute these observations to increased levels of the shorter, dominant negative leukemogenic isoform (p30) of CCAAT enhancer-binding protein α (C/EBPα). We show that this increase is caused, in part, by elevated levels of the activated translation initiation factor eIF4E, overexpression of which also increases translation of C/EBPαp30 in HEK293 cells. In a positive feedback loop, eIF4E expression is further elevated both at the mRNA and protein levels by C/EBPαp30 but not by the full-length C/EBPαp42. Re-expression of C/EBPαp42 or NPM1 but not C/EBPαp30 in MNPM1+/− cells partially rescues the myeloid phenotype. Our observations suggest that the aberrant feed-forward pathway that keeps eIF4E and C/EBPαp30 elevated in NPM1+/− cells contributes to the MDS phenotype associated with NPM1 deficiency.
Protein Substrate Discrimination in the Quiescin-sulfhydryl Oxidase (QSOX) Family

This work explores the substrate specificity of the quiescin sulfhydryl oxidase (QSOX) family of disulfide-generating flavoenzymes to provide enzymological context for investigation of the physiological roles of these facile catalysts of oxidative protein folding. QSOX enzymes are generally unable to form disulfide bonds within well-structured proteins. Use of a temperature-sensitive mutant of ubiquitin-conjugating enzyme 4 (Ubc4') as a model substrate shows that QSOX activity correlates with the unfolding of Ubc4' monitored by circular dichroism. Fusion of Ubc4' with the more stable glutathione-S-transferase domain demonstrates that QSOX can selectively introduce disulfides into the less stable domain of the fusion protein. In terms of intermolecular disulfide bond generation, QSOX is unable to cross-link well-folded globular proteins via their surface thiols. However, the construction of a septuple mutant of RNase A, retaining a single cysteine residue, demonstrates that flexible protein monomers can be directly coupled by the oxidase. Steady- and pre-steady-state kinetic experiments, combined with static fluorescence approaches, indicate that while QSOX is an efficient catalyst for disulfide bond formation between mobile elements of structure, it does not appear to have a significant binding site for unfolded proteins. These aspects of protein substrate discrimination by QSOX family members are rationalized in terms of the stringent steric requirements for disulfide exchange reactions.
Federal land management, carbon sequestration, and climate change in the Southeastern U.S.: a case study with Fort Benning.

Land use activities can have a major impact on the temporal trends and spatial patterns of regional land−atmosphere exchange of carbon. Federal lands generally have substantially different land management strategies from surrounding areas, and the carbon consequences have rarely been quantified and assessed. Using the Fort Benning Installation as a case study, we used the General Ensemble biogeochemical Modeling System (GEMS) to simulate and compare ecosystem carbon sequestration between the U.S. Army’s Fort Benning and surrounding areas from 1992 to 2050. Our results indicate that the military installation sequestered more carbon than surrounding areas from 1992 to 2007 (76.7 vs 18.5 g C m−2 yr−1), and is projected to continue sequestering more carbon from 2008 to 2050 (75.7 vs 25.6 g C m−2 yr−1), mostly because of the proactive management approaches adopted on military training lands. Our results suggest that federal lands might play a positive and important role in sequestering and conserving atmospher...
What is really driving differences and similarities in HRM practices across national boundaries in Europe

The comparative international Human Resource Management (HRM) literature presents competing perspectives as to why HRM looks different in different countries. This paper takes a new approach to exploring relevant drivers behind HRM in European countries by looking simultaneously at three suggested sources of influence: national culture, national institutions, and a supranational institution. To date, national culture and institutions have frequently been used to explore HRM drivers, but rarely simultaneously, whilst the effect of the European Union (EU) Social Charter has received much less attention. Here, countries are clustered according to these three sources of influence, and survey evidence from 17 EU countries is used to explore the extent of difference and similarity in HRM practices within these clusters. Results indicate that all three variables show patterns in HRM practices; however, they only explain relatively small amounts of variance. National-level institutional factors appear to have the strongest influence.
Does Total Knee Arthroplasty Affect Physical Activity Levels? Data from the Osteoarthritis Initiative

Total knee arthroplasty (TKA) is associated with improved patient-reported pain levels, function, and quality of life; however, it is poorly understood whether there is increased physical activity following TKA. Using data from the Osteoarthritis Initiative (OAI), we compare physical activity, as measured using an accelerometer, and patient-reported outcome measures of 60 patients who had already received a TKA with 63 patients who eventually received a TKA during the OAI study. There was no significant difference in activity levels between the two groups as measured by the accelerometer. Total WOMAC, KOOS Quality of Life, KOOS Knee Pain, and KOOS Function scores improved in the post-TKA compared to the pre-TKA group. In both pre-TKA and post-TKA groups, physical activity guidelines were met in only 5% or less.
Phosphomimic S3D Cofilin Binds Actin Filaments but does not Sever them

Cofilin-mediated remodeling of the actin cytoskeleton is critical for many cellular processes. Cofilin changes the filament structure and renders them more compliant in bending and twisting. Filaments partially decorated with cofilin sever more readily than bare or saturated ones, supporting a model where severing occurs preferentially at mechanical and topological boundaries between bare and cofilin-decorated segments. Phosphorylation of cofilin at serine 3 by LIM kinase is a well-established mechanism for regulating cofilin activity. Substitution of serine with aspartate at position three (S3D) is widely used for investigating the mechanism of cofilin phospho-regulation in cells and in biochemical studies with purified protein components. The S3D substitution or phosphorylation weakens cofilin binding to actin filaments, and it is thought that subsequent reduction in cofilin occupancy inhibits filament severing activity. Here, we show that S3D cofilin binds actin filaments with a lower affinity than wild-type (WT) cofilin, but with higher cooperativity. Because of its higher cooperativity, S3D cofilin will form larger clusters along filaments than unmodified cofilin and thus have fewer boundaries between bare and decorated segments where severing occurs. S3D decoration weakly affects filament bending and twisting dynamics, in contrast to WT cofilin. Weak actin filament severing is observed for S3D across a range of occupancies. Reduced boundary density and inability to alter filament mechanics make S3D severing deficient.
Fulleroid Addition Regiochemistry Is Driven by π-Orbital Misalignment

This article reports the first investigation into the regiochemistry of addition to the fulleroid C61H2 by Zn(Cu) reduction and hydroboration. Two major isomers of C61H4 are formed by the reduction with Zn(Cu) while only one major isomer is formed by hydroboration. The structures of the major isomers formed by reduction with Zn(Cu) were identified as 1,2-C61H4 and 3,4-C61H4. The 1,2-C61H4 isomer is the only dominant isomer formed by hydroboration with no indications of the 3,4-C61H4 isomer being formed. The regiochemistry observed in the formation of 1,2-C61H4 is the same regiochemistry seen in the further reactivity of azafulleroids (C60NR). Strain energies (calculated at the B3LYP-6-31G* level of theory) show that the relief of strain is greater for the hydrogenation of the fulleroid C61H2 than it is for the hydrogenation of C60 itself. This indicates that the twisted, anti-Bredt's rule, double bonds of the fulleroid are a source of greater localized strain than the pyramidalization of the carbons in th...
Education, Outreach, and Training for High-Performance Computing

Most current models for delivering HPC education, outreach, and training lack support for the next generation of HPC users. The authors present lessons learned in developing and disseminating HPC-enabled tools and curriculum, including their efforts at developing low-cost hardware, software, and curricular platforms for easy classroom and workshop deployment.
Laboratory Consolidation Methods Applied to Compacted Concrete for Pavements

The paper reports on the effects of consolidation method and specimen size on optimum water content, density, and compressive strength of laboratory-prepared roller-compacted concrete (RCC) specimens for pavement construction. The three selected consolidation methods include the vibrating table/surcharge method presently under consideration by ASTM for casting cylinders, and two impact methods using Marshall and Proctor hammers. The selected mold sizes are 15.2 cm by 30.5 cm (the standard 6 in. x 12 in.) and smaller, 10.2 cm by 20.3 cm (4 in. x 8 in.), cylinders. The experimental results indicated that fabrication method (i.e., vibration/surcharge versus impact) significantly affects optimum moisture content, density, and 28-day compressive strength. Specimen size seems to be less of a factor. The choice of the laboratory consolidation methodÂfor density measurement and specification in particularÂmay have important consequences in the construction, quality control, and overall performance of RCC pavements.
Gender Differences in Adult Sibling Relations in Two‐Child Families

We examine affective closeness, contact, and helping among adult siblings using data for over 1,500 respondents in 2-child families from the National Survey of Families and Households. Using this subsample allows us to investigate differences by gender of respondent and of individual siblings using a nationally representative sample. We find that siblings are central to the lives of adults; most sibling relationships involve frequent contact and positive feelings. Sister pairs phone and exchange advice more often than do other sibling pairs. Women are more likely than men to report feeling close to or getting along with their sibling. We find no consistent differences in visiting. Giving and receiving help appear to reflect gendered forms of intimacy and of household labor.
Tropisetron increases the inhibitory effect of mild restraint on lordosis behavior of hormonally primed, ovariectomized rats

Ovariectomized rats, hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone are resistant to the lordosis-inhibiting effects of a 5 min restraint experience. However, modulation of the serotonergic (5-HT) system alters this resistance to stress. In the following experiment, ovariectomized Fischer inbred rats were hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone. The effect of 5 min restraint on sexual behavior was examined after bilateral hypothalamic infusion or intraperitoneal (ip) treatment with the 5-HT(3) receptor antagonist, 3-tropanylindole-3-carboxylate hydrochloride (tropisetron). Infusion with 50 or 100 ng tropisetron inhibited lordosis behavior. When rats were infused with 10 or 25 ng tropisetron, rats showed normal lordosis behavior. However, when infusion with 10 or 25 ng tropisetron was combined with 5 min restraint, lordosis behavior was inhibited. These findings are consistent with prior work that has implicated hypothalamic serotonin in control of lordosis behavior and in the effect of mild restraint on the behavior. In contrast to the effects of the intracranial infusion, intraperitoneal injection with 1.0 or 2.0 mg/kg tropisetron did not amplify the effects of restraint.
HIGH FREQUENCY OSCILLATORY VENTILATION AUGMENTS THE RESPONSE TO INHALED NITRIC OXIDE IN SEVERE EXPERIMENTAL HYALINE MEMBRANE DISEASE. † 2001

HIGH FREQUENCY OSCILLATORY VENTILATION AUGMENTS THE RESPONSE TO INHALED NITRIC OXIDE IN SEVERE EXPERIMENTAL HYALINE MEMBRANE DISEASE. † 2001
Androstenedione synergizes with stress or prenatal drug exposure to retard fetal growth: Role of IGF

Pregnant Sprague-Dawley dams were implanted with a Silastic capsule (3 or 10 mm) containing androstenedione (AN) or cholesterol prior to being administered one of several treatments that create an endocrine profile of stress: maternal exposure to alcohol, pair feeding (PF), cocaine (COC), or restraint stress (RS). Controls (chow fed, CF) were left undisturbed during pregnancy. Treatments were administered from day 14 to day 22 of gestation. Fetuses were delivered by cesarean section on day 22. Results revealed that administration of AN to pregnant dams at a dose that does not influence fetal growth by itself can retard fetal growth in the presence of alcohol, PF, COC or RS. Data indicate that these effects are not directly attributable to changes in adrenocorticotropin (ACTH) or corticosterone levels. Preliminary results suggest a role for insulinlike growth factor (IGF) binding proteins (IGFBPs). Overall, these data demonstrate that AN can synergize with drugs and/or stress to enhance intrauterine growth retardation (IUGR). One underlying cause of this synergism between stress-related environmental events and androgenic actions on fetal growth may be increased expression of IGFBPs, which can sequester IGFs, thereby inhibiting their trophic actions on fetal and/or placental tissue.
Control of the structure and surface morphology of gallium nitride and aluminum nitride thin films by nitrogen background pressure in pulsed laser deposition

Thin films of AlN and GaN were grown by pulsed laser deposition on c-plane sapphire substrates. It is demonstrated that the structure and surface morphology of layers can actively be controlled by adjusting the nitrogen partial pressure during the growth. The observed trends in the structural quality of the thin films can be attributed to the changes in the surface diffusion of adatoms. It is argued that the surface diffusion of adatoms can be influenced by the collisions between the nitrogen gas molecules and the activated atoms which can reduce the kinetic energy of activated atoms and increase the rate of formation of immobile surface dimers. Through these nitrogen pressure related effects, thin films with microstructure ranging from crystalline to amorphous can be produced. The observed similar impact of nitrogen pressure on the growth of GaN and AlN thin films indicates that a pressure assisted growth procedure is generally applicable to design the surface morphology of group III-nitride thin films. A minimal surface root mean square roughness of 0.7 nm for amorphous AlN is obtained which compares well with the substrate roughness of 0.5 nm. Rutherford backscattering spectroscopy of thin films of GaN and AlN showed a large incorporation of oxygen which was found to reduce the lattice constants of GaN and AlN.
Molecular rotors and motors: recent advances and future challenges

At the “Molecular Rotors and Motors” symposium of the Spring 2009 ACS National Meeting in Salt Lake City (March 22−26), a diverse mix of talks addressed many current issues in the field. Speakers described topics that varied from single-molecule rotors and nanomachines to exquisite synthetic approaches toward building functional materials and mathematical and computational methods aimed at uncovering design opportunities and highlighting the fundamental limitations of molecular motors. While the realization of building useful nanomachines remains far off, a general consensus abounded that investigating biological systems and understanding the implications of the laws of thermodynamics and quantum mechanics for the behavior of nanostructures will help drive important advances in the quest for molecular machinery. Molecular rotors were demonstrated to have practical applications as probes for microviscosity, and many speakers presented experimental studies that indicated that highly directed translation and...
Circular dichroism studies on the variable and constant halves of kappa-type Bence-Jones proteins.

Abstract Two kappa-type Bence-Jones proteins (Ha, Ra) were cleaved into their variable (V κ ) and constant (C κ ) halves by limited tryptic digestion. Circular dichroism studies indicate the presence of some β-structured regions in all these fragments and the amount of β structure seems to be higher in C κ than in V κ (Ha) and V κ (Ra). In both these proteins (Ha, Ra), the sum of the CD spectra of the isolated V κ and C κ halves agrees well with the CD spectra of the intact Bence-Jones proteins. These findings suggest that the variable and constant segments of the light chain have, more or less, independent domains of secondary and tertiary structures. However, these results also show that in the intact light chain the variable and constant domains may have some weak noncovalent interactions between themselves which determine the orientation of one or more tyrosine residues present in the protein.
Diabetes is associated with cognitive impairment no dementia in the Aging, Demographics, and Memory Study (ADAMS).

Individuals with diabetes mellitus have a 1.39 times increased risk of Alzheimer's disease, a 2.38 times increased risk of vascular dementia, and a faster rate of cognitive decline compared to individuals without diabetes (Lu et al., 2009). In a study, over a 9-year follow-up diabetes was associated with accelerated progression from mild cognitive impairment (MCI) to dementia, but was not associated with progression from no impairment to MCI (Xu et al., 2010). Many previous studies on cognitive impairment and diabetes are limited by the use of cognitive screens to diagnose and assess cognitive impairment. A few studies diagnosing cognitive impairment with comprehensive neuropsychological batteries provide mixed results. For instance, Luchinger et al. (2007) found that diabetes was correlated with the presence of MCI, whereas diabetes was not associated with the presence of dementia versus no dementia in the Aging, Demographics, and Memory Study ADAMS; (Llewellyn et al., 2010).
Generating links by mining quotations

Scanning books, magazines, and newspapers has become a widespread activity because people believe that much of the worlds information still resides off-line. In general after works are scanned they are indexed for search and processed to add links. This paper describes a new approach to automatically add links by mining popularly quoted passages. Our technique connects elements that are semantically rich, so strong relations are made. Moreover, link targets point within a work, facilitating navigation. This paper makes three contributions. We describe a scalable algorithm for mining repeated word sequences from extremely large text corpora. Second, we present techniques that filter and rank the repeated sequences for quotations. Third, we present a new user interface for navigating across and within works in the collection using quotation links. Our system has been run on a digital library of over 1 million books and has been used by thousands of people.