bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutions and development: the primacy of microanalysis
Authors: KIMENYI MWANGI S.
Published: February 2011

In recent years, there have been major advances in the empirical analysis of the link between institutions and development. However, a number of methodological problems – both theoretical and empirical – remain unresolved and have been well articulated by Ha-Joon Chang in his article ‘Institutions and Economic Development: Theory, Policy and History’. These problems raise valid concerns about the policy relevance of the evidence arising from the studies. A more reliable approach to study the link between institutions and development and overcome the inherent problems of cross-country empirical analysis is to direct focus to microeconomic analysis of institutions. Such an approach avoids ideologically driven normative judgments about the superiority of particular institutional arrangements and also offers a more credible and tractable avenue to investigate institutional change.
HUME’S PRINCIPLE, BEGINNINGS
Authors: VISSER ALBERT
Published: February 2011

In this note we derive Robinson’s Arithmetic from Hume’s Principle in the context of very weak theories of classes and relations.
Miocene ocean circulation inferred from marine carbon cycle modeling combined with benthic isotope records
Authors: Butzin Martin , Lohmann Gerrit , Bickert Torsten
Published: February 2011

In a modeling sensitivity study we investigate the evolution of the ocean circulation and of marine carbon isotope (δ13C) records during the Miocene (about 23–5 million years ago). For this purpose we ran an ocean‐circulation carbon cycle model of intermediate complexity (Large Scale Geostrophic– Hamburg Ocean Carbon Cycle Model, version 2s) exploring various seaway configurations. Our investigations confirm that the Central American Seaway played a decisive role in the history of the Miocene ocean circulation. In simulations with a deep Central American Seaway (depth range 1–3 km), typical for the early to middle Miocene, deep water production in the North Atlantic is absent or weak, while the meridional overturning circulation is dominated by water mass formation in the Southern Ocean. Deep water formation in the North Atlantic begins when the Central American Seaway shoals to a few hundreds of meters, which is typical for the late Miocene. Our results do not support ideas that the mid‐Miocene closing of the Eastern Tethys contributed to Antarctic glaciation. On the other hand, we find some water exchange between the Indian Ocean and the Atlantic via the Eastern Tethys during the early Miocene. Our model results for the Atlantic meridional overturning circulation and for Atlantic δ13C during the late Miocene are largely independent from depth variations of the Greenland‐Scotland Ridge. To a large extent, the evolution of Miocene deep‐sea δ13C records can be explained with large‐scale ocean circulation changes. Our model‐data comparison for the middle and early Miocene suggests that during the early Neogene the seaway effect on benthic δ13C may have been superimposed by further factors such as climate regime shifts and/or terrestrial carbon cycle changes.
Opal accumulation rates in the equatorial Pacific and mechanisms of deglaciation
Authors: Hayes C. T. , Anderson R. F. , Fleisher M. Q.
Published: February 2011

A possible imprint on equatorial Pacific sediments of a deglacial reinvigoration of the Southern Ocean overturning is increased opal accumulation rate. This would arise from the transmission of silica‐rich deep water to the equatorial thermocline via Subantarctic Mode Water and an associated increase in diatom productivity. In search of this imprint, sediment cores from the central (TT013‐PC72) and eastern (V19‐30) equatorial Pacific have been analyzed for 230Th‐normalized opal accumulation rates over the past five and three glacial terminations, respectively. Equatorial opal accumulation rates sustained relatively low values over much of the records and were punctuated by large increases centered on some terminations, but not all. Furthermore, two periods of increased opal flux were observed that do not coincide with terminations. Sources other than the Southern Ocean may need to be considered in the silica budget of the equatorial Pacific, but the δ13C of Neogloboquadrina dutertrei can be used to support the presence of a deepwater nutrient signal in each case. Although a common deglacial mechanism, or a common imprint thereof, for each of the late Pleistocene glaciations remains elusive, the combination of opal flux and δ13C of N. dutertrei provides a diagnostic for past injection of deepwater nutrients into the Equatorial Undercurrent.
Use of global sensitivity analysis and polynomial chaos expansion for interpretation of nonreactive transport experiments in laboratory‐scale porous media
Authors: Fajraoui Noura , Ramasomanana Fanilo , Younes Anis , Mara Thierry Alex , Ackerer Philippe , Guadagnini Alberto
Published: February 2011

In this work, we show how the use of global sensitivity analysis (GSA) in conjunction with the polynomial chaos expansion (PCE) methodology can provide relevant information for the interpretation of transport experiments in laboratory‐scale heterogeneous porous media. We perform GSA by calculating the Sobol indices, which provide a variance‐based importance measure of the effects of uncertain parameters on the output of a chosen interpretive transport model. The choice of PCE has the following two benefits: (1) it provides the global sensitivity indices in a straightforward manner, and (2) PCE can serve as a surrogate model for the calibration of parameters. The coefficients of the PCE are computed by probabilistic collocation. The methodology is applied to two nonreactive transport experiments available in the literature, while considering both transient and pseudo steady state transport regimes. This method allows a rigorous investigation of the relative effects and importance of different uncertain quantities, which include boundary conditions as well as porous medium hydraulic and dispersive parameters. The parameters that are most relevant to depicting the system's behavior can then be evaluated. In addition, one can assess the space‐time distribution of measurement points, which is the most influential factor for the identifiability of parameters. Our work indicates that these methods can be valuable tools in the proper design of model‐based transport experiments.
Dietary Whey Protein Decreases Food Intake and Body Fat in Rats
Authors: Zhou June , Keenan Michael J. , Losso Jack N. , Raggio Anne M. , Shen Li , McCutcheon Kathleen L. , Tulley Richard T. , Blackman Marc R. , Martin Roy J.
Published: February 2011

We investigated the effects of dietary whey protein on food intake, body fat, and body weight gain in rats. Adult (11–12 week) male Sprague‐Dawley rats were divided into three dietary treatment groups for a 10‐week study: control. Whey protein (HP‐W), or high‐protein content control (HP‐S). Albumin was used as the basic protein source for all three diets. HP‐W and HP‐S diets contained an additional 24% (wt/wt) whey or isoflavone‐free soy protein, respectively. Food intake, body weight, body fat, respiratory quotient (RQ), plasma cholecystokinin (CCK), glucagon like peptide‐1 (GLP‐1), peptide YY (PYY), and leptin were measured during and/or at the end of the study. The results showed that body fat and body weight gain were lower (P < 0.05) at the end of study in rats fed HP‐W or HP‐S vs. control diet. The cumulative food intake measured over the 10‐week study period was lower in the HP‐W vs. control and HP‐S groups (P < 0.01). Further, HP‐W fed rats exhibited lower N2 free RQ values than did control and HP‐S groups (P < 0.01). Plasma concentrations of total GLP‐1 were higher in HP‐W and HP‐S vs. control group (P < 0.05), whereas plasma CCK, PYY, and leptin did not differ among the three groups. In conclusion, although dietary HP‐W and HP‐S each decrease body fat accumulation and body weight gain, the mechanism(s) involved appear to be different. HP‐S fed rats exhibit increased fat oxidation, whereas HP‐W fed rats show decreased food intake and increased fat oxidation, which may contribute to the effects of whey protein on body fat.
The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities
Authors: Hageman Jurre , van Waarde Maria A.W.H. , Zylicz Alicja , Walerych Dawid , Kampinga Harm H.
Published: February 2011

Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol. To test for possible functional differences and/or substrate specificity, we assessed the effect of overexpression of each of these HSPs on refolding of heat-denatured luciferase and on the suppression of aggregation of a non-foldable polyQ (polyglutamine)-expanded Huntingtin fragment. Overexpressed chaperones that suppressed polyQ aggregation were found not to be able to stimulate luciferase refolding. Inversely, chaperones that supported luciferase refolding were poor suppressors of polyQ aggregation. This was not related to client specificity itself, as the polyQ aggregation inhibitors often also suppressed heat-induced aggregation of luciferase. Surprisingly, the exclusively heat-inducible HSPA6 lacks both luciferase refolding and polyQ aggregation-suppressing activities. Furthermore, whereas overexpression of HSPA1A protected cells from heat-induced cell death, overexpression of HSPA6 did not. Inversely, siRNA (small interfering RNA)-mediated blocking of HSPA6 did not impair the development of heat-induced thermotolerance. Yet, HSPA6 has a functional substrate-binding domain and possesses intrinsic ATPase activity that is as high as that of the canonical HSPA1A when stimulated by J-proteins. In vitro data suggest that this may be relevant to substrate specificity, as purified HSPA6 could not chaperone heat-unfolded luciferase but was able to assist in reactivation of heat-unfolded p53. So, even within the highly sequence-conserved HSPA family, functional differentiation is larger than expected, with HSPA6 being an extreme example that may have evolved to maintain specific critical functions under conditions of severe stress.
Observation of fast release of NO from ferrous d1 haem allows formulation of a unified reaction mechanism for cytochrome cd1 nitrite reductases
Authors: Rinaldo Serena , Sam Katharine A. , Castiglione Nicoletta , Stelitano Valentina , Arcovito Alessandro , Brunori Maurizio , Allen James W. A. , Ferguson Stuart J. , Cutruzzolà Francesca
Published: February 2011

Cytochrome cd1 nitrite reductase is a haem-containing enzyme responsible for the reduction of nitrite into NO, a key step in the anaerobic respiratory process of denitrification. The active site of cytochrome cd1 contains the unique d1 haem cofactor, from which NO must be released. In general, reduced haems bind NO tightly relative to oxidized haems. In the present paper, we present experimental evidence that the reduced d1 haem of cytochrome cd1 from Paracoccus pantotrophus releases NO rapidly (k=65–200 s−1); this result suggests that NO release is the rate-limiting step of the catalytic cycle (turnover number=72 s−1). We also demonstrate, using a complex of the d1 haem and apomyoglobin, that the rapid dissociation of NO is largely controlled by the d1 haem cofactor itself. We present a reaction mechanism proposed to be applicable to all cytochromes cd1 and conclude that the d1 haem has evolved to have low affinity for NO, as compared with other ferrous haems.
Role of mitochondrial phosphate carrier in metabolism–secretion coupling in rat insulinoma cell line INS-1
Authors: Nishi Yuichi , Fujimoto Shimpei , Sasaki Mayumi , Mukai Eri , Sato Hiroki , Sato Yuichi , Tahara Yumiko , Nakamura Yasuhiko , Inagaki Nobuya
Published: February 2011

In pancreatic β-cells, glucose-induced mitochondrial ATP production plays an important role in insulin secretion. The mitochondrial phosphate carrier PiC is a member of the SLC25 (solute carrier family 25) family and transports Pi from the cytosol into the mitochondrial matrix. Since intramitochondrial Pi is an essential substrate for mitochondrial ATP production by complex V (ATP synthase) and affects the activity of the respiratory chain, Pi transport via PiC may be a rate-limiting step for ATP production. We evaluated the role of PiC in metabolism–secretion coupling in pancreatic β-cells using INS-1 cells manipulated to reduce PiC expression by siRNA (small interfering RNA). Consequent reduction of the PiC protein level decreased glucose (10 mM)-stimulated insulin secretion, the ATP:ADP ratio in the presence of 10 mM glucose and elevation of intracellular calcium concentration in response to 10 mM glucose without affecting the mitochondrial membrane potential (Δψm) in INS-1 cells. In experiments using the mitochondrial fraction of INS-1 cells in the presence of 1 mM succinate, PiC down-regulation decreased ATP production at various Pi concentrations ranging from 0.001 to 10 mM, but did not affect Δψm at 3 mM Pi. In conclusion, the Pi supply to mitochondria via PiC plays a critical role in ATP production and metabolism–secretion coupling in INS-1 cells.
Functional analysis of RhoGDI inhibitory activity on vacuole membrane fusion
Authors: Logan Michael R. , Jones Lynden , Forsberg Daniel , Bodman Alex , Baier Alicia , Eitzen Gary
Published: February 2011

RhoGDIs (Rho GDP-dissociation inhibitors) are the natural inhibitors of Rho GTPases. They interfere with Rho protein function by either blocking upstream activation or association with downstream signalling molecules. RhoGDIs can also extract membrane-bound Rho GTPases to form soluble cytosolic complexes. We have shown previously that purified yeast RhoGDI Rdi1p, can inhibit vacuole membrane fusion in vitro. In the present paper we functionally dissect Rdi1p to discover its mode of regulating membrane fusion. Overexpression of Rdi1p in vivo profoundly affected cell morphology including increased actin patches in mother cells indicative of polarity defects, delayed ALP (alkaline phosphatase) sorting and the presence of highly fragmented vacuoles indicative of membrane fusion defects. These defects were not caused by the loss of typical transport and fusion proteins, but rather were linked to the reduction of membrane localization and activation of Cdc42p and Rho1p. Subcellular fractionation showed that Rdi1p is predominantly a cytosolic monomer, free of bound Rho GTPases. Overexpression of endogenous Rdi1p, or the addition of exogenous Rdi1p, generated stable cytosolic complexes. Rdi1p structure–function analysis showed that membrane association via the C-terminal β-sheet domain was required for the functional inhibition of membrane fusion. Furthermore, Rdi1p inhibited membrane fusion through the binding of Rho GTPases independent from its extraction activity.
Diet-induced epigenetic regulation in vivo of the intestinal fructose transporter Glut5 during development of rat small intestine
Authors: Suzuki Takuji , Douard Veronique , Mochizuki Kazuki , Goda Toshinao , Ferraris Ronaldo P.
Published: February 2011

Metabolic complications arising from excessive fructose consumption are increasing dramatically even in young children, but little is known about ontogenetic mechanisms regulating Glut5 [glucose transporter 5; encoded by the Slc2a5 (solute carrier family 2 member 5) gene]. Glut5 expression is low postnatally and does not increase, unless luminal fructose and systemic glucocorticoids are present, until ≥14 days of age, suggesting substrate-inducible age- and hormone-sensitive regulation. In the present study, we perfused intestines of 10- and 20-day-old rats with either fructose or glucose then analysed the binding of Pol II (RNA polymerase II) and GR (glucocorticoid receptor), as well as acetylation of histones H3 and H4 by chromatin immunoprecipitation. Abundance of Glut5 mRNA increased only with fructose perfusion and age, a pattern that matched that of Pol II binding and histone H3 acetylation to the Glut5 promoter. Although many regions of the Glut5 promoter respond to developmental signals, fewer regions perceive dietary signals. Age- but not fructose-dependent expression of Sglt1 [sodium-dependent glucose co-transporter 1 encoded by the Slc5a1(solute carrier family 5 member 1) gene] also correlated with Pol II binding and histone H3 acetylation. In contrast, G6Pase (glucose-6-phosphatase; encoded by the G6pc gene) expression, which decreases with age and increases with fructose, is associated only with age-dependent changes in histone H4 acetylation. Induction of Glut5 during ontogenetic development appears to be specifically mediated by GR translocation to the nucleus and subsequent binding to the Glut5 promoter, whereas the glucocorticoid-independent regulation of Sglt1 by age was not associated with any GR binding to the Sglt1 promoter.
Immunoregulatory and anti-HIV-1 enzyme activities of antioxidant components from lotus (Nelumbo nucifera Gaertn.) rhizome
Authors: Jiang Yun , Ng Tzi Bun , Liu Zhaokun , Wang Changrong , Li Ning , Qiao Wentao , Liua Fang
Published: February 2011

In the present study, two antioxidant micromolecular components (L2f-2 and L2f-3) and an antioxidant macromolecular component LB2 were extracted from lotus (Nelumbo nucifera Gaertn.) rhizomes. MS, FTIR (Fourier-transform IR) spectroscopy and NMR were used to identify these compounds. L2f-2 was (+/−)-gallocatechin, L2f-3 was (−)-catechin and LB2 was a polysaccharide–protein complex with a molecular mass of 18.8 kDa. LB2 was identified as a polysaccharide sulfate containing α/β-pyranose and α-furanose according to its FTIR spectrogram. It was composed of mannose, rhamnose, glucose, galactose and xylose with a molar ratio 2:8:7:8:1. The antioxidant components L2f-2, L2f-3 and LB2 strongly inhibited HIV-1 RT (reverse transcriptase) and IN (integrase). LB2 inhibited RT with an IC50 value of 33.7 μM. It also exhibited the highest HIV-1 3′-processing inhibitory activity with an IC50 value of 5.28 μM. Both L2f-2 and L2f-3 up-regulated the expression of IL-2 (interleukin-2) and down-regulated IL-10, while LB2 exhibited positive regulation on IL-2, IL-4 and IL-10. Moreover, L2f-3 and LB2 might inhibit HIV-1 directly by down-regulating TNFα (tumour necrosis factor α). These natural antioxidant components with antiviral and immunoregulatory activities could be potentially important for anti HIV-1 drug development and application to HIV-1 therapy.
Probing the effect of MODY mutations near the co-activator-binding pocket of HNF4α
Authors: Rha Geun Bae , Wu Guangteng , Chi Young-In
Published: February 2011

HNF4α (hepatocyte nuclear factor 4α) is a culprit gene product for a monogenic and dominantly inherited form of diabetes, referred to as MODY (maturity onset diabetes of the young). As a member of the NR (nuclear receptor) superfamily, HNF4α recruits transcriptional co-activators such as SRC-1α (steroid receptor co-activator-1α) and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) through the LXXLL-binding motifs for its transactivation, and our recent crystal structures of the complex provided the molecular details and the mechanistic insights into these co-activator recruitments. Several mutations have been identified from the MODY patients and, among these, point mutations can be very instructive site-specific measures of protein function and structure. Thus, in the present study, we probed the functional effects of the two MODY point mutations (D206Y and M364R) found directly near the LXXLL motif-binding site by conducting a series of experiments on their structural integrity and specific functional roles such as overall transcription, ligand selectivity, target gene recognition and co-activator recruitment. While the D206Y mutation has a subtle effect, the M364R mutation significantly impaired the overall transactivation by HNF4α. These functional disruptions are mainly due to their reduced ability to recruit co-activators and lowered protein stability (only with M364R mutation), while their DNA-binding activities and ligand selectivities are preserved. These results confirmed our structural predictions and proved that MODY mutations are loss-of-function mutations leading to impaired β-cell function. These findings should help target selective residues for correcting mutational defects or modulating the overall activity of HNF4α as a means of therapeutic intervention.
Blood levels of glutamate oxaloacetate transaminase are more strongly associated with good outcome in acute ischaemic stroke than glutamate pyruvate transaminase levels
Authors: Campos Francisco , Rodríguez-Yáñez Manuel , Castellanos Mar , Arias Susana , Pérez-Mato María , Sobrino Tomás , Blanco Miguel , Serena Joaquín , Castillo José
Published: February 2011

Ischaemic stroke is associated with an excessive release of glutamate in brain. GOT (glutamate-oxaloacetate transaminase) and GPT (glutamate-pyruvate transaminase) are two enzymes that are able to metabolize blood glutamate facilitating the lowering of extracellular levels of brain glutamate. Our aim was to study the association between blood levels of both enzymes and stroke outcome in patients with acute ischaemic stroke. We prospectively studied 365 patients with first ischaemic stroke<12 h. Glutamate, GOT and GPT levels were determined in blood samples obtained at admission. We considered functional outcome at 3 months [good outcome: mRS (modified Rankin Scale)≤2; poor outcome mRS >2], END (early neurological deterioration) in the first 72 h [increment ≥4 points in NIHSS (National Institutes of Health Stroke Scale)] and infarct volume [CT (computed tomography) at 36–72 h] as end points. We have found an inverse correlation between GOT and GPT levels and blood glutamate levels. Patients with poor outcome showed lower levels of GOT (11.9±8.2 compared with 22.7±10.2 m-units/ml, P<0.0001) and GPT (19.5±14.3 compared with 24.7±20.3 m-units/ml; P=0.004). A negative correlation has been found between GOT (Pearson coefficient=−0.477, P<0.0001) and GPT (Pearson coefficient=−0.116; P=0.027) levels and infarct volume. Patients with END showed higher levels of blood glutamate (381.7±97.9 compared with 237.6±114.0 μmol/l, P<0.0001) and lower levels of GOT (10.8±6.7 compared with 18.1±10.8 m-units/ml; P<0.0001). This clinical study shows an association between high blood GOT and GPT levels and good outcome in ischaemic stroke patients, this association being stronger for GOT than GPT levels.
Synergy of isoflurane preconditioning and propofol postconditioning reduces myocardial reperfusion injury in patients
Authors: Huang Zhiyong , Zhong Xingwu , Irwin Michael G. , Ji Shangyi , Wong Gordon T. , Liu Yanan , Xia Zhong-yuan , Finegan Barry A. , Xia Zhengyuan
Published: February 2011

Either isoflurane preconditioning or high-dose propofol treatment has been shown to attenuate myocardial IRI (ischaemia/reperfusion injury) in patients undergoing CABG (coronary artery bypass graft) surgery. It is unknown whether isoflurane and propofol may synergistically attenuate myocardial injury in patients. The present study investigated the efficacy of IsoPC (isoflurane preconditioning), propofol treatment (postconditioning) and their synergy in attenuating postischaemic myocardial injury in patients undergoing CABG surgery using CPB (cardiopulmonary bypass). Patients (n=120) selected for CABG surgery were randomly assigned to one of four groups (n=30 each). After induction, anaesthesia was maintained either with fentanyl and midazolam (control; group C); with propofol at 100 μg·kg−1 of body weight·min−1 before and during CPB followed by propofol at 60 μg·kg−1 of body weight·min−1 for 15 min after aortic declamping (group P); with isoflurane 1–1.5% end tidal throughout the surgery (group I) or with isoflurane 1–1.5% end tidal before CPB and switching to propofol at 100 μg·kg−1 of body weight·min−1 during CPB followed by propofol at 60 μg·kg−1 of body weight·min−1 for 15 min after aortic declamping (group IP, i.e. IsoPC plus propofol postconditioning). A joint isoflurane and propofol anaesthesia regimen synergistically reduced plasma levels of cTnI (cardiac troponin I) and CK-MB (creatine kinase MB) and f-FABP (heart-type fatty acid-binding protein) (all P<0.05 compared with control, group P or group I) and facilitated postoperative myocardial functional recovery. During reperfusion, myocardial tissue eNOS (endothelial NO synthase) protein expression in group IP was significantly higher, whereas nitrotyrosine protein expression was lower than those in the control group. In conclusion, a joint isoflurane preconditioning and propofol anaesthesia regimen synergistically attenuated myocardial reperfusion injury in patients.
Altered adipose tissue metabolism in offspring of dietary obese rat dams
Authors: Benkalfat Nassira Batoul , Merzouk Hafida , Bouanane Samira , Merzouk Sid-Ahmed , Bellenger Jérôme , Gresti Joseph , Tessier Christian , Narce Michel
Published: February 2011

To investigate further the mechanisms of developmental programming, we analysed the effects of maternal overnutrition and of postnatal high-fat feeding on adipose tissue metabolism in the offspring. Postnatal changes in serum adiponectin, leptin and TAG [triacylglycerol (triglyceride)] levels, adipose tissue TAGs, fatty acids and enzyme activities were determined in offspring of cafeteria-diet-fed dams during gestation and lactation, weaned on to standard chow or on to cafeteria diet. Obese rats showed higher adiposity (+35% to 85%) as well as a significant increase in serum glucose, insulin, leptin, adiponectin and TAG levels (P<0.01) and adipose tissue LPL (lipoprotein lipase) and GPDH (glycerol-3-phosphate dehydrogenase) activities (P<0.01), compared with control pups at weaning (day 21) and at adulthood (day 90). Adipose HSL (hormone-sensitive lipase) activity was increased only at day 90 (P<0.05), and FAS (fatty acid synthase) activity remained unchanged. The proportions of SFAs (saturated fatty acids) and MUFAs (mono-unsaturated fatty acids) and the Δ9-desaturation index were significantly increased (P<0.05), whereas PUFAs (polyunsaturated fatty acids) were decreased (P<0.01) in serum and adipose TAGs of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal overnutrition induced permanent changes in adipose tissue metabolism of the offspring. These pre-existing alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Consequently, adipose adipokines and enzymes could provide a potential therapeutic target, and new investigations in this field could constitute strategies to improve the impact of early-life overnutrition.
Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold
Authors: Eckert Danny J. , Owens Robert L. , Kehlmann Geoffrey B. , Wellman Andrew , Rahangdale Shilpa , Yim-Yeh Susie , White David P. , Malhotra Atul
Published: February 2011

Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to −15 cmH2O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO2 (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study. Compared with placebo, eszopiclone significantly increased the arousal threshold [−14.0 (−19.9 to −10.9) compared with −18.0 (−22.2 to −15.1) cmH2O; P<0.01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25±6 compared with 14±4 events/h of sleep; P<0.01). In conclusion, eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are probably required to achieve elimination of apnoea.
Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavourable NOS substrate-to-inhibitor ratio: the Hoorn Study
Authors: van der Zwan Leonard P. , Scheffer Peter G. , Dekker Jacqueline M. , Stehouwer Coen D. A. , Heine Robert J. , Teerlink Tom
Published: February 2011

Inflammation is associated with a reduced availability of NO in the vasculature. We investigated the possible involvement of altered levels of the substrate (arginine) and the inhibitor [ADMA (asymmetric ω-NG,NG-dimethylarginine)] of NOS (NO synthase). Plasma concentrations of arginine and ADMA, the inflammatory markers CRP (C-reactive protein) and MPO (myeloperoxidase), and oxLDL [oxidized LDL (low-density lipoprotein)] were measured in 369 male and 377 female participants (aged 50–87 years) of a population-based cohort study. The arginine/ADMA ratio decreased significantly across increasing tertiles of CRP and MPO. These negative associations remained significant in a linear regression model with both MPO (P=0.002) and CRP (P<0.001) as independent variables and adjusted for age, sex and cardiovascular risk factors. In a fully adjusted regression model, MPO was positively associated with ADMA {5.4 [95% CI (confidence interval), 1.3–9.4] nmol/l change of ADMA per S.D. increase in MPO; P=0.010}, whereas CRP was not (P=0.36). Conversely, in a fully adjusted model, CRP was negatively associated with arginine [−2.8 (95% CI, −4.0 to −1.6) μmol/l arginine per S.D. of CRP; P<0.001], without a significant contribution of MPO (P=0.23). The relationship between MPO and ADMA became stronger with increasing levels of oxLDL (1.8, 5.2 and 8.7 nmol/l ADMA per S.D. of MPO for increasing tertiles of oxLDL), consistent with the ability of MPO to amplify oxidative stress. In contrast, the relationship between CRP and arginine was not modified by levels of oxLDL. In conclusion, an unfavourable NOS substrate/inhibitor ratio may contribute to the reduced NO bioavailability associated with inflammation.
Fluids in porous media. III. Scaled particle theory
Authors: Patsahan T. , Holovko M. , Dong W.
Published: February 2011

Based on a new and consistent formulation of scaled particle theory for a fluid confined in random porous media, a series of new approximations are proposed and one of them gives equations of state with excellent accuracy for a hard sphere fluid adsorbed in a hard sphere or an overlapping hard sphere matrix. Although the initial motivation was to remedy a flaw in a previous formulation of the scaled particle theory for a confined fluid, the new formulation is not a trivial and straightforward correction of the previous one. A few conceptual and significant modifications have to be introduced for developing the present formulation.
Determination of natural frequencies by coupled method of homotopy perturbation and variational method for strongly nonlinear oscillators
Authors: Akbarzade M. , Langari J.
Published: February 2011

In this paper a new approach combining the features of the homotopy concept with variational approach is proposed to find accurate analytical solutions for nonlinear oscillators with and without a fractional power restoring force. Since the first-order approximation leads to very accurate results, comparisons with other results are presented to show the effectiveness of this method. The validity of the method is independent of whether or not there exist small or large parameters in the considered nonlinear equations; the obtained results prove the validity and efficiency of the method, which can be easily extended to other strongly nonlinear problems. At the end we compare our procedure with the optimal homotopy perturbation method.
Enhancement-mode AlGaN/GaN heterostructure field effect transistors fabricated by selective area growth technique
Authors: Wen Yuhua , He Zhiyuan , Li Jialin , Luo Ruihong , Xiang Peng , Deng Qingyu , Xu Guangning , Shen Zhen , Wu Zhisheng , Zhang Baijun , Jiang Hao , Wang Gang , Liu Yang
Published: February 2011

In this letter, a method of using selective area growth (SAG) technique was proposed to fabricate the enhancement-mode (E-mode) AlGaN/GaN heterostructure field effect transistors (HFETs), which can effectively avoid the plasma treatment damage to the active region of HFETs in comparison with the conventional methods. The SAG-HFETs exhibited a good performance of the maximum drain current of 300 mA/mm and peak transconductance of 135 mS/mm with a larger positive threshold voltage of 0.4 V. The results indicate that the SAG technique is a promising method to realize the high performance E-mode GaN based HFETs.
Prediction of extremely long mobile electron spin lifetimes at room temperature in wurtzite semiconductor quantum wells
Authors: Harmon N. J. , Putikka W. O. , Joynt Robert
Published: February 2011

Many proposed spintronics devices require mobile electrons at room temperature with long spin lifetimes. One route to achieving this is to use quantum wells with tunable spin-orbit (SO) parameters. Research has focused on zinc-blende materials such as GaAs which do not have long spin lifetimes at room temperature. We show that wurtzite (w) materials, which possess smaller SO coupling due to being low-Z, are better suited for spintronics applications. This leads to predictions of spin lifetimes in w-AlN exceeding 2 ms at helium temperatures and, relevant to spintronic devices, spin lifetimes up to 0.5 μs at room temperature.
Dipolar ferromagnetic phase transition in Fe3O4 nanoparticle arrays observed by Lorentz microscopy and electron holography
Authors: Yamamoto Kazuo , Hogg Charles R. , Yamamuro Saeki , Hirayama Tsukasa , Majetich Sara A.
Published: February 2011

Dipolar ferromagnetism formed in Fe3O4 nanoparticle arrays is revealed by Fresnel Lorentz microscopy and electron holography. Dipolar domain walls do not lie preferentially along macrograin boundaries but depend on the overall shape of the assembly, meaning magnetostatic energy dominates. The domain structures are imaged at different temperatures for both monolayer and bilayer arrays. The domain wall contrast in the monolayer region is visible until 575 °C, and the magnetic order parameter steeply drops toward the temperature. In the bilayer region, finer and more complicated domains are formed.
Haunted Sound: Nothingness, Movement, and the Minimalist Imagination
Authors: Mohaghegh Jason B , Golestaneh Seema
Published: February 2011

This paper explores the topic of ‘haunted sound’ and its overarching significance within minimalist thought, tracing the vast intricacies of this aerial intimation as a new and unforeseen existential horizon. To this end, the paper advances via the entangling concepts of nothingness and movement, including subthematic dimensions as far-reaching as: the zero-degree, disintegration, control/noncontrol, mood, catastrophe, indeterminacy, interruption, repetition, desertion, indifference, stillness, and exhaustion. It is through the formulation of this haunted soundscape, in turn, that the once absolute totalities of consciousness stray toward an increasingly apparitional province, turning perception itself toward the paradoxical borderlands of presence and absence, materiality and immateriality, being and nonbeing. Ultimately, the intent of this project is to devise an innovative outlook on the singular potential of sound to eclipse past existential regimes, to lead the aesthetic toward a vanishing, phantasmatic sphere at once creative and destructive, ethereal yet incisive, and which thereby restores the artwork to its volatile capacity for engaging the chaos of a minimalist imagination.
Genetic mapping and QTL analysis of disease resistance traits in the barley population Baudin×AC Metcalfe
Authors: Cakir Mehmet , Gupta Sanjiv , Li Chengdao , Hayden Matthew , Mather Diane E. , Ablett Gary A. , Platz Greg J. , Broughton Sue , Chalmers Ken J. , Loughman Robert , Jones Michael G. K. , Lance Reg C. M.
Published: February 2011

A genetic map of barley (Hordeum vulgare L.) with 163 amplified fragment length polymorphism and 69 simple sequence repeat (SSR) markers was constructed using a population of 178 doubled haploid lines from a cross between the varieties ‘Baudin’ and ‘AC Metcalfe’. Linkage groups were assigned to barley chromosomes using published map locations of SSR markers as reference points. The total length of the map was 1307.2 cM with an average interval length of 5.6 cM between markers. The genetic map was used to locate quantitative trait loci (QTLs) for several disease resistance traits. The population was tested for spot type net blotch, caused by Pyrenophora teres f. maculata, and net type net blotch, caused by Pyrenophora teres f. teres, in greenhouse experiments and in a range of field environments in Western Australia and Queensland. The response of the lines to leaf rust (caused by Puccinia hordei L.) at adult plant growth stages was evaluated in Western Australia. Significant marker–trait associations were found for seedling resistance and symptom severity in adult plants to these diseases. A new locus conferring resistance to P. teres f. maculata at both seedling and adult plant stages was detected on the short arm of chromosome 6H. From the seedling testing against P. teres f. teres, five highly repeatable QTLs were detected, on chromosomes 2HS, 2HL, 3HS, 4HL, and 6HS. For leaf rust, one highly significant QTL was detected on chromosome 2HL. The markers within these QTL regions present an opportunity for marker-assisted selection for these traits in barley-breeding programs.
Enhanced Processing Fluency Leads to Biases in Source Memory
Authors: Kurilla Brian P.
Published: February 2011

The present experiments were conducted to determine whether processing fluency affects source memory decisions. In the first three experiments, participants decided whether test items appeared in the same sensory modality (Experiments 1A, 1B) or perceptual form (font type, Experiment 2) at study and test. The results were consistent across the three studies and showed that perceptual priming leads to an increase in reports that stimuli were presented in the same sensory or perceptual form during the study and test phase. Experiment 3 showed that conceptual fluency affects source attributions in much the same way as perceptual fluency, and Experiment 4 showed that fluency is associated with a subjective experience of familiarity even when it might serve as a basis for source inference. These results are consistent with recent neuropsychological and neuroimaging evidence that familiarity-based processes contribute to source memory decisions under some circumstances, such as when items and contexts are unitized rather than merely bound together at encoding.
Arguing from experience using multiple groups of agents
Authors: Wardeh Maya , Bench-Capon Trevor , Coenen Frans
Published: February 2011

A framework to support “ Arguing from Experience” using groups of collaborating agents (termed participant agents/players) is described. The framework is an extension of the PISA multi-party arguing from experience framework. The original version of PISA allowed n participants to promote n goals (one each) for a given example. The described extension of PISA allows individuals with the same goals to pool their resources by forming “ groups”. The framework is fully described and its effectiveness illustrated using a number of classification scenarios. The main finding is that by using groups more accurate results can be obtained than when agents operate in isolation.
Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability
Authors: Horn Sarah R. , Thomenius Michael J. , Johnson Erika Segear , Freel Christopher D. , Wu Judy Q. , Coloff Jonathan L. , Yang Chih-Sheng , Tang Wanli , An Jie , Ilkayeva Olga R. , Rathmell Jeffrey C. , Newgard Christopher B. , Kornbluth Sally
Published: February 2011

Homeostatic maintenance of cellular mitochondria requires a dynamic balance between fission and fusion, and controlled changes in morphology are important for processes such as apoptosis and cellular division. Interphase mitochondria have been described as an interconnected network that fragments as cells enter mitosis, and this mitotic mitochondrial fragmentation is known to be regulated by the dynamin-related GTPase Drp1 (dynamin-related protein 1), a key component of the mitochondrial division machinery. Loss of Drp1 function and the subsequent failure of mitochondrial division during mitosis lead to incomplete cytokinesis and the unequal distribution of mitochondria into daughter cells. During mitotic exit and interphase, the mitochondrial network reforms. Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1, catalyzed by the APC/CCdh1 (anaphase-promoting complex/cyclosome and its coactivator Cdh1) E3 ubiquitin ligase complex. Importantly, inhibition of Cdh1-mediated Drp1 ubiquitylation and proteasomal degradation during interphase prevents the normal G1 phase regrowth of mitochondrial networks following cell division.
MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration
Authors: Aranda Juan F. , Reglero-Real Natalia , Kremer Leonor , Marcos-Ramiro Beatriz , Ruiz-Sáenz Ana , Calvo María , Enrich Carlos , Correas Isabel , Millán Jaime , Alonso Miguel A.
Published: February 2011

Membrane organization into condensed domains or rafts provides molecular platforms for selective recruitment of proteins. Cell migration is a general process that requires spatiotemporal targeting of Rac1 to membrane rafts. The protein machinery responsible for making rafts competent to recruit Rac1 remains elusive. Some members of the MAL family of proteins are involved in specialized processes dependent on this type of membrane. Because condensed membrane domains are a general feature of the plasma membrane of all mammalian cells, we hypothesized that MAL family members with ubiquitous expression and plasma membrane distribution could be involved in the organization of membranes for cell migration. We show that myeloid-associated differentiation marker (MYADM), a protein with unique features within the MAL family, colocalizes with Rac1 in membrane protrusions at the cell surface and distributes in condensed membranes. MYADM knockdown (KD) cells had altered membrane condensation and showed deficient incorporation of Rac1 to membrane raft fractions and, similar to Rac1 KD cells, exhibited reduced cell spreading and migration. Results of rescue-of-function experiments by expression of MYADM or active Rac1L61 in cells knocked down for Rac1 or MYADM, respectively, are consistent with the idea that MYADM and Rac1 act on parallel pathways that lead to similar functional outcomes.
The effects of feedback loops on disease comorbidity in human signaling networks
Authors: Le Duc-Hau , Kwon Yung-Keun
Published: February 2011

Motivation: In general, diseases are more likely to be comorbid if they share associated genes or molecular interactions in a cellular process. However, there are still a number of pairs of diseases which show relatively high comorbidity but do not share any associated genes or interactions. This observation raises the need for a novel factor which can explain the underlying mechanism of comorbidity. We here consider a feedback loop (FBL) structure ubiquitously found in the human cell signaling network as a key motif to explain the comorbidity phenomenon, since it is well known to have effects on network dynamics.

Results: For every pair of diseases, we examined its comorbidity and length of all FBLs involved by the disease-associated genes in the human cell signaling network. We found that there is a negative relationship between comorbidity and length of involved FBLs. This indicates that a disease pair is more likely to comorbid if they are connected with FBLs of shorter length. We additionally showed that such a negative relationship is more obvious when the number of positive involved FBLs is larger than that of negative involved FBLs. Moreover, we observed that the negative relationship between comorbidity and length of involved FBLs holds especially for disease pairs that do not share any disease-associated genes. Finally, we proved all these results through intensive simulations, based on a Boolean network model.

Contact:  kwonyk@ulsan.ac.kr

Supplementary information:  Supplementary data are available at BioInformatics online.
Isochronous dynamical systems
Authors: Calogero F.
Published: February 2011

This is a terse review of recent results on isochronous dynamical systems, namely systems of (first-order, generally nonlinear) ordinary differential equations (ODEs) featuring an open set of initial data (which might coincide with the entire set of all initial data), from which emerge solutions all of which are completely periodic (i.e. periodic in all their components) with a fixed period (independent of the initial data, provided they are within the isochrony region). A
leitmotif
of this presentation is that ‘isochronous systems are not rare’. Indeed, it is shown how any (autonomous) dynamical system can be modified or extended so that the new (also autonomous) system thereby obtained is isochronous with an arbitrarily assigned period
T
, while its dynamics, over time intervals much shorter than the period
T
, mimics closely that of the original system, or even, over an arbitrarily large fraction of its period
T
, coincides exactly with that of the original system. It is pointed out that this fact raises the issue of developing criteria providing, for a dynamical system, some kind of measure associated with a finite time scale of the complexity of its behaviour (while the current, standard definitions of integrable versus chaotic dynamical systems are related to the behaviour of a system over infinite time).
Exactly and quasi-exactly solvable ‘discrete’ quantum mechanics
Authors: Sasaki Ryu
Published: February 2011

A brief introduction to discrete quantum mechanics is given together with the main results on various exactly solvable systems. Namely, the intertwining relations, shape invariance, Heisenberg operator solutions, annihilation/creation operators and dynamical symmetry algebras, including theq-oscillator algebra and the Askey–Wilson algebra. A simple recipe to construct exactly and quasi-exactly solvable (QES) Hamiltonians in one-dimensional ‘discrete’ quantum mechanics is presented. It reproduces all the known Hamiltonians whose eigenfunctions consist of the Askey scheme of hypergeometric orthogonal polynomials of a continuous or a discrete variable. Several new exactly and QES Hamiltonians are constructed. The sinusoidal coordinate plays an essential role.
Addition formulae for Abelian functions associated with specialized curves
Authors: Eilbeck J. C. , Matsutani S. , Ônishi Y.
Published: February 2011

We discuss a family of multi-term addition formulae for Weierstrass functions on specialized curves of low genus with many automorphisms, concentrating mostly on the case of genus 1 and 2. In the genus 1 case, we give addition formulae for the equianharmonic and lemniscate cases, and in genus 2 we find some new addition formulae for a number of curves.