bluuebunny/crossref_metadata_2025 huggingface dataset:
A NEW SEPARATION ALGORITHM FOR OVERLAPPING BLOOD CELLS USING SHAPE ANALYSIS
Authors: SONG HAO , WANG WEIXING
Published: June 2009

Blood cell classification is widely used in the biomedical research. Appropriate separation between touching and overlapping blood cells is of great importance for the successful classification. In this paper, a novel algorithm based on shape information is proposed for the separation of partially overlapping blood cells. It is motivated by the problem of finding the borders between adjacent blood cells in microscopy images. The algorithm can not only separate the simple touching blood cells, but also large clusters of overlapping blood cells. In addition, this algorithm can be adopted for other applications, where separation between touching and overlapping particles is required.
MINING FREQUENT ITEMSETS IN DISTORTED DATABASES WITH GRANULAR COMPUTING
Authors: WANG JINLONG , XU CONGFU , LI GANG
Published: June 2009

Data perturbation is a popular method to achieve privacy-preserving data mining. However, distorted databases bring enormous overheads to mining algorithms as compared to original databases. In this paper, we present the GrC-FIM algorithm to address the efficiency problem in mining frequent itemsets from distorted databases. Two measures are introduced to overcome the weakness in existing work: firstly, the concept of independent granule is introduced, and granule inference is used to distinguish between non-independent itemsets and independent itemsets. We further prove that the support counts of non-independent itemsets can be directly derived from subitemsets, so that the error-prone reconstruction process can be avoided. This could improve the efficiency of the algorithm, and bring more accurate results; secondly, through the granular-bitmap representation, the support counts can be calculated in an efficient way. The empirical results on representative synthetic and real-world databases indicate that the proposed GrC-FIM algorithm outperforms the popular EMASK algorithm in both the efficiency and the support count reconstruction accuracy.
PEDESTRIAN DETECTION SYSTEM USING CASCADED BOOSTING WITH INVARIANCE OF ORIENTED GRADIENTS
Authors: WANG CHI-CHEN RAXLE , WU JIN-YI , LIEN JENN-JIER JAMES
Published: June 2009

This study presents a novel learning-based pedestrian detection system capable of automatically detecting individuals of different sizes and orientations against a wide variety of backgrounds, including crowds, even when the individual is partially occluded. To render the detection performance robust toward the effects of geometric and rotational variations in the original image, the feature extraction process is performed using both rectangular- and circular-type blocks of various sizes and aspect ratios. The extracted blocks are rotated in accordance with their dominant orientation(s) such that all the blocks extracted from the input images are rotationally invariant. The pixels within the cells in each block are then voted into rectangular- and circular-type 9-bin histograms of oriented gradients (HOGs) in accordance with their gradient magnitudes and corresponding multivariate Gaussian-weighted windows. Finally, four cell-based histograms are concatenated using a tri-linear interpolation technique to form one 36-dimensional normalized HOG feature vector for each block. The experimental results show that the use of the Gaussian-weighted window approach and tri-linear interpolation technique in constructing the HOG feature vectors improves the detection performance from 91% to 94.5%. In the proposed scheme, the detection process is performed using a cascaded detector structure in which the weak classifiers and corresponding weights of each stage are established using the AdaBoost self-learning algorithm. The experimental results reveal that the cascaded structure not only provides a better detection performance than many of the schemes presented in the literature, but also achieves a significant reduction in the computational time required to classify each input image.
INFINITE WORDS AND CONFLUENT REWRITING SYSTEMS: ENDOMORPHISM EXTENSIONS
Authors: CASSAIGNE JULIEN , SILVA PEDRO V.
Published: June 2009

Infinite words over a finite special confluent rewriting system R are considered and endowed with natural algebraic and topological structures. Their geometric significance is explored in the context of Gromov hyperbolic spaces. Given an endomorphism φ of the monoid generated by R, existence and uniqueness of several types of extensions of φ to infinite words (endomorphism extensions, weak endomorphism extensions, continuous extensions) are discussed. Characterization theorems and positive decidability results are proved for most cases.
NEUTRAL ELEMENTS, FUNDAMENTAL RELATIONS AND n-ARY HYPERSEMIGROUPS
Authors: DAVVAZ B. , DUDEK W. A. , MIRVAKILI S.
Published: June 2009

The main tools in the theory of n-ary hyperstructures are the fundamental relations. The fundamental relation on an n-ary hypersemigroup is defined as the smallest equivalence relation so that the quotient would be the n-ary semigroup. In this paper we study neutral elements in n-ary hypersemigroups and introduce a new strongly compatible equivalence relation on an n-ary hypersemigroup so that the quotient is a commutative n-ary semigroup. Also we determine some necessary and sufficient conditions so that this relation is transitive. Finally, we prove that this relation is transitive on an n-ary hypergroup with neutral (identity) element.
THE BOUSSO ENTROPY BOUND FOR AN IDEAL GAS OF MASSIVE PARTICLES
Authors: GERŠL JAN
Published: June 2009

The Bousso entropy bound is investigated for static, spherically symmetric configurations of an ideal gas with a Bose–Einstein or Fermi–Dirac distribution function. Gas of massive particles is considered. This paper is continuation of the previous work concerning the massless case. Special attention is devoted to light sheets generated by spheres. Conditions under which the Bousso bound can be violated are discussed and it is shown that a possible violating region cannot be arbitrarily large and that it is contained inside a sphere of unit Planck radius if the number of independent spin states gs is small enough. It is also shown that the central temperature must exceed the Planck temperature in order to get a violation of the Bousso bound for gs which is not too large. The situation for higher-dimensional space–times is also discussed and the conditions of Flanagan, Marolf and Wald are investigated.
AN IDENTITY WITH GENERALIZED DERIVATIONS
Authors: LEE TSIU-KWEN , ZHOU YIQIANG
Published: June 2009

Let R be a prime ring that is not commutative and such that R ≇ M2( GF (2)), let D, G be two generalized derivations of R, and let m, n be two fixed positive integers. Then D(xm)xn= xnG(xm) for all x ∈ R iff the following two conditions hold: (1) There exists w ∈ Q, the symmetric Martindale quotient ring of R, such that D(x) = xw and G(x) = wx for all x ∈ R; (2) either w ∈ C, or xmand xnare C-dependent for all x ∈ R. We also consider the situation for the semiprime case.
KRULL DIMENSION OF TENSOR PRODUCTS OF PULLBACKS
Authors: BOUCHIBA SAMIR
Published: June 2009

This paper is concerned with the study of the dimension theory of tensor products of algebras over a field k. We answer an open problem set in [6] and compute dim (A ⊗kB) when A is a k-algebra arising from a specific pullback construction involving AF-domains and B is an arbitrary k-algebra. On the other hand, we deal with the question (Q) set in [5] and show, in particular, that such a pullback A is in fact a generalized AF-domain.
WHITTAKER MODULES FOR THE VIRASORO ALGEBRA
Authors: ONDRUS MATTHEW , WIESNER EMILIE
Published: June 2009

Whittaker modules have been well studied in the setting of complex semisimple Lie algebras. Their definition can easily be generalized to certain other Lie algebras with triangular decomposition, including the Virasoro algebra. We define Whittaker modules for the Virasoro algebra and obtain analogues to several results from the classical setting, including a classification of simple Whittaker modules by central characters and composition series for general Whittaker modules.
RANDOM COINCIDENCE AND FIXED POINTS FOR WEAKLY COMPATIBLE MAPPINGS IN CONVEX METRIC SPACES
Authors: Beg Izmat , Jahangir Adnan , Azam Akbar
Published: June 2009

Some new theorems on random coincidence points and random fixed points for weakly compatible mappings in convex separable complete metric spaces have been established. These results generalize some recent well known comparable results in the literature.
GENERALIZATIONS OF D11 AND $D_{11}^ +$ MODULES
Authors: Talebi Yahya , Talaee Behnam
Published: June 2009

Let M be a module. Then M is called a D11 module if any submodule of M has a supplement which is a direct summand of M. Also M is called [Formula: see text] if every direct summand of M is D11. In this paper we investigate generalizations of D11 and [Formula: see text] modules, namely δ-D11 and [Formula: see text] modules. We will prove that any δ-D11 module M has a decomposition M = M1 ⊕ M2 with δ(M1) ≪δ M1 and δ(M2) = M2.
NECESSARY AND SUFFICIENT CONDITIONS FOR FREQUENT CAUCHY SEQUENCES
Authors: Tian Chuan Jun , Cheng Sui Sun , Gürdal Mehmet
Published: June 2009

In this paper, by means of frequency measure (also called asymptotic density or natural density) defined for integer subsets, we obtain some new explicit sufficient and necessary conditions for real sequences to be frequently convergent. These conditions involve frequent Cauchy sequences and statistical pre-Cauchy sequences as well as statistical Cauchy sequences.
Isotopic signals from Callovian–Kimmeridgian (Middle–Upper Jurassic) belemnites and bulk organic carbon, Staffin Bay, Isle of Skye, Scotland
Authors: Nunn Elizabeth V. , Price Gregory D. , Hart Malcolm B. , Page Kevin N. , Leng Melanie J.
Published: June 2009

The stable isotope data presented here significantly extend and expand upon previous isotopic investigations of the Middle to Late Jurassic interval. The belemnite samples collected from the Staffin Bay and Staffin Shale formations from the Isle of Skye, Scotland, yielded oxygen isotope values consistent with Callovian–Kimmeridgian palaeotemperatures of 6.7–20.6 °C. The carbon isotope data comprise one of the first moderately high-resolution investigations of the relationship between terrestrial δ
13
C
org
(predominantly fossil wood debris) and marine δ
13
C
carb
(belemnites) as derived from a geologically coeval record. The Staffin Bay data reveal a broad Early to Mid-Oxfordian positive carbon isotope excursion. The excursion maximum occurs in the
cordatum
Zone (British Boreal ammonite zonation), although high values persist into the
tenuiserratum
Zone. The correspondence between the marine and terrestrial records indicates a strong coupling of the ocean–atmosphere system and suggests that the total exchangeable carbon reservoir would have been affected at this time. The Mid-Oxfordian negative carbon isotope excursions identified in published Tethyan records and commonly attributed to methane release are not recorded in the Staffin Bay data, which may suggest that the Tethyan excursions do not represent fluctuations in the global carbon reservoir and that the fidelity of the methane hypothesis should be re-evaluated.

Supplementary material:

Isotopic and geochemical data are available at
http://www.geolsoc.org.uk/SUP18339
.
Speleoseismology and palaeoseismicity of Benis Cave (Murcia, SE Spain): coseismic effects of the 1999 Mula earthquake (m
b
4.8)
Authors: Pérez-López R. , Rodríguez-Pascua M. A. , Giner-Robles J. L. , Martínez-Díaz J. J. , Marcos-Nuez A. , Silva P. G. , Bejar M. , Calvo J. P.
Published: June 2009

This work describes the coseismic ceiling block collapse within Benis Cave (−213 m; Murcia, SE Spain), associated with the 1999 Mula earthquake (m
b
=4.8, MSK VII). The collapse occurred at −156 m into the Earthquake Hall, and as a consequence one small gallery became blind. We studied the geology, topography and active tectonic structures relevant to the cave. In addition, we carried out a seismotectonic analysis of the focal mechanism solutions, and also a fault population analysis on slickensides measured in fault planes in the cave. The stress and strain regime is interpreted as being congruent with the palaeoseismic evidence, and agrees with the fault kinematics established for cave galleries developed within fault planes and growth anomalies of coral flowstone. Our analysis suggests that one active segment (NNE–SSW) determined the morphology and topography of the Benis Cave, where strong to moderate palaeoearthquakes (6≤M≤7) took place. As a consequence of this intense seismic activity a small gallery collapsed. A new palaeoseismic structure, or seismothem, has been recognized, namely the effect of palaeoearthquakes affecting the pattern of development of the spatial coral flowstone distribution located at the bottom of the cave.
Tsunami deposits in the western Mediterranean: remains of the 1522 Almerı́a earthquake?
Authors: Reicherter Klaus , Becker-Heidmann Peter
Published: June 2009

Shallow drilling in the lagoon of the Cabo de Gata area proved sedimentary evidence for a palaeo-tsunami along that part of the Spanish Mediterranean coast. Several coarse-grained intervals form fining-up and thinning-up sequences that are interpreted as tsunamites. Inland-extending sand sheets are used to identify tsunamigenic inundations. Other indicative features found are erosive bases, rip-up clasts, broken shells of bivalves and benthic/planktic foraminifera. The coarse-grained intervals consist of up to three sequences separated from each other by a silty mud drape. These intervals are interpreted as deposits of a tsunami train and correspond to three individual waves. Radiocarbon dating reveals evidence that these layers can be ascribed to deposition during the 1522 Almerı́a earthquake.

The 1522 Almerı́a earthquake (M>6.5) affected large areas in the western Mediterranean and caused more than 1000 casualties. The epicentral area was offshore in the Gulf of Almerı́a (southern Spain) along the Carboneras Fault Zone and seismic shaking triggered submarine slides in the Gulf of Almerı́a, which may have caused tsunami waves.

We have also found another intercalation of tsunamites downhole, which are interpreted as either an expression of repeated earthquake activity or tsunami-like waves induced by submarine slides triggered by seismic shaking in the Gulf of Almerı́a. Our evidence suggests a definite tsunami potential and hazard for offshore active and seismogenic faults in the western Mediterranean region.
Recent seismic activity in the NW Himalayan Fold and Thrust Belt, Pakistan: focal mechanism solution and its tectonic implications
Authors: MonaLisa
Published: June 2009

The Himalayas in northern Pakistan have been the site of several disastrous earthquakes of moderate to high intensity. The 8 October 2005 Muzaffarabad earthquake, with magnitude M
w
7.6, occurred in the NW Himalayan Fold and Thrust Belt at 08:50:38 local time. The epicentre of the main shock was located 19 km NE of Muzaffarabad. This earthquake took a death toll of more than 80 000 human lives and caused widespread destruction in Kashmir and north Pakistan, particularly in the towns of Muzaffarabad, Bagh, Rawalakot, Mansehra, Balakot, Abbottabad and Batgram. Based on the information obtained from print and electronic media (and for some areas from field studies), an intensity of X (MMI scale) has been assigned at the epicentral location including the localities of Muzaffarabad and Balakot. Epicentral distribution of 300 aftershocks indicates that more than one tectonic subdivision of the fold belt have experienced instability. Focal depths indicate that most activity is confined to a narrow depth range (5–20 km). Further extension of the Indus Kohistan Seismic Zone in the Hazara–Kashmir syntaxial area and activation of more than one fault seem to be the cause of this seismic activity, as suggested by the focal mechanism of the main event and depth distribution of the aftershocks. About 100 large landslides caused by active faulting have been observed in the rupture zones near Balakot, Muzaffarabad, Kardalla, Hattian Bala, Sarain, Sunddangali and Bagh, through field studies and satellite images.
Pleistocene to Recent rejuvenation of the Hebron Fault, SW Namibia
Authors: White Stephen , Stollhofen Harald , Stanistreet Ian G. , Lorenz Volker
Published: June 2009

The Hebron Fault in SW Namibia is associated with a <1 m to 9.6 m high scarp displacing Proterozoic basement and Middle to Late Pliocene crystalline conglomerates. The young age of strata exposed in the fault scarp together with evidence for displacement of aeolian dunes, post-dating the Middle Stone Age, suggests that latest fault displacements occurred during the Late Pleistocene to recent. Recorded historical seismic events show that the fault zone is still active. Latest movements of the fault are recorded by: down-to-the-SW offset of calcrete-cemented conglomerate; fluvially modified, asymmetric hanging wall, graben-like structures; at least two left-stepping jogs in the fault trace and structural data from basement rocks in which late-stage crush zones overprint earlier cataclasite. These features provide consistent evidence that the present scarp formed predominantly by normal dip-slip displacement on a NW-striking, steeply SW-dipping master fault with only a minor dextral strike-slip component. Strongly veined cataclastic fault rocks adjacent to the scarp in basement most probably originated at depths of 4–10 km. The conclusion is therefore that recent fault activity has reactivated a pre-existing, much older fault.

Aerial photographic lineaments and similar fault scarps identified NW and SE of the present study area are interpreted as extensions of the same fault structure. Hence the total length of the Hebron Fault is at least 300 km subparallel to the Atlantic margin of southern Africa. Our observations confirm that the Hebron Fault is a neotectonic feature of regional significance that may relate to late Cenozoic and particularly Quaternary neotectonic activity in NE Namibia and NW Botswana.
Surface and subsurface palaeoseismic records at the ancient Roman city of
Baelo Claudia
and the Bolonia Bay area, Cádiz (south Spain)
Authors: Silva Pablo G. , Reicherter Klaus , Grützner Christoph , Bardají Teresa , Lario Javier , Goy Jose L. , Zazo Cari , Becker-Heidmann Peter
Published: June 2009

The Roman archaeological site of
Baelo Claudia
(Cádiz, south Spain) is located within the Gibraltar Arch, a region with no significant recent or historical seismicity. However, previous studies have emphasized the occurrence of repeated strong archaeoseismic damage (intensity≥IX MSK) at
Baelo Claudia
tentatively bracketed in this study around
ad
40–60 and
ad
260–290. A multidisciplinary study has been carried out including the detailed mapping of surface deformation and building damage, surface geology and geomorphology, collection of structural data, and an extensive ground penetrating radar (GPR) survey. The obtained data are not conclusive when considered separately, but evident links between archaeoseismic damage, structural and GPR data indicate that the destruction of the city was linked to seismic shaking. The analysis of the pattern and orientation of deformation clearly indicates SW–NE directed compression due to ground shaking. This analysis also focuses on localized landslides and liquefaction processes, which appear to be coeval with the earthquakes, but the poor geotechnical parameters of the clayey substratum were determinant to amplify the observed level of destruction. The application of the present Spanish seismic code (NCSE-02) indicates that intensity VIII MSK (0.24–0.26 g) can be reached in this zone for 500 year return periods.
The Randle cycle revisited: a new head for an old hat
Authors: Hue Louis , Taegtmeyer Heinrich
Published: June 2009

In 1963, Lancet published a paper by Randle et al. that proposed a “glucose-fatty acid cycle” to describe fuel flux between and fuel selection by tissues. The original biochemical mechanism explained the inhibition of glucose oxidation by fatty acids. Since then, the principle has been confirmed by many investigators. At the same time, many new mechanisms controlling the utilization of glucose and fatty acids have been discovered. Here, we review the known short- and long-term mechanisms involved in the control of glucose and fatty acid utilization at the cytoplasmic and mitochondrial level in mammalian muscle and liver under normal and pathophysiological conditions. They include allosteric control, reversible phosphorylation, and the expression of key enzymes. However, the complexity is formidable. We suggest that not all chapters of the Randle cycle have been written.
Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance
Authors: Solomon Thomas P. J. , Haus Jacob M. , Marchetti Christine M. , Stanley William C. , Kirwan John P.
Published: June 2009

Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFAox) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric ( n = 8; −598 ± 125 kcal/day, 66 ± 1 yr, 32.8 ± 1.8 kg/m2) or a eucaloric ( n = 8; 67 ± 2 yr, 35.3 ± 2.1 kg/m2) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-14C]palmitate) were assessed throughout a 7-h, 40 mU·m−2·min−1 hyperinsulinemic euglycemic clamp, during which insulin resistance was induced in the last 5 h by a sustained elevation in plasma FFA (intralipid/heparin infusion). Despite greater weight loss in the hypocaloric group (−7.7 ± 0.5 vs. −3.3 ± 0.7%, P < 0.001), FFA-induced peripheral insulin resistance was improved equally in both groups. However, circulating FFA concentrations (2,123 ± 261 vs. 1,764 ± 194 μmol/l, P < 0.05) and FFA turnover (3.20 ± 0.58 vs. 2.19 ± 0.58 μmol·kg FFM−1·min−1, P < 0.01) during hyperlipemia were suppressed only in the hypocaloric group. In contrast, whole body FFAox was improved in both groups at rest and during hyperlipemia. These changes were driven by increases in intracellular lipid-derived FFAox (12.3 ± 7.7 and 14.7 ± 7.8%, P < 0.05). We conclude that the exercise-induced improvement in FFA-induced insulin resistance is independent of the magnitude of weight loss and FFA turnover, yet it is linked to increased intracellular FFA utilization.
Appetite-modifying actions of pro-neuromedin U-derived peptides
Authors: Bechtold David A. , Ivanov Tina R. , Luckman Simon M.
Published: June 2009

Neuromedin U (NMU) is known to have potent actions on appetite and energy expenditure. Deletion of the NMU gene in mice leads to an obese phenotype, characterized by hyperphagia and decreased energy expenditure. Conversely, transgenic mice that overexpress proNMU exhibit reduced body weight and fat storage. Here, we show that central administration of NMU or the related peptide neuromedin S (NMS) dose-dependently decreases food intake, increases metabolic rate, and leads to significant weight loss in mice. The effects of NMU and NMS on both feeding and metabolism are almost completely lost in mice lacking the putative CNS receptor for NMU and NMS, NMUr2. However, NMUr2 knockout mice do not exhibit overt differences in body weight or energy expenditure compared with wild-type mice, suggesting that the dramatic phenotype of the NMU gene knockout mouse is not due simply to the loss of NMU/NMUr2 signaling. Putative proteolytic cleavage sites indicate that an additional peptide is produced from the NMU precursor protein, which is extremely well conserved between human, mouse, and rat. Here, we demonstrate that this peptide, proNMU104-136, has a pronounced effect on energy balance in mice. Specifically, central administration of proNMU104-136 causes a significant but transient (∼4 h) increase in feeding, yet both food intake and body weight are decreased over the following 24 h. proNMU104-136 administration also significantly increased metabolic rate. These results suggest that proNMU104-136 is a novel modulator of energy balance and may contribute to the phenotype exhibited by NMU knockout mice.
Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature
Authors: Potenza Maria A. , Gagliardi Sara , De Benedictis Leonarda , Zigrino Addolorata , Tiravanti Edy , Colantuono Giuseppe , Federici Antonio , Lorusso Loredana , Benagiano Vincenzo , Quon Michael J. , Montagnani Monica
Published: June 2009

Oxidative stress contributes to cardiovascular complications of diabetes, in part, by reducing the bioavailability of nitric oxide (NO). We investigated the mechanisms whereby the insulin sensitizer rosiglitazone may ameliorate oxidative stress in the vasculature of spontaneously hypertensive rats (SHR). Nine-week-old SHR were treated by gavage for 7 wk with rosiglitazone (5 mg·kg−1·day−1) or vehicle control. Treatment of SHR with rosiglitazone lowered systolic blood pressure, reduced fasting plasma insulin and asymmetrical dimethylarginine, and increased insulin sensitivity (when compared with vehicle treatment). In vessel homogenates and serum from rosiglitazone-treated SHR, SOD activity was enhanced, while 8-iso-PGF2α (lipid peroxidation product) was reduced (when compared with samples from vehicle-treated SHR). Moreover, expression of p22phox (catalytic subunit of NADPH oxidase) as well as nitrotyrosine and superoxide content were all reduced in the aortas of rosiglitazone-treated SHR. In mesenteric vascular beds (MVB) isolated ex vivo from rosiglitazone-treated SHR, NO-dependent vasodilator actions of insulin were improved when compared with MVB from vehicle-treated SHR. Acute pretreatment of MVB from vehicle-treated SHR with apocynin (NADPH oxidase inhibitor) enhanced vasodilator actions of insulin (results comparable to those in MVB from rosiglitazone-treated SHR). In Langendorff heart preparations from rosiglitazone-treated SHR, ischemia/reperfusion injury caused infarcts 40% smaller than in hearts from vehicle-treated SHR. Acute pretreatment of hearts from vehicle-treated SHR with apocynin produced similar results. Finally, rosiglitazone treatment of endothelial cells in primary culture reduced superoxide induced by insulin-resistant conditions. We conclude that rosiglitazone therapy in SHR increases SOD activity and decreases p22phox expression in the vasculature to reduce oxidant stress leading to an improved cardiovascular phenotype.
Molecular mechanism underlying Akt activation in zinc-induced cardioprotection
Authors: Lee SungRyul , Chanoit Guillaume , McIntosh Rachel , Zvara David A. , Xu Zhelong
Published: June 2009

Our previous study demonstrated that zinc prevents cardiac reperfusion injury by targeting the mitochondrial permeability transition pore (mPTP) via Akt and glycogen synthetase kinase 3β (GSK-3β). We aimed to address the mechanism by which zinc activates Akt. Treatment of H9c2 cells with ZnCl2(10 μM) in the presence of the zinc ionophore pyrithione (4 μM) for 20 min enhanced Akt phosphorylation (Ser473), indicating that zinc can rapidly activate Akt. Zinc did not alter either phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation and total PTEN protein levels or PTEN oxidation, implying that PTEN may not play a role in the action of zinc. However, zinc-induced Akt phosphorylation was blocked by both the nonselective receptor tyrosine kinase (RTK) inhibitor genistein and the selective insulin-like growth factor-1 RTK (IGF-1RTK) inhibitor AG1024, indicating that zinc activates Akt via IGF-1RTK. Zinc-induced phosphorylation of protein tyrosine and Ser/Thr was also abolished by AG1024. In addition, zinc markedly enhanced phosphorylation of IGF-1 receptor (IGF-1R), which was again reversed by genistein and AG1024. A confocal imaging study revealed that AG1024 abolished the preventive effect of zinc on oxidant-induced mPTP opening, confirming that IGF-1RTK plays a role in zinc-induced cardioprotection. Furthermore, zinc decreased the activity of protein phosphatase 2A (PP2A), a major protein Ser/Thr phosphatase, implying that protein Ser/Thr phosphatases may also play a role in the action of zinc on Akt activity. Taken together, these findings demonstrate that exogenous zinc activates Akt via IGF-1RTK and prevents the mPTP opening in cardiac cells. Inactivation of Ser/Thr protein phosphatases may also contribute to zinc-induced Akt activation.
Cardiac sarcoplasmic reticulum Ca2+-ATPase: heat production and phospholamban alterations promoted by cold exposure and thyroid hormone
Authors: Ketzer Luisa A. , Arruda Ana Paula , Carvalho Denise P. , de Meis Leopoldo
Published: June 2009

Short-term response to cold promotes a small but significant rise in serum T3 in euthyroid rabbits, where the heart is an important target of T3 action. In this work, we measured changes in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban (PLB) in hearts of hypo- and hyperthyroid rabbits and compared them with modifications induced by short- and long-term cold exposure. Short-term cold exposure promotes a small increase in T3 and, similar to hyperthyroidism, induces an increase of heart SERCA2a expression. The total PLB content does not change in hyperthyroidism, but short-term cold exposure promotes a significant decrease in total PLB and an increase in the ratio between phosphorylated and total PLB. The temperature of a given tissue depends on the balance between the heat provided by blood circulation and the rate of heat production by the tissue. In an attempt to evaluate the heat contribution of cardiac tissue, we measured mitochondrial respiration in permeabilized cardiac muscle and heat produced by cardiac sarcoplasmic reticulum (SR) during Ca2+transport. We observed that there was an increase in oxygen consumption and heat production during Ca2+transport by cardiac SR in both hyperthyroidism and short-term cold exposure. In contrast, both the mitochondrial respiration rate and heat derived from Ca2+transport were decreased in hypothyroid rabbits. The heart changes in oxygen consumption, SERCA2a-PLB ratio, and Ca2+-ATPase activity detected during short-term cold exposure were abolished after cold adaptation. We hypothesize that the transient rise in serum T3 contributes to the short-term response to cold exposure.
Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity
Authors: Wang Wei , Nepiyushchikh Zhanna , Zawieja David C. , Chakraborty Sanjukta , Zawieja Scott D. , Gashev Anatoliy A. , Davis Michael J. , Muthuchamy Mariappan
Published: June 2009

Muscular lymphatics use both phasic and tonic contractions to transport lymph for conducting their vital functions. The molecular mechanisms regulating lymphatic muscle contractions are not well understood. Based on the well-established finding that the phosphorylation of myosin light chain 20 (MLC20) plays an essential role in blood vessel smooth muscle contraction, we investigated if phosphorylated MLC20(pMLC20) would modulate the tonic and/or phasic contractions of lymphatic muscle. The effects of ML-7, a MLC kinase inhibitor (1–10 μM), were tested on the contractile parameters of isolated and cannulated rat mesenteric lymphatics during their responses to the known modulators, pressure (1–5 cmH2O) and substance P (SP; 10−7M). Immunohistochemical and Western blot analyses of pMLC20were also performed on isolated lymphatics. The results showed that 1) increasing pressure decreased both the lymphatic tonic contraction strength and pMLC20-to-MLC20ratio; 2) SP increased both the tonic contraction strength and phosphorylation of MLC20; 3) ML-7 decreased both the lymphatic tonic contraction strength and pMLC20-to-MLC20ratio; and 4) the increase in lymphatic phasic contraction frequency in response to increasing pressure was diminished by ML-7; however, the phasic contraction amplitude was not significantly altered by ML-7 either in the absence or presence of SP. These data provide the first evidence that tonic contraction strength and phasic contraction amplitude of the lymphatics can be differentially regulated, whereby the increase in MLC20phosphorylation produces an activation in the tonic contraction without significant changes in the phasic contraction amplitude. Thus, tonic contraction of rat mesenteric lymphatics appears to be MLC kinase dependent.
What is the purpose of the large sarcolemmal calcium flux on each heartbeat?
Authors: Eisner D. A. , Trafford A. W.
Published: June 2009

In cardiac muscle, although most of the calcium that activates contraction comes from the sarcoplasmic reticulum (SR), a significant fraction (up to 30%, depending on the species) enters from outside the cell and is then pumped out at the end of systole. Although some of this calcium influx is required to trigger calcium release from the SR, the bulk serves to reload the cell (and thence the SR) with calcium to replace the calcium that is pumped out of the cell. An alternative strategy would be for the heart to have a much smaller calcium influx balancing a smaller efflux. We demonstrate that this would result in a slowing of inotropic responses due to changes of SR calcium content. We conclude that the large sarcolemmal calcium fluxes facilitate rapid changes of contractility.
Altered pattern of sympathetic activity with the ovarian cycle in female smokers
Authors: Park Jeanie , Middlekauff Holly R.
Published: June 2009

Smoking increases cardiovascular risk in young women and eliminates the protective effect of the premenopausal state. Increased sympathetic nervous system (SNS) activity is associated with increased cardiovascular risk. One potential mechanism by which smoking increases risk is through chronic SNS activation. It has been reported that premenopausal women have high SNS activity during the midluteal (ML) phase, which falls to low levels during the early follicular (EF) phase. We tested the hypothesis that smoking disrupts this fall in SNS activity during the EF phase. We measured blood pressure and muscle sympathetic nerve activity (MSNA) using microneurography in 11 premenopausal female smokers and 11 age-matched nonsmoking controls at two separate times during the ovarian cycle: ML phase (8–10 days after the luteinizing hormone surge) and EF phase ( days 1–4 of the menstrual cycle). The change in MSNA from the EF phase to the ML phase was significantly different between the smoking and nonsmoking groups ( P = 0.036). Whereas there was a significant decrease in MSNA from the ML phase to the EF phase among nonsmoking controls (22.7 ± 3.3 vs. 17.9 ± 2.8 bursts/min, P = 0.012), MSNA remained elevated during the EF phase in smokers (22.5 ± 3.8 vs. 26.8 ± 4.0 bursts/min, P = 0.28). Surprisingly, mean arterial pressure (MAP) was significantly lower during the ML phase than in the EF phase in both nonsmokers ( P = 0.0080) and smokers ( P = 0.0094). We conclude that smoking disrupts the ovarian pattern of SNS activity by preventing the normal fall in MSNA during the EF phase of the ovarian cycle. Such chronic alterations may contribute to the pathogenesis of cardiovascular risk in young smoking females.
Transient oscillatory force-length behavior of activated airway smooth muscle
Authors: Bates J. H. T. , Bullimore S. R. , Politi A. Z. , Sneyd J. , Anafi R. C. , Lauzon A. -M.
Published: June 2009

Airway smooth muscle (ASM) is cyclically stretched during breathing, even in the active state, yet the factors determining its dynamic force-length behavior remain incompletely understood. We developed a model of the activated ASM strip and compared its behavior to that observed in strips of rat trachealis muscle stimulated with methacholine. The model consists of a nonlinear viscoelastic element (Kelvin body) in series with a force generator obeying the Hill force-velocity relationship. Isometric force in the model is proportional to the number of bound crossbridges, the attachment of which follows first-order kinetics. Crossbridges detach at a rate proportional to the rate of change of muscle length. The model accurately accounts for the experimentally observed transient and steady-state oscillatory force-length behavior of both passive and activated ASM. However, the model does not predict the sustained decrement in isometric force seen when activated strips of ASM are subjected briefly to large stretches. We speculate that this force decrement reflects some mechanism unrelated to the cycling of crossbridges, and which may be involved in the reversal of bronchoconstriction induced by a deep inflation of the lungs in vivo.
Respiratory syncytial virus infection alters surfactant protein A expression in human pulmonary epithelial cells by reducing translation efficiency
Authors: Bruce Shirley R. , Atkins Constance L. , Colasurdo Giuseppe N. , Alcorn Joseph L.
Published: June 2009

Infection of neonatal lung by respiratory syncytial virus (RSV) is a common cause of respiratory dysfunction. Lung alveolar type II and bronchiolar epithelial (Clara) cells secrete surfactant protein A (SP-A), a collectin that is an important component of the pulmonary innate immune system. SP-A binds to the virus, targeting the infectious agent for clearance by host defense mechanisms. We have previously shown that while the steady-state level of SP-A mRNA increases approximately threefold after RSV infection, steady-state levels of cellular and secreted SP-A protein decrease 40–60% in human type II cells in primary culture, suggesting a mechanism where the virus alters components of the innate immune response in infected cells. In these studies, we find that changes in SP-A mRNA and protein levels in RSV-infected NCI-H441 cells (a bronchiolar epithelial cell line) recapitulate the results in SP-A expression observed in primary lung cells. While SP-A protein is normally ubiquitinated, there is no change in the level of SP-A protein ubiquitination or proteasome activity during RSV infection, suggesting that the reduced levels of SP-A protein are not due to degradation by activated proteasomes. SP-A mRNA is appropriately processed and exported from the nucleus to the cytoplasm during RSV infection. As evidenced by polysome analysis of SP-A mRNA and pulse-chase analysis of newly synthesized SP-A protein, we find a decrease in translational efficiency that is specific for SP-A mRNA. Therefore, the decrease in SP-A protein levels observed after RSV infection of pulmonary bronchiolar epithelial cells results from a mechanism that affects SP-A mRNA translation efficiency.
Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness
Authors: Keenan Daniel M. , Roelfsema Ferdinand , Carroll Bernard J. , Iranmanesh Ali , Veldhuis Johannes D.
Published: June 2009

Sex influences adrenal glucocorticoid responses to ACTH in experimental animals. Whether similar sex differences operate in humans is unknown. To test this notion, we estimated ACTH-cortisol dose-response properties analytically in 48 healthy adults ( n = 22 women, n = 26 men), ages 18–77 yr, body mass index (BMI) 18–32 kg/m2, previously studied at two medical centers. Plasma ACTH and cortisol concentrations were measured every 10 min for 24 h. The 145 sample pairs were used in each subject to estimate ACTH-cortisol drive via a logistic function. Statistical analyses revealed that 24-h cortisol secretion (>82% pulsatile) fell in men ( r = −0.38, P = 0.028) and rose in women ( r = +0.37, P = 0.045) with age ( P = 0.01 sex effect). The mechanisms involved decreased ACTH efficacy with age in men ( r = −0.35, P = 0.04), and increased ACTH efficacy with age in women ( r = +0.42, P = 0.025) [ P = 0.009 sex effect]. ACTH potency diminished with higher BMI in men ( r = +0.38, P = 0.029) and in the cohort as a whole ( r = 0.34, P = 0.0085). These outcomes demonstrate that sex, age, and BMI modulate selective properties of endogenous ACTH-cortisol drive in humans, thereby indicating the need to control these three major variables in experimental comparisons.
Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging
Authors: Graf Franziska , Koehler Lena , Kniess Torsten , Wuest Frank , Mosch Birgit , Pietzsch Jens
Published: June 2009

The cyclin-dependent kinase (Cdk)-cyclin D/retinoblastoma (pRb)/E2F cascade, which controls the G1/S transition of cell cycle, has been found to be altered in many neoplasias. Inhibition of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of twoI124-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl-phenylamino)-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA) and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2-yl-amino)-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB)). Our data demonstrate a defined and specific inhibition of tumor cell proliferation through CKIA and CKIB by inhibition of the Cdk4/pRb/E2F pathway emphasizing potential therapeutic benefit of CKIA and CKIB. Furthermore, radiopharmacological properties of[I124]CKIA and[I124]CKIB observed in human tumor cells are promising prerequisites for in vivo biodistribution and imaging studies.
A Fuzzy Pay-Off Method for Real Option Valuation
Authors: Collan Mikael , Fullér Robert , Mezei József
Published: June 2009

Real option analysis offers interesting insights on the value of assets and on the profitability of investments, which has made real options a growing field of academic research and practical application. Real option valuation is, however, often found to be difficult to understand and to implement due to the quite complex mathematics involved. Recent advances in modeling and analysis methods have made real option valuation easier to understand and to implement. This paper presents a new method (fuzzy pay-off method) for real option valuation using fuzzy numbers that is based on findings from earlier real option valuation methods and from fuzzy real option valuation. The method is intuitive to understand and far less complicated than any previous real option valuation model to date. The paper also presents the use of number of different types of fuzzy numbers with the method and an application of the new method in an industry setting.
Flotation—A New Method to Circumvent PCR Inhibitors in the Diagnosis ofLawsonia intracellularis
Authors: Jacobson Magdalena , Norling Börje , Gunnarson Anders , Aspan Anna
Published: June 2009

The obligate intracellular bacteriumLawsonia intracellulariscauses enteritis and poor growth in weaned pigs. Cultivation is difficult and diagnosisante mortemis mainly based on techniques such as polymerase chain reaction. However, false negative results caused by the presence of PCR-inhibitory factors constitute a problem. This study aimed to develop and evaluate a new technique, flotation, to separateL. intracellularisfrom inhibitors in faeces prior to PCR. The technique was evaluated by comparison to two previously evaluated and commonly used methods, preparation by boiling lysate combined with nested PCR and preparation by a commercial kit combined with conventional PCR. Continuous density centrifugation of faecal samples containingL. intracellularissuggested the buoyant density of the microbe to be between 1.064 and 1.077 g/mL. Several flotation setups were tested to achieve optimal separation of the microbe from inhibitors and faecal particles. The finally selected setup floated wholeL. intracellularisfrom the application site at the bottom to the upper part of the gradient while inhibitory components mainly remained in the bottom. PCR was performed directly on material recovered from the upper interphase. The method was evaluated on 116 clinical samples. As compared to sample preparation by boiling combined with nested PCR, fewer samples were inhibited but also fewer positives were identified. In comparison to preparation by a commercial kit combined with conventional PCR, presently used for routine diagnosis, similar results were obtained. However, the new method was comparably faster to perform. The new method, based on flotation ofLawsonia intracellulariscombined with conventional PCR, was well suited for routine diagnosis.
Asymptotic Dichotomy in a Class of Fourth‐Order Nonlinear Delay Differential Equations with Damping
Authors: Hou Chengmin , Cheng Sui Sun
Published: June 2009

All solutions of a fourth‐order nonlinear delay differential equation are shown to converge to zero or to oscillate. Novel Riccati type techniques involving third‐order linear differential equations are employed. Implications in the deflection of elastic horizontal beams are also indicated.
No Incidence of BRAF Mutations in Salivary Gland Carcinomas—Implications for Anti‐EGFR Therapies
Authors: Dahse Regine , Kromeyer-Hauschild Katrin , Berndt Alexander , Kosmehl Hartwig
Published: June 2009

BRAF is the main effector of KRAS in the RAS‐RAF‐MAPK axis, a signaling pathway downstream of EGFR. The activation of this cascade is an important pathway in cancer development and is considered a key pathway for therapeutic molecules. Recent studies in metastatic colorectal cancer found that an oncogenic activation of BRAF by a point mutation in exon 15 (V600E) could bypass the EGFR‐initiated signaling cascade with the effect that patients bearing the mutant BRAF allele are not likely to benefit from EGFR‐targeted therapies. We designed an allele‐specific PCR and screened 65 salivary gland carcinoma (SGC) of the main histopathological types for the BRAF V600E mutation. All 65 SGC in this cohort (100%) presented the BRAF wildtype. In a previous study, we found a KRAS wildtype in 98.5% of SGC.
These findings imply that SGC rarely acquires mutations that result in a constitutive activation of the signaling cascade downstream of EGFR and this pleads in favor of further therapeutic trials with EGFR‐targeting monoclonal
antibodies.
The Neuroelectromagnetic Inverse Problem and the Zero Dipole Localization Error
Authors: Grave de Peralta Rolando , Hauk Olaf , Gonzalez Sara L.
Published: June 2009

A tomography of neural sources could be constructed from EEG/MEG recordings once the neuroelectromagnetic inverse problem (NIP) is solved. Unfortunately the NIP lacks a unique solution and therefore additional constraints are needed to achieve uniqueness. Researchers are then confronted with the dilemma of choosing one solution on the basis of the advantages publicized by their authors. This study aims to help researchers to better guide their choices by clarifying what is hidden behind inverse solutions oversold by their apparently optimal properties to localize single sources. Here, we introduce an inverse solution (ANA) attaining perfect localization of single sources to illustrate how spurious sources emerge and destroy the reconstruction of simultaneously active sources. Although ANA is probably the simplest and robust alternative for data generated by a single dominant source plus noise, the main contribution of this manuscript is to show that zero localization error of single sources is a trivial and largely uninformative property unable to predict the performance of an inverse solution in presence of simultaneously active sources. We recommend as the most logical strategy for solving the NIP the incorporation of sound additional a priori information about neural generators that supplements the information contained in the data.