bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress deflections around salt diapirs in the Gulf of Mexico
Authors: King Rosalind , Backé Guillaume , Tingay Mark , Hillis Richard , Mildren Scott
Published: August 2012

Delta–deepwater fold–thrust belts are linked systems of extension and compression. Margin-parallel maximum horizontal stresses (extension) on the delta top are generated by gravitational collapse of accumulating sediment, and drive downdip margin-normal maximum horizontal stresses (compression) in the deepwater fold–thrust belt (or delta toe). This maximum horizontal stress rotation has been observed in a number of delta systems. Maximum horizontal stress orientations, determined from 32 petroleum wells in the Gulf of Mexico, are broadly margin-parallel on the delta top with a mean orientation of 060 and a standard deviation of 49°. However, several orientations show up to 60° deflection from the regional margin-parallel orientation. Three-dimensional (3D) seismic data from the Gulf of Mexico delta top demonstrate the presence of salt diapirs piercing the overlying deltaic sediments. These salt diapirs are adjacent to wells (within 500 m) that demonstrate deflected stress orientations. The maximum horizontal stresses are deflected to become parallel to the interface between the salt and sediment. Two cases are presented that account for the alignment of maximum horizontal stresses parallel to this interface: (1) the contrast between geomechanical properties of the deltaic sediments and adjacent salt diapirs; and (2) gravitational collapse of deltaic sediments down the flanks of salt diapirs.
Modelling of sediment wedge movement along low-angle detachments using ABAQUS™
Authors: Tuitt A. , King R. , Hergert T. , Tingay M. , Hillis R.
Published: August 2012

Delta–deepwater fold–thrust belts (DDWFTBs) develop over low-angle detachment faults which link extension to downslope contraction. Detachment faults have been examined in previous studies for the Amazon Fan, Niger, Nile, Angola, Baram and Bight Basin DDWFTBs. The driving mechanisms for the movement along the detachment remain uncertain, however. Previous authors have attributed the movement along detachment faults to high pore-fluid pressure, which reduces the effective normal stress acting on a fault surface thereby encouraging sliding along the fault. However, high pore-fluid pressure has not been directly confirmed in many of these faults due to a lack of well data in detachment surfaces. In this study, finite element modelling was used to test the effects of pore-fluid pressure, coefficient of friction, sediment rigidity and sediment wedge angle on sliding along the detachment. The modelling suggests that increased pore-fluid pressures and decreased coefficients of friction increase slip along a detachment. At hydrostatic pore-fluid pressures, sediment rigidity and sediment wedge angle have relatively little effect on the movement of the sediment wedge along the detachment. Modelling of these conditions using ABAQUS™ improves our understanding of the nature and mechanics of DDWFTBs and their underlying detachments.
On the nucleation of non-Andersonian faults along phyllosilicate-rich mylonite belts
Authors: Bistacchi Andrea , Massironi Matteo , Menegon Luca , Bolognesi Francesca , Donghi Valeriano
Published: August 2012

The weakness of fault zones is generally explained by invoking an elevated fluid pressure or the presence of extremely weak minerals in a continuous fault gouge horizon. This allows for faults to slip under an unfavourable normal to shear stress ratio, in contrast to E. M. Anderson's theory of faulting. However, these mechanisms do not explain why faults should nucleate in such an orientation as to make them misoriented and non-Andersonian. Here we present a weakening mechanism, involving the mechanical anisotropy of phyllosilicate-bearing mylonite belts, which is likely to influence the nucleation of faults in addition to their subsequent activity. Considering three natural examples from the Alps (the Simplon, Brenner and Sprechenstein-Mules fault zones) and a review of laboratory tests on anisotropic rocks, we apply anisotropic slip tendency analysis and show that misoriented weak faults can nucleate along a sub-planar phyllosilicate-rich mylonitic foliation, constituting a large-scale mechanical anisotropy belt and preventing the development of Andersonian optimally oriented faults.
Anisotropic poroelasticity and the response of faulted rock to changes in pore-fluid pressure
Authors: Healy David
Published: August 2012

The Law of Effective Stress has found wide application in structural geology, rock mechanics and petroleum geology. The commonly used form of this law relies on an assumption of isotropic porosity. The porosity in and around fluid-saturated fault zones is likely to be dominated by tectonically induced cracks of various shapes and sizes. Previously published field and laboratory data show that these cracks occur in distinct patterns of preferred orientation, and that these patterns vary around the fault zone. This paper uses the more general form of the Law of Effective Stress which incorporates anisotropic poroelasticity to model the geomechanical response of fault zones surrounded by patterns of oriented cracks. Predictions of fault stability in response to fluid pressure changes are shown to depend on both the nature (or symmetry) of the crack pattern and the orientation of the crack patterns with respect to the in situ stress. More complete data on the porosity of natural fault zones will enable more accurate predictions of fault stability in the subsurface.
Andersonian wrench faulting in a regional stress field during the 2010–2011 Canterbury, New Zealand, earthquake sequence
Authors: Sibson R. H. , Ghisetti F. C. , Crookbain R. A.
Published: August 2012

The initial
M
w
7.1 Darfield earthquake sequence was centred west of Christchurch City in the South Island of New Zealand but aftershocks, including a highly destructive
M
w
6.3 event, eventually extended eastwards across the city to the coast. The mainshock gave rise to right-lateral strike-slip of up to 5 m along the segmented rupture trace of a subvertical fault trending 085±5° across the Canterbury Plains for
c
. 30 km, in agreement with teleseismic focal mechanisms. Near-field data however suggest that the mainshock was composite, initiating with reverse-slip north of the surface rupture. Stress determinations for the central South Island show maximum compressive stress σ
1
to be horizontal and oriented 115±5°. The principal dextral rupture therefore lies at
c
. 30° to regional σ
1
, the classic ‘Andersonian’ orientation for a low-displacement wrench fault. An aftershock lineament trending
c
. 145° possibly represents a conjugate left-lateral strike-slip structure. This stress field is also consistent with predominantly reverse-slip reactivation of NNE–NE faults along the Southern Alps range front. The main strike-slip fault appears to have a low cumulative displacement and may represent either a fairly newly formed fault in the regional stress field, or an existing subvertical fault that happens to be optimally oriented for frictional reactivation.
Erythrocyte-derived sphingosine-1-phosphate stabilizes basal hydraulic conductivity and solute permeability in rat microvessels
Authors: Curry F. E. , Clark J. F. , Adamson R. H.
Published: August 2012

Exogenous sphingosine-1-phosphate (S1P), a lipid mediator in blood, attenuates acute microvascular permeability increases via receptor S1P1 to stabilize the endothelium. To evaluate the contribution of erythrocytes as an endogenous source of S1P to the regulation of basal permeability, we measured permeability coefficients in intact individually perfused venular microvessels of rat mesentery. This strategy also enabled the contributions of other endogenous S1P sources to be evaluated. Apparent permeability coefficients ( PS) to albumin and α-lactalbumin and the hydraulic conductivity of mesenteric microvessels were measured in the presence or absence of rat erythrocytes or rat erythrocyte-conditioned perfusate. Rat erythrocytes added to the perfusate were the principal source of S1P in these microvessels. Basal PSto albumin was stable and typical of blood-perfused microvessels (mean 0.5 × 10−6cm/s) when erythrocytes or erythrocyte-conditioned perfusates were present. When they were absent, PSto albumin or α-lactalbumin increased up to 40-fold (over 10 min). When exogenous S1P was added to perfusates, permeability returned to levels comparable with those seen in the presence of erythrocytes. Addition of SEW 2871, an agonist specific for S1P1, in the absence of red blood cells reduced PSBSA(40-fold reduction) toward basal. The specific S1P1 receptor antagonist (W-146) reversed the stabilizing action of erythrocytes and increased permeability (27-fold increase) in a manner similar to that seen in the absence of erythrocytes. Erythrocytes are a primary source of S1P that maintains normal venular microvessel permeability. Absence of erythrocytes or conditioned perfusate in in vivo and in vitro models of endothelial barriers elevates basal permeability.
Enhanced Ca2+ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges
Authors: Korte F. Steven , Feest Erik R. , Razumova Maria V. , Tu An-Yue , Regnier Michael
Published: August 2012

Calcium sensitivity of the force-pCa relationship depends strongly on sarcomere length (SL) in cardiac muscle and is considered to be the cellular basis of the Frank-Starling law of the heart. SL dependence may involve changes in myofilament lattice spacing and/or myosin crossbridge orientation to increase probability of binding to actin at longer SLs. We used the L48Q cardiac troponin C (cTnC) variant, which has enhanced Ca2+ binding affinity, to test the hypotheses that the intrinsic properties of cTnC are important in determining 1) thin filament binding site availability and responsiveness to crossbridge activation and 2) SL dependence of force in cardiac muscle. Trabeculae containing L48Q cTnC-cTn lost SL dependence of the Ca2+ sensitivity of force. This occurred despite maintaining the typical SL-dependent changes in maximal force (Fmax). Osmotic compression of preparations at SL 2.0 μm with 3% dextran increased Fmax but not pCa50 in L48Q cTnC-cTn exchanged trabeculae, whereas wild-type (WT)-cTnC-cTn exchanged trabeculae exhibited increases in both Fmax and pCa50. Furthermore, crossbridge inhibition with 2,3-butanedione monoxime at SL 2.3 μm decreased Fmax and pCa50 in WT cTnC-cTn trabeculae to levels measured at SL 2.0 μm, whereas only Fmax was decreased with L48Q cTnC-cTn. Overall, these results suggest that L48Q cTnC confers reduced crossbridge dependence of thin filament activation in cardiac muscle and that changes in the Ca2+ sensitivity of force in response to changes in SL are at least partially dependent on properties of thin filament troponin.
Diabetes-induced increased oxidative stress in cardiomyocytes is sustained by a positive feedback loop involving Rho kinase and PKCβ2
Authors: Soliman Hesham , Gador Anthony , Lu Yi-Hsuan , Lin Guorong , Bankar Girish , MacLeod Kathleen M.
Published: August 2012

We previously reported that acute inhibition of the RhoA/Rho kinase (ROCK) pathway normalized contractile function of diabetic rat hearts, but the underlying mechanism is unclear. Protein kinase C (PKC) β2has been proposed to play a major role in diabetic cardiomyopathy at least in part by increasing oxidative stress. Further evidence suggests that PKC positively regulates RhoA expression through induction of inducible nitric oxide synthase (iNOS) in diabetes. However, in preliminary studies, we found that inhibition of ROCK itself reduced RhoA expression in diabetic hearts. We hypothesized that there is an interaction between RhoA/ROCK and PKCβ2in the form of a positive feedback loop that sustains their activation and the production of reactive oxygen species (ROS). This was investigated in cardiomyocytes isolated from diabetic and control rat hearts, incubated with or without cytochalasin D or inhibitors of ROCK, RhoA, PKCβ2, or iNOS. Inhibition of RhoA and ROCK markedly attenuated the diabetes-induced increases in PKCβ2activity and iNOS and RhoA expression in diabetic cardiomyocytes, while having no effect in control cells. Inhibition of PKCβ2and iNOS also normalized RhoA expression and ROCK overactivation, whereas iNOS inhibition reversed the increase in PKCβ2activity. Each of these treatments also normalized the diabetes-induced increase in production of ROS. Actin cytoskeleton disruption attenuated the increased expression and/or activity of all of these targets in diabetic cardiomyocytes. These data suggest that, in the diabetic heart, the RhoA/ROCK pathway contributes to contractile dysfunction at least in part by sustaining PKCβ2activation and ROS production via a positive feedback loop that requires an intact cytoskeleton.
Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema
Authors: Szabari M. V. , Parameswaran H. , Sato S. , Hantos Z. , Bartolák-Suki E. , Suki B.
Published: August 2012

The relation between the progression of chronic obstructive pulmonary disease (COPD) and exacerbations is unclear. Currently, no animal model of acute exacerbation of COPD (AECOPD) exists. The objectives of this study were to evaluate the effects of mechanical forces induced by deep inspirations (DIs) on short-term deterioration of lung structure and function to mimic AECOPD. At 2, 7, or 21 days after treatment with elastase, mice were ventilated with or without DIs (35 cmH2O airway pressure for 3 s, 2 times/min) for 1 h. Functional residual capacity (FRC) was measured with body plethysmography, and respiratory compliance, resistance, and hysteresivity were obtained via forced oscillations. From hematoxylin and eosin-stained sections, equivalent airspace diameters (D), alveolar wall thickness (Wt), number of septal ruptures (Nsr), and attachment density (Ad) around airways were determined. FRC, compliance, and hysteresivity statistically significantly increased with time, and both increased due to DIs. Interestingly, DIs also had an effect on FRC, compliance, resistance, and hysteresivity in control mice. The development of emphysema statistically significantly increased D and Wt in time, and the DIs caused subtle differences in D. At 21 days, the application of DIs changed the distribution of D, increased Wt and Nsr, and decreased Ad. These results suggest that once a critical remodeling of the parenchyma has been reached, acute mechanical forces lead to irreversible changes in structure and function, mimicking COPD exacerbations. Thus, the acute application of DIs in mice with emphysema may serve as a useful model of AECOPD.
Characterization of bulbospongiosus muscle reflexes activated by urethral distension in male rats
Authors: Tanahashi Masayuki , Karicheti Venkateswarlu , Thor Karl B. , Marson Lesley
Published: August 2012

The urethrogenital reflex (UGR) is used as a surrogate model of the autonomic and somatic nerve and muscle activity that accompanies ejaculation. The UGR is evoked by distension of the urethra and activation of penile afferents. The current study compares two methods of elevating urethral intraluminal pressure in spinalized, anesthetized male Sprague-Dawley rats ( n = 60). The first method, penile extension UGR, involves extracting the penis from the foreskin, so that urethral pressure rises due to a natural anatomical flexure in the penis. The second method, penile clamping UGR, involves penile extension UGR with the addition of clamping of the glans penis. Groups of animals were prepared that either received no additional treatment, surgical shams, or received bilateral nerve cuts (4 nerve cut groups): either the pudendal sensory nerve branch (SbPN), the pelvic nerves, the hypogastric nerves, or all three nerves. Penile clamping UGR was characterized by multiple bursts, monitored by electromyography (EMG) of the bulbospongiosus muscle (BSM) accompanied by elevations in urethral pressure. The penile clamping UGR activity declined across multiple trials and eventually resulted in only a single BSM burst, indicating desensitization. In contrast, the penile extension UGR, without penile clamping, evoked only a single BSM EMG burst that showed no desensitization. Thus, the UGR is composed of two BSM patterns: an initial single burst, termed urethrobulbospongiosus (UBS) reflex and a subsequent multiple bursting pattern (termed ejaculation-like response, ELR) that was only induced with penile clamping urethral occlusion. Transection of the SbPN eliminated the ELR in the penile clamping model, but the single UBS reflex remained in both the clamping and extension models. Pelvic nerve (PelN) transection increased the threshold for inducing BSM activation with both methods of occlusion but actually unmasked an ELR in the penile extension method. Hypogastric nerve (HgN) cuts did not significantly alter any parameter. Transection of all three nerves eliminated BSM activation completely. In conclusion, penile clamping occlusion recruits penile and urethral primary afferent fibers that are necessary for an ELR. Urethral distension without significant penile afferent activation recruits urethral primary afferent fibers carried in either the pelvic or pudendal nerve that are necessary for the single-burst UBS reflex.
CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats
Authors: Goebel-Stengel Miriam , Stengel Andreas , Wang Lixin , Ohning Gordon , Taché Yvette , Reeve Joseph R.
Published: August 2012

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.
Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells: relevance to diabetic nephropathy
Authors: Kaur Harmeet , Chien Alexander , Jialal Ishwarlal
Published: August 2012

Diabetes is a proinflammatory state. The pattern recognition receptors, Toll-like receptors (TLRs), are increased in diabetic patients and have been suggested to play a role in diabetic nephropathy (DN). Progression of DN involves altered mesangial cell (MC) function with an expansion of the mesangial matrix. There is a paucity of data examining the role of TLR and its expression in MC. We hypothesize the expression of TLRs in the mesangium might be an important factor contributing to mesangium expansion and nephropathy. Thus we evaluated the effect of high glucose on TLR2 and TLR4 expression in mouse mesangial cells (MMC) in vitro. Exposure of MMC to 25 mM glucose for 24 h resulted in increased TLR4 mRNA and cell surface receptor expression compared with 5.5 mM glucose ( P < 0.05). Interestingly, we were not able to detect expression of TLR2 in MMC. Furthermore, expression of a TLR4 downstream signaling cascade including myeloid differentiation factor 88 (MyD88), interferon regulatory factor 3 (IRF3), and Toll interleukin receptor domain containing adaptor inducing interferon-β (TRIF)-related adaptor molecule (TRAM) were significantly increased in cells exposed to 25 mM glucose ( P < 0.05). There was also a significant increase in NF-κB activation along with increased secretion of inflammatory cytokines IL-6 and monocyte chemotactic protein-1. Levels of transforming growth factor-β were also significantly increased in the presence of 25 mM glucose ( P < 0.05). Collectively, these data suggest that hyperglycemia activates TLR4 expression and activity in MC and could contribute to DN.
Recurrent Bilateral Breast Abscesses after Sternotomy
Authors: Cinar Hamza , Ulusoy Ali Naki , Kaya Emir Fatih , Lap Gökhan , Karabulut Kagan , Polat Ayfer Kamalı , Selcuk Özbalci Gökhan
Published: August 2012

Median sternotomy is the most commonly used incision in cardiothoracic procedures. Development of breast abscess after sternotomy is a very rare situation. We present a case of sternal wound infection with recurrent bilateral breast abscess after sternotomy. Our case is the first and only case in the literature due to the presence of sternal wound infection with recurrent bilateral breast abscess after sternotomy.
Application of Anterior Segment Optical Coherence Tomography in Pediatric Ophthalmology
Authors: Cauduro Ricardo Salles , Ferraz Caroline do Amaral , Morales Maira Saad Ávila , Garcia Patricia Novita , Lopes Yara Cristina , Souza Paulo Henrique , Allemann Norma
Published: August 2012

Purpose.Application of anterior segment optical coherence (AS-OCT) in pediatric ophthalmology.Methods.Retrospective clinical study case series of 26 eyes of 19 pediatric patients throughout a 21-month period, presenting anterior segment pathologies, were submitted to AS-OCT examination (OCT Visante, 1310 nm, Zeiss), noncontact technique, no sedation requirement.Results.AS-OCT images were obtained from 19 patients (range: 2 months to 12 years). Clinical diagnosis of anterior segment abnormalities included cornea disease (n=7), congenital anterior segment conditions (n=10), ocular trauma (n=1), anterior segment surgeries (n=2), iridocorneal angle abnormalities (n=4), intermediate uveitis (n=2). The most common OCT findings were corneal hyperreflectivity and thickening (n=15), shallow anterior chamber with iris-lens diaphragm anterior displacement (n=4), atypical corneal curvature (n=4), corneal thinning (n=4), peripheral synechiae with angle closure (n=3), increased anterior chamber depth (n=2), and proximal portion of glaucoma drainage tube (n=2).Conclusion.In the present study, noncontact AS-OCT demonstrated to be a feasible technique to evaluate the anterior segment providing anatomic details and useful to clarify diagnosis in the pediatric population.
The Role of Education and Intellectual Activity on Cognition
Authors: Parisi Jeanine M. , Rebok George W. , Xue Qian-Li , Fried Linda P. , Seeman Teresa E. , Tanner Elizabeth K. , Gruenewald Tara L. , Frick Kevin D. , Carlson Michelle C.
Published: August 2012

Although educational attainment has been consistently related to cognition in adulthood, the mechanisms are still unclear. Early education, and other social learning experiences, may provide the skills, knowledge, and interest to pursue intellectual challenges across the life course. Therefore, cognition in adulthood might reflect continued engagement with cognitively complex environments. Using baseline data from the Baltimore Experience Corps Trial, multiple mediation models were applied to examine the combined and unique contributions of intellectual, social, physical, creative, and passive lifestyle activities on the relationship between education and cognition. Separate models were tested for each cognitive outcome (i.e., reading ability, processing speed, memory). With the exception of memory tasks, findings suggest that education-cognition relations are partially explained by frequent participation in intellectual activities. The association between education and cognition was not completely eliminated, however, suggesting that other factors may drive these associations.
Dynamic Alignment of the Forward-Proton Detectors at the LHC
Authors: Staszewski R. , Trzebiński M. , Chwastowski J.
Published: August 2012

The dynamic alignment method of the forward proton detectors proposed by the CDF collaboration is reviewed. The applicability of the method at the LHC is discussed.
Asymptotic Properties of Derivatives of the Stieltjes Polynomials
Authors: Jung Hee Sun , Sakai Ryozi
Published: August 2012

Let and Pλ,n(x) be the ultraspherical polynomials with respect to wλ(x). Then, we denote the Stieltjes polynomials with respect to wλ(x) by Eλ,n+1(x) satisfying , 0 ≤ m < n + 1, , m = n + 1. In this paper, we investigate asymptotic properties of derivatives of the Stieltjes polynomials Eλ,n+1(x) and the product Eλ,n+1(x)Pλ,n(x). Especially, we estimate the even‐order derivative values of Eλ,n+1(x) and Eλ,n+1(x)Pλ,n(x) at the zeros of Eλ,n+1(x) and the product Eλ,n+1(x)Pλ,n(x), respectively. Moreover, we estimate asymptotic representations for the odd derivatives values of Eλ,n+1(x) and Eλ,n+1(x)Pλ,n(x) at the zeros of Eλ,n+1(x) and Eλ,n+1(x)Pλ,n(x) on a closed subset of (−1, 1), respectively. These estimates will play important roles in investigating convergence and divergence of the higher‐order Hermite‐Fejér interpolation polynomials.
Cholesterol-Lowering Effect of Allicin on Hypercholesterolemic ICR Mice
Authors: Lu Yin , He Zhuojin , Shen Xiuying , Xu Xiaolu , Fan Jie , Wu Shaohua , Zhang Deyong
Published: August 2012

Allicin was discussed as an active compound with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the cholesterol-lowering properties of allicin. In order to examine its effects on hypercholesterolemia in male ICR mice, this compound with doses of 5, 10, or 20 mg/kg body weight was given orally daily for 12 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of serum cholesterol, triglyceride, glucose, and hepatic cholesterol storage were determined. Following a 12-week experimental period, the body weights of allicin-fed mice were less than those of control mice on a high-cholesterol diet by38.24±7.94% (P<0.0001) with 5 mg/kg allicin,39.28±5.03% (P<0.0001) with 10 mg/kg allicin, and41.18±5.00% (P<0.0001) with 20 mg/kg allicin, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Meanwhile, allicin showed a favorable effect in reducing blood cholesterol, triglycerides, and glucose levels and caused a significant decrease in lowering the hepatic cholesterol storage. Accordingly, both in vivo and in vitro results demonstrated a potential value of allicin as a pronounced cholesterol-lowering candidate, providing protection against the onset of atherosclerosis.
Spawning Coordination of Mates in a Shell Brooding Cichlid
Authors: Schütz Dolores , Heg-Bachar Zina , Taborsky Michael , Heg Dik
Published: August 2012

Aim. External fertilisation requires synchronisation of gamete release between the two sexes. Adequate synchronisation is essential in aquatic media because sperm is very short-lived in water. In the cichlidLamprologus callipterus, fertilisation of the eggs takes place inside an empty snail shell, where females stay inside the shell and males have to ejaculate into the shell opening. This spawning pattern makes the coordination of gamete release difficult.Methods. This study examined the synchronisation of males and females during egg laying.Results. The results showed that the male initiates each spawning sequence and that sperm release and egg laying are very well synchronised. 68% of all sperm releases occurred at exactly the same time when the female laid an egg, and 99% of ejaculations occurred within ±5 seconds from egg deposition. On average 95 eggs are laid one by one with intervals of several minutes between subsequent eggs, leading to a total spawning duration in excess of six hours.Conclusions. We discuss this exceptional spawning pattern and how it might reflect a conflict between the sexes, with males attempting to induce egg laying and females extending the egg laying period to raise the chance for parasitic males to participate in spawning.
Robust Maximum Lifetime Routing and Energy Allocation in Wireless Sensor Networks
Authors: Paschalidis Ioannis Ch. , Wu Ruomin
Published: August 2012

We consider the maximum lifetime routing problem in wireless sensor networks in two settings: (a) when nodes’ initial energy is given and (b) when it is subject to optimization. The optimal solution and objective value provide optimal flows and the corresponding predicted lifetime, respectively. We stipulate that there is uncertainty in various network parameters (available energy and energy depletion rates). In setting (a) we show that for specific, yet typical, network topologies, the actual network lifetime will reach the predicted value with a probability that converges to zero as the number of nodes grows large. In setting (b) the same result holds for all topologies. We develop a series of robust problem formulations, ranging from pessimistic to optimistic. A set of parameters enable the tuning of the conservatism of the formulation to obtain network flows with a desirably high probability that the corresponding lifetime prediction is achieved. We establish a number of properties for the robust network flows and energy allocations and provide numerical results to highlight the tradeoff between predicted lifetime and the probability achieved. Further, we analyze an interesting limiting regime of massively deployed sensor networks and essentially solve a continuous version of the problem.
A Case of Classic Raymond Syndrome
Authors: Zaorsky Nicholas George , Luo Jin Jun
Published: August 2012

Classic Raymond syndrome consists of ipsilateral abducens impairment, contralateral central facial paresis, and contralateral hemiparesis. However, subsequent clinical observations argued on the presentation of facial involvement. To validate this entity, we present a case of classic Raymond syndrome with contralateral facial paresis. A 50 year-old man experienced acute onset of horizontal diplopia, left mouth drooling and left-sided weakness. Neurological examination showed he had right abducens nerve palsy, left-sided paresis of the lower part of the face and limbs, and left hyperreflexia. A brain MRI showed a subacute infarct in the right mid-pons. The findings were consistent with those of classic Raymond syndrome. To date, only a few cases of Raymond syndrome, commonly without facial involvement, have been reported. Our case is a validation of classic Raymond syndrome with contralateral facial paresis. We propose the concept of two types of Raymond syndrome: (1) the classic type, which may be produced by a lesion in the mid-pons involving the ipsilateral abducens fascicle and undecussated corticofacial and corticospinal fibers; and (2) the common type, which may be produced by a lesion involving the ipsilateral abducens fascicle and undecussated corticospinal fibers but sparing the corticofacial fibers.
Chaos Control and Synchronization in Fractional-Order Lorenz-Like System
Authors: Bhalekar Sachin
Published: August 2012

The present paper deals with fractional-order version of a dynamical system introduced by Chongxin et al. (2006). The chaotic behavior of the system is studied using analytic and numerical methods. The minimum effective dimension is identified for chaos to exist. The chaos in the proposed system is controlled using simple linear feedback controller. We design a controller to place the eigenvalues of the system Jacobian in a stable region. The effectiveness of the controller in eliminating the chaotic behavior from the state trajectories is also demonstrated using numerical simulations. Furthermore, we synchronize the system using nonlinear feedback.
Growth Culture Conditions and Nutrient Signaling Modulating Yeast Chronological Longevity
Authors: Santos Júlia , Leão Cecília , Sousa Maria João
Published: August 2012

The manipulation of nutrient-signaling pathways in yeast has uncovered the impact of environmental growth conditions in longevity. Studies using calorie restriction show that reducing glucose concentration of the culture media is sufficient to increase replicative and chronological lifespan (CLS). Other components of the culture media and factors such as the products of fermentation have also been implicated in the regulation of CLS. Acidification of the culture media mainly due to acetic acid and other organic acids production negatively impacts CLS. Ethanol is another fermentative metabolite capable of inducing CLS reduction in aged cells by yet unknown mechanisms. Recently, ammonium was reported to induce cell death associated with shortening of CLS. This effect is correlated to the concentration ofNH4+added to the culture medium and is particularly evident in cells starved for auxotrophy-complementing amino acids. Studies on the nutrient-signaling pathways regulating yeast aging had a significant impact on aging-related research, providing key insights into mechanisms that modulate aging and establishing the yeast as a powerful system to extend knowledge on longevity regulation in multicellular organisms.
A Rare Congenital Heart Disease in an Elderly Long-Distance Runner: A Case Report
Authors: Bhamidipati K. R. , Shah N. C. , Connaughton M. C.
Published: August 2012

Introduction. Cor triatriatum is a rare congenital heart disease found incidentally in children. Although cor triatriatum can be an incidental finding in asymptomatic adults; it is extremely rare to find elderly patients without symptoms and is unique in a long distance runner.Case Presentation. We present the case of an 83-year-old long-distance runner with cor triatriatum sinistrum and atrial fibrillation who continues to be asymptomatic and has continued to run long distances, retaining his excellent functional capacity.Conclusion. Cor triatriatum sinistrum is a rare congenital disease, which is often found incidentally in children. Although it is also seen in adults without symptoms at normal exertion, it is rare to have this condition in long-distance runners especially in elderly people with other structural heart disease, that is, atrial fibrillation and mitral regurgitation.
Machine Learning Approach to Extract Diagnostic and Prognostic Thresholds: Application in Prognosis of Cardiovascular Mortality
Authors: Mena Luis J. , Orozco Eber E. , Felix Vanessa G. , Ostos Rodolfo , Melgarejo Jesus , Maestre Gladys E.
Published: August 2012

Machine learning has become a powerful tool for analysing medical domains, assessing the importance of clinical parameters, and extracting medical knowledge for outcomes research. In this paper, we present a machine learning method for extracting diagnostic and prognostic thresholds, based on a symbolic classification algorithm called REMED. We evaluated the performance of our method by determining new prognostic thresholds for well-known and potential cardiovascular risk factors that are used to support medical decisions in the prognosis of fatal cardiovascular diseases. Our approach predicted 36% of cardiovascular deaths with 80% specificity and 75% general accuracy. The new method provides an innovative approach that might be useful to support decisions about medical diagnoses and prognoses.
Hydrogen Storage Enhancement Attained by Fixation of Ti on MWNTs
Authors: Pérez-Bueno J. J. , Mendoza López M. L. , Brieño Enriquez K. M. , Ledesma García J. , Godínez Mora-Tovar L. A. , Angeles Chavez C.
Published: August 2012

Nowadays, hydrogen has a preponderant position among the potentially sustainable energy sources. Due to its power density, its storage is of main concern when considering a broad use in practical applications. Carbon nanotubes constitute promising candidates for the design and construction of hydrogen storage devices. This work explores the use of some procedures involving electrochemistry, aimed to bond atomic Ti on the outer surface of MWNTs. Each titanium atom has the potential of hosting two hydrogen molecules and relinquishing them by heating. Nevertheless, nanotubes are difficult to handle due to electrostatic charge and agglomeration, and in this context, two routes were tested as procedures to spread and stick nanotubes on an electrode: (1) a functionalization capable of attaching gold was tested in two forms, as either using 4 nm particles or a flat gold electrode. The fixation of Au particles was confirmed by HRTEM. (2) A simpler route that consisted on drying a CH2Cl2/nanotubes solution previously spread on a glassy carbon flat electrode. CH2Cl2was selected as the medium and TiCl4as the precursor for attaching atomic Ti to the nanotubes. The results revealed that hydrogen adsorption, estimated from voltamperometry, was five times higher on Ti-MWNTs than on bare nanotubes.
NFAT1 Supports Tumor-induced Anergy of CD4+ T Cells
Authors: Abe Brian T. , Shin Daniel S. , Mocholi Enric , Macian Fernando
Published: August 2012

Cancer cells express antigens that elicit T cell-mediated responses, but these responses are limited during malignant progression by the development of immunosuppressive mechanisms in the tumor microenvironment that drive immune escape. T-cell hyporesponsiveness can be caused by clonal anergy or adaptive tolerance, but the pathophysiological roles of these processes in specific tumor contexts has yet to be understood. In CD4+ T cells, clonal anergy occurs when the T-cell receptor is activated in the absence of a costimulatory signal. Here we report that the key T-cell transcription factor NFAT mediates expression of anergy-associated genes in the context of cancer. Specifically, in a murine model of melanoma, we found that cancer cells induced anergy in antigen-specific CD4+ T-cell populations, resulting in defective production of several key effector cytokines. NFAT1 deficiency blunted the induction of anergy in tumor antigen-specific CD4+ T cells, enhancing antitumor responses. These investigations identified tumor-induced T-cell hyporesponsiveness as a form of clonal anergy, and they supported an important role for CD4+ T-cell anergy in driving immune escape. By illustrating the dependence of tumor-induced CD4+ T-cell anergy on NFAT1, our findings open the possibility of targeting this transcription factor to improve the efficacy of cancer immunotherapy or immunochemotherapy. Cancer Res; 72(18); 4642–51. ©2012 AACR.
CD133+ Melanoma Subpopulations Contribute to Perivascular Niche Morphogenesis and Tumorigenicity through Vasculogenic Mimicry
Authors: Lai Chiou-Yan , Schwartz Brian E. , Hsu Mei-Yu
Published: August 2012

Tumor cell subpopulations that express cancer stem cell markers such as CD133 (prominin1) or ABCB5 are thought to be crucial for tumor initiation and heterogeneity, but their biological significance in melanoma has been controversial. Here, we report that CD133+ and ABCB5+ subpopulations are colocalized in melanomas in perivascular niches that contain CD144 (VE-cadherin)+ melanoma cells forming vessel-like channels, a phenomenon termed vasculogenic mimicry (VM). RNAi-mediated attenuation of CD133 established its critical function in morphogenesis of these perivascular niches as well as in melanoma tumorigenicity. Niche-associated genes CD144 and ABCB5 were downregulated in tumors derived from CD133 knockdown (KD) melanoma cells compared with controls. CD133KD cells also lacked the ability to form CD144+ VM-like channels in a manner that was associated with a depletion of the ABCB5+ cell subpopulation. Finally, CD133 KD cells exhibited poorer tumor growth in vivo. Taken together, our findings corroborate models in which CD133+/ABCB5+ melanoma cells reside in a complex anastomosing microvascular niche that encompasses CD144+ VM channels as well as authentic endothelial cell-lined blood vessels. Further, they indicate that CD133+ cells act as stem-like cells, which drive tumor growth by promoting VM and the morphogenesis of a specialized perivascular niche in melanoma. Cancer Res; 72(19); 5111–8. ©2012 AACR.
Alternative Cleavage and Polyadenylation during Colorectal Cancer Development
Authors: Morris Adam R. , Bos Arnold , Diosdado Begoña , Rooijers Koos , Elkon Ran , Bolijn Anne S. , Carvalho Beatriz , Meijer Gerrit A. , Agami Reuven
Published: August 2012

Purpose: Alternative cleavage and polyadenylation (APA) of mRNAs is a phenomenon that alters 3′-untranslated region length leading to altered posttranscriptional regulation of gene expression. Changing APA patterns have been shown to result in misregulation of genes involved in carcinogenesis; therefore, we hypothesized that altered APA contributes to progression of colorectal cancer, and that measurement of APA may lead to discovery of novel biomarkers.

Experimental Design: We used next-generation sequencing to directly measure global patterns of APA changes during colorectal carcinoma progression in 15 human patient samples. Results were validated in a larger cohort of 50 patients, including 5 normal/carcinoma pairs from individuals.

Results: We discovered numerous genes presenting progressive changes in APA. Genes undergoing untranslated region (3′UTR) shortening were enriched for functional groups such as cell-cycle and nucleic acid–binding and processing factors, and those undergoing 3′UTR lengthening or alternative 3′UTR usage were enriched for categories such as cell–cell adhesion and extracellular matrix. We found indications that APA changes result from differential processing of transcripts because of increased expression of cleavage and polyadenylation factors. Quantitative PCR analysis in a larger series of human patient samples, including matched pairs, confirmed APA changes in DMKN, PDXK, and PPIE genes.

Conclusions: Our results suggest that genes undergoing altered APA during human cancer progression may be useful novel biomarkers and potentially targeted for disease prevention and treatment. We propose that the strategy presented here may be broadly useful in discovery of novel biomarkers for other types of cancer and human disease. Clin Cancer Res; 18(19); 5256–66. ©2012 AACR.
A Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets
Authors: Weisbart Richard H. , Gera Joseph F. , Chan Grace , Hansen James E. , Li Erica , Cloninger Cheri , Levine Arnold J. , Nishimura Robert N.
Published: August 2012

The therapeutic use of antibodies is restricted by the limited access of antibodies to intracellular compartments. To overcome this limitation, we developed a cell-penetrating monoclonal antibody, mAb 3E10, as an intracellular delivery vehicle for the intracellular and intranuclear delivery of antibodies constructed as bispecific single-chain Fv fragments. Because MDM2 is an important target in cancer therapy, we selected monoclonal antibody (mAb) 3G5 for intracellular transport. mAb 3G5 binds MDM2 and blocks binding of MDM2 to p53. Here, we show that the resulting 3E10-3G5 bispecific antibody retains cell-penetrating and MDM2-binding activity, increases tumor p53 levels, and inhibits growth of MDM2-addicted tumors. The use of cell-penetrating bispecific antibodies in targeted molecular therapy will significantly broaden the spectrum of accessible intracellular targets and may have a profound impact in cancer therapy. Mol Cancer Ther; 11(10); 2169–73. ©2012 AACR.
Abstract 100: Somatic mutations in Pyk2 in melanoma alter protein activity, interactions and localization
Authors: Willard Melinda D. , Wulur Isabella H. , Samuels Yardena , Barber Thomas D. , Gartner Jared , Parker Stephen C.J.
Published: August 2012

Data indicates that focal adhesion kinases (FAKs) play a critical role in cancer. Specifically, accumulating evidence suggests that overexpression and altered activity of FAKs promotes tumorigenesis, metastasis, and correlates with reduced survival. Proline-rich tyrosine kinase 2 (PYK2, FAK2) and its role in physiological processes in bone and inflammatory cellular responses have been well-documented. Recently, the role of PYK2 in the induction of endothelial to mesenchymal transition and cancer progression has emerged. Somatic mutations altering the coding region of PTK2B have been detected in melanoma and lung cancer, but the functional significance of these mutations is unknown. Here we demonstrate that cancer-associated mutations of PYK2 found in malignant melanoma lead to altered protein localization, interactions, and activity, and consequently, abnormal cellular behavior. These findings suggest that somatic mutations in PTK2B may promote tumor progression through deregulated protein activity, and highlight the importance of evaluating PYK2 inhibitors to block both the normal and mutant forms of the kinase.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 100. doi:1538-7445.AM2012-100
Abstract 1001: Reductive tricarboxylic acid metabolism of glutamine mediates lipogenesis under hypoxia
Authors: Metallo Christian , Gameiro Paulo , Heiden Matthew Vander , Ilioupoulos Othon , Stephanopoulos Greg
Published: August 2012

Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and adenosine triphosphate citrate lyase (ACL) in the cytosol. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle (TCA) and fatty acid synthesis. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis, the regulation and utilization of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells employ reductive metabolism of alpha-ketoglutarate (aKG) to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase 1 (IDH1) dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived aKG for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau (VHL) tumor suppressor protein preferentially utilize reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon utilization in order to produce AcCoA and support lipid synthesis in mammalian cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1001. doi:1538-7445.AM2012-1001