bluuebunny/crossref_metadata_2025 huggingface dataset:
Random mutagenesis suggests that sequence errors are not a major cause of variation in the activity of individual molecules of β-galactosidase
Authors: Craig Douglas B. , Schwab Thomas , Sterner Reinhard
Published: June 2012

Wild-type Escherichia coli lacZ was subjected to error-prone PCR to generate two plasmid-encoded gene libraries containing approximately 2.6 (SD 1.9) nucleotide exchanges resulting in 1.8 (SD 1.4) amino-acid substitutions. The libraries were used, along with a plasmid containing wild-type lacZ, to transform E. coli lacking genomic lacZ. Cells expressing functional β-galactosidase were identified by blue/white screening. Cell lysates containing the populations of heterogeneously mutagenized β-galactosidase were subjected to single molecule assays using a capillary electrophoresis laser-induced fluorescence-based protocol. There was no significant difference in the average catalytic rate between the random mutagenized and wild-type enzyme populations. Furthermore, there was no clear pattern between error rates and the variances in the population catalytic rates. This suggests that random sequence errors are not a substantial source of the catalytic heterogeneity of this enzyme.
Preliminary methylation analysis of prothymosin α genomic sequences
Authors: Álvarez-Fernández Leoncio , Gómez-Márquez Jaime
Published: June 2012

Prothymosin α is a mammalian nuclear protein involved in cell proliferation and differentiation. Here, we carried out the first study of the methylation status of ProTα genomic sequences in cell lines during differentiation as well as in tumoral tissues. We found that there is hypermethylation in all cell lines analyzed with a pattern that is characteristic of each cell type revealing specific genomic reorganizations. The decrease of ProTα mRNA during differentiation was not accompanied by changes in the methylation status. Remarkably, we found that there is hypomethylation in gastrointestinal tumors when compared with the peritumoral tissue. The biological implications of these findings are discussed.
Dock7: A GEF for Rho-family GTPases and a novel myosin VI-binding partner in neuronal PC12 cells
Authors: Majewski Łukasz , Sobczak Magdalena , Havrylov Serhiy , Jóźwiak Jolanta , Rędowicz Maria Jolanta
Published: June 2012

Myosin VI (MVI), the only known myosin that walks towards the minus end of actin filaments, is involved in several processes such as endocytosis, cell migration, and cytokinesis. It may act as a transporting motor or a protein engaged in actin cytoskeleton remodelling via its binding partners, interacting with its C-terminal globular tail domain. By means of pull-down technique and mass spectrometry, we identified Dock7 (dedicator of cytokinesis 7) as a potential novel MVI-binding partner in neurosecretory PC12 cells. Dock7, expressed mainly in neuronal cells, is a guanine nucleotide exchange factor (GEF) for small GTPases, Rac1 and Cdc42, which are the major regulators of actin cytoskeleton. MVI–Dock7 interaction was further confirmed by co-immunoprecipitation of endogenous MVI complexed with Dock7. In addition, MVI and Dock7 colocalized in interphase and dividing cells. We conclude that in PC12 cells MVI-Dock7 complexes may function at different cellular locations during the entire cell cycle. Of note, MVI and Dock7 colocalized in primary culture hippocampal neurons also, predominantly in the outgrowths. We hypothesize that this newly identified interaction between MVI and Dock7 may help explain a mechanism for MVI-dependent regulation of actin cytoskeleton organization.
Domain specific overexpression of TIMP-2 and TIMP-3 reveals MMP-independent functions of TIMPs duringXenopus laevisdevelopment
Authors: Nieuwesteeg M.A. , Walsh L.A. , Fox M.A. , Damjanovski S.
Published: June 2012

Extracellular matrix remodelling mediates many processes including cell migration and differentiation and is regulated through the enzymatic action of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). TIMPs are secreted proteins, consisting of structurally and functionally distinct N- and C-terminal domains. TIMP N-terminal domains inhibit MMP activity, whereas their C-terminal domains may have cell signalling activity. The in vivo role of TIMP N- and C-terminal domains in regulating developmental events has not previously been demonstrated. Here we investigated the roles of TIMP-2 and TIMP-3 N- and C-terminal domains in Xenopus laevis embryos. We show that overexpression of TIMP-2 N- and C-terminal domains results in severe developmental defects and death, as well as unique changes in MMP-2 and -9 expression, indicating that the individual domains may regulate MMPs through distinct mechanisms. In contrast, we show that only the N-terminal, but not the C-terminal domain of TIMP-3, results in developmental defects.
INFLUENCE OF LIMITED-PROJECTION ON FLUORESCENCE MOLECULAR TOMOGRAPHY
Authors: HE YUN , CAO XU , LIU FEI , LUO JIANWEN , BAI JING
Published: June 2012

Challenges remain in imaging fast biological processes in vivo with fluorescence molecular tomography (FMT) due to the long data acquisition time. Data acquisition with limited projections can greatly reduce the time consumption, but the influence of limited-projection on reconstruction quality is currently unclear. Both numerical simulations and a phantom experiment are conducted to analyze this problem. Through a systematic investigation of all the results reconstructed from different numbers of projections, we evaluate the influence of limited-projection data on FMT. A mouse experiment is also performed to validate our work. A general relationship between the number of projections and reconstruction quality is obtained which indicates that the projection number of three is preferred for fast FMT experiment.
Reservoir characteristics of fault-controlled hydrothermal dolomite bodies: Ramales Platform case study
Authors: Dewit J. , Huysmans M. , Muchez Ph. , Hunt D. W. , Thurmond J. B. , Verges J. , Saura E. , Fernandez N. , Romaire I. , Esestime P. , Swennen R.
Published: June 2012

Hydrothermal dolomite (HTD) bodies are known as high-quality hydrocarbon reservoirs; however few studies focus on the geometry and distribution of reservoir characteristics. Across the platform-to-basin transition of the Ramales Platform, fault-controlled HTD bodies are present. Three kinds of bodies can be distinguished based on their morphology, that is, elongated HTD corridors, a massive HTD body (Pozalagua body) and an HTD-cemented breccia body. The differences in size and shape of the HTD bodies can be attributed to differences in local structural setting. For the Pozalagua body, an additional sedimentological control is invoked to explain the difference in HTD geometry.

A (geo)-statistical investigation of the reservoir characteristics in the Pozalagua body revealed that the HTD types (defined based on their texture) show spatial clustering controlled by the orientation of faults, joints and the platform edge. Porosity and permeability values are distributed in clusters of high and low values; however, they are not significantly different for the three HTD types. Two dolomitization phases (i.e. ferroan and non-ferroan) can be observed in all HTD bodies. In general, the HTDs resulting from the second non-ferroan dolomitization phase have lower porosity values. No difference in permeability is found for the ferroan and non-ferroan dolomites.
Lacustrine carbonates in rift settings: the interaction of volcanic and microbial processes on carbonate deposition
Authors: Wright V. Paul
Published: June 2012

The relatively simplistic facies models for lacustrine carbonates do not currently incorporate either the diversity of microbialite carbonate development or the influence of volcanic-related processes found in rift settings. The basic nature of the carbonate factories in these systems, whether microbial, macrophytic, skeletal or abiogenic, is not resolved. Lacustrine microbialites can develop in shallow lakes as concentrations of microbialite mounds covering many hundreds of square kilometres, or as bathymetrically controlled facies belts, but in many rift settings vent-related thermal and non-thermal carbonates (travertines and tufas) are a major component. Subaqueous vent-related carbonates, with evidence of microbial activity, can produce seismic-scale carbonate build-ups in deeper lakes or apparently more stratiform accumulations in shallow lakes. In lakes with only volcanic catchments, Mg and silica activity, coupled with high carbonate alkalinity and microbial influences, can potentially generate a complex set of mineral–microbe interactions and products, creating a unique set of challenges for predicting and understanding reservoirs in such settings.
Effects of diagenesis (cement precipitation) during fracture opening on fracture aperture-size scaling in carbonate rocks
Authors: Hooker J. N. , Gomez L. A. , Laubach S. E. , Gale J. F. W. , Marrett R.
Published: June 2012

A correlation is demonstrated between the presence of crack-seal texture and power-law kinematic aperture-size (width) distributions among opening-mode fractures in rocks of dominantly carbonate mineralogy. Crack-seal opening increments (opening-displacement increment sizes or ‘gaps’) within individual fractures follow narrow normal or log-normal size distributions, suggesting that fracture widening accumulates in characteristic (usually micrometre-scale) size increments. The scale invariance in overall fracture width distributions present in some fracture sets most likely arises from grouping of these increments (localization) to form larger fractures (millimetre- to centimetre-scale widths). Such localization could be a consequence of the tendency for larger, less cemented fractures to break preferentially during subsequent deformation. Cement accumulation patterns thus provide a mechanism for positive feedback whereby large-fracture growth exceeds small-fracture growth. Using characteristically sized growth increments, a fracture growth model accurately simulates fracture arrays having power-law fracture-width distributions. Model parameters can be altered to produce characteristic-width fracture size distributions. The results have implications for how fracture porosity and permeability evolve in carbonate reservoirs.
Role of IGF-I and the TNFα/NF-κB pathway in the induction of muscle atrogenes by acute inflammation
Authors: Schakman O. , Dehoux M. , Bouchuari S. , Delaere S. , Lause P. , Decroly N. , Shoelson S. E. , Thissen J.-P.
Published: June 2012

Several catabolic states (sepsis, cancer, etc.) associated with acute inflammation are characterized by a loss of skeletal muscle due to accelerated proteolysis. The main proteolytic systems involved are the autophagy and the ubiquitin-proteasome (UPS) pathways. Among the signaling pathways that could mediate proteolysis induced by acute inflammation, the transcription factor NF-κB, induced by TNFα, and the transcription factor forkhead box O (FOXO), induced by glucocorticoids (GC) and inhibited by IGF-I, are likely to play a key role. The aim of this study was to identify the nature of the molecular mediators responsible for the induction of these muscle proteolytic systems in response to acute inflammation caused by LPS injection. LPS injection robustly stimulated the expression of several components of the autophagy and the UPS pathways in the skeletal muscle. This induction was associated with a rapid increase of circulating levels of TNFα together with a muscular activation of NF-κB followed by a decrease in circulating and muscle levels of IGF-I. Neither restoration of circulating IGF-I nor restoration of muscle IGF-I levels prevented the activation of autophagy and UPS genes by LPS. The inhibition of TNFα production and muscle NF-κB activation, respectively by using pentoxifilline and a repressor of NF-κB, did not prevent the activation of autophagy and UPS genes by LPS. Finally, inhibition of GC action with RU-486 blunted completely the activation of these atrogenes by LPS. In conclusion, we show that increased GC production plays a more crucial role than decreased IGF-I and increased TNFα/NF-κB pathway for the induction of the proteolytic systems caused by acute inflammation.
Activin B regulates islet composition and islet mass but not whole body glucose homeostasis or insulin sensitivity
Authors: Bonomi Lara , Brown Melissa , Ungerleider Nathan , Muse Meghan , Matzuk Martin M. , Schneyer Alan
Published: June 2012

Based on the phenotype of the activin-like kinase-7 (ALK7)-null mouse, activins A and B have been proposed to play distinct roles in regulating pancreatic islet function and glucose homeostasis, with activin A acting to enhance islet function and insulin release while activin B antagonizes these actions. We therefore hypothesized that islets from activin B-null (BBKO) mice would have enhanced glucose-stimulated insulin secretion. In addition, we hypothesized that this enhanced islet function would translate into increased whole body glucose tolerance. We tested these hypotheses by analyzing glucose homeostasis, insulin secretion, and islet function in BBKO mice. No differences were observed in fasting glucose or insulin levels, glucose tolerance, or insulin sensitivity compared with weight-matched young or older males. Similarly, there were no significant differences in insulin secretion comparing islets from WT or BBKO males at either age. However, BBKO islets were more sensitive to activin A, myostatin (MSTN), and follistatin (FST) treatments, so that activin A and FST inhibited and MSTN enhanced glucose stimulated insulin secretion. While mean islet area and the distribution of islet areas were not different between the genotypes, islet mass, islet number, and the proportion of α-cells/islet were significantly reduced in BBKO islets. These results indicate that activin B does not antagonize activin A to influence whole body glucose homeostasis or β-cell function but does influence islet mass and proportion of α-cells/islet. Therefore, loss of activin B signaling alone does not account for the ALK7-null phenotype, but activin B may have important roles in modulating islet mass, islet number, and the cellular composition of islets.
Acetylcholinesterase deficiency contributes to neuromuscular junction dysfunction in type 1 diabetic neuropathy
Authors: Garcia Carmen C. , Potian Joseph G. , Hognason Kormakur , Thyagarajan Baskaran , Sultatos Lester G. , Souayah Nizar , Routh Vanessa H. , McArdle Joseph J.
Published: June 2012

Diabetic neuropathy is associated with functional and morphological changes of the neuromuscular junction (NMJ) associated with muscle weakness. This study examines the effect of type 1 diabetes on NMJ function. Swiss Webster mice were made diabetic with three interdaily ip injections of streptozotocin (STZ). Mice were severely hyperglycemic within 7 days after the STZ treatment began. Whereas performance of mice on a rotating rod remained normal, the twitch tension response of the isolated extensor digitorum longus to nerve stimulation was reduced significantly at 4 wk after the onset of STZ-induced hyperglycemia. This mechanical alteration was associated with increased amplitude and prolonged duration of miniature end-plate currents (mEPCs). Prolongation of mEPCs was not due to expression of the embryonic acetylcholine receptor but to reduced muscle expression of acetylcholine esterase (AChE). Greater sensitivity of mEPC decay time to the selective butyrylcholinesterase (BChE) inhibitor PEC suggests that muscle attempts to compensate for reduced AChE levels by increasing expression of BChE. These alterations of AChE are attributed to STZ-induced hyperglycemia since similar mEPC prolongation and reduced AChE expression were found for db/db mice. The reduction of muscle end-plate AChE activity early during the onset of STZ-induced hyperglycemia may contribute to endplate pathology and subsequent muscle weakness during diabetes.
Hydrogen sulfide mediates hypoxic vasoconstriction through a production of mitochondrial ROS in trout gills
Authors: Skovgaard Nini , Olson Kenneth R.
Published: June 2012

Hypoxic pulmonary vasoconstriction (HPV) is an adaptive response that diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts. This response is important for the local matching of blood perfusion to ventilation and improves pulmonary gas exchange efficiency. HPV is an ancient and highly conserved response, expressed in the respiratory organs of all vertebrates, including lungs of mammals, birds, and reptiles; amphibian skin; and fish gills. The mechanism underlying HPV and how cells sense low Po2 remains elusive. In perfused trout gills ( Oncorhynchus mykiss), acute hypoxia, as well as H2S, caused an initial and transient constriction of the vasculature. Inhibition of the enzymes cystathionine-β-synthase and cystathionine-γ-lyase, which blocks H2S production, abolished the hypoxic response. Individually blocking the four complexes in the electron transport chain abolished both the hypoxic and the H2S-mediated constriction. Glutathione, an antioxidant and scavenger of superoxide, attenuated the vasoconstriction in response to hypoxia and H2S. Furthermore, diethyldithiocarbamate, an inhibitor of superoxide dismutase, attenuated the hypoxic and H2S constriction. This strongly suggests that H2S mediates the hypoxic vasoconstriction in trout gills. H2S may stimulate the mitochondrial production of superoxide, which is then converted to hydrogen peroxide (H2O2). Thus, H2O2 may act as the “downstream” signaling molecule in hypoxic vasoconstriction.
On the Impact of Channel Cross-Correlations in High-Sensitivity Receivers for Galileo E1 OS and GPS L1C Signals
Authors: Margaria Davide , Motella Beatrice , Dovis Fabio
Published: June 2012

One of the most promising features of the modernized global navigation satellite systems signals is the presence of pilot channels that, being data-transition free, allow for increasing the coherent integration time of the receivers. Generally speaking, the increased integration time allows to better average the thermal noise component, thus improving the postcorrelation SNR of the receiver in the acquisition phase. On the other hand, for a standalone receiver which is not aided or assisted, the acquisition architecture requires that only the pilot channel is processed, at least during the first steps of the procedure. The aim of this paper is to present a detailed investigation on the impact of the code cross-correlation properties in the reception of Galileo E1 Open Service and GPS L1C civil signals. Analytical and simulation results demonstrate that the S-curve of the code synchronization loop can be affected by a bias around the lock point. This effect depends on the code cross-correlation properties and on the receiver setup. Furthermore, in these cases, the sensitivity of the receiver to other error sources might increase, and the paper shows how in presence of an interfering signal the pseudorange bias can be magnified and lead to relevant performance degradation.
Meniscofibular Ligament: Morphology and Functional Significance of a Relatively Unknown Anatomical Structure
Authors: Natsis K. , Paraskevas G. , Anastasopoulos N. , Papamitsou T. , Sioga A.
Published: June 2012

Purpose. A relatively unknown ligamentous structure of the posterolateral corner of the knee joint, the so-called meniscofibular ligament (MFL), was investigated as regards its macroscopic morphology, its histological features, and its reaction to knee movements. Material and Methods. MFL was exposed on 21 fresh-frozen unpaired knee joints. Its microscopic morphology was examined utilizing for comparison the fibular collateral and the popliteofibular ligament. Results. MFL was encountered in 100% of the specimens as a thin striplike fibrous band extending between the lower border of the lateral meniscus and the head of the fibula. MFL was tense during knee extension and external rotation of the tibia, whereas its histological features were similar to those of fibular collateral and popliteofibular ligament. Discussion. Its precise histological nature is studied as well as its tension alterations during knee movements. The potential functional significance of the MFL with respect to its role in avoidance of lateral meniscus and lateral coronary ligament tears is discussed. Conclusions. MFL presumably provides an additional protection to the lateral meniscus during the last stages of knee extension, as well as to the lateral coronary ligament reducing the possibility of a potential rupture.
The Effect of PPAR Agonists on the Migration of Mature and Immature Eosinophils
Authors: Smith Steven G. , Imaoka Haruki , Punia Neha , Irshad Anam , Janssen Luke L. , Sehmi Roma , Gauvreau Gail M.
Published: June 2012

PPARγagonists can either enhance or inhibit eosinophil migration, which is a sum of directional migration (chemotaxis) and random cell movement (chemokinesis). To date, the effects of PPAR agonists on chemokinesis have not been examined. This study investigates the effects of PPARα,δ, andγagonists on eosinophil migration and chemokinesis. Eosinophils purified from blood of atopic donors were preincubated with rosiglitazone (PPARγagonist), GW9578 (PPARαagonist), GW501516 (PPARδagonist), or diluent. The effects of PPAR agonists were examined on eosinophil chemokinesis, eotaxin-induced migration of eosinophils, and migration of IL-5Rα+ CD34+ cells. Expressions of CCR3, phospho-p38, phospho-ERK, and calcium release were also measured in eosinophils after rosiglitazone treatment. Low concentrations of rosiglitazone, but not GW9578 or GW501516, increased chemokinesis of eosinophils (P=0.0038), and SDF-1α-induced migration of immature eosinophils (P=0.0538). Rosiglitazone had an effect on eosinophil calcium flux but had no effect on expression of CCR3 or phosphorylation of p38 or ERK. In contrast, high concentrations of rosiglitazone inhibited eosinophil migration (P=0.0042). The effect of rosiglitazone on eosinophil migration and chemokinesis appears to be through modification of calcium signaling, which alludes to a novel PPAR-mediated mechanism to modulate eosinophil function.
Penile Enhancement Procedures with Simultaneous Penile Prosthesis Placement
Authors: Hakky Tariq S. , Suber Jessica , Henry Gerard , Smith David , Bradley Paul , Martinez Daniel , Carrion Rafael E.
Published: June 2012

Here we present an overview of various techniques performed concomitantly during penile prosthesis surgery to enhance penile length and girth. We report on the technique of ventral phalloplasty and its outcomes along with augmentation corporoplasty, suprapubic lipectomy, suspensory ligament release, and girth enhancement procedures. For the serious implanter, outcomes can be improved by combining the use of techniques for each scar incision. These adjuvant procedures are a key addition in the armamentarium for the serious implant surgeon.
Optical Properties of Polystyrene‐ZnO Nanocomposite Scattering Layer to Improve Light Extraction in Organic Light‐Emitting Diode
Authors: Nenna G. , De Girolamo Del Mauro A. , Massera E. , Bruno A. , Fasolino T. , Minarini C.
Published: June 2012

In this work, experimental measurements on polystyrene‐ZnO nanocomposite scattering films and on organic light‐emitting device with and without the scattering layers are presented. The results are also compared with Henyey‐Greenstein radiative‐transfer model to narrow down the parameters that can be important in the identification of more suitable scattering layers. As a result, an increase of efficiency of about 30% has been obtained that it can be translated in 60% of outcoupled light in respect to the total generated amount.
Review of Techniques for Fault Diagnosis in Damaged Structure and Engineering System
Authors: Thatoi Dhirendra Nath , Das Harish Ch. , Parhi Dayal R.
Published: June 2012

Focus has been made to give an overview of various methodologies used in fault diagnosis and condition monitoring. A crack in vibrating structures can lead to premature failure if it is not detected in time. Researchers have been working on the dynamics of cracked structures for decades to be able to monitor a structure and diagnose fault at the earliest possible stage. An effort has been made in the current paper to understand different techniques and methodologies for fault diagnosis and condition monitoring of damaged structures subjected to varied dynamic loading. The methods used are classical, wavelet transform, and finite element methods, artificial intelligence methods, and numerical and experimental methods. Using classical methods, engineers are able to predict faults. But using artificial intelligence techniques, it is observed that the forecasting time for fault diagnosis improves a lot in comparison to other methodologies.
Construction of a Llama Bacterial Artificial Chromosome Library with Approximately 9-Fold Genome Equivalent Coverage
Authors: Airmet K. W. , Hinckley J. D. , Tree L. T. , Moss M. , Blumell S. , Ulicny K. , Gustafson A. K. , Weed M. , Theodosis R. , Lehnardt M. , Genho J. , Stevens M. R. , Kooyman D. L.
Published: June 2012

The Ilama is an important agricultural livestock in much of South America. The llama is increasing in popularity in the United States as a companion animal. Little work has been done to improve llama production using modern technology. A paucity of information is available regarding the llama genome. We report the construction of a llama bacterial artificial chromosome (BAC) library of about 196,224 clones in the vector pECBAC1. Using flow cytometry and bovine, human, mouse, and chicken as controls, we determined the llama genome size to be2.4×109 bp. The average insert size of the library is 137.8 kb corresponding to approximately 9-fold genome coverage. Further studies are needed to further characterize the library and llama genome. We anticipate that this new library will help facilitate future genomic studies in the llama.
Glomus Tumor Presenting as Raynaud's Phenomenon
Authors: Abdelrahman M. H. , Hammoudeh M.
Published: June 2012

Glomus tumors are rare tumors that often include hands and feet; they present characteristically with paroxysmal pain, exquisite point tenderness, and cold sensitivity. Such diagnosis needs to be confirmed by imaging like ultrasound and magnetic resonance imaging (MRI). Surgical excision is the treatment of choice for glomus tumors. There are only few case reports of glomus tumors in association with Raynaud’s phenomenon; this is considered to be the 4th case.
Multiple Positive Periodic Solutions for a Gilpin‐Ayala Competition Predator‐Prey System with Harvesting Terms
Authors: Liao Yongzhi , Li Yongkun , Dou Xiaoyan
Published: June 2012

By applying Mawhin’s continuation theorem of coincidence degree theory, we study the existence of multiple positive periodic solutions for a Gilpin‐Ayala competition predator‐prey system with harvesting terms and obtain some sufficient conditions for the existence of multiple positive periodic solutions for the system under consideration. The result of this paper is completely new. An example is employed to illustrate our result.
Hypofractionated Prostate Radiotherapy with or without Conventionally Fractionated Nodal Irradiation: Clinical Toxicity Observations and Retrospective Daily Dosimetry
Authors: McDonald Andrew M. , Bishop Justin M. , Jacob Rojymon , Dobelbower Michael C. , Kim Robert Y. , Yang Eddy S. , Smith Heather , Wu Xingen , Fiveash John B.
Published: June 2012

Purpose. To evaluate toxicity associated with the addition of elective nodal irradiation (ENI) to a hypofractionated regimen for the treatment of prostate cancer.Methods and Materials. Fifty-seven patients received pelvic image-guided IMRT to 50.4 Gy in 28 fractions with a hypofractionated simultaneous boost to the prostate to 70 Gy. Thirty-one patients received prostate-only treatment to 70 Gy in 28 fractions.Results. Median followup was 41.1 months. Early grade ≥2 urinary toxicity rates were 49% (28 of 57) for patients receiving ENI and 58% (18 of 31) for those not (P=0.61). Early grade ≥2 rectal toxicity rates were 40% (23 of 57) and 23% (7 of 31), respectively (P=0.09). The addition of ENI resulted in a 21% actuarial rate of late grade ≥2 rectal toxicity at 4 years, compared to 0% for patients treated to the prostate only (P=0.02). Retrospective daily dosimetry of patients experiencing late rectal toxicity revealed an average increase of 2.67% of the rectal volume receiving 70 Gy compared to the original plan.Conclusions. The addition of ENI resulted in an increased risk of late rectal toxicity. Grade ≥2 late rectal toxicity was associated with worse daily rectal dosimetry compared to the treatment plan.
A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression
Authors: Levine Todd D. , Bowser Robert , Hank Nicole C. , Gately Stephen , Stephan Dietrich , Saperstein David S. , Van Keuren-Jensen Kendall
Published: June 2012

Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators.Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs) were performed to measure cerebrospinal fluid (CSF) biomarker levels.Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of-.86(P=.18). Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression.Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.
Surgical Management of Patients with Chiari I Malformation
Authors: Siasios John , Kapsalaki Eftychia Z. , Fountas Kostas N.
Published: June 2012

Chiari malformations (CMs) constitute a variety of four mainly syndromes (I, II, III, and IV), which describe the protrusion of brain tissue into the spinal canal through the foramen magnum. These malformations frequently occur in combination with other pathological entities such as myelomeningocele, hydrocephalus, and/or hydrosyringomyelia. The recent improvement of imaging techniques has increased not only the rate of CM diagnosis but also the necessity for its early treatment. Several different surgical techniques have been employed in the treatment of patients with symptomatic CM-I. In our current study, a systematic and critical review of the pertinent literature was made for identifying the most commonly employed surgical procedures in the management of these patients. Emphasis was given in outlining the advantages and disadvantages of each surgical approach. Moreover, an attempt was made for defining those parameters that may be prognostic factors for their surgical outcome. There is a consensus that surgical treatment is reserved only for symptomatic patients with CM-I. It has also been postulated that early surgically intervention is usually associated with better outcome. Despite the large number of previously published clinical series, further clinical research with large-scale studies is necessary for defining surgical treatment guidelines in these patients.
Involvement of Stat1 in the Phagocytosis ofM. avium
Authors: Dominici Sabrina , Schiavano Giuditta Fiorella , Magnani Mauro , Buondelmonte Costantina , Celeste Angela Gabriela , Brandi Giorgio
Published: June 2012

Mycobacterium aviumis an intracellular pathogen preferentially infecting human macrophages where they activate the JAK/STAT1 pathway. This activation enhances the survival of infected cells, but, at the same time, makes macrophages optimal targets for drugs development against p-tyr701stat1. In this study, we demonstrate that the fast and transient activity of the JAK/STAT1 pathway occurs immediately after macrophages internalization of heat-killedM. aviumor inert particles. Furthermore, we show that a persistent Stat1 pathway activation occurs only when an intracellularM. aviuminfection is established in macrophages. These results strongly indicate different mechanisms of p-tyr701Stat1 activation. In particular, here we report findings aiming at explaining the short-time enhancement of p-tyr701Stat1 and shows its predominant relationship with FcγRs engagement during the internalization process. Furthermore, we demonstrate that opsonized liveM. aviumis phagocytosed by macrophages involving membrane receptors not related with JAK/STAT1 signalling pathway. On the contrary, heat-inactivated bacilli or latex particles seem to be internalized only after involvement of FcγRs and subsequent Stat1 phosphorylation.
Applying a Common-Sense Approach to Fighting Obesity
Authors: Breland Jessica Y. , Fox Ashley M. , Horowitz Carol R. , Leventhal Howard
Published: June 2012

The obesity epidemic is a threat to the health of millions and to the economic viability of healthcare systems, governments, businesses, and nations. A range of answers come to mind if and when we ask, “What can we, health professionals (physicians, nurses, nutritionists, behavioral psychologists), do about this epidemic?” In this paper, we describe the Common-Sense Model of Self-Regulation as a framework for organizing existent tools and creating new tools to improve control of the obesity epidemic. Further, we explain how the Common-Sense Model can augment existing behavior-change models, with particular attention to the strength of the Common-Sense Model in addressing assessment and weight maintenance beyond initial weight loss.
Estimating a User's Internal State before the First Input Utterance
Authors: Chiba Yuya , Ito Akinori
Published: June 2012

This paper describes a method for estimating the internal state of a user of a spoken dialog system before his/her first input utterance. When actually using a dialog-based system, the user is often perplexed by the prompt. A typical system provides more detailed information to a user who is taking time to make an input utterance, but such assistance is nuisance if the user is merely considering how to answer the prompt. To respond appropriately, the spoken dialog system should be able to consider the user’s internal state before the user’s input. Conventional studies on user modeling have focused on the linguistic information of the utterance for estimating the user’s internal state, but this approach cannot estimate the user’s state until the end of the user’s first utterance. Therefore, we focused on the user’s nonverbal output such as fillers, silence, or head-moving until the beginning of the input utterance. The experimental data was collected on a Wizard of Oz basis, and the labels were decided by five evaluators. Finally, we conducted a discrimination experiment with the trained user model using combined features. As a three-class discrimination result, we obtained about 85% accuracy in an open test.
Improved Degree Search Algorithms in Unstructured P2P Networks
Authors: Liu Guole , Peng Haipeng , Li Lixiang , Yang Yixian , Luo Qun
Published: June 2012

Searching and retrieving the demanded correct information is one important problem in networks; especially, designing an efficient search algorithm is a key challenge in unstructured peer‐to‐peer (P2P) networks. Breadth‐first search (BFS) and depth‐first search (DFS) are the current two typical search methods. BFS‐based algorithms show the perfect performance in the aspect of search success rate of network resources, while bringing the huge search messages. On the contrary, DFS‐based algorithms reduce the search message quantity and also cause the dropping of search success ratio. To address the problem that only one of performances is excellent, we propose two memory function degree search algorithms: memory function maximum degree algorithm (MD) and memory function preference degree algorithm (PD). We study their performance including the search success rate and the search message quantity in different networks, which are scale‐free networks, random graph networks, and small‐world networks. Simulations show that the two performances are both excellent at the same time, and the performances are improved at least 10 times.
Synthesis and Characterization of Graphene Thin Films by Chemical Reduction of Exfoliated and Intercalated Graphite Oxide
Authors: Thema F. T. , Moloto M. J. , Dikio E. D. , Nyangiwe N. N. , Kotsedi L. , Maaza M. , Khenfouch M.
Published: June 2012

Commercial flakes of graphite were prepared into functionalized graphene oxide (GO) by chemical treatment. After the exfoliation and intercalation of graphene into functionalized graphene oxide that formed stable colloidal dispersion in polar aprotic solvent, the reduction process was undertaken by continuous stirring with hydrazine hydrate. The reduced material was characterized by X‐ray diffraction (XRD), attenuated total reflectance (ATR) FT‐IR, ultraviolet visible (UV‐vis), atomic force microscopy (AFM) and Raman spectroscopy which confirm the oxidation of graphite and reduction of graphene oxide into graphene sheet.
Fertility Status of Soil in the Tea Garden Belts of Golaghat District, Assam, India
Authors: Baruah Bhupen K. , Das Bhanita , Medhi Chitrani , Misra Abani K.
Published: June 2012

The increasing land use intensity without adequate and balanced use of chemical fertilizers and with little or no use of organic manure have caused severe fertility deterioration of our soils resulting in stagnating or even declining of crop productivity in Assam. The need of the hour is to achieve substantially higher crop yield than the present yield levels from our limited land resources on a sustainable basis. A study was carried out in the paddy fields of tea garden belts namely, Rungagora, Balijan, Banwaripur, Khomtai, Rungajaun, Lattakoojan, Borjan, Behora, Negheriting, and Borsapori of Golaghat district of Assam to investigate the fertility status of soil during 2008–2010. Results of the present study showed that soil solutions were acidic in nature in all seasons. Medium‐to‐high BD, medium SOM, medium‐to‐high available N and available phosphorous, and low availability of potash showed that soils were not sufficiently fertile for crop production. Depending on the SOM, available N, available P, and exchangeable K in soil, the study areas were grouped in to six fertility classes as MMML, MMHL, MMMM, MHHL, MHHM, and MMHM. Student t‐test values of all the parameters with control sample showed statistically significant results for SOM, available N, and available P in both seasons (dry and wet) and EC in wet seasons and bulk density in dry season only.
The MET Oncogene Is a Functional Marker of a Glioblastoma Stem Cell Subtype
Authors: De Bacco Francesca , Casanova Elena , Medico Enzo , Pellegatta Serena , Orzan Francesca , Albano Raffaella , Luraghi Paolo , Reato Gigliola , D'Ambrosio Antonio , Porrati Paola , Patanè Monica , Maderna Emanuela , Pollo Bianca , Comoglio Paolo M. , Finocchiaro Gaetano , Boccaccio Carla
Published: June 2012

The existence of treatment-resistant cancer stem cells contributes to the aggressive phenotype of glioblastoma. However, the molecular alterations that drive stem cell proliferation in these tumors remain unknown. In this study, we found that expression of the MET oncogene was associated with neurospheres expressing the gene signature of mesenchymal and proneural subtypes of glioblastoma. Met expression was almost absent from neurospheres expressing the signature of the classical subtype and was mutually exclusive with amplification and expression of the EGF receptor (EGFR) gene. Met-positive and Met-negative neurospheres displayed distinct growth factor requirements, differentiated along divergent pathways, and generated tumors with distinctive features. The Methigh subpopulation within Met-pos neurospheres displayed clonogenic potential and long-term self-renewal ability in vitro and enhanced growth kinetics in vivo. In Methigh cells, the Met ligand HGF further sustained proliferation, clonogenicity, expression of self-renewal markers, migration, and invasion in vitro. Together, our findings suggest that Met is a functional marker of glioblastoma stem cells and a candidate target for identification and therapy of a subset of glioblastomas. Cancer Res; 72(17); 4537–50. ©2012 AACR.
Transcription Factor NFATc2 Controls the Emergence of Colon Cancer Associated with IL-6–Dependent Colitis
Authors: Gerlach Katharina , Daniel Carolin , Lehr Hans A. , Nikolaev Alexei , Gerlach Thomas , Atreya Raja , Rose-John Stefan , Neurath Markus F. , Weigmann Benno
Published: June 2012

NFAT transcription factors control T-cell activation and function. Specifically, the transcription factor NFATc2 affects the regulation of cell differentiation and growth and plays a critical role in the development of colonic inflammation. Here, we used an experimental model of colitis-associated colorectal carcinoma to investigate the contribution of NFATc2 to the promotion of colonic tumors. Compared with wild-type animals that readily presented with multiple colon tumors, NFATc2-deficient mice were protected from tumor development. This observed decrease in colonic tumor progression was associated with reduced endoscopic inflammation, increased apoptosis of lamina propria T lymphocytes, and significantly reduced levels of the critical proinflammatory cytokines interleukin (IL)-21 and IL-6. Administration of hyper IL-6 abrogated protection from tumor progression in NFATc2-knockout mice and restored tumor incidence to control levels. Taken together, our findings highlight a pivotal role for NFATc2 in the establishment of inflammation-associated colorectal tumors mediated by control of IL-6 expression. Cancer Res; 72(17); 4340–50. ©2012 AACR.
Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue
Authors: Liska Jan , Eriksson Per , Sverremark-Ekström Eva , Tornvall Per , Ekström Mattias
Published: June 2012

Plasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels of PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis.
Comparative Effectiveness of Preventative Therapy for Venous Thromboembolism After Coronary Artery Bypass Graft Surgery
Authors: Kulik Alexander , Rassen Jeremy A. , Myers Jessica , Schneeweiss Sebastian , Gagne Joshua , Polinski Jennifer M. , Liu Jun , Fischer Michael A. , Choudhry Niteesh K.
Published: June 2012

Background—

Controversy exists regarding the optimal preventative therapy for venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery. We sought to compare the effectiveness and safety of the most commonly used regimens.

Methods and Results—

We assembled a cohort of 92 699 patients who underwent CABG between 2004 and 2008, using the Premier database. Patients were categorized by method of VTE prevention initiated within 48 hours of surgery, including no preventative therapy (n=55 400), mechanical preventative therapy (n=21 162), subcutaneous unfractio-­nated or low-molecular-weight heparin (n=10 718), subcutaneous fondaparinux (n=88), and concurrent mechanical-chemical therapy (n=5331). The incidence of VTE and major bleeding events within 6 weeks of CABG were compared, using multivariable and propensity score adjustment. The overall incidence of VTE for the entire cohort was 0.74%, and the incidence of major bleeding was 1.43%. VTE and bleeding events occurred with similar incidence in each of the patient categories (VTE: 0.70%, 0.79%, 0.81%, 1.14%, and 0.73%; major bleeding: 1.36%, 1.45%, 1.69%, 3.41%, 1.50%; no prevention, mechanical prevention, subcutaneous heparin, subcutaneous fondaparinux, concurrent mechanical-chemical prevention, respectively). Compared with receiving no prevention, the use of mechanical prevention or subcutaneous heparin did not significantly reduce the risk of VTE or change the risk of major bleeding (
P
=NS).

Conclusion—

Venous thromboembolism occurs infrequently after CABG. Compared with the use of no prevention, the administration of chemical or mechanical preventative therapies to CABG patients does not appreciably lower the risk of VTE. These data provide support for the common practice of administering no VTE preventative therapy after CABG, used for nearly 60% of patients within this cohort.
Cost-Effectiveness of Apixaban Compared With Aspirin for Stroke Prevention in Atrial Fibrillation Among Patients Unsuitable for Warfarin
Authors: Lee Soyon , Anglade Moise W. , Meng Joy , Hagstrom Kelly , Kluger Jeffrey , Coleman Craig I.
Published: June 2012

Background—

Compared with aspirin, apixaban reduces stroke risk in atrial fibrillation (AF) patients unsuitable for warfarin by 63% but does not increase major bleeding. We sought to determine the cost-effectiveness of apixaban versus aspirin.

Methods and Results—

Using the Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin-K Antagonist Treatment (AVERROES) trial and other studies, we constructed a Markov model to evaluate the costs (2011US$), quality-adjusted life-years (QALYs), and incremental cost-effectiveness of apixaban versus aspirin from the Medicare perspective. Our base-case assumed a 70-year-old AF patient cohort with a CHADS
2
score=2 and a lower-risk of bleeding. We used a 1-month cycle-length and ran separate base-case analyses assuming a trial-length (1-year) and a longer-term (10-year) follow-up. Total costs/patient were $3454 and $1805 for apixaban and aspirin in the trial-length and $44 232 and $50 066 in the 10-year model. Corresponding QALYs were 0.96 and 0.96 in the trial-length and 6.87 and 6.51 in the 10-year model, making apixaban inferior in the first model but dominant in the latter. Conclusions were sensitive to baseline stroke rate in both models, and the monthly cost of major stroke, relative risk of stroke, and prior vitamin-K antagonist use in the life-time model. Probabilistic sensitivity analysis suggested apixaban would only be a cost-effective alternative (<$50 000/QALY) to aspirin 11% of the time in the trial-length model, but cost-effective or dominant 96.7% and 87.5% of iterations in the 10-year model.

Conclusions—

In our trial-length model, apixaban was more costly and no more effective than aspirin; however, as follow-up was extended, apixaban became cost-effective and eventually dominant.