bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonvolatile memory characteristics of organic thin film transistors using poly(2-hydroxyethyl methacrylate)-based polymer multilayer dielectric
Authors: Chen Ying-Chih , Su Yan-Kuin , Yu Hsin-Chieh , Huang Chun-Yuan , Huang Tsung-Syun
Published: October 2011

A wide hysteresis width characteristic (memory window) was observed in the organic thin film transistors (OTFTs) using poly(2-hydroxyethyl methacrylate) (PHEMA)-based polymer multilayers. In this study, a strong memory effect was also found in the pentacene-based OTFTs and the electric characteristics were improved by introducing PHEMA/poly(methyl methacrylate) (PMMA)/PHEMA trilayer to replace the conventional PHEMA monolayer or PMMA/PHEMA and PHEMA/PMMA bilayer as the dielectric layers of OTFTs. The memory effect was originated from the electron trapping and slow polarization of the dielectrics. The hydroxyl (-OH) groups inside the polymer dielectric were the main charge storage sites of the electrons. This charge-storage phenomenon could lead to a wide flat-band voltage shift (memory window, △VFB = 22 V) which is essential for the OTFTs’ memory-related applications. Moreover, the fabricated transistors also exhibited significant switchable channel current due to the charge-storage and slow charge relaxation.
Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809
Authors: Van Goor Fredrick , Hadida Sabine , Grootenhuis Peter D. J. , Burton Bill , Stack Jeffrey H. , Straley Kimberly S. , Decker Caroline J. , Miller Mark , McCartney Jason , Olson Eric R. , Wine Jeffrey J. , Frizzell Ray A. , Ashlock Melissa , Negulescu Paul A.
Published: October 2011

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508delCFTRmutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC50, 81 ± 19 nM), a level associated with mild CF in patients with less disruptiveCFTRmutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR.
Magnetic filter field dependence of the performance of the RF driven IPP prototype source for negative hydrogen ions
Authors: Franzen P , Schiesko L , Fröschle M , Wünderlich D , Fantz U
Published: October 2011

The ITER neutral beam system requires a negative hydrogen ion beam of 48 A with an energy of 0.87 MeV and a negative deuterium beam of 40 A with an energy of 1 MeV. The beam is extracted from a large RF driven ion source with the dimension of 1.9 × 0.9 m2. An important role for the transport of the negative hydrogen ions to the extractor and the suppression of the co-extracted electrons is the magnetic filter field in front of the extractor. For the large ITER source the filter field will be generated by a current of up to 4 kA flowing through the first grid of the extractor. The extrapolation of the results obtained with the small IPP RF prototype source, where the filter field has a different 3D structure as it is generated by permanent magnets, is not straightforward. Furthermore, the filter field is by far not optimized due to the technical constraints of the RF source. Therefore, a frame that surrounds the ion sources and hosts permanent magnets was constructed for a fast and flexible change of the filter field. First results in hydrogen show that a minimum field of 3 mT in front of the extractor is needed for a sufficiently large number of extracted negative hydrogen ions, whereas sufficient co-extracted electron suppression is achieved by a source integrated magnetic field of more than 1.0 mTm.
Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation
Authors: Matsuzaki Fumiko , Shirane Michiko , Matsumoto Masaki , Nakayama Keiichi I.
Published: October 2011

Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membrane protrusions. We adopted a proteomics approach to identify proteins that associate with protrudin. Among the protrudin-associated proteins, including many with a function related to intracellular trafficking, we focused on KIF5, a motor protein that mediates anterograde vesicular transport in neurons. A coimmunoprecipitation assay confirmed that endogenous protrudin and KIF5 interact in mouse brain. Overexpression of KIF5 induced the formation of membrane protrusions in HeLa cells, reminiscent of the effect of protrudin overexpression. Forced expression of both protrudin and KIF5 promoted protrusion extension in a synergistic manner, whereas depletion of either protein attenuated protrusion formation. Protrudin facilitated the interaction of KIF5 with Rab11, VAP-A and -B, Surf4, and RTN3, suggesting that protrudin serves as an adaptor protein and that the protrudin–KIF5 complex contributes to the transport of these proteins in neurons. Given that mutation of protrudin or KIF5 is a cause of human hereditary spastic paraplegia, the protrudin–KIF5 axis appears to be integral to neuronal function.
Development of an optimized backbone of FRET biosensors for kinases and GTPases
Authors: Komatsu Naoki , Aoki Kazuhiro , Yamada Masashi , Yukinaga Hiroko , Fujita Yoshihisa , Kamioka Yuji , Matsuda Michiyuki
Published: October 2011

Biosensors based on the principle of Förster (or fluorescence) resonance energy transfer (FRET) have shed new light on the spatiotemporal dynamics of signaling molecules. Among them, intramolecular FRET biosensors have been increasingly used due to their high sensitivity and user-friendliness. Time-consuming optimizations by trial and error, however, obstructed the development of intramolecular FRET biosensors. Here we report an optimized backbone for rapid development of highly sensitive intramolecular FRET biosensors. The key concept is to exclude the “orientation-dependent” FRET and to render the biosensors completely “distance-dependent” with a long, flexible linker. We optimized a pair of fluorescent proteins for distance-dependent biosensors, and then developed a long, flexible linker ranging from 116 to 244 amino acids in length, which reduced the basal FRET signal and thereby increased the gain of the FRET biosensors. Computational simulations provided insight into the mechanisms by which this optimized system was the rational strategy for intramolecular FRET biosensors. With this backbone system, we improved previously reported FRET biosensors of PKA, ERK, JNK, EGFR/Abl, Ras, and Rac1. Furthermore, this backbone enabled us to develop novel FRET biosensors for several kinases of RSK, S6K, Akt, and PKC and to perform quantitative evaluation of kinase inhibitors in living cells.
Edge-based compartmental modelling for infectious disease spread
Authors: Miller Joel C. , Slim Anja C. , Volz Erik M.
Published: October 2011

The primary tool for predicting infectious disease spread and intervention effectiveness is the mass action susceptible–infected–recovered model of Kermack & McKendrick. Its usefulness derives largely from its conceptual and mathematical simplicity; however, it incorrectly assumes that all individuals have the same contact rate and partnerships are fleeting. In this study, we introduceedge-based compartmental modelling, a technique eliminating these assumptions. We derive simple ordinary differential equation models capturing social heterogeneity (heterogeneous contact rates) while explicitly considering the impact of partnership duration. We introduce a graphical interpretation allowing for easy derivation and communication of the model and focus on applying the technique under different assumptions about how contact rates are distributed and how long partnerships last.
The Phosphorylation Status of the Chloroplast Protein Kinase STN7 of Arabidopsis Affects Its Turnover
Authors: Willig Adrian , Shapiguzov Alexey , Goldschmidt-Clermont Michel , Rochaix Jean-David
Published: October 2011

The chloroplast serine-threonine protein kinase STN7 of Arabidopsis (Arabidopsis thaliana) is required for the phosphorylation of the light-harvesting system of photosystem II and for state transitions, a process that allows the photosynthetic machinery to balance the light excitation energy between photosystem II and photosystem I and thereby to optimize the photosynthetic yield. Because the STN7 protein kinase of Arabidopsis is known to be phosphorylated at four serine-threonine residues, we have changed these residues by site-directed mutagenesis to alanine (STN7-4A) or aspartic acid (STN7-4D) to assess the role of these phosphorylation events. The corresponding mutants were still able to phosphorylate the light-harvesting system of photosystem II and to perform state transitions. Moreover, we noticed a marked decrease in the level of the STN7 kinase in the wild-type strain under prolonged state 1 conditions that no longer occurs in the STN7-4D mutant. The results suggest a possible role of phosphorylation of the STN7 kinase in regulating its turnover.
Prognosis of implants and fixed restorations after lateral sinus elevation: a literature review
Authors: TUNA T. , YORGIDIS M. , STRUB J. R.
Published: October 2011

Summary  Aim of this review was to investigate the prognosis of implants inserted in augmented sinuses and fixed restorations supported by these implants. Special attention was given to the impact of grafting material, time of implant placement, residual bone height and type of fixed restoration. An electronic search in PubMed, the German database medpilot and the Cochrane Library was executed followed by supplementary manual search in relevant journals. The search was limited to human studies published up to November 2010. Only publications in English and German, in peer‐reviewed journals, were considered. After the initial search and application of selection criteria on titles and abstracts, a full‐text analysis of 67 articles was performed, out of which six prospective and three retrospective studies were finally included in the review. The heterogeneous properties of the identified articles did not allow systematic analysis of the data. Success rates of implants were between 96·3% and 100%, survival rates were between 75% and 100%, and survival rates of single crowns, splinted crowns and fixed partial dentures ranged between 96·4% and 100% after a follow‐up of 12–101 months. Within the limits of this review, the prognosis of implants and fixed restorations seemed not to be influenced by the type of restorations, graft material, residual bone height and time of implant placement. However, conclusions of this review are based on studies with low level of evidence; therefore, careful interpretation is required. Multicentre randomised controlled clinical trials with sufficient statistical power concentrating on few factors are needed to reach sound conclusions.
Smoking and other factors associated with short‐term partial remission of Type 1 diabetes in adults
Authors: Pilacinski S. , Adler A. I. , Zozulinska‐Ziolkiewicz D. A. , Gawrecki A. , Wierusz‐Wysocka B.
Published: October 2011

Diabet. Med. 29, 464–469 (2012)

Aims  The duration of partial remission of Type 1 diabetes is associated with the degree of initial metabolic disturbance and features of insulin resistance. Cigarette smoking decreases insulin sensitivity, but its influence on the length of remission is unknown. Therefore, this study assessed the relationship between cigarette smoking and duration of partial remission in adults with newly diagnosed Type 1 diabetes.

Methods  We recruited 149 patients (48 women and 101 men, aged 16–35 years, median age 25 years), admitted to a teaching hospital with newly diagnosed Type 1 diabetes and followed them for a median period of 1 year and 9 months. We introduced intensive insulin therapy in multiple injections (basal‐bolus) in all patients. We defined partial remission as an insulin dose of ≤ 0.3 U/kg body weight/24 h, an HbA1c value < 53 mmol/mol (7.0%) and a random serum C‐peptide concentration over 0.5 ng/ml. Cigarette smoking was determined by self‐report.

Results  Of 149 patients, 68 (46%) fulfilled the criteria for partial remission at 1 year after diagnosis of diabetes. Fewer patients who were in partial remission at 1 year smoked (19/68, 28%) than did patients that were not in partial remission (41/81, 51%). In logistic regression analyses, non‐smoking was associated with remission at 1 year independent of age, sex, HbA1c and presence of diabetic ketoacidosis, all measured at onset of diabetes (OR 3.32, 95% CI 1.42–7.75, P = 0.005).

Conclusion  Relative to individuals in this study who smoked, those who did not smoke at diagnosis of Type 1 diabetes experienced a longer duration of partial remission.
Seasonal variations of urinary albumin creatinine ratio in Japanese subjects with Type 2 diabetes and early nephropathy
Authors: Wada Y. , Hamamoto Y. , Ikeda H. , Honjo S. , Kawasaki Y. , Mori K. , Koshiyama H.
Published: October 2011

Diabet. Med. 29, 506–508 (2012)

Aims  It has been recognized that blood pressure shows a seasonal variation, but it remains unknown whether diabetic nephropathy shows a seasonal variation. In the present study, we investigated the change in urinary albumin/creatinine ratio in relation to the season in Japanese patients with Type 2 diabetes.

Methods  A total of 430 subjects (275 male, 155 female) with Type 2 diabetes and early nephropathy (defined by UACR 30–300 mg/g creatinine) were included. One year was divided into four seasons and each season was defined as winter (December–February), spring (March–May), summer (June–August), and fall (September–November), and systolic and diastolic blood pressure, serum creatinine levels, and the urinary albumin/creatinine ratio were examined. The estimated glomerular filtration rate was also calculated and evaluated.

Results  The mean age (± SE) was 64.8 ± 0.8 years. The mean systolic blood pressure was significantly higher in winter than in summer (136 ± 0.68 vs. 133 ± 0.68 mmHg, P < 0.001). The urinary albumin/creatinine ratio showed a significantly higher value in winter than in summer (72.8 ± 4.4 vs. 54.6 ± 3.4 mg/g creatinine, P < 0.001). The curve of seasonal variation of this ratio showed a similar change to that of systolic blood pressure. No significant seasonal variation was observed in estimated glomerular filtration rate and diastolic blood pressure.

Conclusions  Our results suggest that there is a hitherto unknown seasonal variation in the urinary albumin/creatinine ratio, and that it may be necessary to consider this seasonal change, especially when performing an intervention study of nephropathy.
Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period
Authors: MCLINTOCK Claire , BRIGHTON Tim , CHUNILAL Sanjeev , DEKKER Gus , MCDONNELL Nolan , MCRAE Simon , MULLER Peter , TRAN Huyen , WALTERS Barry N.J. , YOUNG Laura
Published: October 2011

Venous thromboembolism (VTE) in pregnancy and the postpartum is an important cause of maternal morbidity and mortality; yet, there are few robust data from clinical trials to inform an approach to diagnosis and management. Failure to investigate symptoms suggestive of pulmonary embolism (PE) is a consistent finding in maternal death enquiries, and clinical symptoms should not be relied on to exclude or diagnose VTE. In this consensus statement, we present our recommendations for the diagnosis and management of acute deep venous thrombosis (DVT) and PE. All women with suspected DVT in pregnancy should be investigated with whole leg compression ultrasonography. If the scan is negative and significant clinical suspicion remains, then further imaging for iliofemoral DVT maybe required. Imaging should be undertaken in all women with suspected PE, as the fetal radiation exposure with both ventilation/perfusion scans and CT pulmonary angiography is within safe limits. Low‐molecular‐weight heparin (LMWH) is the preferred therapy for acute VTE that occur during pregnancy. In observational cohort studies, using once‐daily regimens appears adequate, in particular with the LMWH tinzaparin; however, pharmacokinetic data support twice‐daily therapy with other LMWH and is recommended, at least initially, for PE or iliofemoral DVT in pregnancy. Treatment should continue for a minimum duration of six months, and until at least six weeks postpartum. Induction of labour or planned caesarean section maybe required to allow an appropriate transition to unfractionated heparin to avoid delivery in women in therapeutic doses of anticoagulation.
Timing versus Buy and Hold: A Model for Determining Predictive Accuracy Required for Superior Performance
Authors: Hilliard Jimmy E. , Hilliard Jitka
Published: October 2011

In this application, we develop a model to simulate the decisions of a trader whose subjective distribution of returns may be correlated with realized stock returns. Using empirically estimated parameters from stocks in the CRSP database, we obtain performance data on a number of measures, including mean returns, volatility, the Sharpe measure, and the probability of a correct trading decision. The model suggests that daily trading of a portfolio of 20 volatile stocks gives a Sharpe measure better than that of buying and holding the S&P 500 when timing accuracy is 53% or better.
Board Independence and Mutual Fund Manager Turnover
Authors: Fu Richard , Wedge Lei
Published: October 2011

This paper studies the relationship between board independence and manager turnover in the mutual fund industry. Using the Lipper 2003 mutual fund board data, we find that manager turnover is more likely to happen to funds with poor prior performance and more independent boards. Consistent with previous studies such as Tufano and Sevick (1997), our research provides new evidence in support of the Securities and Exchange Commission's approach of improving fund governance by promoting board independence.
Determinants of the Method of Payment in Asset Sell‐Off Transactions
Authors: Cao Kien , Madura Jeff
Published: October 2011

Using a sample of asset sell‐off transactions from January 1990 to April 2010, we find that the method of payment used in asset sell‐off transactions is associated with several characteristics cited in the acquisitions research that reflect cash constraints of the bidder. Specifically, bidders facing more stringent cash constraints are more likely to use equity when purchasing assets, while sellers subjected to cash constraints prefer cash when selling assets. Second, we find that the variation in method of payment among asset sell‐off transactions also is partially explained by variables representing asymmetric information. Third, we apply our model to an expanded sample that includes non‐U.S. sellers of assets and find that an equity payment is more likely when sellers are based in countries that have relatively high country risk (more government restrictions), weak shareholder rights, and a weak legal system. Thus, it appears that bidders prefer that sellers share in the risk of the transaction under these conditions.
HSP70i is a critical component of the immune response leading to vitiligo
Authors: Mosenson Jeffrey A. , Zloza Andrew , Klarquist Jared , Barfuss Allison J. , Guevara‐Patino Jose A. , Le Poole I. Caroline
Published: October 2011

HSP70i and other stress proteins have been used in anti‐tumor vaccines. This begs the question whether HSP70i plays a unique role in immune activation. We vaccinated inducible HSP70i (Hsp70‐1) knockout mice and wild‐type animals with optimized TRP‐1, a highly immunogenic melanosomal target molecule. We were unable to induce robust and lasting depigmentation in the Hsp70‐1 knockout mice, and in vivo cytolytic assays revealed a lack of cytotoxic T‐lymphocyte activity. Absence of T‐cell infiltration to the skin and maintenance of hair follicle melanocytes were observed. By contrast, depigmentation proceeded without interruption in mice lacking a tissue‐specific constitutive isoform of HSP70 (Hsp70‐2) vaccinated with TRP‐2. Next, we demonstrated that HSP70i was necessary and sufficient to accelerate depigmentation in vitiligo‐prone Pmel‐1 mice, accompanied by lasting phenotypic changes in dendritic cell subpopulations. In summary, these studies assign a unique function to HSP70i in vitiligo and identify HSP70i as a targetable entity for treatment.
An Old Friend in a New Light: The Role of Osteocalcin in Energy Metabolism
Authors: Sullivan Tim R. , Duque Gustavo , Keech Anthony C. , Herrmann Markus
Published: October 2011

Accumulating evidence suggests interactions between bone and energy metabolism, which may affect the risk of cardiovascular disease. Recent animal studies indicate that osteocalcin (OC) plays a key role in the coordinated regulation of glucose and insulin metabolism while insulin receptors on osteoblasts may regulate bone turnover and circulating OC levels. Association studies, weight loss interventions, and observational data lend some support to the existence and relevance of these mechanisms in humans. However, corroborating evidence from pharmacologic interventions in either bone or glucose metabolism is limited by the number, design, and complex pharmacological effects of the drugs used. Furthermore, such clinical trials are complicated by the alteration of metabolic feedback mechanisms in the insulin resistant state. Purpose‐designed studies are needed to further establish the existence and significance of the role of OC and its subfractions in human insulin metabolism. In this review we summarize existing animal evidence regarding the role of OC and its subfractions in bone and energy metabolism and assess current clinical trial evidence relating to the significance and consequences of this relationship in humans.
A 3D Finite Element Study of Fatigue Life Dispersion in Rolling Line Contacts
Authors: Weinzapfel Nick , Sadeghi Farshid , Bakolas Vasilios , Liebel Alexander
Published: October 2011

Rolling contact fatigue of rolling element bearings is a statistical phenomenon that is strongly affected by the heterogeneous nature of the material microstructure. Heterogeneity in the microstructure is accompanied by randomly distributed weak points in the material that lead to scatter in the fatigue lives of an otherwise identical lot of rolling element bearings. Many life models for rolling contact fatigue are empirical and rely upon correlation with fatigue test data to characterize the dispersion of fatigue lives. Recently developed computational models of rolling contact fatigue bypass this requirement by explicitly considering the microstructure as a source of the variability. This work utilizes a similar approach but extends the analysis into a 3D framework. The bearing steel microstructure is modeled as randomly generated Voronoi tessellations wherein each cell represents a material grain and the boundaries between them constitute the weak planes in the material. Fatigue cracks initiate on the weak planes where oscillating shear stresses are the strongest. Finite element analysis is performed to determine the magnitude of the critical shear stress range and the depth where it occurs. These quantities exhibit random variation due to the microstructure topology which in turn results in scatter in the predicted fatigue lives. The model is used to assess the influence of (1) topological randomness in the microstructure, (2) heterogeneity in the distribution of material properties, and (3) the presence of inherent material flaws on relative fatigue lives. Neither topological randomness nor heterogeneous material properties alone account for the dispersion seen in actual bearing fatigue tests. However, a combination of both or the consideration of material flaws brings the model’s predictions within empirically observed bounds. Examination of the critical shear stress ranges with respect to the grain boundaries where they occur reveals the orientation of weak planes most prone to failure in a three-dimensional sense that was not possible with previous models.
Loss of solutions in shear banding fluids driven by second normal stress differences
Authors: Skorski S. , Olmsted P. D.
Published: October 2011

Edge fracture occurs frequently in non-Newtonian fluids. A similar instability has often been reported at the free surface of fluids undergoing shear banding and leads to expulsion of the sample. In this paper, the distortion of the free surface of such a shear banding fluid is calculated by balancing the surface tension against the second normal stresses induced in the two shear bands, and simultaneously requiring a continuous and smooth meniscus. We show that wormlike micelles typically retain meniscus integrity when shear banding, but in some cases can lose integrity for a range of average applied shear rates during which one expects shear banding. This meniscus fracture would lead to ejection of the sample as the shear banding region is swept through. We further show that entangled polymer solutions are expected to display a propensity for fracture because of their much larger second normal stresses. These calculations are consistent with available data in the literature. We also estimate the meniscus distortion of a three-band configuration, as has been observed in some wormlike micellar solutions in a cone and plate geometry.
Dispersible Exfoliated Zeolite Nanosheets and Their Application as a Selective Membrane
Authors: Varoon Agrawal Kumar , Zhang Xueyi , Elyassi Bahman , Brewer Damien D. , Gettel Melissa , Kumar Sandeep , Lee J. Alex , Maheshwari Sudeep , Mittal Anudha , Sung Chun-Yi , Cococcioni Matteo , Francis Lorraine F. , McCormick Alon V. , Mkhoyan K. Andre , Tsapatsis Michael
Published: October 2011

Thin zeolite films prepared through a polymer exfoliation method were used as selective membranes.
Novel One-Step Method for Detection and Isolation of Active-Toxin-Producing Clostridium difficile Strains Directly from Stool Samples
Authors: Darkoh Charles , DuPont Herbert L. , Kaplan Heidi B.
Published: October 2011

The alarming emergence of hypervirulent strains of
Clostridium difficile
with increased toxin production, severity of disease, morbidity, and mortality emphasizes the need for a culture method that permits simultaneous isolation and detection of virulent strains. The
C. difficile
toxins A and B are critical virulence factors, and strains can either be toxin-producing (virulent) or non-toxin-producing (nonvirulent). Strains that are isolated from human infections generally produce either toxin A or toxin B or both. The methods currently available for culturing
C. difficile
do not differentiate strains that produce active toxins from strains that do not produce toxins or produce inactive toxins. As a result, the identification and isolation of toxin-producing strains from stool is currently a two-step process. First, the stool is plated on a selective medium, and then suspected colonies are analyzed for toxin production or the presence of the toxin genes. We describe here a novel selective and differential culture method, the Cdifftox plate assay, which combines in a single step the specific isolation of
C. difficile
strains and the detection of active toxin. This assay was developed based on our recent finding that the A and B toxins of
C. difficile
cleave chromogenic substrates that have stereochemical characteristics similar to their natural substrate, UDP-glucose. The Cdifftox plate assay is shown here to be extremely accurate (99.8% effective) in detecting toxin-producing strains through the analysis of 528
C. difficile
isolates selected from 50 tissue culture cytotoxicity assay-positive clinical stool samples. The Cdifftox plate assay advances and improves the culture approach such that only
C. difficile
strains will grow on this agar, and virulent strains producing active toxins can be differentiated from nonvirulent strains, which do not produce active toxins. This new method reduces the time and effort required to isolate and confirm toxin-producing
C. difficile
strains.
Original Findings Associated with Two Cases of Bovine Papular Stomatitis
Authors: Dal Pozzo F. , Martinelle L. , Gallina L. , Mast J. , Sarradin P. , Thiry E. , Scagliarini A. , Büttner M. , Saegerman C.
Published: October 2011

Bovine papular stomatitis virus was isolated from two calves in an animal house with biosafety level 3 confinement. The hypotheses on the origin of the infection, the interesting features of the partial amino acid sequences of the major envelope viral protein, and the importance of diagnostic tools available for animal diseases that are not listed by the World Organization for Animal Health (OIE) are discussed.
KINETIC ENERGY DRIVEN SUPERCONDUCTIVITY AND SUPERFLUIDITY
Authors: HIRSCH J. E.
Published: October 2011

The theory of hole superconductivity proposes that superconductivity is driven by lowering of quantum kinetic energy and is associated with expansion of electronic orbits and expulsion of negative charge from the interior to the surface of superconductors and beyond. This physics provides a dynamical explanation of the Meissner effect. Here we propose that similar physics takes place in superfluid helium 4. Experimental manifestations of this physics in 4 He are the negative thermal expansion of 4 He below the λ point and the "Onnes effect", the fact that superfluid helium will creep up the walls of the container and escape to the exterior. The Onnes effect and the Meissner effect are proposed to originate in macroscopic zero point rotational motion of the superfluids. It is proposed that this physics indicates a fundamental inadequacy of conventional quantum mechanics.
Skeletal muscle regeneration is delayed by reduction in Xin expression: consequence of impaired satellite cell activation?
Authors: Nissar Aliyah A. , Zemanek Bart , Labatia Rita , Atkinson Daniel J. , van der Ven Peter F. M. , Fürst Dieter O. , Hawke Thomas J.
Published: October 2011

Xin is a striated muscle-specific actin-binding protein whose mRNA expression has been observed in damaged skeletal muscle. Here we demonstrate increased Xin protein expression early postinjury (≤12 h) and localization primarily to the periphery of damaged myofibers. At 1 day postinjury, Xin is colocalized with MyoD, confirming expression in activated satellite cells (SCs). By 5 days postinjury, Xin is evident in newly regenerated myofibers, with a return to preinjury levels by 14 days of regeneration. To determine whether the increased Xin expression is functionally relevant, tibialis anterior muscles of wild-type mice were infected with Xin-short hairpin RNA (shRNA) adenovirus, whereas the contralateral tibialis anterior received control adenovirus (Control). Four days postinfection, muscles were harvested or injured with cardiotoxin and collected at 3, 5, or 14 days thereafter. When compared with Control, Xin-shRNA infection attenuated muscle regeneration as demonstrated by Myh3 expression and fiber areas. Given the colocalization of Xin and MyoD, we isolated single myofibers from infected muscles to investigate the effect of silencing Xin on SC function. Relative to Control, SC activation, but not proliferation, was significantly impaired in Xin-shRNA-infected muscles. To determine whether Xin affects the G0-G1 transition, cell cycle reentry was assessed on infected C2C12 myoblasts using a methylcellulose assay. No difference in reentry was noted between groups, suggesting that Xin contributes to SC activation by means other than affecting G0-G1 transition. Together these data demonstrate a critical role for Xin in SC activation and reduction in Xin expression results in attenuated skeletal muscle repair.
High glucose-induced RhoA activation requires caveolae and PKCβ1-mediated ROS generation
Authors: Zhang Y. , Peng F. , Gao B. , Ingram A. J. , Krepinsky J. C.
Published: October 2011

Glomerular matrix accumulation is a hallmark of diabetic nephropathy. We previously showed that RhoA activation by high glucose in mesangial cells (MC) leads to matrix upregulation (Peng F, Wu D, Gao B, Ingram AJ, Zhang B, Chorneyko K, McKenzie R, Krepinsky JC. Diabetes 57: 1683–1692, 2008). Here, we study the mechanism whereby RhoA is activated. In primary rat MC, RhoA activation required glucose entry and metabolism. Broad PKC inhibitors (PMA, bisindolylmaleimide, Gö6976), as well as specific PKCβ blockade with an inhibitor and small interfering RNA (siRNA), prevented RhoA activation by glucose. PKCβ inhibition also abrogated reactive oxygen species (ROS) generation by glucose. The ROS scavenger N-acetylcysteine (NAC) or NADPH oxidase inhibitors apocynin and DPI prevented glucose-induced RhoA activation. RhoA and some PKC isoforms localize to caveolae. Chemical disruption of these microdomains prevented RhoA and PKCβ1 activation by glucose. In caveolin-1 knockout cells, glucose did not induce RhoA and PKCβ1 activation; these responses were rescued by caveolin-1 reexpression. Furthermore, glucose-induced ROS generation was significantly attenuated by chemical disruption of caveolae and in knockout cells. Downstream of RhoA signaling, activator protein-1 (AP-1) activation was also inhibited by disrupting caveolae, was absent in caveolin-1 knockout MC and rescued by caveolin-1 reexpression. Finally, transforming growth factor (TGF)-β1 upregulation, mediated by AP-1, was prevented by RhoA signaling inhibition and by disruption or absence of caveolae. In conclusion, RhoA activation by glucose is dependent on PKCβ1-induced ROS generation, most likely through NADPH oxidase. The activation of PKCβ1 and its downstream effects, including upregulation of TGF-β1, requires caveolae. These microdomains are thus important mediators of the profibrogenic process associated with diabetic nephropathy.
V̇o2 on-kinetics in isolated canine muscle in situ during slowed convective O2 delivery
Authors: Goodwin Matthew L. , Hernández Andrés , Lai Nicola , Cabrera Marco E. , Gladden L. Bruce
Published: October 2011

The purpose of this study was to examine O2 uptake (V̇o2) on-kinetics when the spontaneous blood flow (and therefore O2 delivery) on-response was slowed by 25 and 50 s. The isolated gastrocnemius muscle complex (GS) in situ was studied in six anesthetized dogs during transitions from rest to a submaximal metabolic rate (≈50–70% of peak V̇o2). Four trials were performed: 1) a pretrial in which resting and steady-state blood flows were established, 2) a control trial in which the blood flow on-kinetics mean response time (MRT) was set at 20 s (CT20), 3) an experimental trial in which the blood flow on-kinetics MRT was set at 45 s (EX45), and 4) an experimental trial in which the blood flow on-kinetics MRT was set at 70 s (EX70). Slowing O2 delivery via slowing blood flow on-kinetics resulted in a linear slowing of the V̇o2 on-kinetics response ( R = 0.96). Average MRT values for CT20, EX45, and EX70 V̇o2 on-kinetics were (means ± SD) 17 ± 2, 23 ± 4, and 26 ± 3 s, respectively ( P < 0.05 among all). During these transitions, slowing blood flow resulted in greater muscle deoxygenation (as indicated by near-infrared spectroscopy), suggesting that lower intracellular Po2 values were reached. In this oxidative muscle, V̇o2 and O2 delivery were closely matched during the transition period from rest to steady-state contractions. In conjunction with our previous work showing that speeding O2 delivery did not alter V̇o2 on-kinetics under similar conditions, it appears that spontaneously perfused skeletal muscle operates at the nexus of sufficient and insufficient O2 delivery in the transition from rest to contractions.
Self‐Commutators of Composition Operators with Monomial Symbols on the Dirichlet Space
Authors: Abdollahi A. , Mehrangiz S.
Published: October 2011

Let φ(z) = zn, z ∈ 𝕌, for some positive integer n and Cφ the composition operator on the Dirichlet space 𝒟 induced by φ. In this paper, we completely determine the point spectrum, spectrum, essential spectrum, and essential norm of the operators and self‐commutators of Cφ, which expose that the spectrum and point spectrum coincide. We also find the eigenfunctions of the operators.
Novel Histone Demethylase LSD1 Inhibitors Selectively Target Cancer Cells with Pluripotent Stem Cell Properties
Authors: Wang Jing , Lu Fei , Ren Qi , Sun Hong , Xu Zhengshuang , Lan Rongfeng , Liu Yuqing , Ward David , Quan Junmin , Ye Tao , Zhang Hui
Published: October 2011

Histone modification determines epigenetic patterns of gene expression with methylation of histone H3 at lysine 4 (H3K4) often associated with active promoters. LSD1/KDM1 is a histone demethylase that suppresses gene expression by converting dimethylated H3K4 to mono- and unmethylated H3K4. LSD1 is essential for metazoan development, but its pathophysiologic functions in cancer remain mainly uncharacterized. In this study, we developed specific bioactive small inhibitors of LSD1 that enhance H3K4 methylation and derepress epigenetically suppressed genes in vivo. Strikingly, these compounds inhibited the proliferation of pluripotent cancer cells including teratocarcinoma, embryonic carcinoma, and seminoma or embryonic stem cells that express the stem cell markers Oct4 and Sox2 while displaying minimum growth-inhibitory effects on non-pluripotent cancer or normal somatic cells. RNA interference–mediated knockdown of LSD1 expression phenocopied these effects, confirming the specificity of small molecules and further establishing the high degree of sensitivity and selectivity of pluripotent cancer cells to LSD1 ablation. In support of these results, we found that LSD1 protein level is highly elevated in pluripotent cancer cells and in human testicular seminoma tissues that express Oct4. Using these novel chemical inhibitors as probes, our findings establish LSD1 and histone H3K4 methylation as essential cancer-selective epigenetic targets in cancer cells that have pluripotent stem cell properties. Cancer Res; 71(23); 7238–49. ©2011 AACR.
Circulating Markers of Interstitial Lung Disease and Subsequent Risk of Lung Cancer
Authors: Shiels Meredith S. , Chaturvedi Anil K. , Katki Hormuzd A. , Gochuico Bernadette R. , Caporaso Neil E. , Engels Eric A.
Published: October 2011

Background: Inflammation and pulmonary diseases, including interstitial lung diseases, are associated with increased lung cancer risk. Circulating levels of surfactant protein-D (SP-D) and Krebs von Lungren-6 (KL-6) are elevated in interstitial lung disease patients and may be useful markers of processes contributing to lung cancer.

Methods: We conducted a nested case–control study, including 532 lung cancer cases, 582 matched controls, and 150 additional controls with chest X-ray (CXR) evidence of pulmonary scarring, in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serum SP-D and KL-6 levels were measured using enzyme immunoassay. Logistic regression was used to estimate the associations of SP-D and KL-6 with lung cancer and CXR scarring.

Results: Cases had higher levels than controls for SP-D (median 118.7 vs. 105.4 ng/mL, P = 0.008) and KL-6 (372.0 vs. 325.8 μg/mL, P = 0.001). Lung cancer risk increased with SP-D (Ptrend = 0.0003) and KL-6 levels (Ptrend = 0.005). Compared with the lowest quartile, lung cancer risk was elevated among those with the highest quartiles of SP-D (OR = 1.87, 95% CI: 1.32–2.64) or KL-6 (OR = 1.58, 95% CI: 1.11–2.25). Among controls, participants with CXR scarring were more likely than those without scarring to have elevated levels of SP-D (quartile 4 vs. quartile 1: OR = 1.67, 95% CI: 1.04–2.70, Ptrend = 0.05) but not of KL-6 (OR = 1.04, 95% CI: 0.64–1.68, Ptrend = 0.99).

Conclusion: Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk.

Impact: Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed. Cancer Epidemiol Biomarkers Prev; 20(10); 2262–72. ©2011 AACR.
Consideration of Quality of Life in Cancer Survivorship Research
Authors: Jacobsen Paul B. , Jim Heather S.L.
Published: October 2011

Quality of life assessment has a number of important applications in research on cancer survivors. These applications include use in observational studies to characterize the nature and extent of problems patients experience as well as use in randomized controlled trials to evaluate the relative impact of different cancer treatments or to evaluate the efficacy of interventions designed to improve patient well-being. The aims of this article are to provide an overview of the construct of quality of life and describe strategies commonly used to measure quality of life in adult cancer survivors. In addition, several priorities for future research are identified that involve how quality of life is measured, in whom it is measured, and what uses are made of quality of life data in the clinical care of cancer survivors. Cancer Epidemiol Biomarkers Prev; 20(10); 2035–41. ©2011 AACR.
Dental Caries Prevalence as a Product of Agriculture and Subsistence Pattern at the Yean-ri Site, South Korea
Authors: Fujita H. , Hashimoto H. , Shoda S. , Suzuki T.
Published: October 2011

Yean-ri human skeletal remains from South Korea have been dated to the fourth to seventh century AD. They have morphological similarities to immigrants of the Yayoi period excavated in northern Kyushu and Yamaguchi prefecture in Japan. The overall dental caries prevalence was 8.1% in the Yean-ri skeletal remains, indicating a much lower prevalence than that of most Yayoi immigrant skeletal remains from Japan, although similar to that of the Kofun people (8.3%) in Japan. There was no significant difference in the dental caries prevalence between the males and females of the same age group, but there were differences in the prevalence by age. The late middle age and elderly males and females had significantly higher dental caries prevalence than the early middle age males and females, indicating increased prevalence with age. Root caries prevalence tended to increase in old age. The percentage of root caries increased, accounting for 80% of all caries in Yean-ri human skeletal remains. Agriculture is believed to have arisen approximately 3,000 years ago in Korea. Therefore, agriculture was practiced during this period, but since the Yean-ri tumuli are from coastal areas, their diet may have retained a significant marine component. Additionally, caries prevalence was not very high in Nukdo human remains (ca. 2100–2000 BC) in Korea. We speculate that they maintained subsistence activities suitable for their environment despite their knowledge of agriculture. This hypothesis is supported by differences in the caries prevalence between excavation sites of the Yayoi and Kofun periods in Japan.
Establishing Pass/Fail Criteria for Bronchoscopy Performance
Authors: Konge Lars , Clementsen Paul , Larsen Klaus Richter , Arendrup Henrik , Buchwald Christian , Ringsted Charlotte
Published: October 2011

Background: Several tools have been created to assess competence in bronchoscopy. However, educational guidelines still use an arbitrary number of performed procedures to decide when basic competency is acquired. Objectives: The purpose of this study was to define pass/fail scores for two bronchoscopy assessment tools, and investigate how these scores relate to physicians’ experience regarding the number of bronchoscopy procedures performed. Methods: We studied two assessment tools and used two standard setting methods to create cut scores: the contrasting-groups method and the extended Angoff method. In the first we compared bronchoscopy performance scores of 14 novices with the scores of 14 experienced consultants to find the score that best discriminated between the two groups. In the second we asked an expert group of 7 experienced bronchoscopists to judge how a borderline trainee would perform on each item of the test. Results: Using the contrasting-groups method we found a standard that would fail all novices and pass all consultants. A clear pass related to prior experience of 75 procedures. The consequences of using the extended Angoff method were also acceptable: all trainees who had performed less than 50 bronchoscopies failed the test and all consultants passed. A clear pass related to 80 procedures. Conclusions: Our proposed pass/fail scores for these two methods seem appropriate in terms of consequences. Prior experience with the performance of 75 and 80 bronchoscopies, respectively, seemed to ensure basic competency. In the future objective assessment tools could become an important aid in the certification of physicians performing bronchoscopies.
Intra-articular injections of sodium hyaluronate (Hyalgan®) in osteoarthritis of the knee. a randomized, controlled, double-blind, multicenter trial in the asian population
Authors: Huang Teng-Le , Chang Chi-Ching , Lee Chian-Her , Chen Shih-Ching , Lai Chien-Hung , Tsai Ching-Lin
Published: October 2011

Background

The efficacy and tolerability of 500-730 kDa sodium hyaluronate (Hyalgan®) for treatment of osteoarthritis (OA) pain has been established in clinical trials, but few data are available in the Asian population. We conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and tolerability of this preparation in a Taiwanese population.

Methods

Two hundred patients with mild to moderate OA of the knee were randomized to receive five weekly intra-articular injections of sodium hyaluronate or placebo. The primary efficacy outcome was the change from baseline to Week 25 in patients' evaluation of pain using a 100-mm visual analog scale (VAS) during the 50-foot walking test. Additional outcomes included Western Ontario and McMaster Universities (WOMAC) scores, time on the 50-foot walking test, patient's and investigator's subjective assessment of effectiveness, acetaminophen consumption, and the amounts of synovial fluid.

Results

The Hyalgan® treatment group showed a significantly greater improvement from baseline to Week 25 in VAS pain on the 50-foot walking test than the placebo group (p = 0.0020). The Hyalgan® group revealed significant improvements from baseline to week 25 in WOMAC pain and function score than the placebo group (p = 0.005 and 0.0038, respectively) Other outcomes, such as time on the 50-foot walking test and subjective assessment of effectiveness, did not show any significant difference between groups. Both groups were safe and well tolerated.

Conclusions

The present study suggests that five weekly intra-articular injections of sodium hyaluronate are well tolerated, can provide sustained relief of pain, and can improve function in Asian patients with osteoarthritis of the knee.

Level of Evidence

Therapeutic study, Level I-1a (randomized controlled trial with a significant difference).

Trial registration

ClinicalTrials.gov Identifier: NCT01319461