bluuebunny/crossref_metadata_2025 huggingface dataset:
THE BIODIVERSITY OF THERMODURIC BACTERIA ISOLATED FROM WHEY
Authors: WALSH C. , MEADE J. , MCGILL K. , FANNING S.
Published: April 2012

Thermoduric gram‐positive bacteria are indigenous in milk, cheese, whey and other dairy products. They are capable of surviving heat processes and can result in quality defects and a shortened product shelf life. In Ireland, premium products such as whey protein concentrate (WPC) are often adversely affected by these microorganisms, particularly during the winter months. A high bacterial count in the WPC can result in the product being sold at a lower grade, with an overall loss of revenue for the manufacturer.

This study recovered thermoduric bacterial isolates (n = 140) from an Irish WPC process during the months of November–February. Using molecular 16S rRNA gene identification, Bacillus licheniformis, Microbacterium lacticum, Staphylococcus warneri, Enterococcus durans and Bacillus subtilis were recorded as the predominant microorganisms in this process line. This is the first known study to report the detection of Microbacterium phyllosphaerae, Neisseria subflava, Rothia aeria and Streptococcus mitis in dairy produce or indeed in any food product. The identification of bacteria at various stages of the WPC production process will support future measures in reducing/removing microorganisms from the process line in question and assist the dairy manufacturer in tackling this costly problem.

PRACTICAL APPLICATIONS

Through the use of 16S rRNA gene typing, we have accurately identified the bacteria that were present at various stages of the WPC production process in this facility. Molecular methods are not routinely used in this setting. Nonetheless, they can confer important advantages in terms of their accuracy and speed. These findings support a translated improvement in bacterial identification, allowing us to not only trace but also to strategically reduce/eliminate certain microflora from the production process. The latter step can have the effect of reducing the overall bacterial load of the matrix while simultaneously improving its shelf‐life characteristics. These findings will assist in the development of measures to improve the quality and safety of WPC production at this plant. This study highlights the potential benefits of using molecular techniques in a food processing environment.
Who Owns the Customer? Disentangling Customer Loyalty in Indirect Distribution Channels
Authors: Eggert Andreas , Henseler Jörg , Hollmann Sabine
Published: April 2012

Increasing levels of vertical competition make the possession of end customers' loyalty an issue of major concern for brand manufacturers and distributors alike. While we can rely on a solid body of knowledge on the drivers and outcomes of customer loyalty, empirical insights into the interplay between different forms of customer loyalty in channels of distribution remain limited, ambiguous and void of theoretical explanations. Based on a nationwide survey of customers in a detail‐intensive industry in the Netherlands and drawing on information integration theory and balance theory, this research identifies a positive and unidirectional spillover effect from customers' brand loyalty to distributor loyalty. Hence, distributors can “free ride” on a brand manufacturer's investments in customer loyalty. From the brand manufacturer's perspective, the loyalty spillover can have positive or negative consequences, depending on the level of vertical competition among channel members. While the spillover increases end customers' loyalty toward the channel, it decreases the brand manufacturer's odds of keeping end customers when it comes to the contest between a brand manufacturer and its distributor.
Operational Governance in Horizontal Cooperations of Logistics Service Providers: Performance Effects and the Moderating Role of Cooperation Complexity
Authors: Schmoltzi Christina , Wallenburg Carl Marcus
Published: April 2012

Various market challenges have led logistics service providers (LSPs) to engage in horizontal cooperations with each other, while maintaining their general legal independence. As an idiosyncrasy, horizontal cooperations entail the opposing forces of competition and cooperation, also referred to as “co‐opetition” (Bengtsson and Kock 2000; Tsai 2002). This constellation facilitates the development of opportunism and conflicts, which raise the risk of relationship failure. Adequate governance mechanisms provide a basis to avoid failure and drive cooperation success. This paper focuses on the postformation cooperation management phase and identifies the specific effects that operational governance has on cooperation commitment and cooperation effectiveness. Based on survey data from 226 LSP cooperations, we show that both formal and social governance mechanisms have a substantial performance effect. In this regard, the results differ fundamentally from studies on vertical buyer‐supplier relationships. With respect to the specific setup of the cooperation, a differentiated view is provided. Results indicate that two types of cooperation complexity are of relevance: organizational complexity and strategic complexity. The former drives the relevance of formal control; the latter increases the relevance of both formal and social control for cooperation success.
Humanitarian and Disaster Relief Supply Chains: A Matter of Life and Death
Authors: Day Jamison M. , Melnyk Steven A. , Larson Paul D. , Davis Edward W. , Whybark D. Clay
Published: April 2012

With an increasing number of disasters disrupting commerce and community life around the world, it is timely to position humanitarian and disaster relief supply chains (HDRSC) within the broad field of supply chain management. This article presents a framework to that end. It distinguishes attributes of the environment that illustrate the difficulties encountered in supply chain management. Although considerable research has been conducted in logistics issues affecting HDRSCs, very little management research speaks to the complicating attributes. Thus, this article describes activities such as demand determination, supply chain coordination, recognizing when to move along the life cycle and post‐disaster reconstruction that differentiates supply chain concerns from logistics concerns. From this backdrop, some of the areas where research into HDRSCs can inform supply chain management in general are presented. The article concludes by discussing critical areas of research need as identified by experienced practitioners. Research in these areas will provide insights for supply chain managers facing similar issues in other environments.
Analytical Solution for Well Design with Respect to Discharge Ratio
Authors: Holzbecher Ekkehard
Published: April 2012

For a well in the vicinity of a surface water body, a formula is developed that relates the share of bank filtrate on total pumpage, that is, the discharge ratio, on one side, to basic well and aquifer characteristics on the other. The application of the formula is demonstrated for solving the inverse problem: for an aimed discharge ratio, well characteristics (pumping rate, distance to shore) can be determined. Other useful applications of the formula are outlined.
Potential Contaminant Pathways from Hydraulically Fractured Shale to Aquifers
Authors: Myers Tom
Published: April 2012

Hydraulic fracturing of deep shale beds to develop natural gas has caused concern regarding the potential for various forms of water pollution. Two potential pathways—advective transport through bulk media and preferential flow through fractures—could allow the transport of contaminants from the fractured shale to aquifers. There is substantial geologic evidence that natural vertical flow drives contaminants, mostly brine, to near the surface from deep evaporite sources. Interpretative modeling shows that advective transport could require up to tens of thousands of years to move contaminants to the surface, but also that fracking the shale could reduce that transport time to tens or hundreds of years. Conductive faults or fracture zones, as found throughout the Marcellus shale region, could reduce the travel time further. Injection of up to 15,000,000 L of fluid into the shale generates high pressure at the well, which decreases with distance from the well and with time after injection as the fluid advects through the shale. The advection displaces native fluids, mostly brine, and fractures the bulk media widening existing fractures. Simulated pressure returns to pre‐injection levels in about 300 d. The overall system requires from 3 to 6 years to reach a new equilibrium reflecting the significant changes caused by fracking the shale, which could allow advective transport to aquifers in less than 10 years. The rapid expansion of hydraulic fracturing requires that monitoring systems be employed to track the movement of contaminants and that gas wells have a reasonable offset from faults.
DIFFERENTIAL SUSCEPTIBILITY? IMMIGRANT YOUTH AND PEER INFLUENCE*
Authors: DIPIETRO STEPHANIE M. , MCGLOIN JEAN MARIE
Published: April 2012

There is reason to suspect that lower levels of exposure to criminogenic peer‐based risks help explain why immigrant youth are less involved in crime and violence. However, it also is possible that if and when they do encounter these risks, immigrant youth are more vulnerable to them than are native‐born youth. Drawing from literature on the adaptation experiences of immigrant adolescents, we hypothesize that immigrant youth will be relatively more susceptible to the effects of both 1) exposure to deviant peers and 2) unstructured and unsupervised socializing with peers when compared with their nonimmigrant counterparts.
Using a sample of approximately 1,800 adolescents from the Project on Human Development in Chicago Neighborhoods (PHDCN) study, we find support for our first hypothesis but not the second.
Specifically, in both cross‐sectional and longitudinal models, we find that exposure to deviant peers has a greater impact on violence among immigrant youth than it does for native‐born youth. Furthermore, this pattern of results is supported with supplemental, sensitivity analysis using the AddHealth data. In contrast, there are no statistically significant differences across immigrant generation status with regard to the effect of informal socializing with peers on violence.
Altered re‐excitation thresholds and conduction of extrasystolic action potentials contribute to arrhythmogenicity in murine models of long QT syndrome
Authors: Duehmke R. M. , Pearcey S. , Stefaniak J. D. , Guzadhur L. , Jeevaratnam K. , Costopoulos C. , Pedersen T. H. , Grace A. A. , Huang C. L.‐H.
Published: April 2012

Aim

QT interval prolongation reflecting delayed action potential (AP) repolarization is associated with polymorphic ventricular tachycardia and early after depolarizations potentially initiating extrasystolic APs if of sufficient amplitude. The current experiments explored contributions of altered re‐excitation thresholds for, and conduction of, such extrasystolic APs to arrhythmogenesis in Langendorff‐perfused, normokalaemic, control wild‐type hearts and two experimental groups modelling long QT (LQT). The two LQT groups consisted of genetically modified, Scn5a
+/Δ

KPQ
and hypokalaemic wild‐type murine hearts.

Methods

Hearts were paced from their right ventricles and monophasic AP electrode recordings obtained from their left ventricular epicardia, with recording and pacing electrodes separated by 1 cm. An adaptive programmed electrical stimulation protocol applied pacing (S1) stimulus trains followed by premature (S2) extrastimuli whose amplitudes were progressively increased with progressive decrements in S1S2 interval to maintain stimulus capture. Such protocols culminated in either arrhythmic or refractory endpoints.

Results

Arrhythmic outcomes were associated with (1) lower conduction velocities in their initiating extrasystolic APs than refractory outcomes and (2) higher conduction velocities in the LQT groups than in controls. Furthermore, (3) the endpoints were reached at longer S1S2 coupling intervals and with smaller stimulus amplitudes in the LQT groups compared with controls. This was despite (4) similar relationships between conduction velocity and S1S2 coupling interval and between re‐excitation thresholds and S1S2 coupling interval in all three experimental groups.

Conclusions

Arrhythmias induced by extrasystolic APs in the LQT groups thus occur under conditions of higher conduction velocity and greater sensitivity to extrastimuli than in controls.
Postoperative pain and perioperative analgesic administration in dogs: practices, attitudes and beliefs of Queensland veterinarians
Authors: Weber GH , Morton JM , Keates H
Published: April 2012

Objective The aim of this study was to describe the practices, attitudes and beliefs of Queensland veterinarians in relation to postoperative pain and perioperative analgesia in dogs.

Methods One veterinarian from each of the 50 randomly selected Queensland veterinary practices was enrolled after selection by convenience sampling.

Results The study response rate was 94.3%. Demeanour, vocalisation and heart rate were the most common postoperative pain assessment tools used, even though the most sensitive tools were considered to be demeanour, heart rate and respiratory rate. Only 20% of respondents used formalised pain scoring systems. Preoperative analgesic administration was always used by 72% of respondents. There was marked variability in the frequency with which analgesia was administered perioperatively for ovariohysterectomy. Only 24% of veterinarians discharged animals with ongoing analgesia even though 38% agreed that pain is still present 7 days postoperatively. Multimodal analgesia was used by 82% of respondents. Epidural and local anaesthetic analgesic techniques were not being utilised by any respondents.

Conclusions These results indicate that management of postoperative pain in dogs in Queensland is frequently suboptimal and, at times, is not consistent with the veterinarian's attitudes and beliefs. Continuing education into analgesic use and pain evaluation may be effective in addressing this.
Waterbird movement across the Great Dividing Range and implications for arbovirus irruption into southern Victoria
Authors: Guay P‐J , Azuolas JK , Warner S
Published: April 2012

Background  Waterbirds are the major hosts of various arboviruses. Murray Valley encephalitis virus (MVEV) is an arbovirus native to northern Australia, the major hosts of which are Phalacrocoraciformes (cormorants), Ciconiiformes (herons) and other waterbirds. MVEV is transmitted to humans by mosquitoes and can cause acute encephalomyelitis. In Victoria, MVEV is restricted to the northern side of the Great Dividing Range (GDR), suggesting that waterbirds cannot cross the high country.

Methods and results  We tested this hypothesis by analysing data on waterbird banding and recovery and discovered that 12 species can cross the GDR.

Conclusion  Waterbirds have the potential to carry arboviruses, including MVEV, into southern Victoria.
Socioeconomic status and self‐reported oral health in Iranian adolescents: the role of selected oral health behaviors and psychological factors
Authors: Ravaghi Vahid , Underwood Martin , Marinho Valeria , Eldridge Sandra
Published: April 2012

Objectives: This study investigated health inequality for self‐reported oral health outcomes among adolescents. The role of oral health behaviors and psychological factors in explaining oral health inequality was investigated using the hypothesis of mediation.

Methods: This was a cross‐sectional study that used self‐completed questionnaires. This study sampled 639 (315 male and 324 female) 15‐ to 17‐year‐old adolescents (second and third grade high school students) of both sexes in the city of Sanandaj in the province of Kurdistan, western Iran. Socioeconomic indicators of the study were subjective socioeconomic status, wealth index, and parental education. Oral health behaviors were measured as toothbrushing frequency, dental flossing frequency, and dental visits. Psychological factors were self‐esteem, anxiety, and depression. Self‐reported oral health outcomes were single item self‐rated oral health and the experience of dental pain. Regression analysis was used to test four conditions for the hypothesis of mediation.

Results: The results showed that the inequality is present in oral health for some pairs of relationships between socioeconomic status and oral health outcomes. Adjustment for oral health behaviors and psychological factors, individually and simultaneously, led to loss of statistical significance for some pairs of the relationships. However, adjustment for oral health behaviors and psychological factors led to only small changes in the associations between socioeconomic status and self‐reported oral health outcomes.

Conclusions: This study found a graded oral health inequality, but no strong evidence to support the hypothesis that oral health behaviors and psychological factors mediate oral health inequality for self‐reported oral health outcomes.
Caregiver acceptability and preferences for preventive dental treatments for young African‐American children
Authors: Adams Sally H. , Rowe Corie R. , Gansky Stuart A. , Cheng Nancy F. , Barker Judith C. , Hyde Susan
Published: April 2012

Our prior research focused on parental treatment acceptability (TA) and treatment preferences (TPs) for preventive dental treatments for young Hispanic children. We adapted the interview for administration to parents of young African‐American children.

Objective: In a sample of African‐American parents, determine parental TA and TP for five dental treatments to prevent early childhood caries.

Methods: Interviewed 48 parents/caregivers of African‐American children attending Head Start, assessing TA and TP for three treatments for children: toothbrushing (TB) with fluoride toothpaste, fluoride varnish (FV), and xylitol in food (XF); and two treatments for mothers: xylitol gum (XG) and chlorhexidine (CHX) rinse. The interview included verbal information, illustrated treatment cards, photos/video clips, and samples. Parents provided TA of each treatment (one to five scale), TP between each of 10 pairs of the five treatments, and open‐ended reasons for their preferences. TPs were summed (zero to four) to create overall preference.

Results: All treatments were acceptable (means 4.4‐4.9). TB was more acceptable than FV and XF (P < 0.05). Summed TP revealed a strong preference for TB (mean 3.1) above other treatments (all P < 0.01). Primary reasons for preferring TB were the following: promotes healthy habits; child focused; and effectiveness.

Conclusions: All treatments were acceptable, however, parents/guardians strongly preferred TB. Parents' emphasis on healthy habits and child‐focused treatment supports efforts for oral health education programs in early childhood settings. Some parents expressed concerns about FV, XF, and CHX. Results may be useful in planning prevention programs for young children in African‐American communities.
Short‐ and long‐term results following standing fracture repair in 34 horses
Authors: Payne R. J. , Compston P. C.
Published: April 2012

Reasons for performing study:Standing fracture repair in the horse is a recently described surgical procedure and currently there are few follow‐up data. This case series contains 2 novel aspects in the standing horse: repair of incomplete sagittal fractures of the proximal phalanx and medial condylar repair from a lateral aspect.

Objectives:To describe outcome in a case series of horses that had lower limb fractures repaired under standing sedation at Rossdales Equine Hospital.

Method:Case records for all horses that had a fracture surgically repaired, by one surgeon at Rossdales Equine Hospital, under standing sedation and local anaesthesia up until June 2011, were retrieved. Hospital records, owner/trainer telephone questionnaire and the Racing Post website were used to evaluate follow‐up.

Results:Thirty‐four horses satisfied the inclusion criteria. Fracture sites included the proximal phalanx (incomplete sagittal fracture, n = 14); the third metacarpal bone (lateral condyle, n = 12, and medial condyle, n = 7); and the third metatarsal bone (lateral condyle, n = 1). One horse required euthanasia due to caecal rupture 10 days post operatively. Twenty horses (66.7% of those with available follow‐up) have returned to racing. Where available, mean time from operation to return to racing was 226 days (range 143–433 days).

Conclusions:Standing fracture repair produced similar results to fracture repair under general anaesthesia in terms of both the number of horses that returned to racing and the time between surgery and race.

Potential relevance:Repair of lower limb fracture in the horse under standing sedation is a procedure that has the potential for tangible benefits, including avoidance of the inherent risks of general anaesthesia. The preliminary findings in this series of horses are encouraging and informative when discussing options available prior to fracture repair.
Reduction of motion artifacts during in vivo two‐photon imaging of brain through heartbeat triggered scanning
Authors: Paukert Martin , Bergles Dwight E.
Published: April 2012

Key points

Two‐photon fluorescence microscopy enables analysis of the structure and dynamic activity of different cell types in the brains of living animals at high temporal and spatial resolution.

Our ability to accurately resolve small structures, including dendrites and organelles in vivo, is hampered by pulsations in brain tissue that are caused by vital functions such as breathing and beating of the heart.

Here we show that beating of the heart is the major cause of brain pulsations in the cerebral cortex and find that synchronizing imaging scans to cardiac cycles significantly reduces motion artifacts.

We introduce a strategy (interlaced scanning) that enables electrocardiogram (ECG)‐triggered scanning of large brain volumes, and provide software for implementation of ECG‐triggered scanning on conventional two‐photon microscopes.

Abstract  Two‐photon imaging of fluorescence in brain enables analysis of the structure and dynamic activity of neurons and glial cells in living animals. However, vital functions such as beating of the heart cause pulsations in brain tissue, leading to image distortion and loss of resolution. We find that synchronizing imaging scans to the cardiac cycle reduces motion artifacts, significantly improving the resolution of cellular structures. By interlacing multiple heartbeat triggered imaging scans, it was possible to image large brain volumes with negligible distortion. This approach can be readily incorporated into conventional microscopes to achieve substantial reductions in motion artifacts during two‐photon imaging.
In an expanding universe, what doesn’t expand?
Authors: Price Richard H. , Romano Joseph D.
Published: April 2012

The expansion of the universe is often viewed as a uniform stretching of space that would affect compact objects such as atoms and stars, as well as the separation of galaxies. One usually hears that bound systems do not take part in the general expansion, but a much more subtle question is whether bound systems expand partially. In this paper, a definitive answer is given for a very simple system: a classical “atom” bound by electrical attraction. With a mathematical description appropriate for undergraduate physics majors, we show that this bound system either completely follows the cosmological expansion, or, after initial transients, completely ignores it. This all-or-nothing behavior can be understood using analysis techniques used in junior-level mechanics. We also demonstrate that this simple description is a justifiable approximation of the relativistically correct formulation of the problem.
Synthetic Signal Propagation Through Direct Cell-Cell Interaction
Authors: Matsuda Mitsuhiro , Koga Makito , Nishida Eisuke , Ebisuya Miki
Published: April 2012

An engineered system based on Notch and Delta in mammalian cultured cells recapitulates signal propagation, a phenomenon that occurs in development.
Computational Approaches for Analyzing Information Flow in Biological Networks
Authors: Kholodenko Boris , Yaffe Michael B. , Kolch Walter
Published: April 2012

Signaling network construction and analysis provide insights into biology and
medicine.
Worldwide Appraisal and Update (2010) of Telavancin Activity Tested against a Collection of Gram-Positive Clinical Pathogens from Five Continents
Authors: Mendes Rodrigo E. , Sader Helio S. , Farrell David J. , Jones Ronald N.
Published: April 2012

A total of 15,480 Gram-positive pathogens were collected from 89 sites in the United States, Europe, the Asia-Pacific region, and Latin America in 2010. Telavancin was active against indicated
Staphylococcus aureus
(MIC
50/90
, 0.12/0.25 μg/ml), vancomycin-susceptible
Enterococcus faecalis
(MIC
50/90
, 0.5/0.5 μg/ml), and beta-hemolytic (MIC
50/90
, 0.06/0.12 μg/ml) and viridans group streptococcus (MIC
50/90
, 0.03/0.06 μg/ml) isolates. These MIC results showed potency for telavancin equal to or greater than that of comparators. These
in vitro
data confirm a continued potent activity of telavancin when tested against contemporary Gram-positive clinical isolates.
In Vitro
Susceptibility of Pythium insidiosum Isolates to Aminoglycoside Antibiotics and Tigecycline
Authors: Mahl Deise Luiza , de Jesus Francielli Pantella Kunz , Loreto Érico Silva , Zanette Régis Adriel , Ferreiro Laerte , Pilotto Maiara Ben , Alves Sydney Hartz , Santurio Janio Morais
Published: April 2012

This study evaluated the
in vitro
activity of aminoglycoside antibiotics and tigecycline against
Pythium insidiosum
. The susceptibility tests were carried out using the broth microdilution method in accordance with the CLSI document M38-A2. MIC values for gentamicin, neomycin, paromomycin, and streptomycin ranged from 32 to 64 mg/liter, and the minimal fungicidal concentration (MFC) ranged from 32 to 128 mg/liter, which are incompatible with safe concentrations of these drugs in plasma
in vivo
. Tigecycline showed the lowest MIC (0.25 to 2 mg/liter) and MFC (1 to 8 mg/liter) range values. The
in vitro
susceptibility observed to tigecycline makes this drug a good option in future tests
in vitro
and
in vivo
for the management of pythiosis.
The Antidepressant Sertraline Provides a Promising Therapeutic Option for Neurotropic Cryptococcal Infections
Authors: Zhai Bing , Wu Cheng , Wang Linqi , Sachs Matthew S. , Lin Xiaorong
Published: April 2012

Therapeutic treatment for systemic mycoses is severely hampered by the extremely limited number of antifungals. The difficulty of treatment of fungal infections in the central nervous system is further compounded by the poor central nervous system (CNS) penetration of most antifungals due to the blood-brain barrier. Only a few fungistatic azole drugs, such as fluconazole, show reasonable CNS penetration. Here we demonstrate that sertraline (Zoloft), the most frequently prescribed antidepressant, displays potent antifungal activity against
Cryptococcus neoformans
, the major causative agent of fungal meningitis. In
in vitro
assays, this neurotropic drug is fungicidal to all natural
Cryptococcus
isolates tested at clinically relevant concentrations. Furthermore, sertraline interacts synergistically or additively with fluconazole against
Cryptococcus
. Importantly, consistent with our
in vitro
observations, sertraline used alone reduces the brain fungal burden at an efficacy comparable to that of fluconazole in a murine model of systemic cryptococcosis. It works synergistically with fluconazole in reducing the fungal burden in brain, kidney, and spleen. In contrast to its potency against
Cryptococcus
, sertraline is less effective against strains of
Candida
species and its interactions with fluconazole against
Candida
strains are often antagonistic. Therefore, our data suggest the unique application of sertraline against cryptococcosis. To understand the antifungal mechanisms of sertraline, we screened a whole-genome deletion collection of
Saccharomyces cerevisiae
for altered sertraline susceptibility. Gene ontology analyses of selected mutations suggest that sertraline perturbs translation.
In vitro
translation assays using fungal cell extracts show that sertraline inhibits protein synthesis. Taken together, our findings indicate the potential of adopting this antidepressant in treating cryptococcal meningitis.
UC781 Microbicide Gel Retains Anti-HIV Activity in Cervicovaginal Lavage Fluids Collected following Twice-Daily Vaginal Application
Authors: Haaland Richard E. , Evans-Strickfaden Tammy , Holder Angela , Pau Chou-Pong , McNicholl Janet M. , Chaikummao Supraporn , Chonwattana Wannee , Hart Clyde E.
Published: April 2012

The potent nonnucleoside reverse transcriptase inhibitor UC781 has been safety tested as a vaginal microbicide gel formulation for prevention of HIV-1 sexual transmission. To investigate whether UC781 retained anti-infective activity following exposure to the female genital tract, we conducted anex vivoanalysis of the UC781 levels and antiviral activity in cervicovaginal lavage (CVL) fluids from 25 Thai women enrolled in a 14-day safety trial of twice-daily vaginal application of two concentrations of the UC781 microbicide gel. CVL samples were collected from women in the 0.1% (n= 5), 0.25% (n= 15), and placebo (n= 5) gel arms following the first application of gel (T15 min) and 8 to 24 h after the final application (T8-24 h) and separated into cell-free (CVL-s) and pelletable (CVL-p) fractions. As UC781 is highly hydrophobic, there were significantly higher levels of UC781 in the CVL-p samples than in the CVL-s samples for the UC781 gel arms. InT8-24 hCVL-p samples, 2/5 and 13/15 samples collected from the 0.1% and 0.25% UC781 gel arms, respectively, efficiently blocked infection with ≥4 log1050% tissue culture infective dose (TCID50) of a CCR5-tropic CRF01_AE HIV-1 virus stock. Independent of the arm, the 11 CVL-p samples with UC781 levels of ≥5 μg/CVL sample reduced infectious HIV by ≥4 log10TCID50. Our results suggest that the levels and anti-infective activities of UC781 gel formulations are likely to be associated with a cellular or pelletable component in CVL samples. Therefore, cellular and pelletable fractions should be assayed for drug levels and anti-infective activity in preclinical studies of candidate microbicides.
The Anthelmintic Triclabendazole and Its Metabolites Inhibit the Membrane Transporter ABCG2/BCRP
Authors: Barrera Borja , Otero Jon A. , Egido Estefanía , Prieto Julio G. , Seelig Anna , Álvarez Ana I. , Merino Gracia
Published: April 2012

ABCG2/BCRP is an ATP-binding cassette transporter that extrudes compounds from cells in the intestine, liver, kidney, and other organs, such as the mammary gland, affecting pharmacokinetics and milk secretion of antibiotics, anticancer drugs, and other compounds and mediating drug-drug interactions. In addition, ABCG2 expression in cancer cells may directly cause resistance by active efflux of anticancer drugs. The development of ABCG2 modulators is critical in order to improve drug pharmacokinetic properties, reduce milk secretion of xenotoxins, and/or increase the effective intracellular concentrations of substrates. Our purpose was to determine whether the anthelmintic triclabendazole (TCBZ) and its main plasma metabolites triclabendazole sulfoxide (TCBZSO) and triclabendazole sulfone (TCBZSO
2
) inhibit ABCG2 activity. ATPase assays using human ABCG2-enriched membranes demonstrated a clear ABCG2 inhibition exerted by these compounds. Mitoxantrone accumulation assays using murine Abcg2- and human ABCG2-transduced MDCK-II cells confirmed that TCBZSO and TCBZSO
2
are ABCG2 inhibitors, reaching inhibitory potencies between 40 and 55% for a concentration range from 5 to 25 μM. Transepithelial transport assays of ABCG2 substrates in the presence of both TCBZ metabolites at 15 μM showed very efficient inhibition of the Abcg2/ABCG2-mediated transport of the antibacterial agents nitrofurantoin and danofloxacin. TCBZSO administration also inhibited nitrofurantoin Abcg2-mediated secretion into milk by more than 2-fold and increased plasma levels of the sulfonamide sulfasalazine by more than 1.5-fold in mice. These results support the potential role of TCBZSO and TCBZSO
2
as ABCG2 inhibitors to participate in drug interactions and modulate ABCG2-mediated pharmacokinetic processes.
In Vitro
Reconstitution of the Complete Clostridium thermocellum Cellulosome and Synergistic Activity on Crystalline Cellulose
Authors: Krauss Jan , Zverlov Vladimir V. , Schwarz Wolfgang H.
Published: April 2012

Artificial cellulase complexes active on crystalline cellulose were reconstituted
in vitro
from a native mix of cellulosomal enzymes and CipA scaffoldin. Enzymes containing dockerin modules for binding to the corresponding cohesin modules were prepared from culture supernatants of a
C. thermocellum cipA
mutant. They were reassociated to cellulosomes via dockerin-cohesin interaction. Recombinantly produced mini-CipA proteins with one to three cohesins either with or without the carbohydrate-binding module (CBM) and the complete CipA protein were used as the cellulosomal backbone. The binding between cohesins and dockerins occurred spontaneously. The hydrolytic activity against soluble and crystalline cellulosic compounds showed that the composition of the complex does not seem to be dependent on which CipA-derived cohesin was used for reconstitution. Binding did not seem to have an obvious local preference (equal binding to Coh1 and Coh6). The synergism on crystalline cellulose increased with an increasing number of cohesins in the scaffoldin. The
in vitro
-formed complex showed a 12-fold synergism on the crystalline substrate (compared to the uncomplexed components). The activity of reconstituted cellulosomes with full-size CipA reached 80% of that of native cellulosomes. Complexation on the surface of nanoparticles retained the activity of protein complexes and enhanced their stability. Partial supplementation of the native cellulosome components with three selected recombinant cellulases enhanced the activity on crystalline cellulose and reached that of the native cellulosome. This opens possibilities for
in vitro
complex reconstitution, which is an important step toward the creation of highly efficient engineered cellulases.
The Spx Regulator Modulates Stress Responses and Virulence in Enterococcus faecalis
Authors: Kajfasz Jessica K. , Mendoza Jorge E. , Gaca Anthony O. , Miller James H. , Koselny Kristy A. , Giambiagi-deMarval Marcia , Wellington Melanie , Abranches Jacqueline , Lemos José A.
Published: April 2012

The ability to cope with endogenous or host-generated reactive oxygen species is considered a key virulence attribute of the opportunistic pathogen
Enterococcus faecalis
, a leading cause of hospital-acquired infections. In this study, we used
in silico
and mutational analyses to identify and characterize the role of the Spx global regulator in oxidative stress tolerance and virulence in
E. faecalis
. While the Δ
spx
strain grew as well as the wild-type strain under anaerobic conditions, the mutant strain exhibited impaired growth under aerobic conditions and was highly sensitive to oxidative stress agents. The
spx
mutant strain was also sensitive to a variety of other stressful conditions, including antibiotic stress and killing by the mouse-derived macrophage cell line J774. Using a murine model of foreign body-associated peritonitis, we demonstrated that the ability of the Δ
spx
strain to colonize the peritoneum and disseminate in the bloodstream was significantly reduced compared to that of the parent strain. Transcriptional analysis revealed that a large number of known oxidative stress genes are under positive control by Spx. Collectively, our results show that Spx is a major stress gene regulator and is implicated in the pathophysiology of
E. faecalis
. The relationship of Spx to other oxidative stress regulators is also discussed.
Enhanced involvement of general practitioners in cancer rehabilitation: a randomised controlled trial
Authors: Bergholdt Stinne Holm , Larsen Pia Veldt , Kragstrup Jakob , Søndergaard Jens , Hansen Dorte Gilså
Published: April 2012

Objective

To test the hypothesis that a multimodal intervention giving the general practitioner (GP) an enhanced role in cancer rehabilitation improves patients' health-related quality of life and psychological distress.

Design

Cluster randomised controlled trial. All general practices in Denmark were randomised to an intervention group or to a control group. Patients were subsequently allocated to intervention or control (usual procedures) based on the randomisation status of their GP.

Setting

All clinical departments at a public regional hospital treating cancer patients and all general practices in Denmark.

Participants

Adult patients treated for incident cancer at Vejle Hospital, Denmark, between 12 May 2008 and 28 February 2009. A total of 955 patients (486 to the intervention group and 469 to the control group) registered with 323 general practices were included.

Intervention

The intervention included an interview about rehabilitation needs with a rehabilitation coordinator at the regional hospital, information from the hospital to the GP about individual needs for rehabilitation and an encouragement of the GP to contact the patient to offer his support with rehabilitation.

Main outcome measures

The primary outcome was health-related quality of life measured 6 months after inclusion using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Secondary outcomes included quality of life at 14 months and additional subscales of the EORTC QLQ-C30 at 6 and 14 months and psychological distress at 14 months using the Profile of Mood States Scale.

Results

No effect of the intervention was observed on primary and/or secondary outcomes after 6 and 14 months.

Conclusion

A multimodal intervention aiming to give the GP an enhanced role in cancer patients' rehabilitation did not improve quality of life or psychological distress.

Trial registration

ClinicalTrials.gov, registration ID numberNCT01021371.
Do adverts increase the probability of finding online cognitive behavioural therapy for depression? Cross-sectional study
Authors: Jones Ray B , Goldsmith Lesley , Hewson Paul , Kamel Boulos Maged N , Williams Christopher J
Published: April 2012

Objective

To estimate the effect of online adverts on the probability of finding online cognitive behavioural therapy (CBT) for depression.

Design

Exploratory online cross-sectional study of search experience of people in the UK with depression in 2011. (1) The authors identified the search terms over 6 months entered by users who subsequently clicked on the advert for online help for depression. (2) A panel of volunteers across the UK recorded websites presented by normal Google search for the term ‘depression’. (iii) The authors examined these websites to estimate probabilities of knowledgeable and naive internet users finding online CBT and the improved probability by addition of a Google advert.

Participants

(1) 3868 internet users entering search terms related to depression into Google. (2) Panel, recruited online, of 12 UK participants with an interest in depression.

Main outcome measures

Probability of finding online CBT for depression with/without an advert.

Results

The 3868 users entered 1748 different search terms but the single keyword ‘depression’ resulted in two-thirds of the presentations of, and over half the ‘clicks’ on, the advert. In total, 14 different websites were presented to our panel in the first page of Google results for ‘depression’. Four of the 14 websites had links enabling access to online CBT in three clicks for knowledgeable users. Extending this approach to the 10 most frequent search terms, the authors estimated probabilities of finding online CBT as 0.29 for knowledgeable users and 0.006 for naive users, making it unlikely CBT would be found. Adding adverts that linked directly to online CBT increased the probabilities to 0.31 (knowledgeable) and 0.02 (naive).

Conclusions

In this case, online CBT was not easy to find and online adverts substantially increased the chance for naive users. Others could use this approach to explore additional impact before committing to long-term Google AdWords advertising budgets.

Trial registration

This exploratory case study was a substudy within a cluster randomised trial, registered onhttp://www.clinicaltrials.gov(reference:NCT01469689). (The trial will be reported subsequently).
EFFECTS OF CP VIOLATING PHASES ON THE INVERSE NEUTRINOLESS DOUBLE BETA SCATTERING e-e- → W-W-
Authors: AKASLAN S. , YILMAZER A. U.
Published: April 2012

The most important open problems of the today's neutrino physics are the absolute values of the neutrino masses, the determination of the Dirac or the Majorana character and better measurements of the mixing matrix elements. Results of the neutrino oscillations experiments strongly confirm that the neutrinos have nonzero masses. Experiments give information about the differences between the squares of the masses but not any knowledge on their absolute values. Similarly neutrino oscillation phenomena does not help us to understand their Dirac or Majorana character. One of the processes that could clarify this important point is the double beta decay and the search is still going on but not yielded any positive results due to the big experimental difficulties. Also the inverse of this decay, e-e- → W-W- is another process that could be tested at the accelerators. This process is possible only if the neutrinos have masses and they are Majorana particles. Since neutrinos could have very tiny masses and the cross section of the above process is proportional to the square of the effective neutrino mass it is an extremely rare process. Also it violates total lepton number by two units, Δ = 2. In the literature the inverse neutrinoless double beta scattering have been extensively studied, in this article we obtain the relevant helicity amplitudes, investigate the effects of the neutrino mixing matrix elements, especially the roles of the CP violating phases and the possible CP asymmetries.
TWIST DEFORMATION OF DOUBLY ENLARGED NEWTON–HOOKE HOPF ALGEBRA
Authors: DASZKIEWICZ MARCIN
Published: April 2012

We provide 15 twist-deformed doubly enlarged Newton–Hooke quantum spacetimes. In τ approaching infinity limit the twisted doubly enlarged Galilei spaces are obtained as well.
THE BOUNDARY FACE METHOD WITH VARIABLE APPROXIMATION BY B-SPLINE BASIS FUNCTION
Authors: GU JINLIANG , ZHANG JIANMING , SHENG XIAOMIN
Published: April 2012

B-spline basis functions as a new approximation method is introduced in the boundary face method (BFM) to obtain numerical solutions of 3D potential problems. In the BFM, both boundary integration and variable approximation are performed in the parametric spaces of the boundary surfaces, therefore, keeps the exact geometric information of a body in which the problem is defined. In this paper, local bivariate B-spline functions are proposed to alleviate the influence of B-spline tensor product that will deteriorate the exactness of numerical results. Numerical tests show that the new method has well performance in both exactness and convergence.
OVERSET-RANS COMPUTATIONS OF TWO SURFACE SHIPS MOVING IN VISCOUS FLUIDS
Authors: WAN DECHENG , SHEN ZHIRONG
Published: April 2012

A structured overset grid approach coupled with Reynolds-Averaged Navier-Stokes (overset-RANS) method is presented to provide an accurate resolution of two surface ships moving with opposite velocity in viscous fluids. The RANS equations with shear stress transport (SST) k - ω model are employed to treat the viscous turbulent flows. The fully nonlinear boundary condition at the free surface is satisfied at each time step and the evolution of the free surface is achieved by using the level set method. A structured overset grid approach is used to allow flexibility in grid generation, local mesh refinement, as well as the simulation of moving objects while maintaining good grid quality. The presented overset-RANS method is demonstrated by two surface Wigley ship hulls moving with opposite velocity in still water. The simulating results illustrate the feasibility of the presented method to compute the complex viscous free surface flows interacting with many moving ships in still water or in waves.
Relationship between Concentration of Initiator and Image-Sticking Phenomenon of Polymer-Sustained-Alignment Liquid Crystal Displays
Authors: Nakanishi Yohei , Okamoto Kenji
Published: April 2012

We investigated the image-sticking phenomenon of polymer-sustained-alignment liquid crystal displays (PSA-LCDs). According to our experimental results, the image-sticking level of PSA-LCDs depends on the concentration of the photoinitiator in the liquid crystal of PSA-LCDs and the best concentration of the photoinitiator was zero. We found that polymerization of the monomer occurs without the photoinitiator, and clarified the mechanism of polymerization.
Electrostatic Properties of Organic Monolayers on Silicon Oxides Studied by Kelvin Probe Force Microscopy
Authors: Mishima Ryota , Loan Ngyuen Thu , Tada Hirokazu
Published: April 2012

The vacuum level (VL) shifts of pentacene (PEN), perfluoro-PEN (PFP), α,ω-dihexylsexithiophene (DH-6T) and N,N-ditridecyl-3,4,9,10-perylenetetracarboxylic diimide (PTCDI-C13) monolayers on SiO2 terminated with various chemical species were studied by Kelvin probe force microscopy (KPFM). The PEN and PFP monolayers deposited on OH– and CH3–SiO2 showed a downward VL shift, while those on CF3–SiO2 showed an upward VL shift. The VL shift is considered to originate not from the charge transfer but from the dipole induced in molecules by surface charges. The KPFM of the DH-6T and PTCDI-C13 monolayers on OH–SiO2 revealed that the alkyl chains between the π-system and SiO2 reduce the effect of surface charges. The structural asymmetry of these molecules causes the VL shift.
Theoretical Analysis on Mechanical Deformation of Membrane-Based Photomask Blanks
Authors: Marumoto Kenji , Aya Sunao , Yabe Hedeki , Okada Tatsunori , Sumitani Hiroaki
Published: April 2012

Membrane-based photomask is used in proximity X-ray lithography including that in LIGA (Lithographie, Galvanoformung und Abformung) process, and near-field photolithography. In this article, out-of-plane deformation (OPD) and in-plane displacement (IPD) of membrane-based photomask blanks are theoretically analyzed to obtain the mask blanks with flat front surface and low stress absorber film. First, we derived the equations of OPD and IPD for the processing steps of membrane-based photomask such as film deposition, back-etching and bonding, using a theory of symmetrical bending of circular plates with a coaxial circular hole and that of deformation of cylinder under hydrostatic pressure. The validity of the equations was proved by comparing the calculation results with experimental ones. Using these equations, we investigated the relation between the geometry of the mask blanks and the distortions generally, and gave the criterion to attain the flat front surface. Moreover, the absorber stress-bias required to obtain zero-stress on finished mask blanks was also calculated and it has been found that only little stress-bias was required for adequate hole size of support plate.
Synthesis of Nitrogen-Doped Graphene by Plasma-Enhanced Chemical Vapor Deposition
Authors: Terasawa Tomo-o , Saiki Koichiro
Published: April 2012

Synthesis of nitrogen-doped graphene on Cu foils by plasma-enhanced chemical vapor deposition (PE-CVD) and the growth mechanism of doped graphene were investigated. Nitrogen atoms are incorporated into the graphene lattice and most of them exist at a graphitic (quaternary) site. Plasma reaction facilitates the doping of nitrogen atoms even at a substrate temperature as high as 950 °C. Doped nitrogen atoms seem to distort the graphene lattice, which causes island-like growth rather than a layer-by-layer growth.