bluuebunny/crossref_metadata_2025 huggingface dataset:
Tools for visualizing and integrating pest risk assessment ratings and uncertainties*
Authors: Holt J. , Leach A. W. , Knight J. D. , Griessinger D. , MacLeod A. , van der Gaag D. J. , Schrader G. , Mumford J. D.
Published: April 2012

The application of pest risk analysis (PRA) decision‐support schemes, such as that used by the European and Mediterranean Plant Protection Organization (EPPO), generates many ratings for likelihood or magnitude of risk factors, each with an associated uncertainty. In accordance with the international standard ISPM 11 (FAO, 2004), questions have been devised to assess the key elements of pest risk in the four main sections of pest risk assessment: Entry, Establishment, Spread and Impact. After completing each section, risk assessors are required to give a summary rating and an uncertainty score for that section. The large number of question ratings and uncertainty scores make the task of summarizing each section and its uncertainty quite difficult. Two graphical tools have been developed to aid this task: the PRA Risk score and uncertainty visualizer (Visualizer) and the Rule‐based matrix model (RBMM). The Visualizer presents a case summary graph on a single page in such a way that the risk assessors and peer reviewers can see rating scores and uncertainties in a pictorial manner; the RBMM integrates all the individual questions in the assessment through a hierarchy of rules that attempt to mimic the logic used by the assessors and are arranged in the form of a flow chart to give an overall rating with an accompanying expression of uncertainty.
Phase‐dependent generation and transmission of time information by the KaiABC circadian clock oscillator through SasA‐KaiC interaction in cyanobacteria
Authors: Valencia S. J. , Bitou Kyouhei , Ishii Kentaro , Murakami Reiko , Morishita Megumi , Onai Kiyoshi , Furukawa Yukio , Imada Katsumi , Namba Keiichi , Ishiura Masahiro
Published: April 2012

Circadian clocks allow organisms to predict environmental changes of the day/night cycle. In the cyanobacterial circadian clock machinery, the phosphorylation level and ATPase activity of the clock protein KaiC oscillate with a period of approximately 24 h. The time information is transmitted from KaiC to the histidine kinase SasA through the SasA autophosphorylation‐enhancing activity of KaiC, ultimately resulting in genome‐wide transcription cycles. Here, we showed that SasA derived from the thermophilic cyanobacterium Thermosynechococcus elongatus BP‐1 has the domain structure of an orthodox histidine kinase and that its C‐terminal domain, which contains a phosphorylation site at His160, is responsible for the autophosphorylation activity and the temperature‐ and phosphorylation state‐dependent trimerization / hexamerization activity of SasA. SasA and KaiC associate through their N‐terminal domains with an affinity that depends on their phosphorylation states. Furthermore, the SasA autophosphorylation‐enhancing activity of KaiC requires the C‐terminal ATPase catalytic site and depends on its phosphorylation state. We show that the phosphotransfer activity of SasA is essential for the generation of normal circadian gene expression in cyanobacterial cells. Numerical simulations suggest that circadian time information (free phosphorylated SasA) is released mainly by unphosphorylated KaiC during the late subjective night.
Antioxidant, toxicity, and iridoid tests of processed Cornelian cherry fruits
Authors: West Brett J. , Deng Shixin , Jensen C. Jarakae , Palu Afa K. , Berrio Lincoln F.
Published: April 2012

The antioxidant activity, potential toxicity, and iridoid content of processed Cornelian cherry products were assessed. Cornus officinalis L. juice and Cornus mas L. fruit puree possessed antioxidant activity in the 2,2‐diphenylpicrylhydrazyl radical scavenging, reducing power and oxygen radical absorbance capacity assays. Both products were non‐genotoxic in reverse mutation tests in Salmonella typhimurium. Both C. officinalis juice and C. mas puree were non‐toxic in acute oral toxicity tests, with respective LD50 values >5100 mg kg−1 body weight (b.w.) and >5200 mg kg−1 b.w. The major iridoid identified in C. mas puree was loganic acid, while the major iridoid in C. officinalis juice was found to be morroniside. The presence of iridoids in C. mas is reported for the first time.
Flextime and Profitability
Authors: LEE BYRON Y. , DeVOE SANFORD E.
Published: April 2012

Despite the well‐documented benefits of flexible work schedules (flextime), generalizable assessments of how flextime influences organizational profitability have proven elusive. Using a unique data set representative of organizations in Canada, we examine the effect of flextime in combination with organizational strategies to predict profitability. Using fixed effects and controlling for prior profitability, we find that flextime increases profitability when implemented within a strategy centered on employees but decreases profitability when implemented within a strategy focused on cost reduction.
Mega‐interest on Microcredit: Are Lenders Exploiting the Poor?
Authors: Sandberg Joakim
Published: April 2012

abstract

Microcredit is often hailed as an effective way of alleviating poverty. In recent years, however, microfinance institutions have been the target of much criticism due to their comparatively high interest rates (which may be as high as 70–100% per annum). This paper discusses whether it can be morally justified to charge very high rates of interest when lending money to the poor. Arguments are drawn from contemporary as well as historical debates on usury, exploitation, egalitarianism and consequentialism. It is conceded that it would be preferable if interest rates could be reduced, but it is argued that typical microlenders today do nothing wrong in setting their rates at the current levels. Instead the responsibility rests on governments, commercial banks and overseas investors to facilitate an environment where rates could be reduced.
Age and gender differences in depression across adolescence: real or ‘bias’?
Authors: van Beek Yolanda , Hessen David J. , Hutteman Roos , Verhulp Esmée E. , van Leuven Mirande
Published: April 2012

Background:  Since developmental psychologists are interested in explaining age and gender differences in depression across adolescence, it is important to investigate to what extent these observed differences can be attributed to measurement bias. Measurement bias may arise when the phenomenology of depression varies with age or gender, i.e., when younger versus older adolescents or girls versus boys differ in the way depression is experienced or expressed.

Methods:  The Children’s Depression Inventory (CDI) was administered to a large school population (N = 4048) aged 8–17 years. A 4‐factor model was selected by means of factor analyses for ordered categorical measures. For each of the four factor scales measurement invariance with respect to gender and age (late childhood, early and middle adolescence) was tested using item response theory analyses. Subsequently, to examine which items contributed to measurement bias, all items were studied for differential item functioning (DIF). Finally, it was investigated how developmental patterns changed if measurement biases were accounted for.

Results:  For each of the factors Self‐Deprecation, Dysphoria, School Problems, and Social Problems measurement bias with respect to both gender and age was found and many items showed DIF. Developmental patterns changed profoundly when measurement bias was taken into account. The CDI seemed to particularly overestimate depression in late childhood, and underestimate depression in middle adolescent boys.

Conclusions:  For scientific as well as clinical use of the CDI, measurement bias with respect to gender and age should be accounted for.
The effects of biofilms formed on whey reverse osmosis membranes on the microbial quality of the concentrated product
Authors: ANAND SANJEEV , HASSAN ASHRAF , AVADHANULA MALLIKA
Published: April 2012

The study investigated the development of bacterial biofilms on spiral wound reverse osmosis (RO) whey concentration membranes and their influence on the microbial quality and safety of concentrated whey (retentate). Used RO membranes, obtained from a commercial whey processing plant, were evaluated at intervals of 2 months for a total duration of 14 months using standard techniques. Results confirmed the presence of multi‐species bacterial biofilms on whey RO membranes. Considerable variations were noticed in the distribution pattern of biofilms constitutive microflora as the membranes aged. A greater increase in retentate counts as compared to feed suggested the possibilities of cross‐contamination from the membrane biofilms.
DEET (N,N‐Diethyl‐meta‐toluamide) Induced Delay of Blowfly Landing and Oviposition Rates on Treated Pig Carrion (Sus scrofaL.)
Authors: Shelomi Matan , Matern Leia M. , Dinstell Jenna M. , Harris Daren W. , Kimsey Robert B.
Published: April 2012

Abstract: The question of whether the insect repellent N,N‐Diethyl‐meta‐toluamide (DEET) affected fly attraction, oviposition, and larval development was investigated; in part, to determine whether the common habit of wearing DEET as a repellent could affect the rate of human decomposition. Experiments using pig surrogates of human decedents were carried out in a rural environment. Dead piglets were sprayed with DEET, and fly behavior, colonization levels, and maggot development were compared with those in nonsprayed controls. Piglets treated with DEET experienced significant delays in fly visitation and oviposition and delayed appearance of each larval instar, as well as reduced total larval numbers (p < 0.01 for all variables), with subsequently reduced decomposition (p < 0.05). Such changes in fly behavior and larval population development would significantly impact the estimation of the period following the death from entomological evidence in decedents wearing DEET at the time of their death.
Frost as a limiting factor for recruitment and establishment of early development stages in an alpine glacier foreland?
Authors: Marcante Silvia , Sierra‐Almeida Angela , Spindelböck Joachim P. , Erschbamer Brigitta , Neuner Gilbert
Published: April 2012

Questions

How frost resistant are the early development stages (seeds, seedlings, plantlets and juveniles) of alpine plant species? Do summer frosts impair establishment of plant species typical of different successional stages on a central alpine glacier foreland?

Location

Rotmoos glacier foreland, Austrian Central Alps (Obergurgl, Tyrol, Austria).

Methods

Seeds of 12 species typical of different successional stages were collected in the glacier foreland and either sown directly in the field or in a growth chamber (25/10 °C, 16/8 h) and grown to the investigated development stages. Frost resistance of the early development and adult stages was determined by exposing them to a set of freezing temperatures and assessing viability with the tetrazolium test (LT
50, i.e. 50% of samples being lethally frost damaged).

Results

Dry seeds had the highest frost resistance (LT
50: −19 °C), followed by wet seeds after imbibition (LT
50: −8 °C). With the onset of germination, frost resistance decreased rapidly. While germinated seeds tolerated a mean of −3.2 °C, seedlings and juveniles were less frost resistant (LT
50: −2.5 °C). Along the primary succession, seedlings of pioneer species were significantly less frost resistant than early‐ and late‐successional species. However, field grown seedlings, mainly of pioneer species, showed higher frost resistance (mean: −5 °C) than the growth chamber seedlings (mean: −3 °C), indicating that frost hardening (transition from a lower to a higher level of frost resistance) is already possible during these early stages of development.

Conclusions

The low frost resistance during and after germination may not suffice to survive summer frosts and may at least in certain years explain the high seedling mortality rates recognized in the glacier foreland.
Concentrations of alpha‐ and gamma‐tocopherols in human breast milk during the first months of lactation and in infant formulas
Authors: Martysiak‐Żurowska Dorota , Szlagatys‐Sidorkiewicz Agnieszka , Zagierski Maciej
Published: April 2012

The aim of this study was to determine the concentrations of alpha‐ and gamma‐tocopherols in human breast milk samples from different periods of lactation and to compare them with tocopherol content in commercially available formulas for infants at corresponding ages. The study included 93 breast milk samples obtained on the 2nd (colostrum, n = 17), 14th (n = 30), 30th (n = 27) and 90th day of lactation (n = 19), along with 90 samples of commercially available initial and follow‐on infant formulas. Concentrations of tocopherols were determined using normal‐phase high‐performance liquid chromatography. Depending on the stage of lactation, human breast milk contained 2.07–9.99 mg L−1 of alpha‐tocopherol and 0.22–0.60 mg L−1 of gamma‐tocopherol. Breast milk concentrations of alpha‐tocopherol decreased with the time of lactation, while significant differences in gamma‐tocopherol concentration were observed only between the 14th and 30th day of lactation. There was no significant correlation between the dietary intake of vitamin E and its estimated breast milk concentration, also in women who declared vitamin supplementation. Compared with colostrum, infant formulas were characterised by significantly lower concentrations of alpha‐tocopherol and vitamin E. This finding indicates the need of additional vitamin E supplementation of bottle‐fed infants during the initial 2–3 days of life.
Role of head computed tomography in the evaluation of children admitted to the paediatric intensive care unit with new‐onset seizure
Authors: Bautovich Tanya , Numa Andrew
Published: April 2012

Objective: The role of neuroimaging in children presenting with new‐onset seizure is poorly defined. This study evaluates the incidence of abnormal CT findings in children admitted to the paediatric intensive care unit (PICU) with new‐onset seizure and examines potential clinical variables associated with abnormal head CT findings.

Methods: A retrospective analysis of 89 previously asymptomatic children admitted to Sydney Children's Hospital (Sydney, Australia) PICU between November 2005 and September 2009 with new‐onset seizure was undertaken. Demographic data, clinical details and head CT findings were abstracted from medical records. The clinical significance and the impact of CT findings on acute management decisions was analysed. Clinical variables associated with abnormal clinically significant CT results were examined.

Results: A total of 71/89 patients underwent head CT. Of the children who underwent head CT (n= 71), clinically significant CT results were found in 19.7% of patients and head CT findings resulted in a change in acute management in 7% of patients. Children without fever were more than twice as likely to have a positive CT scan (P= 0.049); however, a substantial proportion (6/45) of febrile children also had abnormal scans. Focal seizures were not predictive of abnormal CT results. There was a significant relationship between abnormal CT and multiple seizures (P < 0.02), and age less than 24 months (P < 0.049).

Conclusion: In this highly selected group head CT findings are frequently abnormal and might change acute management. Children admitted to the PICU with first presentation of seizure who have multiple seizures and/or are aged <2 years should have immediate CT or MRI scanning.
Design, Synthesis, and Antimycobacterial Property of PEG–bis(INH) Conjugates
Authors: Kakkar Dipti , Tiwari Anjani K. , Chuttani Krishna , Khanna Alka , Datta Anupama , Singh Harpal , Mishra Anil K.
Published: April 2012

Poly(ethylene glycol) derivatives of isoniazid with varying molecular weight of poly(ethylene glycol) were designed as antimycobacterial agents. Poly(ethylene glycol)‐diacrylate of three different molecular weights (MW 258, 575, and 700) was conjugated with isoniazid by the Michael addition approach. The poly(ethylene glycol)–bis(isoniazid) conjugates thus obtained were completely characterized by FT‐IR, 1H and 13C NMR, and ESI‐MS spectroscopic techniques. Comparative MTT assay of the poly(ethylene glycol)–bis(isoniazid) conjugates showed much lower cytotoxicity than the neat isoniazid. MIC studies on Mycobaterium tuberculosis H37Rv showed potential antimycobacterial activity than the free isoniazid on a molar basis. The poly(ethylene glycol)–bis(isoniazid) conjugates were successfully radiolabeled with 99m‐Technetium with more than 97% efficiency and stability to assess their in vivo fate. The 99mTc labeled poly(ethylene glycol)–bis(isoniazid) conjugates showed higher blood retention time in New Zealand rabbits which increased with increasing molecular weight of poly(ethylene glycol). Biodistribution studies in infection‐induced murine models (BALB/c mice) showed significant retention of these conjugates at the site of infection for 72 h. The results of this study illustrate the potential utility of the PEGylated isoniazid conjugates as long circulating carriers for improved antitubercular drug therapy.
Europeanisation and the restraint of trade doctrine
Authors: Lucey Mary Catherine
Published: April 2012

The common law restraint of trade doctrine continues to provide valuable protection in a variety of business contexts. This paper analyses an incompatibility problem that has arisen between that doctrine and EU competition rules (in particular Art 101 Treaty on the Functioning of the EU [TFEU]) as implemented by EU Regulation 1/2003, which, amongst other matters, delineates the interface between national law and EU competition law. According to the High Court, once a court has applied Art 101 TFEU, Art 3 of the Regulation prevents a court from reaching a contrary finding under the restraint of trade doctrine. Thus, the court cannot find a clause is void under the doctrine if the clause comes within the scope of, but is not prohibited by, Art 101 TFEU. In effect, this conclusion displaces the restraint of trade doctrine for parties who are subject to unreasonable restraints that fall foul of the doctrine but are not prohibited by Art 101 TFEU. The interface problem and the possible solution are presented as issues of Europeanisation. The negative impact on national law deriving from an EU measure is portrayed as a ‘top down’ Europeanisation scenario. A contrary ‘uploading’ perspective reveals how and why Art 3 and associated Recitals in Regulation 1/2003 were ‘constructed’. These findings on the intended scope of Art 3 are used to challenge the High Court's view on the negative implications of the Regulation for the restraint of trade doctrine. Finally, this paper offers specific proposals as to how courts in the United Kingdom and Ireland could ensure that the restraint of trade doctrine is not an inevitable casualty of Europeanisation. It argues that when looking for a solution to the ‘top-down’ Europeanisation problem faced by the restraint of trade doctrine, the ‘uploading’ perspective of Europeanisation suggests a solution.
Development and Application of Reverse Transcription Loop‐Mediated Isothermal Amplification for Detecting Live Shewanella putrefaciens in Preserved Fish Sample
Authors: Li Chenghua , Ying Qi , Su Xiurong , Li Taiwu
Published: April 2012

Abstract:  Given that live Shewanella putrefaciens is one of the major causes of spoilage for aquatic products even in chill storage, the rapid and accurate detection process is the first priority. In the present study, a novel reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) detecting assay was developed by targeting internal transcribed spacer (ITS) sequence between 16S and 23S rRNA. At the same time, a new procaryotic mRNA isolation strategy was also established by introducing a polyA tail to RNA during cDNA synthesis step. Under the optimal reaction time (60 min) and temperature (64.1 °C), S. putrefaciens could be specially identified from a variety of other tested bacteria by RT‐LAMP. The sensitivity analysis showed that RT‐LAMP could be identified as lower as 5.4 copies per reaction, which is over 200‐fold higher than that of standard PCR (1.08 × 103 copies per reaction). The method could be effectively identified S. putrefaciens in artificially contaminated or spoilaged fish samples with dose‐dependent manners. To our knowledge, this is the first report using RT‐LAMP assay to detect live S. putrefaciens in fish.

Practical Application:  The study provided a rapid and accurate detection method for live bacteria in aquatic food and established a new procaryotic mRNA isolation strategy at the same time, which will be useful for food preservation.
Improved Microbial Quality of Buckwheat using Antimicrobial Solutions in a Fluidized Bed
Authors: Dhillon B. , Wiesenborn D. , Sidhu H. , Wolf‐Hall C.
Published: April 2012

Abstract:  Buckwheat (Fagopyrum esculentum, Moench) is a specialty crop of interest because of its numerous nutritional, health, and agronomic benefits. A high microbial load on the seed often limits its export and use in functional foods; therefore, these generally recognized as safe antimicrobial treatments were evaluated for buckwheat disinfection: ozone gas, ozonated water, acetic acid (AA), acidic calcium sulfate (ACS), and combinations thereof. The liquid treatments were sprayed on buckwheat grain in a fluidized bed and the treated buckwheat was analyzed for aerobic plate count (APC) and yeast and mold count (YMC). Ozone gas and ozonated water treatments were not significantly (P < 0.05) effective in reducing the microbial load, and AA + ozonated water had significant but low effectiveness. Electron microscopic imaging suggested that rough surfaces and crevices in the seed hull shielded microbes from ozone treatments. Effectiveness of treatments was also limited by the industry limits on the amount of moisture that can be added to buckwheat grain. The ACS (50 mL/L) treatment was most effective with 3.9‐log10 reduction in APC and complete elimination of YMC. ACS (50 mL/L) caused bleaching and increased redness. Sufficient reduction of microbes could be achieved at a lower concentration of ACS, thereby reducing the effect on color.
Mathematical Modeling of Growth of Non‐O157 Shiga Toxin‐Producing Escherichia coli in Raw Ground Beef
Authors: Huang Lihan , Tu Shu‐I , Phillips John , Fratamico Pina
Published: April 2012

Abstract:  The objective of this study was to investigate the growth of Shiga toxin‐producing Escherichia coli (STEC, including serogroups O45, O103, O111, O121, and O145) in raw ground beef and to develop mathematical models to describe the bacterial growth under different temperature conditions. Three primary growth models were evaluated, including the Baranyi model, the Huang 2008 model, and a new growth model that is based on the communication of messenger signals during bacterial growth. A 5 strain cocktail of freshly prepared STEC was inoculated to raw ground beef samples and incubated at temperatures ranging from 10 to 35 °C at 5 °C increments. Minimum relative growth (<1 log10 cfu/g) was observed at 10 °C, whereas at other temperatures, all 3 phases of growth were observed. Analytical results showed that all 3 models were equally suitable for describing the bacterial growth under constant temperatures. The maximum cell density of STEC in raw ground beef increased exponentially with temperature, but reached a maximum of 8.53 log10 cfu/g of ground beef. The specific growth rates estimated by the 3 primary models were practically identical and can be evaluated by either the Ratkowsky square‐root model or a Bělehrádek‐type model. The temperature dependence of lag phase development for all 3 primary models was also developed. The results of this study can be used to estimate the growth of STEC in raw ground beef at temperatures between 10 and 35 °C.

Practical Application:  Incidents of foodborne infections caused by non‐O157 Shiga toxin‐producing Escherichia coli (STEC) have increased in recent years. This study reports the growth kinetics and mathematical modeling of STEC in ground beef. The mathematical models can be used in risk assessment of STEC in ground beef.
Cytotoxicity of All‐Trans‐Retinal Increases Upon Photodegradation†
Authors: Różanowska Małgorzata , Handzel Kinga , Boulton Michael E. , Różanowski Bartosz
Published: April 2012

All‐trans‐retinal (AtRal) can accumulate in the retina as a result of excessive exposure to light. The purpose of this study was to compare cytotoxicity of AtRal and photodegraded AtRal (dAtRal) on cultured human retinal pigment epithelial cells in dark and upon exposure to visible light. AtRal was degraded by exposure to visible light. Cytotoxicity was monitored by imaging of cell morphology, propidium iodide staining of cells with permeable plasma membrane and measurements of reductive activity of cells. Generation of singlet oxygen photosensitized by AtRal and dAtRal was monitored by time‐resolved measurements of characteristic singlet oxygen phosphorescence. Photodegradation of AtRal resulted in a decrease in absorption of visible light and accumulation of the degradation products with absorption maximum at ∼330 nm. Toxicity of dAtRal was concentration‐dependent and was greater during irradiation with visible light than in dark. DAtRal was more cytotoxic than AtRal both in dark and during exposure to visible light. Photochemical properties of dAtRal indicate that it may be responsible for the maximum in the action spectra of retinal photodamage recorded in animals. In conclusion, photodegradation products of AtRal may impose a significant threat to the retina and therefore their roles in retinal pathology need to be explored.
Laparoendoscopic single‐site surgery for urachal remnants
Authors: Iida T , Kawa G , Takizawa N , Kawabata T , Komai Y , Kinoshita H , Matsuda T
Published: April 2012

Introduction

Urachal remnants are relatively rare but may potentially cause various symptoms and an increased risk for developing adenocarcinoma. Open or laparoscopic surgery is usually used for their resection. Laparoendoscopic single‐site surgery has been recently applied in several surgical procedures. This report describes two cases of vesicourachal diverticulum treated by resection using laparoendoscopic single‐site surgery.

Materials and Surgical Technique

In each case, laparoendoscopic single‐site surgery was performed transperitoneally via one port at a subumbilical semicircular incision. Except for a flexible camera and SILS Port, traditional, non‐flexible laparoscopic instruments were used. After the induction of general anesthesia, the patient was placed in a supine position (or lithotomy position). A 2.0‐cm incision was made semicircumferentially following the natural subumbilical folds. After the umbilical ligament was cut under direct vision, a SILS Port was placed at the incision. The urachus was liberated distally down to the roof of the urinary bladder using 0° 5‐mm flexible camera. Vesicourachal diverticulum with a bladder cuff was completely excised under the supporting view of cystoscopy. Both patients' perioperative days were uneventful.

Discussion

Our findings suggest that the laparoendoscopic single‐site surgery procedure is safe, minimally invasive and cosmetically acceptable. Therefore, this procedure is an excellent option for the radical resection of urachal remnants.
Novel organotypic culture model of cholangiocarcinoma progression
Authors: Campbell Deanna J. W. , Dumur Catherine I. , Lamour Nadia F. , DeWitt Jennifer L. , Sirica Alphonse E.
Published: April 2012

Aim:  Recent studies have suggested that increased α‐smooth muscle‐actin positive myofibroblastic cells (α‐SMA positive CAF) in the desmoplastic stroma may relate to a more aggressive cancer and worse survival outcomes for intrahepatic cholangiocarcinoma (ICC) patients. To facilitate investigating cellular and molecular interactions between α‐SMA positive CAF and cholangiocarcinoma cells related to ICC progression, we developed a novel 3‐D organotypic culture model of cholangiocarcinoma that more accurately mimics the stromal microenvironment, gene expression profile and select pathophysiological characteristics of desmoplastic ICC in vivo.

Methods:  This unique model was established by co‐culturing within a type I collagen gel matrix, a strain of cholangiocarcinoma cells (derived from an ICC formed in syngeneic rat liver following bile duct inoculation of spontaneously‐transformed rat cholangiocytes) with varying numbers of clonal α‐SMA positive CAF established from the same tumor type.

Results:  Cholangiocarcinoma cells and α‐SMA positive CAF in monoculture each exhibited cell‐specific biomarker gene expression profiles characteristic of stromal myofibroblastic cell versus malignant cholangiocyte cell types. In comparison, the gene expression profile and histopathological characteristics exhibited by the organotypic co‐culture closely resembled those of whole tissue samples of the parent orthotopic ICC. We further showed α‐SMA positive CAF to significantly enhance cholangiocarcinoma cell “ductal‐like” growth and cancer cell migration/invasiveness in vitro, as well as to promote upregulated expression of select genes known to be associated with ICC invasion.

Conclusion:  This novel organotypic model provides an important new resource for studying the effects of microenvironment on cholangiocarcinoma progression in vitro and may have potential as a preclinical model for identifying molecularly targeted therapies.
Solution-Processible Electrodes
Authors: Helander Michael G.
Published: April 2012

Polymer-coated surfaces may provide a low-cost route for processing and fabricating organic-based electronic devices.
Making Waves for Segments
Authors: Roth Siegfried , Panfilio Kristen A.
Published: April 2012

Vertebrates and arthropods share a common molecular mechanism for controlling body segmentation during development.
Will Dutch Allow ‘Export’ of Controversial Flu Study?
Authors: Enserink Martin
Published: April 2012

The Dutch government must decide whether it will invoke export-control laws in a bid to prevent virologist Ron Fouchier from submitting a revised version of his controversial H5N1 paper to
Science
.
Modulation of the Myxoma Virus Plaque Phenotype by Vaccinia Virus Protein F11
Authors: Irwin Chad R. , Evans David H.
Published: April 2012

Vaccinia virus (VACV) produces large plaques consisting of a rapidly expanding ring of infected cells surrounding a lytic core, whereas myxoma virus (MYXV) produces small plaques that resemble a focus of transformed cells. This is odd, because bioinformatics suggests that MYXV carries homologs of nearly all of the genes regulating
Orthopoxvirus
attachment, entry, and exit. So why does MYXV produce foci? One notable difference is that MYXV-infected cells produce few of the actin microfilaments that promote VACV exit and spread. This suggested that although MYXV carries homologs of the required genes (A33R, A34R, A36R, and B5R), they are dysfunctional. To test this, we produced MYXV recombinants expressing these genes, but we could not enhance actin projectile formation even in cells expressing all four VACV proteins. Another notable difference between these viruses is that MYXV lacks a homolog of the F11L gene. F11 inhibits the RhoA-mDia signaling that maintains the integrity of the cortical actin layer. We constructed an MYXV strain encoding F11L and observed that, unlike wild-type MYXV, the recombinant virus disrupted actin stress fibers and produced plaques up to 4-fold larger than those of controls, and these plaques expanded ∼6-fold faster. These viruses also grew to higher titers in multistep growth conditions, produced higher levels of actin projectiles, and promoted infected cell movement, although neither process was to the extent of that observed in VACV-infected cells. Thus, one reason for why MYXV produces small plaques is that it cannot spread via actin filaments, although the reason for this deficiency remains obscure. A second reason is that leporipoxviruses lack vaccinia's capacity to disrupt cortical actin.
Differential Impact of Interferon Regulatory Factor 7 in Initiation of the Type I Interferon Response in the Lymphocytic Choriomeningitis Virus-Infected Central Nervous System versus the Periphery
Authors: Christensen Jeanette Erbo , Fenger Christina , Issazadeh-Navikas Shohreh , Krug Anna , Liljestrøm Peter , Goriely Stanislas , Paludan Søren Riis , Finsen Bente , Christensen Jan Pravsgaard , Thomsen Allan Randrup
Published: April 2012

Interferon (IFN) regulatory factors (IRFs) are a family of transcription factors involved in regulating type I IFN genes and other genes participating in the early antiviral host response. To better understand the mechanisms involved in virus-induced central nervous system (CNS) inflammation, we studied the influence of IRF1, -3, -7, and -9 on the transcriptional activity of key genes encoding antiviral host factors in the CNS of mice infected with lymphocytic choriomeningitis virus (LCMV). A key finding is that neither IRF3 nor IRF7 is absolutely required for induction of a type I IFN response in the LCMV-infected CNS, whereas concurrent elimination of both factors markedly reduces the virus-induced host response. This is unlike the situation in the periphery, where deficiency of IRF7 almost eliminates the LCMV-induced production of the type I IFNs. This difference is seemingly related to the local environment, as peripheral production of type I IFNs is severely reduced in intracerebrally (i.c.) infected IRF7-deficient mice, which undergo a combined infection of the CNS and peripheral organs, such as spleen and lymph nodes. Interestingly, despite the redundancy of IRF7 in initiating the type I IFN response in the CNS, the response is not abolished in IFN-β-deficient mice, as might have been expected. Collectively, these data demonstrate that the early type I IFN response to LCMV infection in the CNS is controlled by a concerted action of IRF3 and -7. Consequently this work provides strong evidence for differential regulation of the type I IFN response in the CNS versus the periphery during viral infection.
EXCITON-CATALYZED RECOMBINATION-GENERATION OF ELECTRONS AND HOLES IN SEMICONDUCTORS: A KINETIC APPROACH
Authors: ROSSANI A.
Published: April 2012

An asymptotic procedure is proposed for solving the kinetic equations of carriers and phonons, together with photons and excitons. Both the direct and the exciton-catalized generation-recombination processes are accounted for. The generation rate shows a nonlinear behavior with respect to the product of the number densities of electrons and holes.
MULTI-GRANULARITY KNOWLEDGE MINING ON THE WEB
Authors: XIE MING
Published: April 2012

We tackle the problem of knowledge mining on the Web. In this paper, we propose MGKM algebraic system for iterative search documents sets, and then develop an approach to extract topics on the web with Multi-Granularity Knowledge Mining algorithm (MGKM). The proposed approach maps the data space of the original method to a vector space of sentence, improving the original DBCO algorithm. We outline the interface between our scheme and the current data Web, and show that, in contrast to the existing approaches, no exponential blowup is produced by the MGKM. Based on the experiments with real-world data sets of 310 users in three study sites, we demonstrate that knowledge mining in the proposed approach is efficient, especially for large-scale web learning resources. According to the user ratings data of four learning sites in the 150 days, the average rate of increase of user rating after the system is used reaches 25.18%.
Activation of NPY receptors suppresses excitatory synaptic transmission in a taste-feeding network in the lower brain stem
Authors: Chen Zhixiong , Travers Susan P. , Travers Joseph B.
Published: April 2012

Consummatory responses to taste stimuli are modulated by visceral signals processed in the caudal nucleus of the solitary tract (cNST) and ventrolateral medulla. On the basis of decerebrate preparations, this modulation can occur through local brain stem pathways. Among the large number of neuropeptides and neuromodulators implicated in these visceral pathways is neuropeptide Y (NPY), which is oftentimes colocalized in catecholaminergic neurons themselves implicated in glucoprivic-induced feeding and satiety. In addition to the cNST and ventrolateral medulla, noradrenergic and NPY receptors are found in circumscribed regions of the medullary reticular formation rich in preoromotor neurons. To test the hypothesis that NPY may act as a neuromodulator on preoromotor neurons, we recorded the effects of bath application of NPY and specific Y1 and Y2 agonists on currents elicited from electrical stimulation of the rostral (taste) NST in prehypoglossal neurons in a brain stem slice preparation. A high proportion of NST-driven responses were suppressed by NPY, as well as Y1 and Y2 agonists. On the basis of paired pulse ratios and changes in membrane resistance, we concluded that Y1 receptors influence these neurons both presynaptically and postsynaptically and that Y2 receptors have a presynaptic locus. To test the hypothesis that NPY may act in concert with norepinephrine (NE), we examined neurons showing suppressed responses in the presence of a Y2 agonist and demonstrated a greater degree of suppression to a Y2 agonist/NE cocktail. These suppressive effects on preoromotoneurons may reflect a satiety pathway originating from A2 neurons in the caudal brain stem.
Blood flow augmentation by intrinsic venular contraction in vivo
Authors: Dongaonkar Ranjeet M. , Quick Christopher M. , Vo Jonathan C. , Meisner Joshua K. , Laine Glen A. , Davis Michael J. , Stewart Randolph H.
Published: April 2012

Venomotion, spontaneous cyclic contractions of venules, was first observed in the bat wing 160 years ago. Of all the functional roles proposed since then, propulsion of blood by venomotion remains the most controversial. Common animal models that require anesthesia and surgery have failed to provide evidence for venular pumping of blood. To determine whether venomotion actively pumps blood in a minimally invasive, unanesthetized animal model, we reintroduced the batwing model. We evaluated the temporal and functional relationship between the venous contraction cycle and blood flow and luminal pressure. Furthermore, we determined the effect of inhibiting venomotion on blood flow. We found that the active venous contractions produced an increase in the blood flow and exhibited temporal vessel diameter-blood velocity and pressure relationships characteristic of a peristaltic pump. The presence of valves, a characteristic of reciprocating pumps, enhances the efficiency of the venular peristaltic pump by preventing retrograde flow. Instead of increasing blood flow by decreasing passive resistance, venular dilation with locally applied sodium nitroprusside decreased blood flow. Taken together, these observations provide evidence for active venular pumping of blood. Although strong venomotion may be unique to bats, venomotion has also been inferred from venous pressure oscillations in other animal models. The conventional paradigm of microvascular pressure and flow regulation assumes venules only act as passive resistors, a proposition that must be reevaluated in the presence of significant venomotion.
Increased right ventricular output and central pulmonary reservoir function support rise in pulmonary blood flow during adenosine infusion in the ovine fetus
Authors: Smolich Joseph J. , Penny Daniel J. , Mynard Jonathan P.
Published: April 2012

Although adenosine markedly increases fetal pulmonary blood flow, the specific changes in pulmonary trunk (PT), ductus arteriosus (DA), and conduit pulmonary artery (PA) flow interactions that support this increased flow are unknown. To address this issue, seven anesthetized late-gestation fetal sheep were instrumented with PT, DA, and left PA micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and after adenosine infusion to increase PA flow approximately fivefold. With adenosine infusion, DA mean and phasic flows were unchanged, but increases in mean PT (500 ± 256 ml/min, P = 0.002) and the combined left and right PA flow (479 ± 181 ml/min, P < 0.001) were similar ( P > 0.7) and related to a larger flow-increasing forward-running compression wave arising from right ventricular (RV) impulsive contraction. Moreover, while the increased PT flow was confined to systole, the rise in PA flow spanned systole (316 ml/min) and diastole (163 ml/min). This elevated PA diastolic flow was accompanied by a 170% greater discharge from a PT and main PA reservoir filled in systole ( P < 0.001), but loss of retrograde blood discharge from a conduit PA reservoir that was evident at baseline. These data suggest that 1) an increase in fetal pulmonary blood flow produced by adenosine infusion is primarily supported by a higher PT blood flow (i.e., RV output); 2) about two-thirds of this increased RV output passes into the pulmonary circulation during systole; and 3) the remainder is transiently stored in a central PT and main PA systolic reservoir, from where it discharges into the lungs in diastole.
The Role of Thyrotrophin Receptor Antibody Assays in Graves’ Disease
Authors: Kamath C. , Adlan M. A. , Premawardhana L. D.
Published: April 2012

Thyrotrophin receptor antibodies (TRAb) exist as stimulating or blocking antibodies in the serum (neutral TRAb have been identified recently). The clinical features of GD occur when stimulating TRAb predominate. But the relationship of TRAb to clinical phenotype and outcome is not clear when current assay methods are used. Therefore no consensus exists about its utility in diagnosing and predicting outcome in GD. The most commonly used TRAb assays, measure thyroid binding inhibiting immunoglobulins (TBII or “receptor assays”) and don’t differentiate between stimulating and blocking antibodies. However, the more expensive, technically demanding and less freely available “biological assays” differentiate between them by their ability to stimulate cyclic AMP or failure to do so. Failure to differentiate between TRAb types and its heterogeneous molecular and functional properties has limited TBII use to GD diagnosis and differentiating from other forms of thyrotoxicosis. The current 2nd-3rd generation receptor assays are highly sensitive and specific when used for this purpose. TRAb assays should also be done in appropriate pregnant women. Current data do not support its use in outcome prediction as there is a significant variability of assay methodology, population characteristics and study design in published data, resulting in a lack of consensus.
Bone Dielectric Property Variation as a Function of Mineralization at Microwave Frequencies
Authors: Meaney Paul M. , Zhou Tian , Goodwin Douglas , Golnabi Amir , Attardo Elia A. , Paulsen Keith D.
Published: April 2012

A critical need exists for new imaging tools to more accurately characterize bone quality beyond the conventional modalities of dual energy X-ray absorptiometry (DXA), ultrasound speed of sound, and broadband attenuation measurements. In this paper we investigate the microwave dielectric properties of ex vivo trabecular bone with respect to bulk density measures. We exploit a variation in our tomographic imaging system in conjunction with a new soft prior regularization scheme that allows us to accurately recover the dielectric properties of small, regularly shaped and previously spatially defined volumes. We studied six excised porcine bone samples from which we extracted cylindrically shaped trabecular specimens from the femoral heads and carefully demarrowed each preparation. The samples were subsequently treated in an acid bath to incrementally remove volumes of hydroxyapatite, and we tested them with both the microwave measurement system and a micro-CT scanner. The measurements were performed at five density levels for each sample. The results show a strong correlation between both the permittivity and conductivity and bone volume fraction and suggest that microwave imaging may be a good candidate for evaluating overall bone health.
Double-Blinded, Vehicle-Controlled Proof of Concept Study to Investigate the Recurrence of Inflammatory and Noninflammatory Acne Lesions Using Tretinoin Gel (Microsphere) 0.04% in Male Patients after Oral Isotretinoin Use
Authors: Vender Reid , Vender Ronald
Published: April 2012

Background. Although isotretinoin orally is commonly used for moderate to severe or scarring acne, it is not a cure. Unfortunately recurrence is unpredictable and varies within the acne population.Objectives. Using a proof of concept study, determine the recurrence of acne after isotretinoin use in male patients.Methods. Twenty males aged 18–45 years old were enrolled. Subjects successfully completed a treatment of acne vulgaris with oral isotretinoin (120–150 mg/kg/course). Subjects were randomized 1 to 1. The study duration was 24 weeks. The primary endpoint measured was the absolute change in lesion counts from baseline to weeks 16 and 24. Local tolerability assessments were measured.Results. There were favorable changes in all outcomes measured. Overall, there was a 38.7% lower lesion count with tretinoin 0.04% microsphere gel use versus vehicle. The active product was well tolerated with great patient satisfaction. There were no significant safety issues. The limitations included the low number of patients enrolled, average age, and percentage of patients lost to follow-up.Conclusion. In summary, the results favored tretinoin 0.04% microsphere gel in the prevention of recurrent acne after isotretinoin use in male patients over 18 years old over a six-month period.
Neural Substrates Underlying Interactions between Appetite Stress and Reward
Authors: Menzies John R.W. , Skibicka Karolina P , Dickson Suzanne L. , Leng Gareth
Published: April 2012

Neurobiological mechanisms that normally control food intake and energy expenditure can be overcome by environmental cues and by stress. Of particular importance is the influence of the mesolimbic reward pathway. In genetically susceptible individuals, problematic over-eating likely reflects a changing balance in the control exerted by homeostatic versus reward circuits that are strongly influenced by environmental factors such as stress. Both stress and activation of the reward pathway have been shown to increase food intake and promote a preference for palatable, high-energy foods. Recent research has focused on the important role of circulating and central neuropeptides that powerfully regulate the brain response to food cues. For example, ghrelin has a potent positive effect on the motivational aspects of food intake, and central oxytocin may be involved in satiety. Thus, the decision to eat, or indeed to over-eat, involves a complex integrated neurobiology that includes brain centres involved in energy balance, reward and stress and their regulation by metabolic and endocrine factors.
De-Idealizing Democracy: On Thomas Hirschhorn's Postsocialist Projects
Authors: Gardner Anthony
Published: April 2012

“I want to give form to the end of the Idealization of Democracy,” claims one of Europe's leading artists, Thomas Hirschhorn. The statement may seem surprising, given Hirschhorn's status as a poster-boy for promoting democracy through art, yet the drive to de-idealize democracy has long been crucial to his practice. This article examines how de-idealization has emerged in such projects as Swiss Swiss Democracy and Chalet Lost History, as a critique of art theory's promotion of Democracy during the “War on Terror,” and by remobilizing critiques of Democracy seen in earlier, late-communist practices. The coalescence of these two factors is central to understanding Hirschhorn's work in terms of postsocialism as distinct from postcommunism: as a remobilization of past nonconformism outside the space and time of late-communist Europe, and as the overlooked core to Hirschhorn's practice of “making art politically.”