bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term functional outcome after restorative proctocolectomy in patients with ulcerative colitis
Authors: Karlbom U. , Lindfors A. , Påhlman L.
Published: November 2011

Aim  The aim of this study was to evaluate the long‐term functional outcome of ileal pouch–anal anastomosis for ulcerative colitis and to compare symptoms over time.

Methods  In all, 188 patients were operated with an ileal pouch–anal anastomosis. Short‐term functional outcome has previously been evaluated with a symptom questionnaire. The same questionnaire was sent to the 162 patients who were alive and had an intact pouch. A symptom index was studied over time and in relation to early complications and pouchitis.

Results  The response rate of the questionnaire was 139/162 at a median of 12.5 (9.5–21) years postoperatively. Overall, the symptom index remained unchanged over time but both the frequency of night‐time defaecation and episodes of night‐time incontinence increased. Patients’ global assessment was unchanged with approximately 80% stating an excellent or a good result. Frequency of pouchitis doubled in 10 years. Symptom index for patients with episodic pouchitis [median 40 (8–89), P = 0.018] and recurrent/chronic pouchitis [71 (8–136), P < 0.001] was higher than in patients without pouchitis [29 (0–105)]. Early complications did not affect the symptom index.

Conclusion  The overall functional outcome of ileal pouch–anal surgery for ulcerative colitis is stable over time. Patients’ satisfaction with outcome remains high. Pouchitis is a determinant of functional outcome.
Neutralizing antibodies against rotavirus produced in transgenically labelled purple tomatoes
Authors: Juárez Paloma , Presa Silvia , Espí Joaquín , Pineda Benito , Antón María T. , Moreno Vicente , Buesa Javier , Granell Antonio , Orzaez Diego
Published: November 2011

Edible fruits are inexpensive biofactories for human health‐promoting molecules that can be ingested as crude extracts or partially purified formulations. We show here the production of a model human antibody for passive protection against the enteric pathogen rotavirus in transgenically labelled tomato fruits. Transgenic tomato plants expressing a recombinant human immunoglobulin A (hIgA_2A1) selected against the VP8* peptide of rotavirus SA11 strain were obtained. The amount of hIgA_2A1 protein reached 3.6 ± 0.8% of the total soluble protein in the fruit of the transformed plants. Minimally processed fruit‐derived products suitable for oral intake showed anti‐VP8* binding activity and strongly inhibited virus infection in an in vitro virus neutralization assay. In order to make tomatoes expressing hIgA_2A1 easily distinguishable from wild‐type tomatoes, lines expressing hIgA_2A1 transgenes were sexually crossed with a transgenic tomato line expressing the genes encoding Antirrhinum majus Rosea1 and Delila transcription factors, which confer purple colour to the fruit. Consequently, transgenically labelled purple tomato fruits expressing hIgA_2A1 have been developed. The resulting purple‐coloured extracts from these fruits contain high levels of recombinant anti‐rotavirus neutralizing human IgA in combination with increased amounts of health‐promoting anthocyanins.
Serial sections of atrophic acne scars help in the interpretation of microscopic findings and the selection of good therapeutic modalities
Authors: Lee W.J. , Jung H.J. , Lim H.J. , Jang Y.H. , Lee S.‐J. , Kim D.W.
Published: November 2011

Background  Acne scar causes problems cosmetically and psychologically. Although microscopic examination of acne scars is a necessity for understanding and treatment of them, and it is not easy to find a paper reporting the microscopic characterization of acne scars.

Objective  The aim of this study was to examine the microscopic findings of acne scars and to select a good therapeutic modality based on the findings.

Methods  Thirty‐one atrophic scars obtained from five patients for cosmesis and 18 serial sections were made from each atrophic scar. The sections were stained with H&E, Masson‐trichrome or Verhoeff van Gieson stains. Immunohistochemistry was done with antibodies against transforming growth factor‐β, metalloproteinase‐1 (MMP‐1), MMP‐2, MMP‐9 and MMP‐13. The stained sections were examined under the microscope.

Results  The epidermis of the acne scar was characterized by keratin plugging in the hair follicle orifice (32%) and multi‐channelled tracts (29%). The dermis of the acne scar had characteristics including a decrease in the dermal thickness and loss of pilosebaceous units. In addition, inflammatory cell infiltrates were seen in the dermis (77%), and insufficient dense collagen fibre deposition was found in the whole dermis (29%). Other findings such as calcium deposition and foreign body reaction were discovered.

Conclusion  We have found the characteristics of acne scar through the serial sections of several atrophic scars, and suggest that the treatment must reflect several considerations, including the understanding of histopathological findings and the use of combination therapy.
Ecological and environmental correlates of territory occupancy and breeding performance of migratory Golden EaglesAquila chrysaetosin interior Alaska
Authors: MCINTYRE CAROL L. , SCHMIDT JOSHUA H.
Published: November 2011

Understanding relationships between environmental conditions and reproductive parameters is important when interpreting variation in animal population size. The northwestern North American population of Golden EaglesAquila chrysaetos canadensisinitiates courtship and nesting in early spring when prey diversity is low and weather conditions are severe. Snowshoe HareLepus americanusand Willow PtarmiganLagopus lagopus, the primary prey of Golden Eagles early in their nesting season in interior Alaska, both exhibit cyclical fluctuations in abundance, providing the opportunity to investigate such relationships. We used Bayesian hierarchical models to explore variation in territory occupancy, nesting rates, nesting success and productivity of Golden Eagles from 1988 to 2010 in Denali National Park and Preserve, Alaska, in relation to annual and site‐specific parameters including prey abundance, weather conditions, elevation and human activity. We also investigated the long‐term fluctuations of breeding performance over the course of the study. The abundance of Hares influenced both the number of Eagles that laid eggs and the number of Eagles that produced fledglings. The conditions on the breeding ground did not explain observed declines in nesting rates and fledgling production, suggesting that other factors such as change in the age structure of the population, increased intraspecific competition or deterioration of migration and wintering habitat are driving the long‐term trends of these parameters.
Analysis of a simple capacity game
Authors: Song J. , Parlar M.
Published: November 2011

We study a two‐player two‐fare‐class static single‐period capacity allocation game with complete information. Nonnested (partitioned) booking limit policies are investigated in both noncooperative and cooperative situations. We show the existence of unique Nash equilibrium in the noncooperative situation. In the cooperative game, we analyze the cost saving of the two players and investigate the concavity of the objective function. For both noncooperative and cooperative settings, we assume the demands to be a truncated normal distribution and provide a comprehensive sensitivity analysis to discover the effects of unit revenue, rejection cost, and transfer rate on the equilibrium solution. Our numerical experiments show that the nonnested model can be a good approximation to the nested booking limit model. For the cooperative setting, we identify conditions that give rise to improvements in the total system revenue. Finally, under each game‐theoretic setting, we present the managerial implications of our solutions along with numerical examples.
Inotropes and vasopressors: more than haemodynamics!
Authors: Bracht Hendrik , Calzia Enrico , Georgieff Michael , Singer Joel , Radermacher Peter , Russell James A
Published: November 2011

Circulatory shock is characterized by arterial hypotension requiring fluid resuscitation combined with inotropes and/or vasopressors to correct the otherwise life‐threatening impairment of oxygen supply to peripheral tissues. Catecholamines represent the current therapeutic choice, but this standard is only based on empirical clinical experience. Although there is evidence that some catecholamines may be better than others, it is a matter of debate which one may be the most effective and/or the safest for the different situations. In their review in this issue of the British Journal of Pharmacology, Bangash et al. provide an overview of the pharmacology as well as the available clinical data on the therapeutic use of endogenous catecholamines, their synthetic derivatives and a range of other agents (vasopressin and its analogues, PDE inhibitors and levosimendan). The authors point out that, despite well‐established receptor pharmacology, the clinical effects of these treatments are poorly understood. Hence, further investigations are essential to determine which catecholamine, or, in a broader sense, which alternative vasopressor and/or inotrope is the most appropriate for a particular clinical condition.

LINKED ARTICLES This article is a commentary on Bangash et al., pp. 2015–2033 of this issue and is commented on by De Backer and Scolletta, pp. 2012–2014 of this issue. To view Bangash et al. visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01588.x and to view De Backer and Scolletta visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01746.x
The role of HSAL (SALL) genes in proliferation and differentiation in normal hematopoiesis and leukemogenesis
Authors: Chai Li
Published: November 2011

The National Blood Foundation (NBF) support was critical in the author's research career development. The NBF support came in the form of a start‐up seed grant that she got from the American Association of Blood Banks, an organization that advances the practice and standards of transfusion medicine and cellular therapies and an organization in which she is a proud member. The NBF grant enabled her to keep up with her transfusion medicine practice while pursuing her passion to be a physician scientist. During its funding period, she was able to obtain critical preliminary bench data and to secure several National Institutes of Health grants with over a million dollars direct cost. In addition, the knowledge gained from the NBF‐supported projects is currently being translated into medical practice in her lab by testing on cord blood expansion. She is looking forward to spending the upcoming years of her professional career bridging bedside observations on transfusion medicine with bench experiences and then utilizing that bench‐derived knowledge in the practice of transfusion medicine.
Evaluation of a Community Intervention for Promotion of Safe Motherhood in Eritrea
Authors: Turan Janet Molzan , Tesfagiorghis Mekonnen , Polan Mary Lake
Published: November 2011

Introduction: We evaluated a community‐based intervention to promote safe motherhood, focusing on knowledge and behaviors that may reduce maternal mortality and birth complications. The intervention aimed to increase women's birth preparedness, knowledge of birth danger signs, use of antenatal care services, and birth at a health care facility.

Methods: Volunteers from a remote rural community in Northern Eritrea were trained to lead participatory educational sessions on safe motherhood with women and men. The evaluation used a quasiexperimental design (nonequivalent group pretest‐posttest) including cross‐sectional surveys with postpartum women (pretest n = 466, posttest n = 378) in the intervention area and in a similar remote rural comparison area.

Results: Women's knowledge of birth danger signs increased significantly in the intervention area but not in the comparison area. There was a significant increase in the proportion of women who had the recommended 4 or more antenatal care visits during pregnancy in the intervention area (from 18% to 80%, P < .001), although this proportion did not change significantly in the comparison area (from 53% to 47%, P= .194). There was a greater increase in birth in a health care facility in the intervention area.

Discussion: Participatory sessions led by community volunteers can increase safe motherhood knowledge and encourage use of essential maternity services.
Adverse Drug Reactions in Women's Health Care
Authors: Tharpe Nell
Published: November 2011

Adverse drug reactions (ADRs) are drug‐related adverse events that occur in individuals using usual or therapeutic doses of medication. Women have a nearly 2‐fold greater risk for developing ADRs than men, and they are more likely to be hospitalized secondary to an ADR. This article reviews the physiologic mechanisms of ADRs, common clinical manifestations of ADRs to medications often prescribed in women's health care, documentation and reporting of ADRs, and ADR prevention strategies.
ELIMINATING PELVIC EXAMINATIONS AND PAP SCREENING FOR ADOLESCENTS INITIATING CONTRACEPTION
Authors: Gabzdyl Elizabeth , McFarlin Barbara , Camune Barbara , Engstrom Janet L.
Published: November 2011

Purpose: To decrease unnecessary Pap screenings in adolescents while increasing access to contraception, thereby decreasing unintended pregnancies without increasing cervical cancer risk. To implement and evaluate a multifaceted educational program for health care providers (HCP) and office staff to determine level of adherence to recommendations for Pap screening and prescribing hormonal contraception, examining obstacles preventing adherence to current practice recommendations. Background: The United States has 1 of the highest rates of unintended pregnancies in the world among industrialized nations. Adolescents often avoid contraception initiation fearing Pap screening and pelvic examinations. Adolescents may initiate contraception earlier if not required to undergo these examinations. Methods: Complete data were collected on 192 adolescent records, pre‐intervention (n = 95), post‐intervention (n = 97), to determine if a practice change occurred after a multifaceted education program. Adolescents were aged 15 to 21 years. Pre‐ and post‐intervention surveys were conducted to assess attitudes and beliefs of HCPs and office staff. Results: Before and after the intervention, the earliest age of first Pap screening was very young. HCP did not always require Pap screening for contraception initiation: 48% pre‐intervention and 71% post‐intervention. No adolescents had serious abnormal Pap results. Conclusions: Resistance to change was apparent from the office staff. Having written guidelines and meeting periodically to discuss how care is provided will help keep staff discussions with patients congruent with HCP's practices.
USING QUALITATIVE DATA TO DEVELOP LOCALLY RELEVANT AND VALID QUANTITATIVE MEASUREMENT TOOLS: A CASE EXAMPLE OF TRUST IN ETHIOPIA
Authors: Dynes Michelle , Hadley Craig , Sibley Lynn
Published: November 2011

Purpose: To build a new measure of trust from the ground up that is valid and locally relevant. Background: Little is known about the influence of trust among health workers in low‐resource settings. Trust may be particularly salient among health workers in developing countries such as Ethiopia where skilled health worker shortages have led to reliance on lower‐skilled community‐level health workers to provide services. Methods: Ethnographic data on the conceptualization of trust were collected through semi‐structured interviews with 30 health workers in Amhara region, Ethiopia. Transcripts underwent thematic analysis to identify characteristics of trustworthiness. Respondents’ own words were used to build a 25‐item trust scale which was subsequently pilot tested with 92 health workers. Cultural consensus analysis and Quadratic Assignment Procedure (QAP) assessed the level of shared cultural knowledge within and between cadres of health workers. Results: Psychometric testing of the trust scale reveals strong internal consistency. Cultural consensus analysis and QAP provide preliminary evidence for the existence of divergent models of trust among health worker cadres. Conclusions: This represents a case example of how rapid formative work can lead to the development of a scale that is both valid and locally relevant. Next steps in the research involve assessing the association between trust and teamwork, and linking trust and teamwork with delivery of health services and outcomes. Funding: Bill and Melinda Gates Foundation
Price floors and technical inefficiency in India's sugar processing industry
Authors: Patlolla Sandhyarani , Goodhue Rachael E. , Sexton Richard J.
Published: November 2011

In India, cane is processed into sugar by cooperatives, public enterprises, and private (for‐profit) firms. The Indian government sets a unique floor price for each processor that is increasing in the firm's effectiveness in converting cane into sugar. The floor price binds for public and private firms but not for cooperatives, which rebate profits to members. We argue that this price floor policy creates a disincentive for private and public firms to be technically efficient in converting cane to sugar. In support of this hypothesis an analysis of 593 Indian sugar factories from 1992 to 2007 reveals statistically significant differences in technical efficiency, with cooperatives being the most efficient and public firms least efficient. We estimate welfare losses due to the technical inefficiency attributable to the price‐floor policy and argue that it can be eliminated by enacting policy to base price floors upon quality of the cane input received by a factory.
Recent Changes in Patch Characteristics and Plant Communities in the Jalca Grasslands of the Peruvian Andes
Authors: Tovar Carolina , Duivenvoorden Joost F. , Sánchez‐Vega Isidoro , Seijmonsbergen Arie C.
Published: November 2011

Habitat loss and fragmentation are considered major threats to biodiversity, especially in tropical mountain ecosystems. Most studies focus on the relationships between biodiversity and patch characteristics such as patch size, connectivity or degree of contrast with the surrounding matrix, but leave the rate of change within these variables little explored. We analyzed the importance of changes in patch characteristics over time on species diversity and species composition in the paramo of northern Peru, a tropical grassland ecosystem, locally known as jalca. We obtained land use/cover maps for 1987 and 2007 spanning an area of 6300 km2, and quantified land use change, jalca patch characteristics and their proportional changes over 20 yr. In 2009, 371 vascular plant species were recorded in 92 plots, each plot representative of single patches. Between 1987 and 2007, jalca cover decreased from 47 to 35 percent due to encroaching agriculture. This activity showed an upward shift probably favored by climate change. The number of jalca patches increased, mean patch size decreased, and the patches showed a higher contrast with the surrounding matrix. Multiple linear regression failed to show that species diversity relates to changes in patch characteristics. Canonical correspondence analysis indicated that species composition relates to the degree of contrast between the patch and its surrounding matrix and its changes through time. We concluded that changes in patch characteristics are important only for species composition. This study highlights the importance of considering matrix management with a long term perspective for conservation efforts.
The use of ice‐lollies for pain relief post‐paediatric tonsillectomy. A single‐blinded, randomised, controlled trial
Authors: Sylvester D.C. , Rafferty A. , Bew S. , Knight L.C.
Published: November 2011

Clin. Otolaryngol. 2011, 36, 566–570

Objectives:  To assess whether the use of ice‐lollies after tonsillectomy with or without adenoidectomy in children aged 2–12 reduces pain in the immediate postoperative period.

Design:  A prospective, randomised, single‐blinded study design consisting of two groups with an intention to treat analysis.

Setting:  Tertiary referral centre.

Participants:  Children aged 2–12 undergoing tonsillectomy with or without adenoidectomy.

Main outcome measures:  Pain assessment by nursing staff in the form of the validated modified Children’s Hospital of Eastern Ontario Pain Scale at 15, 30 and 60 min and 4 h.

Results:  Ninety‐two patients were recruited into the study with 46 allocated to receive an ice‐lolly and 41 not to receive an ice‐lolly after exclusion of those with incomplete data. The two groups were comparable for number, age, sex and diagnosis. The pain score at every time interval was lower in the group that had received the ice‐lolly compared with the group that had not. This was statistically significant at 30 (P = 0.008) and 60 min (P = 0.049).

Conclusion:  Our data suggest that ice‐lollies are a cheap, effective and safe method of reducing postoperative pain up to one hour following paediatric tonsillectomy.
3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins: a new class of P-glycoprotein modulators
Authors: Shen Xiaoling , Chen Guangying , Zhu Guoyuan , Cai Jiazhong , Wang Lu , Hu Yingjie , Fong Wang-Fun
Published: November 2011

Objectives

P-glycoprotein (Pgp) overexpression in tumour cells leads to multidrug resistance (MDR) and causes failure in cancer chemotherapy. We have previously identified (±)-praeruptorin A (PA) as a potential lead compound for Pgp modulators. In this study we investigated the MDR-reversing activities of PA derivatives.

Methods

Series 7,8-pyranocoumarins with various C-3′ and C-4′ side chains had been semi-synthesized and their MDR-reversing activity was investigated in Pgp-overexpressing MDR tumour cell line HepG2/Dox and in a KB V1 xenograft animal model.

Key findings

All 7,8-pyranocoumarins exhibited equal or higher activity in modulating Pgp. DCK (12), DMDCK (15), 16, 21, 23 and 24 at 4 µm achieved 91%∼99% decrease in IC50 value (concentration inhibiting cell growth by 50%) of anticancer agents vinblastine, doxorubicin, puromycin and paclitaxel, and were more active than others. DMDCK also remarkably enhanced the growth inhibitory effect of paclitaxel on KB V1 xenografts (P < 0.05), showing a potency required for clinical usage. Mechanistic studies suggested that these 7,8-pyranocoumarins might reverse Pgp-MDR through directly binding to substrate binding site(s) or allosteric site(s) on Pgp therefore impairing Pgp-mediated drug transport.

Conclusions

Results from the study suggested that 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins could serve as a new class of Pgp modulator. Acyls play an important role in maintaining and enhancing the Pgp-modulating ability of pyranocoumarins. 3,4-Dimethoxyl substituted aromatic acyls, bearing a methoxy that might interact with Pgp as hydrogen bond accepter, were shown to be the most potent for reversing MDR.
Contribution of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 to hepatic uptake of nateglinide, and the prediction of drug–drug interactions via these transporters
Authors: Takanohashi Toshiyuki , Kubo Satoru , Arisaka Harumi , Shinkai Kenji , Ubukata Kazuyuki
Published: November 2011

Objectives

We have investigated the contributions of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 to the hepatic uptake of nateglinide, and the possibility of drug–drug interactions via these transporters.

Methods

Uptake studies using transporter-expressing HEK293 cells and cryopreserved human hepatocytes were performed to examine the contributions of each transporter. Inhibition studies using cryopreserved human hepatocytes were performed to examine the possibility of drug–drug interactions.

Key findings

The rate of saturable hepatic uptake of nateglinide using human hepatocytes was 47.6%. A certain increase in uptake was observed in the examination using transporter-expressing HEK293 cells, indicating contributions of OATP1B1 and OATP1B3 to hepatic nateglinide uptake. The 50% inhibitory concentration (IC50) values of nateglinide using cryopreserved human hepatocytes for uptake of estrone 3-sulfate (substrate of OATP1B1), and cholecystokinin octapeptide (substrate of OATP1B3) were 168 and 17.4 µmol/l, respectively. Moreover, ciclosporin inhibited saturable hepatic uptake of nateglinide with an IC50 value of 6.05 µmol/l. The calculated 1 + Iin,max,u/IC50 values for inhibition of OATP1B1 and OATP1B3 by nateglinide, and the inhibition of saturable uptake of nateglinide by ciclosporin, were all close to 1, indicating a low clinical risk of drug–drug interaction with nateglinide taken up via OATP1B1 and OATP1B3.

Conclusions

OATP1B1 and OATP1B3 may have contributed to the hepatic uptake of nateglinide, but the possibility of drug–drug interactions appeared to be low.
Everted gut sac model as a tool in pharmaceutical research: limitations and applications
Authors: Alam Mohd Aftab , Al-Jenoobi Fahad Ibrahim , Al-mohizea Abdullah M
Published: November 2011

Objectives

This review discusses the limitations and applications of the everted gut sac model in studying drug absorption, metabolism, and interaction.

Key findings

The mechanism of drug absorption, interaction and the effect of factors such as age, sex, species, chronic therapy, and disease state on drug absorption have been summarized. The experimental conditions and their effects on the outcomes of trials have been discussed also.

The everted sac model is an efficient tool for studying in-vitro drug absorption mechanisms, intestinal metabolism of drugs, role of transporter in drug absorption, and for investigating the role of intestinal enzymes during drug transport through the intestine.
Transient receptor potential vanilloid-1 participates in the inhibitory effect of ginsenoside Rg1 on capsaicin-induced interleukin-8 and prostaglandin E2 production in HaCaT cells
Authors: Huang Jin , Ding Li , Shi Duo , Hu Jin-hong , Zhu Quan-gang , Gao Shen , Qiu Lei
Published: November 2011

Objectives

Ginsenoside Rg1 (GRg1), one of the major active constituents of Panax notoginseng, has shown anti-inflammatory and antinocioceptic activity, but its role in keratinocytes needs further study. We have examined the inhibitory effect of GRg1 on transient receptor potential vanilloid-1 (TRPV1) activation in keratinocyte HaCaT cells and explored its involved mechanism.

Methods

HEK 293T cells over-expressing exogenous TRPV1 were constructed and named HEK 293T-TRPV1 cells. The effects of GRg1 on production of interleukin-8 (IL-8) and prostaglandin E2 (PGE2), calcium influx, the expression of cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) transcriptional activity in HEK 293T-TRPV1 and HaCaT cells were examined by ELISA, Fluo 3-AM fluorescence probe, Western blot and Dual-Luciferase Reporter Assay, respectively.

Key findings

The results showed that GRg1 blocked intracellular calcium by both capsaicin and proton activation in a TRPV1-dependent manner. Furthermore, GRg1 inhibited the expression of COX-2 and NF-κB transcriptional activity induced by capsaicin in keratinocytes. The inhibitory effect of GRg1 was similar to capsazepine, an antagonist of TRPV1. More importantly, GRg1 dose-dependently inhibited capsaicin-induced PGE2 and IL-8 secretion in HaCaT cells and HEK 293T-TRPV1 cells.

Conclusions

These data showed that GRg1 could inhibit TRPV1 mediated responses in HaCaT cells, indicating that GRg1 acted as a TRPV1 antagonist.
Cointegration methodology for psychological researchers: An introduction to the analysis of dynamic process systems
Authors: Stroe‐Kunold Esther , Gruber Antje , Stadnytska Tetiana , Werner Joachim , Brosig Burkhard
Published: November 2011

Longitudinal data analysis focused on internal characteristics of a single time series has attracted increasing interest among psychologists. The systemic psychological perspective suggests, however, that many long‐term phenomena are mutually interconnected, forming a dynamic system. Hence, only multivariate methods can handle such human dynamics appropriately. Unlike the majority of time series methodologies, the cointegration approach allows interdependencies of integrated (i.e., extremely unstable) processes to be modelled. This advantage results from the fact that cointegrated series are connected by stationary long‐run equilibrium relationships. Vector error‐correction models are frequently used representations of cointegrated systems. They capture both this equilibrium and compensation mechanisms in the case of short‐term deviations due to developmental changes. Thus, the past disequilibrium serves as explanatory variable in the dynamic behaviour of current variables. Employing empirical data from cognitive psychology, psychosomatics, and marital interaction research, this paper describes how to apply cointegration methods to dynamic process systems and how to interpret the parameters under investigation from a psychological perspective.
Di-block copolymer directed anodization of hexagonally ordered nanoporous aluminum oxide
Authors: Noh Kunbae , Choi Chulmin , Kim Hyunsu , Oh Young , Kim Jin-Yeol , Jung Se-Yeon , Seong Tae-Yeon , Jin Sungho
Published: November 2011

Porous anodized aluminum oxide (AAO) nanostructures have been extensively investigated as versatile templates for nanodots and nanowires for many applications. Such self-ordered AAO structures are often achieved by so-called two-step anodization. Ordered pore arrangements can be obtained in the second step after removing the AAO layer formed in the first anodizing step, during which hexagonally ordered, concave-pored Al surface is formed so as to serve as vertical pore nucleation sites for the subsequent anodization step. Although such a two-step anodization process has proven useful for bulk Al surface, the relatively large amount of Al material that needs to be used up to obtain a well ordered AAO template is an issue when the starting material is a thin film layer of Al rather than a bulk Al foil. In this paper, we demonstrate successful fabrications of ordered and vertically aligned AAO nanopore patterns directed by a hexagonally patterned poly(styrene-b-4-vinylpyridine) di-block copolymer layer placed on a thin Al film surface. In addition, a successful electrodeposition of Ni nanowires into the AAO nanopores is demonstrated and their magnetization properties are studied.
N
2
Reduction and Hydrogenation to Ammonia by a Molecular Iron-Potassium Complex
Authors: Rodriguez Meghan M. , Bill Eckhard , Brennessel William W. , Holland Patrick L.
Published: November 2011

A molecular iron complex offers insights into the industrial iron catalyst used to split nitrogen to make ammonia.
Factors Influencing the Microbial Composition of Metalworking Fluids and Potential Implications for Machine Operator's Lung
Authors: Murat Jean-Benjamin , Grenouillet Frédéric , Reboux Gabriel , Penven Emmanuelle , Batchili Adam , Dalphin Jean-Charles , Thaon Isabelle , Millon Laurence
Published: November 2011

Hypersensitivity pneumonitis, also known as “machine operator's lung” (MOL), has been related to microorganisms growing in metalworking fluids (MWFs), especially
Mycobacterium immunogenum
. We aimed to (i) describe the microbiological contamination of MWFs and (ii) look for chemical, physical, and environmental parameters associated with variations in microbiological profiles. We microbiologically analyzed 180 MWF samples from nonautomotive plants (e.g., screw-machining or metal-cutting plants) in the Franche-Comté region in eastern France and 165 samples from three French automotive plants in which cases of MOL had been proven. Our results revealed two types of microbial biomes: the first was from the nonautomotive industry, showed predominantly Gram-negative rods (GNR), and was associated with a low risk of MOL, and the second came from the automotive industry that was affected by cases of MOL and showed predominantly Gram-positive rods (GPR). Traces of
M. immunogenum
were sporadically detected in the first type, while it was highly prevalent in the automotive sector, with up to 38% of samples testing positive. The use of chromium, nickel, or iron was associated with growth of Gram-negative rods; conversely, growth of Gram-positive rods was associated with the absence of these metals. Synthetic MWFs were more frequently sterile than emulsions. Vegetable oil-based emulsions were associated with GNR, while mineral ones were associated with GPR. Our results suggest that metal types and the nature of MWF play a part in MWF contamination, and this work shall be followed by further
in vitro
simulation experiments on the kinetics of microbial populations, focusing on the phenomena of inhibition and synergy.
Vanillin Catabolism in Rhodococcus jostii RHA1
Authors: Chen Hao-Ping , Chow Mindy , Liu Chi-Chun , Lau Alice , Liu Jie , Eltis Lindsay D.
Published: November 2011

Genes encoding vanillin dehydrogenase (
vdh
) and vanillate
O
-demethylase (
vanAB
) were identified in
Rhodococcus jostii
RHA1 using gene disruption and enzyme activities. During growth on vanillin or vanillate,
vanA
was highly upregulated while
vdh
was not. This study contributes to our understanding of lignin degradation by RHA1 and other actinomycetes.
α1,3 Glucans Are Dispensable in Aspergillus fumigatus
Authors: Henry Christine , Latgé Jean-Paul , Beauvais Anne
Published: November 2011

A triple α1,3 glucan synthase mutant of
Aspergillus fumigatus
obtained by successive deletions of the three α1,3 glucan synthase genes (
AGS1
,
AGS2
, and
AGS3
) has a cell wall devoid of α1,3 glucans. The lack of α1,3 glucans affects neither conidial germination nor mycelial vegetative growth and is compensated by an increase in β1,3 glucan and/or chitin content.
Activation of the Cryptic PhnE Permease Promotes Rapid Adaptive Evolution in a Population of Escherichia coli K-12 Starved for Phosphate
Authors: Guillemet Mélanie L. , Moreau Patrice L.
Published: November 2011

Escherichia coli
K-12 suffers acetic acid stress during prolonged incubation in glucose minimal medium containing a limiting concentration of inorganic phosphate (0.1 mM P
i
), which decreases the number of viable cells from 6 × 10
8
to ≤10 CFU/ml between days 6 and 14 of incubation. Here we show that following two serial transfers into P
i
-limiting medium, evolved mutants survived prolonged incubation (≈10
7
CFU/ml on day 14 of incubation). The evolved strains that overtook the populations were generally PhnE
+
, whereas the ancestral K-12 strain carries an inactive
phnE
allele, which prevents the transport of phosphonates. The switching in
phnE
occurred with a high frequency as a result of the deletion of an 8-bp repeated sequence. In a mixed culture starved for P
i
that contained the K-12 ancestral strain in majority, evolved strains grew through PhnE-dependent scavenging of probably organic phosphate esters (not phosphonates or P
i
) released by
E. coli
K-12 between days 1 and 3, before acetic acid excreted by
E. coli
K-12 reached toxic levels. The growth yield of
phnE
+
strains in mixed culture was dramatically enhanced by mutations that affect glucose metabolism, such as an
rpoS
mutation inactivating the alternative sigma factor RpoS. The long-term viability of evolved populations was generally higher when the ancestral strain carried an inactive rather than an active
phnE
allele, which indicates that cross-feeding of phosphorylated products as a result of the
phnE
polymorphism may be essential for the spread of mutants which eventually help populations to survive under P
i
starvation conditions.
Characterization of the Escherichia coli SecA Signal Peptide-Binding Site
Authors: Grady Lorry M. , Michtavy Jennifer , Oliver Donald B.
Published: November 2011

SecA signal peptide interaction is critical for initiating protein translocation in the bacterial Sec-dependent pathway. Here, we have utilized the recent nuclear magnetic resonance (NMR) and Förster resonance energy transfer studies that mapped the location of the SecA signal peptide-binding site to design and isolate signal peptide-binding-defective
secA
mutants. Biochemical characterization of the mutant SecA proteins showed that Ser226, Val310, Ile789, Glu806, and Phe808 are important for signal peptide binding. A genetic system utilizing alkaline phosphatase secretion driven by different signal peptides was employed to demonstrate that both the PhoA and LamB signal peptides appear to recognize a common set of residues at the SecA signal peptide-binding site. A similar system containing either SecA-dependent or signal recognition particle (SRP)-dependent signal peptides along with the
prlA
suppressor mutation that is defective in signal peptide proofreading activity were employed to distinguish between SecA residues that are utilized more exclusively for signal peptide recognition or those that also participate in the proofreading and translocation functions of SecA. Collectively, our data allowed us to propose a model for the location of the SecA signal peptide-binding site that is more consistent with recent structural insights into this protein translocation system.
Escape from a Dominant HLA-B*15-Restricted CD8
+
T Cell Response against Hepatitis C Virus Requires Compensatory Mutations outside the Epitope
Authors: Ruhl Marianne , Chhatwal Patrick , Strathmann Heiko , Kuntzen Thomas , Bankwitz Dorothea , Skibbe Kathrin , Walker Andreas , Heinemann Falko M. , Horn Peter A. , Allen Todd M. , Hoffmann Daniel , Pietschmann Thomas , Timm Jörg
Published: November 2011

Antiviral CD8
+
T cells are a key component of the adaptive immune system against hepatitis C virus (HCV). For the development of immune therapies, it is essential to understand how CD8
+
T cells contribute to clearance of infection and why they fail so often. A mechanism for secondary failure is mutational escape of the virus. However, some substitutions in viral epitopes are associated with fitness costs and often require compensatory mutations. We hypothesized that compensatory mutations may point toward epitopes under particularly strong selection pressure that may be beneficial for vaccine design because of a higher genetic barrier to escape. We previously identified two HLA-B*15-restricted CD8
+
epitopes in NS5B (LLRHHNMVY
2450-2458
and SQRQKKVTF
2466-2474
), based on sequence analysis of a large HCV genotype 1b outbreak. Both epitopes are targeted in about 70% of HLA-B*15-positive individuals exposed to HCV. Reproducible selection of escape mutations was confirmed in an independent multicenter cohort in the present study. Interestingly, mutations were also selected in the epitope flanking region, suggesting that compensatory evolution may play a role. Covariation analysis of sequences from the database confirmed a significant association between escape mutations inside one of the epitopes (H2454R and M2456L) and substitutions in the epitope flanking region (S2439T and K2440Q). Functional analysis with the subgenomic replicon Con1 confirmed that the primary escape mutations impaired viral replication, while fitness was restored by the additional substitutions in the epitope flanking region. We concluded that selection of escape mutations inside an HLA-B*15 epitope requires secondary substitutions in the epitope flanking region that compensate for fitness costs.
Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease
Authors: Frieman Matthew , Yount Boyd , Agnihothram Sudhakar , Page Carly , Donaldson Eric , Roberts Anjeanette , Vogel Leatrice , Woodruff Becky , Scorpio Diana , Subbarao Kanta , Baric Ralph S.
Published: November 2011

SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.
Cross-Species Transmission of Simian Foamy Virus to Humans in Rural Gabon, Central Africa
Authors: Mouinga-Ondémé Augustin , Caron Mélanie , Nkoghé Dieudonné , Telfer Paul , Marx Preston , Saïb Ali , Leroy Eric , Gonzalez Jean-Paul , Gessain Antoine , Kazanji Mirdad
Published: November 2011

In order to characterize simian foamy retroviruses (SFVs) in wild-born nonhuman primates (NHPs) in Gabon and to investigate cross-species transmission to humans, we obtained 497 NHP samples, composed of 286 blood and 211 tissue (bush meat) samples. Anti-SFV antibodies were found in 31 of 286 plasma samples (10.5%). The integrase gene sequence was found in 38/497 samples, including both blood and tissue samples, with novel SFVs in several
Cercopithecus
species. Of the 78 humans, mostly hunters, who had been bitten or scratched by NHPs, 19 were SFV seropositive, with 15 cases confirmed by PCR. All but one were infected with ape SFV. We thus found novel SFV strains in NHPs in Gabon and high cross-species transmission of SFVs from gorilla bites.
A pH-Sensitive Heparin-Binding Sequence from Baculovirus gp64 Protein Is Important for Binding to Mammalian Cells but Not to Sf9 Insect Cells
Authors: Wu Chunxiao , Wang Shu
Published: November 2011

Binding to heparan sulfate is essential for baculovirus transduction of mammalian cells. Our previous study shows that gp64, the major glycoprotein on the virus surface, binds to heparin in a pH-dependent way, with a stronger binding at pH 6.2 than at 7.4. Using fluorescently labeled peptides, we mapped the pH-dependent heparin-binding sequence of gp64 to a 22-amino-acid region between residues 271 and 292. Binding of this region to the cell surface was also pH dependent, and peptides containing this sequence could efficiently inhibit baculovirus transduction of mammalian cells at pH 6.2. When the heparin-binding peptide was immobilized onto the bead surface to mimic the high local concentration of gp64 on the virus surface, the peptide-coated magnetic beads could efficiently pull down cells expressing heparan sulfate but not cells pretreated with heparinase or cells not expressing heparan sulfate. Interestingly, although this heparin-binding function is essential for baculovirus transduction of mammalian cells, it is dispensable for infection of Sf9 insect cells. Virus infectivity on Sf9 cells was not reduced by the presence of heparin or the identified heparin-binding peptide, even though the peptide could bind to Sf9 cell surface and be efficiently internalized. Thus, our data suggest that, depending on the availability of the target molecules on the cell surface, baculoviruses can use two different methods, electrostatic interaction with heparan sulfate and more specific receptor binding, for cell attachment.
Differences in coronary heart disease, stroke and cancer mortality rates between England, Wales, Scotland and Northern Ireland: the role of diet and nutrition
Authors: Scarborough Peter , Morgan Robert David , Webster Premila , Rayner Mike
Published: November 2011

Introduction

It is unclear how much of the geographical variation in coronary heart disease (CHD), stroke and cancer mortality rates within the UK is associated with diet. The aim of this study is to estimate how many deaths from CHD, stroke and cancer would be delayed or averted if Wales, Scotland and Northern Ireland adopted a diet equivalent in nutritional quality to the English diet.

Methods

Mortality data for CHD, stroke and 10 diet-related cancers for 2007–2009 were used to calculate the mortality gap (the difference between actual mortality and English mortality rates) for Wales, Scotland and Northern Ireland. Estimates of mean national consumption of 10 dietary factors were used as baseline and counterfactual inputs in a macrosimulation model (DIETRON). An uncertainty analysis was conducted using a Monte Carlo simulation with 5000 iterations.

Results

The mortality gap in the modelled scenario (achieving the English diet) was reduced by 81% (95% credible intervals: 62% to 108%) for Wales, 40% (33% to 51%) for Scotland and 81% (67% to 99%) for Northern Ireland, equating to approximately 3700 deaths delayed or averted annually. For CHD only, the mortality gap was reduced by 88% (69% to 118%) for Wales, 58% (47% to 72%) for Scotland, and 88% (70% to 111%) for Northern Ireland.

Conclusion

Improving the average diet in Wales, Scotland and Northern Ireland to a level already achieved in England could have a substantial impact on reducing geographical variations in chronic disease mortality rates in the UK. Much of the mortality gap between Scotland and England is explained by non-dietary risk factors.
Condom use and partnership intimacy among drug injectors and their sexual partners in Estonia: Table 1
Authors: Uusküla Anneli , Abel-Ollo Katri , Markina Anna , McNutt Louise-Anne , Heimer Robert
Published: November 2011

Objectives

Young age coupled with a high HIV prevalence among injection drug users (IDUs) and the prevalence of drug use in Eastern Europe can lead from an HIV epidemic concentrated among IDU to a self-sustained heterosexual HIV epidemic. Our objective was to explore the contexts of the prevention of sexual transmission of HIV among IDUs and their sexual partners and to provide insight into beliefs and behaviours related to condom use.

Methods

The authors undertook in-depth qualitative interviews to explore narratives about experience of preventing sexual transmission of HIV among 27 individuals (15 current IDUs and 12 main sexual partners of IDUs) in Kohtla-Järve, Estonia.

Results

The safe-sex ‘norm’ was not common and factors that tended to reduce condom use included valuing the relationship above health risks, established gender roles, perceptions that condoms distributed via harm reduction programmes were of low quality and the stigma attached to HIV status disclosure. HIV risk management strategies among participants included consistent condom use and serosorting but were countered by a fatalism that encompassed consciously subjecting oneself to the inevitability of HIV infection in an HIV-discordant sexual partnership.

Conclusions

Qualitative methods can significantly contribute to the prevention of sexual transmission of HIV among and beyond IDUs by improving our understanding of risky behaviours and the reasons for such behaviours that can be incorporated into tailored public health interventions.