bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile Crisis Team Intervention to Enhance Linkage of Discharged Suicidal Emergency Department Patients to Outpatient Psychiatric Services: A Randomized Controlled Trial
Authors: Currier Glenn W. , Fisher Susan G. , Caine Eric D.
Published: December 2009

Objectives:  Many suicidal patients treated and released from emergency departments (ED) fail to follow through with subsequent outpatient psychiatric appointments, often presenting back for repeat ED services. Thus, the authors sought to determine whether a mobile crisis team (MCT) intervention would be more effective than standard referral to a hospital‐based clinic as a means of establishing near‐term clinical contact after ED discharge. This objective was based on the premise that increased attendance at the first outpatient mental health appointment would initiate an ongoing treatment course, with subsequent differential improvements in psychiatric symptoms and functioning for patients successfully linked to care.

Methods:  In a rater‐blinded, randomized controlled trial, 120 participants who were evaluated for suicidal thoughts, plans, or behaviors, and who were subsequently discharged from an urban ED, were randomized to follow‐up either in the community via a MCT or at an outpatient mental health clinic (OPC). Both MCTs and OPCs offered the same structured array of clinical services and referral options.

Results:  Successful first clinical contact after ED discharge (here described as “linkage” to care) occurred in 39 of 56 (69.6%) participants randomized to the MCT versus 19 of 64 (29.6%) to the OPC (relative risk = 2.35, 95% CI = 1.55–3.56, p < 0.001). However, we detected no significant differences between groups using intention‐to‐treat analyses in symptom or functional outcome measures, at either 2 weeks or 3 months after enrollment. We also found no significant differences in outcomes between participants who did attend their first prescribed appointment via MCT or OPC versus those who did not. However divided (MCT vs. OPC, present at first appointment vs. no show), groups showed significant improvements but maintained clinically significant levels of dysfunction and continued to rely on ED services at a similar rate in the 6 months after study enrollment.

Conclusions:  Community‐based mobile outreach was a highly effective method of contacting suicidal patients who were discharged from the ED. However, establishing initial postdischarge contact in the community versus the clinic did not prove more effective at enhancing symptomatic or functional outcomes, nor did successful linkage with outpatient psychiatric care. Overall, participants showed some improvement shortly after ED discharge regardless of outpatient clinical contact, but nonetheless remained significantly symptomatic and at risk for repeated ED presentations.

ACADEMIC EMERGENCY MEDICINE 2010; 17:36–43 © 2009 by the Society for Academic Emergency Medicine
Session 1 ‐ Reflecting our roles, skills and ethics Hiroshi Tamura (Hakuhoda, Japan), Curator: Taking the Driver's Seat: Sustaining Critical Enquiry While Becoming a Legitimate Corporate Decision‐Maker
Authors: Depaula Rogerio , Thomas Suzanne L. , Lang Xueming
Published: December 2009

Staying relevant (to the business) is at the heart of career‐advancement and (increasingly) job‐security, particularly, in a business unit. It embodies a number of different meanings to the different players in corporate–from supporting product definition to creating strategic plans to making the appropriate business decisions. Rather surprisingly, though, we find EPIC talking about it with a certain discomfort, particularly when it comes to affect our identities as social researchers. On the other hand, we, in the industry, have little choice but to “play the game” and find ways whereby we can best utilize our knowledge, experiences, skills, our unique perspective to endow us an edge–creating interesting possibilities to stay relevant. This paper investigates our own trajectories in the past few years in a product group at Intel where we suddenly found ourselves increasingly more involved with decision‐making, taking actions that would ultimately affect the course of the business and our own careers. Unwittingly or not, this shift has become part of a strategy for negotiating relevance in ever changing business environments.
The De‐Skilling of Ethnographic Labor: Signs of an Emerging Predicament
Authors: Lombardi Gerald
Published: December 2009

An oft‐stated rule in design and engineering is, “Good, fast, cheap: pick two”. The success of ethnography in business has forced this rule into action with a vengeance. As a result, ethnographers now face a threat experienced by many categories of worker over the past two centuries: job de‐skilling. Some mechanisms of de‐skilling in business‐world ethnography are reviewed, including:

simplifications that invert the conventional depth‐vs.‐breadth balance of ethnographic knowledge;

standardizations that permit research to be distributed among workers of varying cost;

the rise of ethnographic piecework suppliers who rely on pools of underemployed social scientists.

I argue that pressures leading in this direction must be contested, and that only by altering the cost‐time‐quality paradigm that controls our work can we restore its value to our employers and clients.
Session 2 ‐ Redefining what's CORE Brian Rink (IDEO, USA), Curator: Flexibility and the Curatorial Eye: Why and How Well‐Documented Fieldwork Sustains Value Over Time
Authors: Churchill Elizabeth F. , Elliott Ame
Published: December 2009

This paper discusses two distinguishing features of ethnographic work, program flexibility and data flexibility. These forms of flexibility deliver business benefits at two different timeframes. Within the timeframe of a given project, ethnographic practice is necessarily reflective and reflexive; ethnographic training insists researchers be flexible. This means projects are responsive to emerging results, and can be reframed in situ without significant additional investment. After the project has completed, carefully managed, stored and curated ethnographic materials can answer new questions, perhaps posed years after the project has ended. Thus, ethnographic work can generate business impact by sustaining value over time. Two cases illustrate the value‐generating qualities of ethnographic work: one recently conducted investigation of drinking water in India and one conducted ten years ago looking at changes in collaborative practices as a result of the adoption of mobile technologies. Discussion of these cases illustrates the importance of flexibility and the curatorial eye for generating business value from ethnography.
“Name That Segment!”: Questioning the Unquestioned Authority of Numbers
Authors: Flynn Donna K. , Lovejoy Tracey , Siegel David , Dray Susan
Published: December 2009

In many companies, numbers equal authority. Quantitative data is often viewed as more definitive than qualitative data, while its shortcomings are overlooked. Many of us have worked to marry quantitative with qualitative methods inside organizations to present a fuller view of the people for whom we develop. One area of research that increasingly needs to blend quantitative and qualitative methods is user segmentations. Our software technology product team has been using a segmentation based on quantitative data since 2005. One outcome of this effort has been the development of an algorithm‐based “typing” tool intended to be used as a standard tool in recruiting for all segmentation‐focused research. We learned that the algorithm was an indecipherable black box, its inner workings opaque even to those who owned it internally. This case study looks at how qualitative research came up against the impenetrable authority of a quantitative segmentation and its associated typing tool, and subsequently contributed to the redesign of future segmentation methodologies and the integration of qualitative research as a key component of segmentation creation.
“Let's bring it up to b flat” ‐ What Style Offers Applied Ethnographic Work
Authors: Robinson Rick E.
Published: December 2009

Ethnographic and design work share, deeply, the challenge of conveying the truth of the work we do to interlocutors from very different backgrounds. Writing is hard work even with the shared culture that an academic discipline or a single firm can draw upon. How, then, to write well for broad and varied audiences? By writing like novelists. Literary critic James Wood encapsulates the central tradition of the novel as: “Truthfulness to the way things are […] Life on the page, life brought to different life by the highest artistry.” (2008:247) It is hard to conceive of a better description of what most of us would like to achieve. “Truthfulness to the way things are” gets nicely to all of the important moments of what we do–observation, description, interpretation, inscription. In this paper, I try to move ‘style’ up the ladder of importance in how we think, write, and talk about the work we do.
Session 3 ‐ New Niches for Old: Adding Value in an Economic Downturn Paul Durrenberger (Penn State Univ, USA), Curator: Challenges and Opportunities for Ethnographic Market Research in Uncertain Times
Authors: Zelt Ean
Published: December 2009

While we believe in‐depth, observational approaches are still the most powerful way of developing an understanding of users, we must adapt our approach to fit within current economic constraints. One way is to employ economical phases of research that support and strengthen data gathered from in‐person, in‐context engagements. Specifically, these are preliminary landscape and trends analysis, which provides focused paths of inquiry, and online engagement, which allows us to interact with people over a longer period of time and identify stronger participants for in‐person research. The second is to demonstrate to clients how our approaches are broadly applicable and scalable–in terms of activities, participant numbers, and length of engagement–to meet today's immediate goals. Instead of seeing merely compromise, we see opportunity. The adaptations brought on by our new reality are helping us to develop new ways to bring value to clients and challenging us to be creative in ways that will continue to be relevant even after the economy rebounds.
Contextualizing Customers
Authors: Johnsnen Truls Erik , Helmersen Per
Published: December 2009

This paper is based on fieldwork in Pakistan and Malawi and focuses on the importance of communicating contextualizing stories to HQ and business developer teams. By means of an explorative approach–even in highly structured commercial projects with formalized needs–we've uncovered findings and generated understandings that would be hard to pinpoint from a desktop‐based pre‐study or demand driven fieldwork. These findings in turn have proven to be important tools for said business developers in spite of the fact that they were not included in the initial fieldwork specification. Since our respondents are seen, heard and understood as far as possible within their own framework of values, priorities and aspirations, we, as researchers, are in a position to communicate a well‐grounded and more refined picture of their daily lives rather than merely communicating the measurable hard facts back to corporate business developers.
Designing for Turkish Users: Analyzing the Industrial Designer ‐ User Relationship in Turkey
Authors: Oygur Isil
Published: December 2009

From the perspective of industrial design, user‐centered design denotes more than a methodology to understand users. More importantly, it is a medium to create a relationship between designers and users. While user‐centered design has much to offer, user research is not a convention in emerging economies. In this context, this paper puts one such emerging market, Turkey, under scrutiny. Six case studies give a snapshot of the current status of product design in general, and user‐centered design in particular, in this country. One of the key findings is that, compared to the West, there is a wider gap between designers and users in the Turkish context. Besides economic situations, the eclectic character of Turkish culture plays the biggest role in the expansion of this gap. The application of Western oriented research methods and concentration on global trends also stand as barriers for user‐centeredness. In order to ensure products' success through research, Turkey needs to develop its own user‐centered design model.
Consumerization and Renewing Peoples and Practices Research
Authors: Nafus Dawn , de Paula Rogerio , Kitner Kathi , Kuriyan Renee , Mainwaring Scott
Published: December 2009

This paper documents the beginnings of Intel's recently launched Consumerization project, and uses these early experiences as a way into exploring new paths to business relevance and impact. These paths weave in and out of the increasingly institutionalized position of corporate ethnography as research that takes place before products are designed. These paths are one response to wider transformations in the business environment, and are not a general prescription, “ethnography should now do X in corporations.” However, this project does embody a significant move away from past modalities of conducting and applying research, and in doing so reveals broader possibilities for ethnography that may prove viable for others in different contexts. We begin by providing some institutional history and exploring the wider industry transformations that compelled us to design a research project in the way that we did. The paper goes on to describe our approach in meeting the challenges of this new environment, both conceptually and methodologically. Finally we reflect on some of the very early partnerships we are now able to cultivate and grow as a result.
Tangible Steps Toward Tomorrow: Designing a Vision for Early Childhood Education
Authors: Carey Hillary , Howard Suzanne Gibbs
Published: December 2009

“The area of early education is experiencing tremendous experimentation and progress, but what has been missing are right brain thinkers. These are individuals whose craft is seeing patterns, making connections, adapting what works in one context to the realities of another context.” ‐ Tony Berkley, Program Director, Youth and Education, The W. K. Kellogg Foundation

In 2007 the W. K. Kellogg Foundation engaged the innovation and design firm, IDEO, to design a compelling vision for the future of early childhood education. The foundation was ready for a new perspective on a well‐explored topic. IDEO's design thinking approach engaged the foundation and its stakeholders in new ways that promoted feasible, yet innovative, solutions.

In this paper we describe the combined use of ethnographic‐style research and design thinking in a project addressing a complex, systemic and philanthropic challenge: public education in the United States. We seek to provide the reader with a clear and convincing case study demonstrating the value of ethnography plus design thinking in any business context or social system where many stakeholders need to be brought together to work toward a system wide solution.
How transgenic and classically bred apple genotypes affect non‐target organisms on higher trophic levels
Authors: Vogler Ute , Rott Anja S. , Gessler Cesare , Dorn Silvia
Published: December 2009

Current plant breeding comprises classical techniques as well as biotechnological methods suitable to insert target genes into the plant genome. Potential non‐target effects of these newly developed plants have to be evaluated in appropriate risk assessment studies. We investigated non‐target effects of four apple genotypes (Malus × domestica L. Borkh.; Rosaceae). They were either susceptible or resistant to the fungal phytopathogen causing apple scab, Venturia inaequalis (Cke.) Wint. (Ascomycotina: Pleosporales), and were either of transgenic origin or classically bred, differing in or sharing a single trait each. Experiments on insect performance were carried out with two non‐target species, namely the apple leafminer Phyllonorycter blancardella Fabricius (Lepidoptera: Gracillariidae) and its parasitoid Pholetesor circumscriptus Nees (Hymenoptera: Braconidae). Development time of the apple leafminer was not affected by the four apple genotypes. By contrast, the number of emerged adult moths significantly differed between the two classically bred cultivars, whereas no effect of the two transgenic apple genotypes was detected. Paralleling the observations of the apple leafminer development, no impact of the four apple genotypes on parasitoid development time and parasitism success could be detected. Although mean numbers of emerged parasitoids were lower on the cultivars with fewer emerged apple leafminers, these differences were not significant. Herbivore and parasitoid performance was not altered in the presence of pathogen inoculation. In conclusion, host plant suitability was found to be more determined by variability among classically bred apple cultivars than by the transgenic genotypes tested. To elucidate possible effects of transgenic plants within multitrophic interactions, an appropriate risk assessment incorporating the relevant controls is crucial.
25‐Hydroxy‐vitamin D levels among Callithrix penicillata primate species raised in captivity
Authors: Teixeira Danilo Simonini , Castro Luiz Claudio G. , Nóbrega Yanna Karla M. , Almeida Rodrigo Coutinho , Gandolfi Lenora , Pratesi Riccardo
Published: December 2009

Background  Animals in captivity should receive adequate sunlight exposure for sufficient generation of vitamin D [25(OH)D]. In the present study, 25(OH)D serum levels of 84 Callithrix penicillata primates were evaluated.

Objectives  To determine 25(OH)D levels of those animals; to evaluate the influence of gender and period of sunlight exposure on their 25(OH)D levels.

Methods  Three groups were evaluated: group 1 (n = 29) on free sunlight exposure; group 2 (n = 34) on partial sunlight exposure; group 3 (n = 21) without sunlight exposure.

Results  The obtained 25(OH)D values were: group 1, 121.2 ± 33.3 ng/ml; group 2, 115.2 ± 32.2 ng/ml; group 3, 53.3 ± 10.4 ng/ml. Significant statistical differences were obtained between groups 1 and 3 (p < 0.001) and groups 2 and 3 (p < 0.001); no statistical difference was found between genders.

Conclusion  Direct sunlight exposure is essential for 25(OH)D sufficiency and it is proposed that the 25(OH)D normal range for captive Callithrix penicillata would be from 104.8 to 137.1 ng/ml (CI = 95%).
From Control to Ownership: China's Managerial Revolution
Authors: Walder Andrew G.
Published: December 2009

Over the past decade, the ownership and control of China's corporate sector has finally begun to depart fundamentally from patterns typical in the socialist past. Students of corporate governance have watched these changes with an intense curiosity about their impact on firm performance. Students of comparative economic institutions have examined them for hints of a new variety of Asian capitalism and have sought to anticipate China's international competitiveness and impact. But these changes potentially will create a new corporate elite with greater compensation, personal wealth, and independence from government agencies than ever before. This transformation of China's political economy may eventually alter the Chinese state itself, although the extent and nature of this change are still far from clear. The key questions of interest are the social origins of the new elite, the scale of the economic assets they control, and especially their continuing relationships with party and government agencies. The answers will vary decisively by sector, four of which are described here: a state-owned sector, a privatized sector, a transactional sector, and an entrepreneurial sector. The evolving mix of these sectors will determine the future contours of the Chinese corporate economy.
Enhanced sensitivity to hydrogen peroxide‐induced apoptosis in Evi1 transformed Rat1 fibroblasts due to repression of carbonic anhydrase III
Authors: Roy P. , Reavey E. , Rayne M. , Roy S. , Abed El Baky M. , Ishii Y. , Bartholomew C.
Published: December 2009

EVI1 is a nuclear zinc finger protein essential to normal development, which participates in acute myeloid leukaemia progression and transforms Rat1 fibroblasts. In this study we show that enforced expression of Evi1 in Rat1 fibroblasts protects from paclitaxel‐induced apoptosis, consistent with previously published studies. Surprisingly, however, these cells show increased sensitivity to hydrogen peroxide (H2O2)‐induced apoptosis, demonstrated by elevated caspase 3 catalytic activity. This effect is caused by a reduction in carbonic anhydrase III (caIII) production. caIII transcripts are repressed by 92–97% by Evi1 expression, accompanied by a similar reduction in caIII protein. Reporter assays with the rat caIII gene promoter show repressed activity, demonstrating that Evi1 either directly or indirectly modulates transcription of this gene in Rat1 cells. Targeted knockdown of caIII alone, with Dicer‐substrate short inhibitory RNAs, also increases the sensitivity of Rat1 fibroblasts to H2O2, which occurs in the absence of any other changes mediated by Evi1 expression. Enforced expression of caIII in Evi1‐expressing Rat1 cells reverts the phenotype, restoring H2O2 resistance. Together these data show that Evi1 represses transcription of caIII gene expression, leading to increased sensitivity to H2O2‐induced apoptosis in Rat1 cells and might suggest the basis for the development of a novel therapeutic strategy for the treatment of leukaemias and solid tumours where EVI1 is overexpressed.
Novel l‐amino acid oxidase with antibacterial activity against methicillin‐resistant Staphylococcus aureus isolated from epidermal mucus of the flounder Platichthys stellatus
Authors: Kasai Kosuke , Ishikawa Takashi , Komata Takafumi , Fukuchi Kaori , Chiba Mitsuru , Nozaka Hiroyuki , Nakamura Toshiya , Sato Tatsusuke , Miura Tomisato
Published: December 2009

Fish produce mucus substances as a defensive outer barrier against environmental xenobiotics and predators. Recently, we found a bioactive protein in the mucus layer of the flounder Platichthys stellatus, which showed antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus and methicillin‐resistant S. aureus. In this study, we isolated and identified the antibacterial protein from the mucus components of P. stellatus using a series of column chromatography steps. We then performed gel electrophoresis and cDNA cloning to characterize the protein. The antibacterial protein in the mucus had a molecular mass of approximately 52 kDa with an isoelectric point of 5.3, and cDNA sequencing showed that it corresponded completely with the peptide sequence of antibacterial protein from the gill. A BLAST search suggested that the cDNA encoded an antibacterial protein sharing identity with a number of l‐amino acid oxidases (LAAOs) and possessing several conserved motifs found in flavoproteins. RT‐PCR using a specific primer, and immunohistochemical analysis with anti‐LAAO IgG, demonstrated tissue‐specific expression and localization in the gill. Moreover, the anti‐LAAO IgG was able to neutralize the antibacterial activity of the protein against methicillin‐resistant S. aureus. Thus, we demonstrated that this antibacterial protein, identified from P. stellatus‐derived epidermal mucus, is a novel LAAO‐like protein with antibacterial activity, similar to snake LAAOs.
Application of the Fc fusion format to generate tag‐free bi‐specific diabodies
Authors: Asano Ryutaro , Ikoma Keiko , Kawaguchi Hiroko , Ishiyama Yuna , Nakanishi Takeshi , Umetsu Mitsuo , Hayashi Hiroki , Katayose Yu , Unno Michiaki , Kudo Toshio , Kumagai Izumi
Published: December 2009

We previously reported the use of a humanized bi‐specific diabody that targets epidermal growth factor receptor and CD3 (hEx3‐Db) for cancer immunotherapy. Bacterial expression can be used to express small recombinant antibodies on a large scale; however, their overexpression often results in the formation of insoluble aggregates, and in most cases artificial affinity peptide tags need to be fused to the antibodies for purification by affinity chromatography. Here, we propose a novel method for preparing refined, functional, tag‐free bi‐specific diabodies from IgG‐like bi‐specific antibodies (BsAbs) in a mammalian expression system. We created an IgG‐like BsAb in which bi‐specific diabodies were fused to the human Fc region via a designed human rhinovirus 3C (HRV3C) protease recognition site. The BsAb was purified by protein A affinity chromatography, and the refined tag‐free hEx3‐Db was efficiently produced from the Fc fusion format by protease digestion. The tag‐free hEx3‐Db from the Fc fusion format showed a greater inhibition of cancer growth than affinity‐tagged hEx3‐Db prepared directly from Chinese hamster ovary cells. We also applied our novel method to another small recombinant antibody fragment, hEx3 single‐chain diabody (hEx3‐scDb), and demonstrated the versatility and advantages of our proposed method compared with papain digestion of hEx3‐scDb. This approach may be used for industrial‐scale production of functional tag‐free small therapeutic antibodies.
From meiosis to postmeiotic events: Uncovering the molecular roles of the meiosis‐specific recombinase Dmc1
Authors: Kagawa Wataru , Kurumizaka Hitoshi
Published: December 2009

In meiosis, the accurate segregation of maternal and paternal chromosomes is accomplished by homologous recombination. A central player in meiotic recombination is the Dmc1 recombinase, a member of the RecA/Rad51 recombinase superfamily, which is widely conserved from viruses to humans. Dmc1 is a meiosis‐specific protein that functions with the ubiquitously expressed homolog, the Rad51 recombinase, which is essential for both mitotic and meiotic recombination. Since its discovery, it has been speculated that Dmc1 is important for unique aspects of meiotic recombination. Understanding the distinctive properties of Dmc1, namely, the features that distinguish it from Rad51, will further clarify the mechanisms of meiotic recombination. Recent structural, biochemical, and genetic findings are now revealing the molecular mechanisms of Dmc1‐mediated homologous recombination and its regulation by various recombination mediators.
Very long-term X-ray variations in LMXBs: solar cycle-like variations in the donor?
Authors: Kotze M. M. , Charles P. A.
Published: December 2009

Long-term monitoring of Low Mass X-ray Binaries (LMXBs) by the All Sky Monitor on board the Rossi X-ray Timing Explorer now covers ∼13 yr and shows that certain LMXB types display very long-term (approximately several to tens of years) quasi-periodic modulations. These time-scales are much longer than any ‘super-orbital’ periods reported hitherto and likely have a different origin. We suggest here that they are due to long-term variations in the mass-transfer rate from the donor, which are a consequence of solar-like magnetic cycles that lead to Porb changes (as proposed by Richman, Applegate & Patterson for similar long-term variations in cataclysmic variables). Atoll sources display much larger amplitude modulations than Z sources over these time-scales, presumably because Z sources are Eddington limited and hence unable to respond as readily as Atoll sources to fluctuations in the mass-transfer rate from the donor.
Endoscopic removal of an endodontic file accidentally swallowed: Clinical and legal approaches
Authors: Silva Rhonan F. , Martins Emerson C. , Prado Felippe B. , Júnior Jacy R.C. , Júnior Eduardo D.
Published: December 2009

The use of a rubber dam is an essential procedure when treating root canals, and not using it may compromise the success of the treatment, as well as the patient's health. This report presents a case in which a K‐file was accidentally swallowed during an endodontic procedure, performed without the use of a rubber dam. Given the absence of immediate clinical complications, the subject underwent a chest radiograph. The file was located at the oesophagogastric junction and was later removed by endoscopy. In addition to the clinical repercussions, this example also illustrates the ethical‐legal aspects of this type of accident.
DIAGENETIC EVOLUTION OF INCISED CHANNEL SANDSTONES: IMPLICATIONS FOR RESERVOIR CHARACTERISATION OF THE LOWER CARBONIFEROUS MARAR FORMATION, GHADAMES BASIN, WESTERN LIBYA
Authors: Fröhlich S. , Redfern J. , Petitpierre L. , Marshall J.D. , Power M. , Grech P.V.
Published: December 2009

This paper assesses the diagenetic history of potential fluvial hydrocarbon reservoir rocks deposited within incised valley systems of the Lower Carboniferous Marar Formation in western Libya. Outcrop data were collected in the Tinedhan Anticline, located at the southern margin of the Ghadames Basin. Four discrete intervals with channelized sandstones were identified in a section dominated by alternating offshore mudstones and shallow‐marine clastics. The incised channels were cut during major sea‐level lowstands, and filled by fluvial sandstone packages up to 50 m thick. Fifty‐eight samples from four different localities, representing three lowstand systems tracts, were analysed to obtain a statistically meaningful mineralogical and compositional dataset.

In addition to burial compaction, three main diagenetic events influenced the reservoir quality of the sandstones. Firstly, early eodiagenesis involved kaolinitization of plagioclase grains. This began before subsequent calcite cementation, probably as a result of flushing by meteoric pore‐waters. The deformation of kaolinite during later compaction resulted in the formation of pseudomatrix which further reduced porosity and permeability. Kaolinite is commonly transformed to illite at temperatures above 140°C in the presence of K‐feldspar. Although K‐feldspar was recorded in the samples, no illite was observed, suggesting that the Lower Carboniferous strata in the study area were not buried in excess of approximately 3.5 km.

The second diagenetic phase was the precipitation of calcite cement, present either dispersed throughout the sandbodies or as concretions up to 2 m across, in both cases reducing reservoir quality. The high intergranular volumes (IGV) of calcite‐cemented sandstones (ranging between 35% and 40%) suggest that cementation occurred at burial depths of <500 m. Sandstones without calcite cement have lower IGV of between 17% and 25% as a result of mechanical and chemical compaction. Stable C and O isotope analysis of the calcite cement also supports precipitation at shallow burial depths, indicating a meteoric pore‐water source for the calcite. The third and final diagenetic stage was partial chloritisation of kaolinite during meso‐diagenesis. The elevated temperatures required for this transformation indicate burial to a minimum depth of approximately 2.5 km, which is consistent with the compaction data.

Despite these diagenetic effects, the fluvial sandstones have an average porosity of 12%, with a range from 0.5% up to 25%. Permeability measurements on four sandstone samples indicate that the development of pseudomatrix did not reduce permeability significantly.
DOLOMITIZATION AND ANHYDRITE PRECIPITATION IN PERMO‐TRIASSIC CARBONATES AT THE SOUTH PARS GASFIELD, OFFSHORE IRAN: CONTROLS ON RESERVOIR QUALITY
Authors: Rahimpour‐Bonab H. , Esrafili‐Dizaji B. , Tavakoli V.
Published: December 2009

Dolomitization and related anhydrite cementation can complicate the characterization of carbonate reservoirs. Both processes have affected the Permo‐Triassic Upper Dalan – Kangan carbonates, the main reservoir at the South Pars gasfield, offshore Iran. The carbonates were deposited in a shallow‐marine ramp or epeiric platform and, according to previous studies, underwent intense near‐surface diagenesis and minor burial modification. Detailed petrographical and geochemical analyses indicate that dolomitization and anhydrite precipitation can be explained in terms of the sabkha/seepage‐reflux models. The early dolomites then re‐equilibrated or re‐crystallized in a shallow burial setting. Evaluation of poroperm values in different reservoir intervals indicates that replacive dolomitization in the absence of anhydrite precipitation or with only patchy anhydrite has enhanced the reservoir quality. Where anhydrite cement is pervasive and has plugged the rock fabric, poroperm values are significantly decreased.

As emphasized in previous studies and confirmed here, dolomitization and anhydrite cementation, together with original facies type, are the major factors controlling reservoir quality in the Dalan – Kangan carbonates at South Pars. When associated with minor anhydrite cementation, replacive dolomitization has enhanced reservoir quality by increasing permeability. However, porosity in fabric‐retentive dolomite was apparently inherited from the precursor rock and therefore reflects the original depositional environment.

Low‐temperature dolomitization is commonly fabric‐selective and partially fabric‐retentive. Whole rock stable isotope thermometry indicates that fabric‐destructive dolomites in the reservoir rocks formed at temperatures above 22°C, whereas fabric‐retentive dolomites and associated anhydrites formed in surface and near‐surface conditions. Fabric‐destructive dolomite or dolomite neomorphism post‐date fabric‐retentive dolomite and continued to form in deep burial conditions (∼1400m). These observations may explain why fabric‐retentive dolomite and anhydrite fabrics are traversed by stylolites.
Smoothable del Pezzo surfaces with quotient singularities
Authors: Hacking Paul , Prokhorov Yuri
Published: December 2009

We classify del Pezzo surfaces with quotient singularities and Picard rank one which admit a ℚ-Gorenstein smoothing. These surfaces arise as singular fibres of del Pezzo fibrations in the 3-fold minimal model program and also in moduli problems.
Evaluation of WLBU2 Peptide and 3-
O
-Octyl-
sn
-Glycerol Lipid as Active Ingredients for a Topical Microbicide Formulation Targeting
Chlamydia trachomatis
Authors: Skinner M. C. , Kiselev A. O. , Isaacs C. E. , Mietzner T. A. , Montelaro R. C. , Lampe M. F.
Published: December 2009

Topical microbicides for prevention of sexually transmitted diseases (STDs) would be especially useful for women who are not able to persuade their partner(s) to take precautions. Many topical microbicides are in various stages of development, based on a variety of active ingredients. We investigated the
in vitro
activity of an engineered antimicrobial peptide (WLBU2) and a lipid (3-
O
-octyl-
sn
-glycerol [3-OG]) which could potentially be used as active ingredients in such a product. Using commercially available cytotoxicity reagents [Alamar Blue, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH)], we first determined the toxicity of WLBU2 and 3-OG to the host cells in our assay procedure and excluded toxic concentrations from further testing. To determine activity against
Chlamydia trachomatis
, we used an assay previously developed by our laboratory in which chlamydial elementary bodies (EBs) were exposed to microbicides prior to contact with epithelial cells: the minimum (microbi)cidal concentration (MCC) assay. To further simulate conditions of transmission, we carried out the same assay in the presence of a simulated vaginal fluid, a simulated seminal fluid, human serum albumin, and a range of pH values which might be found in the human vagina at the time of exposure. Last, we tested WLBU2 and 3-OG in combination to determine if adding them together resulted in synergistic activity. We found that WLBU2 and 3-OG both have excellent activity
in vitro
against
C. trachomatis
and significantly more activity when added together. The simulated fluids reduced activity, but the synergy seen is good evidence that they would be effective when combined in a microbicide formulation.
Constitutive SoxS Expression in a Fluoroquinolone-Resistant Strain with a Truncated SoxR Protein and Identification of a New Member of themarA-soxS-robRegulon,mdtG
Authors: Fàbrega Anna , Martin Robert G. , Rosner Judah L. , Tavio M. Mar , Vila Jordi
Published: December 2009

Elevated levels of fluoroquinolone resistance are frequently found amongEscherichia coliclinical isolates. This study investigated the antibiotic resistance mechanisms of strain NorE5, derivedin vitroby exposing anE. coliclinical isolate, PS5, to two selection steps with increasing concentrations of norfloxacin. In addition to the amino acid substitution in GyrA (S83L) present in PS5, NorE5 has an amino acid change in ParC (S80R). Furthermore, we now find by Western blotting that NorE5 has a multidrug resistance phenotype resulting from the overexpression of the antibiotic resistance efflux pump AcrAB-TolC. Microarray and gene fusion analyses revealed significantly increased expression in NorE5 ofsoxS, a transcriptional activator ofacrABandtolC. The highsoxSactivity is attributable to a frameshift mutation that truncates SoxR, rendering it a constitutive transcriptional activator ofsoxS. Furthermore, microarray and reverse transcription-PCR analyses showed thatmdtG(yceE), encoding a putative efflux pump, is overexpressed in the resistant strain. SoxS, MarA, and Rob activated anmdtG::lacZfusion, and SoxS was shown to bind to themdtGpromoter, showing thatmdtGis a member of themarA-soxS-robregulon. ThemdtGmarbox sequence is in the backward or class I orientation within the promoter, and its disruption resulted in a loss of inducibility by MarA, SoxS, and Rob. Thus, chromosomal mutations inparCandsoxRare responsible for the increased antibiotic resistance of NorE5.
Newly Identified Antibacterial Compounds Are Topoisomerase Poisons in African Trypanosomes
Authors: Tang Sonya C. , Shapiro Theresa A.
Published: December 2009

Human African trypanosomiasis, caused by the
Trypanosoma brucei
protozoan parasite, is fatal when left untreated. Current therapies are antiquated, and there is a need for new pharmacologic agents against
T. brucei
targets that have no human ortholog. Trypanosomes have a single mitochondrion with a unique mitochondrial DNA, known as kinetoplast DNA (kDNA), a topologically complex network that contains thousands of interlocking circular DNAs, termed minicircles (∼1 kb) and maxicircles (∼23 kb). Replication of kDNA depends on topoisomerases, enzymes that catalyze reactions that change DNA topology.
T. brucei
has an unusual type IA topoisomerase that is dedicated to kDNA metabolism. This enzyme has no ortholog in humans, and RNA interference (RNAi) studies have shown that it is essential for parasite survival, making it an ideal drug target. In a large chemical library screen, two compounds were recently identified as poisons of bacterial topoisomerase IA. We found that these compounds are trypanocidal in the low micromolar range and that they promote the formation of linearized minicircles covalently bound to protein on the 5′ end, consistent with the poisoning of mitochondrial topoisomerase IA. Surprisingly, however, band depletion studies showed that it is topoisomerase II
mt
, and not topoisomerase IA
mt
, that is trapped. Both compounds are planar aromatic polycyclic structures that intercalate into and unwind DNA. These findings reinforce the utility of topoisomerase II
mt
as a target for development of new drugs for African sleeping sickness.
Characterization of Small ColE-Like Plasmids Mediating Widespread Dissemination of the
qnrB19
Gene in Commensal Enterobacteria
Authors: Pallecchi Lucia , Riccobono Eleonora , Sennati Samanta , Mantella Antonia , Bartalesi Filippo , Trigoso Christian , Gotuzzo Eduardo , Bartoloni Alessandro , Rossolini Gian Maria
Published: December 2009

In this work, we have characterized two small ColE-like plasmids (pECY6-7, 2.7 kb in size, and pECC14-9, of 3.0 kb), encoding the QnrB19 quinolone resistance determinant, that were carried by several clonally unrelated quinolone-resistant commensal
Escherichia coli
strains isolated from healthy children living in different urban areas of Peru and Bolivia. The two plasmids are closely related to each other and carry the
qnrB19
gene as the sole resistance determinant, located in a conserved genetic context between the plasmid RNAII sequence (which controls plasmid replication) and the plasmid Xer site (involved in plasmid dimer resolution). IS
Ecp1
-like or other putative insertion sequences are not present in the
qnrB19
-flanking regions or elsewhere on the plasmids. Since we previously observed a high prevalence (54%) of
qnrB
genes in the metagenomes of commensal enterobacteria from the same population of healthy children, the presence of pECY6-7- and pECC14-9-like plasmids in those
qnrB
-positive metagenomes was investigated by PCR mapping. Both plasmids were found to be highly prevalent (67% and 16%, respectively) in the
qnrB
-positive metagenomes, suggesting that dissemination of these small plasmids played a major role in the widespread dissemination of
qnrB
genes observed in commensal enterobacteria from healthy children living in those areas.
Regulatory Role of the MisR/S Two-Component System in Hemoglobin Utilization in
Neisseria meningitidis
Authors: Zhao Shuming , Montanez Grisselle E. , Kumar Pradeep , Sannigrahi Soma , Tzeng Yih-Ling
Published: December 2009

Outer membrane iron receptors are some of the major surface entities that are critical for meningococcal pathogenesis. The gene encoding the meningococcal hemoglobin receptor, HmbR, is both independently transcribed and transcriptionally linked to the upstream gene
hemO
, which encodes a heme oxygenase. The MisR/S two-component system was previously determined to regulate
hmbR
transcription, and its
hemO
and
hmbR
regulatory mechanisms were characterized further here. The expression of
hemO
and
hmbR
was downregulated in
misR
/
S
mutants under both iron-replete and iron-restricted conditions, and the downregulation could be reversed by complementation. No significant changes in expression of other iron receptors were detected, suggesting that the MisR/S system specifically regulates
hmbR
. When hemoglobin was the sole iron source, growth defects were detected in the mutants. Primer extension analysis identified a promoter upstream of the
hemO
-associated Correia element (CE) and another promoter at the proximal end of CE, and processed transcripts previously identified for other cotranscribed CEs were also detected, suggesting that there may be posttranscriptional regulation. MisR directly interacts with sequences upstream of the CE and upstream of the
hmbR
Fur binding site and thus independently regulates
hemO
and
hmbR
. Analysis of transcriptional reporters of
hemO
and
hmbR
further demonstrated the positive role of the MisR/S system and showed that the transcription of
hmbR
initiated from
hemO
was significantly reduced. A comparison of the effects of the
misS
mutation under iron-replete and iron-depleted conditions suggested that activation by the MisR/S system and iron-mediated repression by Fur act independently. Thus, the expression of
hemO
and
hmbR
is coordinately controlled by multiple independent regulatory mechanisms, including the MisR/S two-component system.
High Matrix Metalloproteinase Production Correlates with Immune Activation and Leukocyte Migration in Leprosy Reactional Lesions
Authors: Teles Rosane M. B. , Teles Rose B. , Amadeu Thais P. , Moura Danielle F. , Mendonça-Lima Leila , Ferreira Helen , Santos Ítalo M. C. F. , Nery José A. C. , Sarno Euzenir N. , Sampaio Elizabeth P.
Published: December 2009

Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] anderythema nodosum leprosum[ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) thein vitroinduction of MMP-9 byMycobacterium lepraeand/or TNF-α. It was observed that IFN-γ, TNF-α, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-α, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/in situzymography). Moreover, followingin vitrostimulation of peripheral blood cells,M. lepraeinduced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.
Shiga Toxin 1-Induced Inflammatory Response in Lipopolysaccharide-Sensitized Astrocytes Is Mediated by Endogenous Tumor Necrosis Factor Alpha
Authors: Landoni Verónica I. , de Campos-Nebel Marcelo , Schierloh Pablo , Calatayud Cecilia , Fernandez Gabriela C. , Ramos M. Victoria , Rearte Bárbara , Palermo Marina S. , Isturiz Martín A.
Published: December 2009

Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producingEscherichia coli. Endothelial dysfunction mediated by Stx is a central aspect in HUS development. However, inflammatory mediators such as bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) contribute to HUS pathophysiology by potentiating Stx effects. Acute renal failure is the main feature of HUS, but in severe cases, patients can develop neurological complications, which are usually associated with death. Although the mechanisms of neurological damage remain uncertain, alterations of the blood-brain barrier associated with brain endothelial injury is clear. Astrocytes (ASTs) are the most abundant inflammatory cells of the brain that modulate the normal function of brain endothelium and neurons. The aim of this study was to evaluate the effects of Stx type 1 (Stx1) alone or in combination with LPS in ASTs. Although Stx1 induced a weak inflammatory response, pretreatment with LPS sensitized ASTs to Stx1-mediated effects. Moreover, LPS increased the level of expression of the Stx receptor and its internalization. An early inflammatory response, characterized by the release of tumor necrosis factor alpha (TNF-α) and nitric oxide and PMN-chemoattractant activity, was induced by Stx1 in LPS-sensitized ASTs, whereas activation, evidenced by higher levels of glial fibrillary acid protein and cell death, was induced later. Furthermore, increased adhesion and PMN-mediated cytotoxicity were observed after Stx1 treatment in LPS-sensitized ASTs. These effects were dependent on NF-κB activation or AST-derived TNF-α. Our results suggest that TNF-α is a pivotal effector molecule that amplifies Stx1 effects on LPS-sensitized ASTs, contributing to brain inflammation and leading to endothelial and neuronal injury.