bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of the late-Holocene changes in the Sub-Arctic Front position at the Reykjanes Ridge, north Atlantic
Authors: Moros Matthias , Jansen Eystein , Oppo Delia W , Giraudeau Jacques , Kuijpers Antoon
Published: March 2012

Changes in the dynamics of the North Atlantic subpolar gyre are involved in the modulation of the northward salinity and heat transport in the northern North Atlantic via the North Atlantic Current (NAC). Variations in the strength of the East Greenland Current (EGC) can influence the gyre dynamics by impacting deep convection in the Labrador Sea. Oxygen isotope data of three planktonic foraminiferal species (surface water Neogloboquadrina pachyderma dextral coiling and Globigerina bulloides; thermocline recorder Globorotalia inflata) from a site located close to the present Sub-Arctic Front at the Reykjanes Ridge suggest significant strengthening or shifting of the Sub-Arctic Front throughout the late Holocene. The oxygen isotope based inferences are supported by Mg/Ca-derived temperature reconstructions from Neogloboquadrina pachyderma dextral coiling, alkenone-derived sea surface temperature and other paleoclimatic proxy data. The late-Holocene strengthening/shift of the Sub-Arctic Front appears caused by an increasingly more defined and fresher EGC. The proposed subpolar gyre changes may modulate the northward heat transport, and explain the geographically different long-term climatic trends in the North Atlantic during the late Holocene, i.e. a cooling of the EGC-influenced regions and a warming of the NAC-influenced areas from c. 4 to 5 ka. This mechanism cannot, however, explain the simultaneous occurrence of millennial-scale events at c. 5.6, 3.9, 2.7, 1.3 ka and the ‘Little Ice Age’ in both areas. Noteworthy is the steadily increasing amplitude of these cold events at the Reykjanes Ridge, likely induced by drift ice and/or EGC-influence culminating in the ‘Little Ice Age’. A widespread pronounced warming at 2.0 ka seems to represent the ‘Roman Warm Period’ and reflects the warmest period of the late Holocene.
An improved methodology for the recovery of Zea mays and other large crop pollen, with implications for environmental archaeology in the Neotropics
Authors: Whitney Bronwen S , Rushton Elizabeth AC , Carson John F , Iriarte José , Mayle Francis E
Published: March 2012

We present a simple sieving methodology to aid the recovery of large cultigen pollen grains, such as maize ( Zea mays L.), manioc ( Manihot esculenta Crantz), and sweet potato ( Ipomoea batatas L.), among others, for the detection of food production using fossil pollen analysis of lake sediments in the tropical Americas. The new methodology was tested on three large study lakes located next to known and/or excavated pre-Columbian archaeological sites in South and Central America. Five paired samples, one treated by sieving, the other prepared using standard methodology, were compared for each of the three sites. Using the new methodology, chemically digested sediment samples were passed through a 53 µm sieve, and the residue was retained, mounted in silicone oil, and counted for large cultigen pollen grains. The filtrate was mounted and analysed for pollen according to standard palynological procedures. Zea mays (L.) was recovered from the sediments of all three study lakes using the sieving technique, where no cultigen pollen had been previously recorded using the standard methodology. Confidence intervals demonstrate there is no significant difference in pollen assemblages between the sieved versus unsieved samples. Equal numbers of exotic Lycopodium spores added to both the filtrate and residue of the sieved samples allow for direct comparison of cultigen pollen abundance with the standard terrestrial pollen count. Our technique enables the isolation and rapid scanning for maize and other cultigen pollen in lake sediments, which, in conjunction with charcoal and pollen records, is key to determining land-use patterns and the environmental impact of pre-Columbian societies.
Effect of Rosuvastatin Monotherapy and in Combination With Fenofibrate or Omega-3 Fatty Acids on Serum Vitamin D Levels
Authors: Makariou Stefania E. , Liberopoulos Evangelos N. , Agouridis Aris P. , Challa Anna , Elisaf Moses
Published: March 2012

Background:

Low levels of 25(OH) vitamin D [25(OH)VitD] have been recognized as a new cardiovascular disease (CVD) risk factor. Statins seem to increase 25(OH)VitD concentration.

Aim:

To investigate whether combined treatment with the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids would increase 25(OH)VitD levels compared with the high-dose rosuvastatin monotherapy in participants with mixed dislipidemia.

Methods:

We randomly allocated 60 patients with mixed dyslipidemia (low-density lipoprotein cholesterol: >160 mg/dL plus triglycerides: >200 mg/dL) to receive rosuvastatin 40 mg (n = 22), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 21), or rosuvastatin 10 mg plus omega-3 fatty acids 2 g (n = 17) daily for 3 months. Our primary end point was changes in the levels of serum 25(OH)VitD.

Results:

Rosuvastatin monotherapy was associated with a 53% increase in 25(OH)VitD (from 14.6 [1.0-38.0] to 17.8 [5.3-49.6] ng/mL; P = .000). Rosuvastatin plus micronized fenofibrate and rosuvastatin plus omega-3 fatty acids were associated with increases of 64% (from 14.1 [1.0-48.0] to 18.4 [6.7-52.4] ng/mL, P = .001) and 61% (from 10.4 [6.6-38.4] to 14.0 [9.6-37.6] ng/mL, P = .04), respectively. The changes in 25(OH)VitD after treatment were comparable in the 3 groups.

Conclusion:

High-dose rosuvastatin monotherapy and the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids are associated with significant and similar increases in the 25(OH)VitD levels. This increase may be relevant in terms of CVD risk prevention.
Mean Platelet Volume in the Diagnosis and Prognosis of Crimean–Congo Hemorrhagic Fever
Authors: Ekiz Fuat , Gürbüz Yunus , Başar Ömer , Aytekin Gökhan , Ekiz Özlem , Şentürk Gönül Çiçek , Aktaş Bora , Yılmaz Barış , Altınbaş Akif , Çoban Şahin , Şencan İrfan
Published: March 2012

Introduction:

Crimean–Congo hemorrhagic fever (CCHF) is a viral tick-borne zoonosis, which is a severe illness, causing hemorrhages in humans. Mean platelet volume (MPV) is used as a surrogate marker of platelet function and has been shown to be a sign of inflammation. The objective of the present study is to examine the association between MPV and CCHF. We also aimed to investigate the association between MPV and coagulopathy markers in the mortality rates and prognosis of patients with CCHF.

Patients and Methods:

Ninety-three patients with CCHF were enrolled retrospectively into the study and 15 of them were excluded according to the exclusion criteria. Twenty-five healthy individuals were included as a control group which was age and gender matched with CCHF patients. We compared the levels of MPV between the patient and the control groups. We also compared the coagulopathy markers of fatal CCHF patients (n = 9) with nonfatal cases (n = 69).

Results:

Platelet counts were significantly lower in the CCHF group. Levels of international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) were significantly higher in CCHF group ( P < .001, <.001, <.001, respectively). A statistically significant increase in MPV was observed in patients with CCHF compared with healthy controls (8.63 ± 1.23 fL vs 7.65 ± 0.42 fL, P < .001). Receiver–operating characteristic curve analysis suggested that the optimum MPV level cutoff points for patients with CCHF was 8.15 fL, with a sensitivity and specificity of 65% and 88%, respectively. The MPV levels were not significantly different between group 2 (nonsurvivor) and group 1 (survivor). However, platelet count, d-dimer, INR, PT, and aPTT were also positively correlated with the mortality rates ( P = .008, <.001, <.001, <.001, and <.001, respectively). Multivariable logistic regression model showed an independent correlation between MPV and mortality rate ( P < .001).

Conclusion:

In conclusion, MPV may be a beneficial marker in the diagnosis of CCHF, especially in cases with thrombocytopenia, the MPV levels are high. We also conclude that MPV may independently predict the prognosis of patients with CCHF.
Creating Meaning From Chaos
Authors: Russell Laura D.
Published: March 2012

The event of a family crisis calls for crucial reactions with kin in response to intense uncertainty. In this autoethnographic reflection, the author narrates her family’s struggle for meaning after learning that her brother suffered a near-fatal fall from a mountain peak of the Grand Tetons. In this article, the author depicts various perspectives she witnessed as her family dealt with multiple ambiguities surrounding her brother’s accident. The author then explores how crisis awakens an individual’s attention to present time and summons him or her to reorient his or her temporal self to focus on immediate moments. Moreover, the author demonstrates how dialogue and narrative interweave to shape family members’ interpretations of unprecedented circumstances and new relational meanings.
Use of Forensic Science in Investigating Crimes of Sexual Violence
Authors: Johnson Donald , Peterson Joseph , Sommers Ira , Baskin Deborah
Published: March 2012

This article contrasts the theoretical potential of modern forensic science techniques in the investigation of sexual violence cases with empirical research that has assessed the role played by scientific evidence in the criminal justice processing of sexual assault cases. First, the potential of forensic scientific procedures (including DNA testing) are outlined and the sexual assault literature that examines the importance of physical and forensic evidence in resolving such cases is reviewed. Then, empirical data from a recent National Institute of Justice (NIJ) study of 602 rapes are presented that describe the forensic evidence collected and examined in such cases and its impact on decisions to arrest, prosecute, adjudicate, and sentence defendants. The article closes with a discussion of research and policy recommendations to enhance the role played by forensic science evidence in sexual assault investigations.
Large-scale fast Fourier transform on a heterogeneous multi-core system
Authors: Li Yan , Diamond Jeffrey R , Wang Xu , Lin Haibo , Yang Yudong , Han Zhenxing
Published: March 2012

As interest in hybrid computing systems increases, people are eager to find new ways to exploit the unique and efficient computational power of the heterogeneous multi-core systems. Although there has been much interest in implementing high-performance fast Fourier transform (FFT) libraries on this kind of system, most existing libraries focus on small-scale FFTs whose data can fit in the local storage of a single accelerator. Real-world FFT applications often require much larger scale FFTs, but it is extremely challenging for heterogeneous multi-core system with distributed architectures to make efficient large FFT implementations. In this paper, we introduce the first known FFT library for the heterogeneous multi-core system with distributed architecture that can solve one-dimensional FFTs larger than what fits in a single accelerator. Our implementation achieves 67% performance improvement of FFTW 3.2.2 (Fastest Fourier Transform in the West) and sustains over 36 single precision FFT GFLOPs ‘end-to-end’ Achieving such high performance requires novel schemes for large-scale FFT factorization, data permutation and all-to-all exchanges, and buffer designs to maximize use of the local storage while minimizing communication overhead. One important finding in this paper is that large-scale FFT on this kind of architecture behaves as data transfer bound which is quite different from other architectures. A significant contribution of this paper is that for each major component of our algorithm, we explore many possible design options and present quantitative performance comparisons. This provides value beyond specific architecture, as it illustrates the fundamental features associated with different communication paradigms and mechanisms for the heterogeneous multi-core system. Today’s computer systems are increasingly being designed to include general purpose accelerators. The techniques in this paper can also be applied to these architectures especially when they have limited local storage or steep cache hierarchies. We also provide insights on applying techniques in this paper to similar architectures.
Identity regulation in neo-liberal societies: Constructing the ‘occupationally disabled’ individual
Authors: Holmqvist Mikael , Maravelias Christian , Skålén Per
Published: March 2012

This article studies the formation and regulation of individual identities among a group of people who after long periods of unemployment are put in a specialized work program for so called ‘occupationally disabled’ individuals. In contrast to its official aim to activate and rehabilitate participants back to the labour market, the study suggests that the work program constitutes the participants as passive and unable to meet the criteria of employability on the labour market. The term ‘occupationally disabled’ emerges not as a medical label referring to already existing, inner characteristic of the individuals concerned, but as an identity that they take on as they pass through the work program. The article contributes to existing research of the formation and regulation of individual identities in organizations in two regards: first, by showing how medicine participates in the formation and regulation of individual identities in organizations, and second, by relating the formation and regulation of individual identities to broader societal issues concerning neoliberal government. Our study suggests that there is a tendency in neo-liberal societies to combine medical and economic expertise into a ‘medico-economic discourse’ within which issues concerning individuals’ activity and agency are transformed into matters of illness and disability. That is, whereas active and self-governing individuals are governed as parts of a high-performing segment of the working population, our study suggests that passive and dependent individuals tend to be governed not just as parts of a low performing segment of the working population, but also as a disabled segment.
Parties, cleavages and issue evolution
Authors: Raymond Christopher , Feltch Brian M Barros
Published: March 2012

Several recent articles have reached different conclusions regarding the impact of the religious–secular cleavage in Chile. The resolution of this debate has important consequences for the understanding of cleavages. Studies subscribing to the view that parties have considerable agency in the maintenance of cleavages have found that religiosity no longer affects vote choice, while studies rooted in a sociological perspective argue that religiosity still matters. We show that the reason for the discrepant results is because a partisan realignment is underway, whereby religious voters are gradually shifting their loyalties from the parties of the left to the parties of the right, matching a division that has taken place at the elite level. These results are consistent with an issue evolution perspective, which provides a clearer articulation of how cleavages form than either the agency or the sociological approaches.
The explicit teaching of reading comprehension in science class: A pilot professional development program
Authors: Concannon-Gibney Tara , McCarthy Mary Jean
Published: March 2012

This pilot study aimed to address persistent gaps in the research regarding effective professional development models associated with reading comprehension pedagogy in content area classrooms (science). An appropriate instructional model was developed, (Do-Read-Do) which attempts to embed the explicit teaching of reading comprehension strategies within a science investigation. This model was then explored in workshops, discussion groups and in reciprocal in-class coaching situations over the course of a semester in a case study school. Findings highlighted many positive aspects of the professional development program such as the use of the gradual release of responsibility model that included modeling, practical application of the new methodology (both within the workshop and in the actual classroom) and ample opportunities for discussion and reflection. Despite some initial difficulties with the instructional model, it proved to be an effective method of embedding explicit reading comprehension instruction within a science investigation.
Sustainable cities, sustainable minds, sustainable schools: Pop-Up-Farm as a connecting device
Authors: Clarke Paul
Published: March 2012

This paper argues that modern education is premised upon urban industrial society, and that this has been conceived around a false notion of progress which perpetuates fracture between people and planet. If education maintains this illusion of progress whilst ignoring the reality of environmental meltdown it serves no reliable purpose in preparing, guiding and establishing the conditions for a sustainable future. Some practical examples of action are provided.
Support for the euro, political knowledge, and voting behavior in the 2001 and 2005 UK general elections
Authors: Tillman Erik R
Published: March 2012

This article examines the effect of political knowledge on support for the euro and voting on the euro issue in the 2001 and 2005 UK general elections. Political knowledge increased support for the euro in 2001 but had no effect in 2005 and it conditioned the effect of the euro issue on vote choice in both elections. The effect of the euro issue on voting was stronger among knowledgeable voters, who were more likely to vote correctly on the issue by choosing a party closest to their own views on the euro. These findings demonstrate heterogeneity in voting on the euro issue in these elections and should motivate further inquiry into the role that political knowledge plays in conditioning voting behavior on European issues.
Linking students to appropriate interventions: A typology for social workers based on general strain theory
Authors: Weller Bridget E , Bowen Natasha K , Bowen Gary L
Published: March 2012

• Summary:

The present study employed recent elaborations on general strain theory (GST) to develop a typology of vicarious and anticipated strain. The typology also considered gender-race combinations. The study used a sample of 11,222 adolescents who completed the School Success Profile for school assessment purposes.

• Findings:

Latent class analysis identified four patterns of vicarious and anticipated strain among adolescents. The patterns varied by sample members’ gender-race combinations. The latent class solution was replicated with two subsamples and validated by testing its association with behavior problems.

• Application:

Evidence-based practices are suggested for students experiencing different combinations of strain, and specific applications for social work practice are presented.
(Re)scaling identities: Embodied others and alternative spaces of identification
Authors: Koefoed Lasse , Simonsen Kirsten
Published: March 2012

This article draws attention to life as an ‘internal stranger’ in the city, the nation and other spatial formations. It explores the habitability of the different spatial formations and the possibilities of identification for ethnic minority groups. Drawing on research on citizens in Copenhagen of Pakistani origin, the study employs theoretical ideas of estrangement, identification and recognition in order to obtain a thorough understanding of the complexity and the contradictory character of their spatial identities and affiliations. A turning point in the double processes of estrangement and identification is ambivalence in affiliation to the Danish nation expressing the discrepancy between feeling Danish and not being recognized as a full member of the Danish imagined community. This emotional ambivalence gives rise to what we call jumping scale in identification and a search for alternative spaces of identity.
The challenge of dementia care knowledge exchange: Key factors in a national approach
Authors: Parke Belinda , Woo Tricia K.W. , Cruttenden Kathleen E. , Sapergia Sophie , D’Hondt Allison
Published: March 2012

We report a dementia knowledge-to-practice exchange activity to describe the process undertaken to improve care and support for older adults living with dementia. We describe the team’s early development and decision-making process (including its early focus on family physicians), and eventual creation of a Dementia Pocket Card tool. The tool can support health professionals and families with dementia case-finding, assessment, diagnosis and appropriate service provision.
A seafarer’s reliability assessment incorporating subjective judgements
Authors: Riahi Ramin , Bonsall Steve , Jenkinson Ian , Wang Jin
Published: March 2012

More than 80% of international cargo moves through seaports, making a contribution to the world economy. As a result, the performance of seafarers plays a major role in the safety of international trade and the maritime environment. This paper presents a novel approach to monitoring the performance of seafarers in terms of their conditional reliability. Unlike a traditional reliability analysis of a seafarer, this approach contains a dynamic model capable of coping with continually changing conditions that affect a seafarer’s performance. The proposed methodology enables and facilitates decision makers to assess the performance of a seafarer before his or her designation to any activities and during his or her seafaring period. To evaluate a seafarer’s reliability, a generic model is constructed and a combination of different techniques such as fuzzy logic, a fuzzy rule base, an analytical hierarchy process, evidential reasoning, a mapping process and expected utility is used. Furthermore, by changing the conditions that affect the reliability of an ideal seafarer and through calculating a value for this reliability, a benchmark is constructed. A seafarer’s reliability depends upon many variables and their dependencies; alteration of a criterion value will ultimately alter a seafarer’s reliability. In order to correct any deviation on time, a seafarer’s reliability has to be measured appropriately and regularly.
Police–youth relationships: A qualitative analysis of Flemish adolescents’ attitudes toward the police
Authors: Dirikx Astrid , Gelders Dave , Parmentier Stephan
Published: March 2012

This article reports on focus group interview-based research conducted to improve knowledge of European adolescents’ Attitudes Toward the Police (ATP). The study explores Flemish Belgian youths’ perceptions of three main aspects of policing (performance, procedural justice and distributive justice) and how much importance they attach to those perceptions. The 106 13–19 year olds who participated in 12 focus group interviews proved to have nuanced and mature conceptions of police work. They stated that proclaiming a negative ATP is ‘part of the deal’ of being young rather than a reflection of negative perceptions of police functioning. This study shows the importance of complementing the largely survey-based research on adolescents’ ATP with qualitative research.
Acoustic and Perceptual Description of Vowels in a Speaker With Congenital Aglossia
Authors: McMicken Betty , Von Berg Shelley , Iskarous Khalil
Published: March 2012

The goals of this study were to (a) compare the vowel space produced by a person with congenital aglossia (PWCA) with a typical vowel space; (b) investigate listeners’ intelligibility for single vowels produced by the PWCA, with and without visual information; and (c) determine whether there is a correlation between scores of speech intelligibility of PWCA speech and the acoustic properties of those speech samples. The main objective of this study was to determine whether a PWCA was able to compensate for the lack of tongue and whether listeners were able to compensate perceptually for the possible atypical acoustics of the PWCA. Cineradiography for this article was limited to observation of gross function of the tongue base and mylohyoid. An audiovisual recording of the PWCA speaker’s output was obtained for a series of isolated vowels, diphthongized vowels, and vowels in monosyllables. Production of vowels was analyzed acoustically and perceptually. Vowels were presented to listeners under two conditions: audiovisual and audio only. Paired differences sample tests revealed no statistical differences in intelligibility for the audio versus audiovisual conditions. Mean intelligibility for vowels was 78.5% overall. Intelligibility was a function of vowel position, with the front vowels revealing the least intelligibility and the back vowels revealing the greatest intelligibility. Quantitative analysis of F1–F2 formant data revealed that the speaker’s front vowels showed greater distances from the back vowels when compared with the F1–F2 means of normative data.
Evaluation of an Ecological Interface Design for Military Command and Control
Authors: Hall Daniel S. , Shattuck Lawrence G. , Bennett Kevin B.
Published: March 2012

Two alternative interfaces developed for military command and control were evaluated. The theoretical frameworks and concepts used during their development are discussed, and the findings are related to larger issues in display, interface, and system design. Key aspects of cognitive systems engineering (CSE) and ecological interface design (EID) are discussed. An ecological interface was designed with principles of direct perception, direct manipulation, and visual momentum. An experimental version of an existing interface was also developed. An experiment was conducted with a synthetic task environment that incorporated scenarios of tactical operations. Participants were experienced army officers. Dependent variables included status reports for friendly and enemy resources and activities, subjective workload, and information access. Significant results favoring the ecological interface were obtained for six of seven dependent measures. The ecological interface was easy to learn, easy to use, and dramatically more effective than the existing interface. The results are interpreted from the CSE-EID perspective, but insights from naturalistic decision making and situation awareness are also described. The specific design features of the ecological interface are directly applicable to military command and control and similar domains; the overall CSE-EID approach is applicable to interface design for all work domains.
Ubiquitous high-level gene expression in hematopoietic lineages provides effective lentiviral gene therapy of murine Wiskott-Aldrich syndrome
Authors: Astrakhan Alexander , Sather Blythe D. , Ryu Byoung Y. , Khim Socheath , Singh Swati , Humblet-Baron Stephanie , Ochs Hans D. , Miao Carol H. , Rawlings David J.
Published: March 2012

The immunodeficiency disorder Wiskott-Aldrich syndrome (WAS) leads to life-threatening hematopoietic cell dysfunction. We used WAS protein (WASp)–deficient mice to analyze the in vivo efficacy of lentiviral (LV) vectors using either a viral-derived promoter, MND, or the human proximal WAS promoter (WS1.6) for human WASp expression. Transplantation of stem cells transduced with MND-huWASp LV resulted in sustained, endogenous levels of WASp in all hematopoietic lineages, progressive selection for WASp+ T, natural killer T and B cells, rescue of T-cell proliferation and cytokine production, and substantial restoration of marginal zone (MZ) B cells. In contrast, WS1.6-huWASp LV recipients exhibited subendogenous WASp expression in all cell types with only partial selection of WASp+ T cells and limited correction in MZ B-cell numbers. In parallel, WS1.6-huWASp LV recipients exhibited an altered B-cell compartment, including higher numbers of λ-light-chain+ naive B cells, development of self-reactive CD11c+FAS+ B cells, and evidence for spontaneous germinal center (GC) responses. These observations correlated with B-cell hyperactivity and increased titers of immunoglobulin (Ig)G2c autoantibodies, suggesting that partial gene correction may predispose toward autoimmunity. Our findings identify the advantages and disadvantages associated with each vector and suggest further clinical development of the MND-huWASp LV for a future clinical trial for WAS.
EUTOS score is not predictive for survival and outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience
Authors: Jabbour Elias , Cortes Jorge , Nazha Aziz , O'Brien Susan , Quintas-Cardama Alfonso , Pierce Sherry , Garcia-Manero Guillermo , Kantarjian Hagop
Published: March 2012

To validate the recently reported European Treatment and Outcomes Study (EUTOS) score, we applied it to 465 patients with early chronic phase chronic myeloid leukemia treated with standard-dose imatinib (n = 71), high-dose imatinib (n = 208), or second-generation tyrosine kinase inhibitors (n = 186), and assessed its ability to predict event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS). The median follow-up was 69 months. The overall complete cytogenetic response and major molecular response rates were 92% and 85%, respectively. The 3-year EFS, TFS, and OS rates were 86%, 95%, and 97%, respectively. Of the 465 patients, 427 (92%) were in low EUTOS score category. There was no difference in the major molecular response, TFS, EFS, and OS rates between patients with low and high EUTOS score, overall and within specific therapies. In conclusion, 8% of patients with chronic phase chronic myeloid leukemia treated at our institution are in the high EUTOS score; in this population, the EUTOS score was not predictive for outcome.
Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome
Authors: Zhang Su-Jiang , Rampal Raajit , Manshouri Taghi , Patel Jay , Mensah Nana , Kayserian Andrew , Hricik Todd , Heguy Adriana , Hedvat Cyrus , Gönen Mithat , Kantarjian Hagop , Levine Ross L. , Abdel-Wahab Omar , Verstovsek Srdan
Published: March 2012

Leukemic transformation (LT) of myeloproliferative neoplasms (MPNs) is associated with a poor prognosis and resistance to therapy. Although previous candidate genetic studies have identified mutations in MPN patients who develop acute leukemia, the complement of genetic abnormalities in MPN patients who undergo LT is not known nor have specific molecular abnormalities been shown to have clinical relevance in this setting. We performed high-throughput resequencing of 22 genes in 53 patients with LT after MPN to characterize the frequency of known myeloid mutations in this entity. In addition to JAK2 and TET2 mutations, which occur commonly in LT after MPN, we identified recurrent mutations in the serine/arginine-rich splicing factor 2 (SRSF2) gene (18.9%) in acute myeloid leukemia (AML) transformed from MPNs. SRSF2 mutations are more common in AML derived from MPNs compared with LT after myelodysplasia (4.8%) or de novo AML (5.6%), respectively (P = .05). Importantly, SRSF2 mutations are associated with worsened overall survival in MPN patients who undergo LT in univariate (P = .03; HR, 2.77; 95% CI, 1.10-7.00) and multivariate analysis (P < .05; HR, 2.11; 95% CI, 1.01-4.42). These data suggest that SRSF2 mutations contribute to the pathogenesis of LT and may guide novel therapeutic approaches for MPN patients who undergo LT.
BCR-ABL1 doubling times more reliably assess the dynamics of CML relapse compared with the BCR-ABL1 fold rise: implications for monitoring and management
Authors: Branford Susan , Yeung David T. , Prime Jodi A. , Choi Soo-Young , Bang Ju-hee , Park Jin Eok , Kim Dong-Wook , Ross David M. , Hughes Timothy P.
Published: March 2012

Rising BCR-ABL1 transcripts indicate potential loss of imatinib response in CML. We determined whether the BCR-ABL1 doubling time could distinguish nonadherence from resistance as the cause of lost response. Distinct groups were examined: (1) acquired clinical resistance because of blast crisis and/or BCR-ABL1 mutations; and (2) documented imatinib discontinuation/interruption. Short doubling times occurred with blast crisis (median, 9.0 days; range, 6.1-17.6 days; n = 12 patients), relapse after imatinib discontinuation in complete molecular response (median, 9.0 days; range, 6.9-26.5 days; n = 17), and imatinib interruption during an entire measurement interval (median, 9.4 days; range, 4.2-17.6 days; n = 12; P = .72). Whereas these doubling times were consistently short and indicated rapid leukemic expansion, fold rises were highly variable: 71-, 9.5-, and 10.5-fold, respectively. The fold rise depended on the measurement interval, whereas the doubling time was independent of the interval. Longer doubling times occurred for patients with mutations who maintained chronic phase (CP: median, 48 days; range, 17.3-143 days; n = 29; P < .0001). Predicted short and long doubling times were validated on an independent cohort monitored elsewhere. The doubling time revealed major differences in kinetics according to clinical context. Long doubling times observed with mutations in CP allow time for intervention. A short doubling time for a patient in CP should raise the suspicion of nonadherence.
Prognostic role of SOX11 in a population-based cohort of mantle cell lymphoma
Authors: Nygren Lina , Baumgartner Wennerholm Stefanie , Klimkowska Monika , Christensson Birger , Kimby Eva , Sander Birgitta
Published: March 2012

The prognostic role of the transcription factor SOX11 in mantle cell lymphoma (MCL) is controversial. We investigated prognostic markers in a population-based cohort of 186 MCL cases. Seventeen patients (9%) did not require any therapy within the first 2 years after diagnosis and were retrospectively defined as having an indolent disease. As expected, indolent MCL had less frequent B symptoms and extensive nodal involvement and 88% of these cases expressed SOX11. In our cohort 13 cases (7.5%) lacked nuclear SOX11 at diagnosis. SOX11− MCL had a higher frequency of lymphocytosis, elevated level of lactate dehydrogenase (LDH), and p53 positivity. The overall survival in the whole cohort, excluding 37 patients receiving autologous stem cell transplantation, was 3.1 year and in patients with indolent or nonindolent disease, 5.9 and 2.8 years, respectively (P = .004). SOX11− cases had a shorter overall survival, compared with SOX11+ cases, 1.5 and 3.2 years, respectively (P = .014). In multivariate analysis of overall survival, age > 65 (P = .001), Eastern Cooperative Oncology Group score ≥ 2 (P = .022), elevated LDH level (P = .001), and p53 expression (P = .001) remained significant, and SOX11 lost significance. We conclude that most indolent MCLs are SOX11+ and that SOX11 cannot be used for predicting an indolent disease course.
Genome-wide dynamic transcriptional profiling in clostridium beijerinckii NCIMB 8052 using single-nucleotide resolution RNA-Seq
Authors: Wang Yi , Li Xiangzhen , Mao Yuejian , Blaschek Hans P
Published: March 2012

Background

Clostridium beijerinckiiis a prominent solvent-producing microbe that has great potential for biofuel and chemical industries. Although transcriptional analysis is essential to understand gene functions and regulation and thus elucidate proper strategies for further strain improvement, limited information is available on the genome-wide transcriptional analysis forC. beijerinckii.

Results

The genome-wide transcriptional dynamics ofC. beijerinckiiNCIMB 8052 over a batch fermentation process was investigated using high-throughput RNA-Seq technology. The gene expression profiles indicated that the glycolysis genes were highly expressed throughout the fermentation, with comparatively more active expression during acidogenesis phase. The expression of acid formation genes was down-regulated at the onset of solvent formation, in accordance with the metabolic pathway shift from acidogenesis to solventogenesis. The acetone formation gene (adc), as a part of thesoloperon, exhibited highly-coordinated expression with the othersolgenes. Out of the > 20 genes encoding alcohol dehydrogenase inC. beijerinckii, Cbei_1722 and Cbei_2181 were highly up-regulated at the onset of solventogenesis, corresponding to their key roles in primary alcohol production. Most sporulation genes inC. beijerinckii8052 demonstrated similar temporal expression patterns to those observed inB. subtilisandC. acetobutylicum, while sporulation sigma factor genessigEandsigGexhibited accelerated and stronger expression inC. beijerinckii8052, which is consistent with the more rapid forespore and endspore development in this strain. Global expression patterns for specific gene functional classes were examined using self-organizing map analysis. The genes associated with specific functional classes demonstrated global expression profiles corresponding to the cell physiological variation and metabolic pathway switch.

Conclusions

The results from this work provided insights for furtherC. beijerinckiistrain improvement employing system biology-based strategies and metabolic engineering approaches.
Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways
Authors: Yang Yao-Jong , Chuang Ching-Chun , Yang Hsiao-Bai , Lu Cheng-Chan , Sheu Bor-Shyang
Published: March 2012

Background

H. pyloriinfection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improveH. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.

Results

Challenge withH. pyloriincreased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased afterH. pyloriinfection in a dose-dependent manner. A higher dose (MOI 100) ofL. acidophiluspre-treatment attenuated theH. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB.L. acidophilusalso inhibitedH. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway.L. acidophiluspre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting.

Conclusions

H. pyloriinfection induces Smad7, NFκB, IL-8, and TNF-α productionin vitro. Higher doses ofL. acidophiluspre-treatment reduceH. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.
EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors
Authors: Florkowska Magdalena , Tymoszuk Piotr , Balwierz Aleksandra , Skucha Anna , Kochan Jakub , Wawro Mateusz , Stalinska Krystyna , Kasza Aneta
Published: March 2012

Background

Tristetraprolin (TTP) is a key mediator of processes such as inflammation resolution, the inhibition of autoimmunity and in cancer. It carries out this role by the binding and degradation of mRNA transcripts, thereby decreasing their half-life. Transcripts modulated by TTP encode proteins such as cytokines, pro-inflammatory agents and immediate-early response proteins. TTP can also modulate neoplastic phenotypes in many cancers. TTP is induced and functionally regulated by a spectrum of both pro- and anti-inflammatory cytokines, mitogens and drugs in a MAPK-dependent manner. So far the contribution of p38 MAPK to the regulation of TTP expression and function has been best described.

Results

Our results demonstrate the induction of the gene coding TTP (ZFP36) by EGF through the ERK1/2-dependent pathway and implicates the transcription factor ELK-1 in this process. We show that ELK-1 regulates ZFP36 expression by two mechanisms: by binding the ZFP36 promoter directly through ETS-binding site (+ 883 to +905 bp) and by inducing expression of EGR-1, which in turn increases ZFP36 expression through sequences located between -111 and -103 bp.

Conclusions

EGF activates TTP expression via ELK-1 and EGR-1 transcription factors.
Differential effects of environment on potato phenylpropanoid and carotenoid expression
Authors: Payyavula Raja S , Navarre Duroy A , Kuhl Joseph C , Pantoja Alberto , Pillai Syamkumar S
Published: March 2012

Background

Plant secondary metabolites, including phenylpropanoids and carotenoids, are stress inducible, have important roles in potato physiology and influence the nutritional value of potatoes. The type and magnitude of environmental effects on tuber phytonutrients is unclear, especially under modern agricultural management that minimizes stress. Understanding factors that influence tuber secondary metabolism could facilitate production of more nutritious crops. Metabolite pools of over forty tuber phenylpropanoids and carotenoids, along with the expression of twenty structural genes, were measured in high-phenylpropanoid purple potatoes grown in environmentally diverse locations in North America (Alaska, Texas and Florida).

Results

Phenylpropanoids, including chlorogenic acid (CGA), were higher in samples from the northern latitudes, as was the expression of phenylpropanoid genes including phenylalanine ammonia lyase (PAL), which had over a ten-fold difference in relative abundance. Phenylpropanoid gene expression appeared coordinately regulated and was well correlated with metabolite pools, except for hydroxycinnamoyl-CoA:quinatehydroxcinnamoyl transferase (HQT; r = -0.24).In silicopromoter analysis identified two cis-acting elements in the HQT promoter not found in the other phenylpropanoid genes. Anthocyanins were more abundant in Alaskan samples and correlated with flavonoid genes includingDFR(r = 0.91),UFGT(r = 0.94) andF3H(r = 0.77). The most abundant anthocyanin was petunidin-3-coum-rutinoside-5-glu, which ranged from 4.7 mg g-1in Alaska to 2.3 mg g-1in Texas. Positive correlations between tuber sucrose and anthocyanins (r = 0.85), suggested a stimulatory effect of sucrose. Smaller variation was observed in total carotenoids, but marked differences occurred in individual carotenoids, which had over a ten-fold range. Violaxanthin, lutein or zeaxanthin were the predominant carotenoids in tubers from Alaska, Texas and Florida respectively. Unlike in the phenylpropanoid pathway, poor correlations occurred between carotenoid transcripts and metabolites.

Conclusion

Analysis of tuber secondary metabolism showed interesting relationships among different metabolites in response to collective environmental influences, even under conditions that minimize stress. The variation in metabolites shows the considerable phenotypical plasticity possible with tuber secondary metabolism and raises questions about to what extent these pathways can be stimulated by environmental cues in a manner that optimizes tuber phytonutrient content while protecting yields. The differences in secondary metabolites may be sufficient to affect nutritional quality.
Usefulness of health registries when estimating vaccine effectiveness during the influenza A(H1N1)pdm09 pandemic in Norway
Authors: Guzmán Herrador Bernardo Rafael , Aavitsland Preben , Feiring Berit , Riise Bergsaker Marianne A , Borgen Katrine
Published: March 2012

Background

During the 2009-2010 pandemic in Norway, 12 513 laboratory-confirmed cases of pandemic influenza A(H1N1)pdm09, were reported to the Norwegian Surveillance System for Communicable Diseases (MSIS). 2.2 million persons (45% of the population) were vaccinated with an AS03-adjuvanted monovalent vaccine during the pandemic. Most of them were registered in the Norwegian Immunisation Registry (SYSVAK). Based on these registries, we aimed at estimating the vaccine effectiveness (VE) and describing vaccine failures during the pandemic in Norway, in order to evaluate the role of the vaccine as a preventive measure during the pandemic.

Methods

We conducted a population-based retrospective cohort study, linking MSIS and SYSVAK with pandemic influenza vaccination as exposure and laboratory-confirmed pandemic influenza as outcome. We measured VE by week and defined two thresholds for immunity; eight and 15 days after vaccination.

Results

The weekly VE ranged from 77% to 96% when considering 15 days or more after vaccination as the threshold of immunity and from 73% to 94% when considering eight days or more. Overall, 157 individuals contracted pandemic influenza eight or more days after vaccination (8.4/100,000 vaccinated), of these 58 had onset 15 days or more after vaccination (3.0/100,000 vaccinated). Most of the vaccine failures occurred during the first weeks of the vaccination campaign. More than 30% of the vaccine failures were found in people below 10 years of age.

Conclusions

Having available health registries with data regarding cases of specific disease and vaccination makes it feasible to estimate VE in a simple and rapid way. VE was high regardless the immunity threshold chosen. We encourage public health authorities in other countries to set up such registries. It is also important to consider including information on underlying diseases in registries already existing, in order to make it feasible to conduct more complete VE estimations.
Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells
Authors: Jia Dongxuan , Entersz Ildiko , Butler Christine , Foty Ramsey A
Published: March 2012

Background

Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells.

Methods

Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA.

Results

We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment.

Conclusions

We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade.