bluuebunny/crossref_metadata_2025 huggingface dataset:
Aliskiren: review of efficacy and safety data with focus on past and recent clinical trials
Authors: Şen Selçuk , Sabırlı Soner , Özyiğit Tolga , Üresin Yağız
Published: July 2013

Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. Clinical data have substantiated that the antihypertensive effectiveness of aliskiren is similar to that of the other major antihypertensive agents. Furthermore, aliskiren has a similar safety profile to placebo. Combination treatment with aliskiren showed significant blood pressure and proteinuria reductions compared with monotherapy. Aliskiren decreases plasma renin activity in contrast to other renin–angiotensin–aldosterone related drugs. The efficacy of aliskiren in treating major cardiovascular events and the prevention of end-organ damage are being investigated in the ASPIRE HIGHER program. Although the first studies of the ASPIRE HIGHER program such as ALOFT, AVOID, AGELESS showed favorable findings, ASPIRE and AVANT-GARDE studies provided contradictory results. Subsequently, the ALTITUDE study was terminated early because of safety issues and lack of beneficial effects. Most recently, the ASTRONAUT trial showed no reduction in cardiovascular death or heart failure rehospitalization with the addition of aliskiren to standard therapy in patients who were hospitalized for heart failure and with reduced left-ventricular ejection fraction. The results of ongoing studies in other patient groups such as the ATMOSPHERE trial are awaited.
The Rachel Carson Letters and the Making of Silent Spring
Authors: Paull John
Published: July 2013

Environment, conservation, green, and kindred movements look back to Rachel Carson’s 1962 book Silent Spring as a milestone. The impact of the book, including on government, industry, and civil society, was immediate and substantial, and has been extensively described; however, the provenance of the book has been less thoroughly examined. Using Carson’s personal correspondence, this paper reveals that the primary source for Carson’s book was the extensive evidence and contacts compiled by two biodynamic farmers, Marjorie Spock and Mary T. Richards, of Long Island, New York. Their evidence was compiled for a suite of legal actions (1957-1960) against the U.S. Government and that contested the aerial spraying of dichlorodiphenyltrichloroethane (DDT). During Rudolf Steiner’s lifetime, Spock and Richards both studied at Steiner’s Goetheanum, the headquarters of Anthroposophy, located in Dornach, Switzerland. Spock and Richards were prominent U.S. anthroposophists, and established a biodynamic farm under the tutelage of the leading biodynamics exponent of the time, Dr. Ehrenfried Pfeiffer. When their property was under threat from a government program of DDT spraying, they brought their case, eventually lost it, in the process spent US$100,000, and compiled the evidence that they then shared with Carson, who used it, and their extensive contacts and the trial transcripts, as the primary input for Silent Spring. Carson attributed to Spock, Richards, and Pfeiffer, no credit whatsoever in her book. As a consequence, the organics movement has not received the recognition, that is its due, as the primary impulse for Silent Spring, and it is, itself, unaware of this provenance.
Daily Mobility and Residential Migrations in the Montréal Metropolitan Region
Authors: Sénécal Gilles , Hamel Pierre J. , Collin Jean-Pierre , Jastremski Kathryn , Vachon Nathalie , Lafortune Marie-Ève
Published: July 2013

The purpose of this article is to simultaneously examine two types of mobility by developing a model of metropolitan organization that emphasizes the axis structure of mobility. The model is based on the realities of daily mobility and long-term residential mobility. Origin−Destination study results validated the axis representation of the metropolitan structure. Furthermore, building on data from a telephone survey, we considered the interactions between the two types of mobility along the Center-North axis of Montréal’s Census Metropolitan Area (CMA). The ensuing discussion on various models of metropolitan structure and their relevance today is framed in terms of the axes of mobility defined as territorial practices that are established within the patterns of daily life and are a significant factor in residential location decisions. The study raises broader issues concerning the relevance of drawing on standard models such as Burgess’s concentric zone model, Hoyt’s sector theory, Adam’s directional bias, or recent findings from the literature to understand urban form dynamics in the CMA.
Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia
Authors: Ferrajoli Alessandra , Shanafelt Tait D. , Ivan Cristina , Shimizu Masayoshi , Rabe Kari G. , Nouraee Nazila , Ikuo Mariko , Ghosh Asish K. , Lerner Susan , Rassenti Laura Z. , Xiao Lianchun , Hu Jianhua , Reuben James M. , Calin Steliana , You M. James , Manning John T. , Wierda William G. , Estrov Zeev , O’Brien Susan , Kipps Thomas J. , Keating Michael J. , Kay Neil E. , Calin George A.
Published: July 2013

Key Points

miR-155 levels are significantly and increasingly overexpressed as normal B cells progress to MBL and to CLL. Plasma levels of miR-155 before treatment were significantly lower in patients with CLL who experienced complete response than in all others.
NOTCH1, SF3B1, and TP53 mutations in fludarabine-refractory CLL patients treated with alemtuzumab: results from the CLL2H trial of the GCLLSG
Authors: Schnaiter Andrea , Paschka Peter , Rossi Marianna , Zenz Thorsten , Bühler Andreas , Winkler Dirk , Cazzola Mario , Döhner Konstanze , Edelmann Jennifer , Mertens Daniel , Kless Sabrina , Mack Silja , Busch Raymonde , Hallek Michael , Döhner Hartmut , Stilgenbauer Stephan
Published: July 2013

Key Points

In the refractory cohort of the CLL2H trial PFS was significantly longer in patients with NOTCH1 mutation. SF3B1 mutation had no impact on response rates or survival times in fludarabine-refractory patients.
Chromosomal diversification and karyotype evolution of diploids in the cytologically diverse genus Prospero(Hyacinthaceae)
Authors: Jang Tae-Soo , Emadzade Khatere , Parker John , Temsch Eva M , Leitch Andrew R , Speta Franz , Weiss-Schneeweiss Hanna
Published: July 2013

Background

Prospero(Hyacinthaceae) provides a unique system to assess the impact of genome rearrangements on plant diversification and evolution. The genus exhibits remarkable chromosomal variation but very little morphological differentiation. Basic numbers ofx = 4, 5, 6 and 7, extensive polyploidy, and numerous polymorphic chromosome variants were described, but only three species are commonly recognized:P. obtusifolium,P. hanburyi, andP. autumnales.l., the latter comprising four diploid cytotypes. The relationship between evolutionary patterns and chromosomal variation in diploids, the basic modules of the extensive cytological diversity, is presented.

Results

Evolutionary inferences were derived from fluorescencein situhybridization (FISH) with 5S and 35S rDNA, genome size estimations, and phylogenetic analyses of internal transcribed spacer (ITS) of 35S rDNA of 49 diploids in the three species and all cytotypes ofP. autumnales.l. All species and cytotypes possess a single 35S rDNA locus, interstitial except inP. hanburyiwhere it is sub-terminal, and one or two 5S rDNA loci (occasionally a third inP. obtusifolium) at fixed locations. The localization of the two rDNA types is unique for each species and cytotype. Phylogenetic data in theP. autumnalecomplex enable tracing of the evolution of rDNA loci, genome size, and direction of chromosomal fusions: mixed descending dysploidy ofx = 7 tox = 6 and independently tox = 5, rather than successive descending dysploidy, is proposed.

Conclusions

All diploid cytotypes are recovered as well-defined evolutionary lineages. The cytogenetic and phylogenetic approaches have provided excellent phylogenetic markers to infer the direction of chromosomal change inProspero. Evolution inProspero, especially in theP. autumnalecomplex, has been driven by differentiation of an ancestral karyotype largely unaccompanied by morphological change. These new results provide a framework for detailed analyses of various types of chromosomal rearrangements and karyotypic variation in polyploids.
Adaptation of maize source leaf metabolism to stress related disturbances in carbon, nitrogen and phosphorus balance
Authors: Schlüter Urte , Colmsee Christian , Scholz Uwe , Bräutigam Andrea , Weber Andreas PM , Zellerhoff Nina , Bucher Marcel , Fahnenstich Holger , Sonnewald Uwe
Published: July 2013

Background

Abiotic stress causes disturbances in the cellular homeostasis. Re-adjustment of balance in carbon, nitrogen and phosphorus metabolism therefore plays a central role in stress adaptation. However, it is currently unknown which parts of the primary cell metabolism follow common patterns under different stress conditions and which represent specific responses.

Results

To address these questions, changes in transcriptome, metabolome and ionome were analyzed in maize source leaves from plants suffering low temperature, low nitrogen (N) and low phosphorus (P) stress. The selection of maize as study object provided data directly from an important crop species and the so far underexplored C4metabolism. Growth retardation was comparable under all tested stress conditions. The only primary metabolic pathway responding similar to all stresses was nitrate assimilation, which was down-regulated. The largest group of commonly regulated transcripts followed the expression pattern: down under low temperature and low N, but up under low P. Several members of this transcript cluster could be connected to P metabolism and correlated negatively to different phosphate concentration in the leaf tissue. Accumulation of starch under low temperature and low N stress, but decrease in starch levels under low P conditions indicated that only low P treated leaves suffered carbon starvation.

Conclusions

Maize employs very different strategies to manage N and P metabolism under stress. While nitrate assimilation was regulated depending on demand by growth processes, phosphate concentrations changed depending on availability, thus building up reserves under excess conditions. Carbon and energy metabolism of the C4maize leaves were particularly sensitive to P starvation.
May early intervention with high dose intravenous immunoglobulin pose a potentially successful treatment for severe cases of tick-borne encephalitis?
Authors: Růžek Daniel , Dobler Gerhard , Niller Hans Helmut
Published: July 2013

Background

Arthropod-borne viral encephalitis of diverse origins shows similar clinical symptoms, histopathology and magnetic resonance imaging, indicating that the patho mechanisms may be similar. There is no specific therapy to date. However, vaccination remains the best prophylaxis against a selected few. Regardless of these shortcomings, there are an increasing number of case reports that successfully treat arboviral encephalitis with high doses of intravenous immunoglobulins.

Discussion

To our knowledge, high dose intravenous immunoglobulin has not been tested systematically for treating severe cases of tick-borne encephalitis. Antibody-dependent enhancement has been suspected, but not proven, in several juvenile cases of tick-borne encephalitis. Although antibody-dependent enhancement during secondary infection with dengue virus has been documented, no adverse effects were noticed in a controlled study of high dose intravenous immunoglobulin therapy for dengue-associated thrombocytopenia. The inflammation-dampening therapeutic effects of generic high dose intravenous immunoglobulins may override the antibody-dependent enhancement effects that are potentially induced by cross-reactive antibodies or by virus-specific antibodies at sub-neutralizing levels.

Analogous to the increasing number of case reports on the successful treatment of other arboviral encephalitides with high dose intravenous immunoglobulins, we postulate whether it may be possible to also treat severe cases of tick-borne encephalitis with high dose intravenous immunoglobulins as early in the course of the disease as possible.
Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade
Authors: Yung Mingo Ming Ho , Chan David Wai , Liu Vincent Wing Sun , Yao Kwok-Ming , Ngan Hextan Yuen-Sheung
Published: July 2013

Background

Although advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic sensor, hampers cervical cancer cell growth through blocking the Wnt/β-catenin signaling activity. Here, we report that activated AMPK (p-AMPK) also inhibits cervical cancer cell growth by counteracting FOXM1 function.

Methods

Effect of the activation of AMPK on FOXM1 expression was examined by hypoxia and glucose deprivation, as well as pharmacological AMPK activators such as A23187, AICAR and metformin. RT Q-PCR and Western blot analysis were employed to investigate the activities of AMPK, FOXM1 and AKT/FOXO3a signaling.

Results

Consistent with our previous findings, the activation of AMPK by either AMPK activators such as AICAR, A23187, metformin, glucose deprivation or hypoxia significantly inhibited the cervical cancer cell growth. Importantly, we found that activated AMPK activity was concomitantly associated with the reduction of both the mRNA and protein levels of FOXM1. Mechanistically, we showed that activated AMPK was able to reduce AKT mediated phosphorylation of p-FOXO3a (Ser253). Interestingly, activated AMPK could not cause any significant changes in FOXM1 in cervical cancer cells in which endogenous FOXO3a levels were knocked down using siRNAs, suggesting that FOXO3a is involved in the suppression of FOXM1.

Conclusion

Taken together, our results suggest the activated AMPK impedes cervical cancer cell growth through reducing the expression of FOXM1.
The utility of fat mass index vs. body mass index and percentage of body fat in the screening of metabolic syndrome
Authors: Liu Pengju , Ma Fang , Lou Huiping , Liu Yanping
Published: July 2013

Background

It has been well documented that obesity is closely associated with metabolic syndrome (MetS). Although body mass index (BMI) is the most frequently used method to assess overweightness and obesity, this method has been criticized because BMI does not always reflect true body fatness, which may be better evaluated by assessment of body fat and fat-free mass. The objective of this study was to investigate the best indicator to predict the presence of MetS among fat mass index, BMI and percentage of body fat (BF %) and determine its optimal cut-off value in the screening of MetS in practice.

Methods

A cross-sectional study of 1698 subjects (aged 20–79 years) who participated in the annual health check-ups was employed. Body composition was measured by bioelectrical impedance analysis (BIA). Fat mass index (FMI) was calculated. Sex-specific FMI quartiles were defined as follows: Q1: <4.39, Q2:4.39- < 5.65, Q3:5.65- < 7.03, Q4:≥7.03,in men; and Q1:<5.25, Q2:5.25- < 6.33, Q3:6.33- < 7.93,Q4:≥7.93, in women. MetS was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. The association between FMI quartiles and MetS was assessed using Binary logistic regression. Receiver operating curve(ROC) analysis was used to determine optimal cutoff points for BMI,BF% and FMI in relation to the area under the curve(AUC),sensitivity and specificity in men and women.

Results

The adjusted odds ratios (95% CI) for the presence of MetS in the highest FMI quartile versus lowest quartile were 79.143(21.243-294.852) for men( P < 0.01) and 52.039(4.144-653.436) for women( P < 0.01) after adjusting age, BMI, BF%, TC, LDL, CRP, smoking status and exercise status, and the odds ratios were 9.166(2.157-38.952) for men( P < 0.01) and 25.574(1.945-336.228) for women( P < 0.05) when WC was also added into the adjustment. It was determined that BMI values of 27.45 and 23.85 kg/m2, BF% of 23.95% and 31.35% and FMI of 7.00 and 7.90 kg/m2 were the optimal cutoff values to predict the presence of MetS among men and women according to the ROC curve analysis. Among the indicators used to predict MetS, FMI was the index that showed the greatest area under the ROC curve in both sexes.

Conclusions

Higher FMI levels appear to be independently and positively associated with the presence of MetS regardless of BMI and BF%. FMI seems to be a better screening tool in prediction of the presence of metabolic syndrome than BMI and percentage of body fat in men and women.
In vitro chloroquine resistance for Plasmodium vivax isolates from the Western Brazilian Amazon
Authors: Chehuan Yonne F , Costa Monica RF , Costa Jacqueline S , Alecrim Maria GC , Nogueira Fátima , Silveira Henrique , Brasil Larissa W , Melo Gisely C , Monteiro Wuelton M , Lacerda Marcus VG
Published: July 2013

Background

Chloroquine (CQ) and primaquine (PQ) are still the drugs of choice to treat Plasmodium vivax malaria in many endemic areas, Brazil included. There is in vivo evidence for the P. vivax resistance to CQ in the Brazilian Amazon, where the increase in the proportion of P. vivax malaria parallels the increase of unusual clinical complications related to this species. In this study, in vitro CQ and mefloquine (MQ)-susceptibility of P. vivax isolates from the Western Brazilian Amazon was tested using the double-site enzyme-linked lactate dehydrogenase immunodetection (DELI) assay.

Methods

A total of 112 P. vivax isolates were tested in vitro for CQ-susceptibility and out of these 47 were also tested for MQ-susceptibility. The DELI assay was used to detect P. vivax growth at 48-hour short-term culture in isolates with ring stages ranging from 50 to %. Each isolate was tested in triplicate and geometric means of IC50’s was obtained. Nineteen isolates were genetically characterized for pvdhfr, pvmrp1, pvmdr1 and pvdhps candidate genes likely related to CQ resistance (10 with IC50<40 nM and 9 with IC50 >100 nM).

Results

Twelve out of 112 isolates were considered resistant to CQ, resulting in 10.7% (IC95% 5.0-16.4), while 3 out of 47 (6.4%; IC95% 0.0-12.8) were resistant to MQ. A discrete correlation was observed between IC50’s of CQ and MQ (Spearman=0.294; p=0.045). For pvdhps gene, a non-synonymous mutation was found at codon 382 (S→C) in 5/8 CQ-sensitive samples and 1/9 CQ-resistant samples (p=0.027). The other molecular markers were not associated to CQ-susceptibility.

Conclusions

In vitro CQ-resistance estimated in this study, estimated by the DELI test, was very similar to that observed in clinical trials, suggesting that in vitro procedures developed by capable local laboratories are useful in the surveillance of CQ-resistance in the Amazon; concurrent Amazon P. vivax strains with both CQ and MQ resistance may be common; and a non-synonymous mutation at pvdhps codon 382 (S→C) was associated to in vitro susceptibility to CQ, needing further studies to be confirmed.
Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus
Authors: Wistuba-Hamprecht Kilian , Frasca Daniela , Blomberg Bonnie , Pawelec Graham , Derhovanessian Evelyna
Published: July 2013

Background

Despite the common perception that latent Cytomegalovirus (CMV) infection is usually symptom-free, emerging epidemiological evidence suggests that it may in fact be associated with higher mortality over extended follow-up. Mechanisms responsible for this potentially important effect are unclear. CMV infection is known to have a large impact on the distribution of T cell phenotypes, especially the accumulation of late-stage differentiated CD8+, as well as Vδ2-γδ T-cells, which are the main subset of γδ T-cells involved in anti-CMV immunity. Its impact on γδ T-cells in the aging context is less well-defined.

Results

Here, we investigated a group of healthy individuals aged between 21 and 89 years, in order to correlate the frequency and differentiation status of γδ T-cells with age. We found that these parameters were only marginally influenced by age, but were marked in people with a latent CMV infection. Thus, we observed a significant age-associated accumulation of late-differentiated T-cells within the Vδ2-population, but only in CMV-seropositive donors. There was also a strong trend towards reduced frequency of early-differentiated cells within the Vδ2-phenotype. Older people had significantly higher anti-CMV IgG titers, which in turn correlated significantly with a lower Vδ2+/Vδ2-ratio and a shift from early- to a late-differentiated Vδ2-T-cell phenotype.

Conclusions

Our findings demonstrate a strong influence of CMV on γδ T-cells during human ageing, similar to that observed for αβ T-cells. Differences between donors of different ages are more marked in CMV-infected individuals. The biological implications of this potent age-associated CMV-mediated immune-modulation require clarification.
Comparison 30-day clinical complications between transfemoral versus transapical aortic valve replacement for aortic stenosis: a meta-analysis review
Authors: Li Xuebiao , Kong Minjian , Jiang Daming , Dong Aiqiang
Published: July 2013

Background

Since 2002, transapical aortic valve replacement has been developed as a clinical pathway for transcatheter aortic valve implantation (TAVI). However the appropriate role of TA in the AS population versus TF remains unclear. We performed a meta-analysis to assess if TF has any benefit in reduction of 30-day clinical complications in AS.

Methods

We conducted a comprehensive search on pub-med and web of knowledge from 2002 through September 2012 using following terms: aortic stenosis, aortic valve replacement, transcatheter aortic valve implantation, TAVI, trans-artery, transfemoral, trans-apical. Studies in the original research or review articles were also considered. Included studies must meet the preconditioned criterias. Two investigators independently browsed the studies by title and abstract, finally making decision according to full-text. Disagreements were discussed in group.

Results

A total of 20 studies met inclusion criteria’s and were included in the analysis (including 4267 patients in TF group, 2242 in TA group). No random clinical trial, one was a retrospective study, others were prospective trials. Our meta-analysis found that TF had the low incidence of 30-day mortality compared with TA procedure (7.5% versus 11.3%). The incidence of stroke at ≤ 30 days was relatively low (3.8% in TF versus 4.0% in TA). Although the incidence of post-operative heart block was high (8.5% versus 7.5%), but no differences were indicated [1.06,95% CI(0.85,1.33)].

Conclusions

The result of our meta-analysis suggested that TF may have a low risk for 30-day mortality against TA procedure. No difference was found in the incidence of post-operative stroke and heart block.
GenePattern flow cytometry suite
Authors: Spidlen Josef , Barsky Aaron , Breuer Karin , Carr Peter , Nazaire Marc-Danie , Hill Barbara Allen , Qian Yu , Liefeld Ted , Reich Michael , Mesirov Jill P , Wilkinson Peter , Scheuermann Richard H , Sekaly Rafick-Pierre , Brinkman Ryan R
Published: July 2013

Background

Traditional flow cytometry data analysis is largely based on interactive and time consuming analysis of series two dimensional representations of up to 20 dimensional data. Recent technological advances have increased the amount of data generated by the technology and outpaced the development of data analysis approaches. While there are advanced tools available, including many R/BioConductor packages, these are only accessible programmatically and therefore out of reach for most experimentalists. GenePattern is a powerful genomic analysis platform with over 200 tools for analysis of gene expression, proteomics, and other data. A web-based interface provides easy access to these tools and allows the creation of automated analysis pipelines enabling reproducible research.

Results

In order to bring advanced flow cytometry data analysis tools to experimentalists without programmatic skills, we developed the GenePattern Flow Cytometry Suite. It contains 34 open source GenePattern flow cytometry modules covering methods from basic processing of flow cytometry standard (i.e., FCS) files to advanced algorithms for automated identification of cell populations, normalization and quality assessment. Internally, these modules leverage from functionality developed in R/BioConductor. Using the GenePattern web-based interface, they can be connected to build analytical pipelines.

Conclusions

GenePattern Flow Cytometry Suite brings advanced flow cytometry data analysis capabilities to users with minimal computer skills. Functionality previously available only to skilled bioinformaticians is now easily accessible from a web browser.
Neutrophil activation by Campylobacter concisus
Authors: Sørensen Nina B , Nielsen Hans L , Varming Kim , Nielsen Henrik
Published: July 2013

Background

Campylobacter concisus is an emerging enteric pathogen associated with prolonged diarrhoea and possibly inflammatory bowel disease in children as well as adults, but the interaction with cells of the innate immune system is unclear. The magnitude of systemic immunoglobulin response in acute infection is unknown.

Methods

Neutrophils from healthy volunteers were activated with five faecal isolates of C. concisus from patients with gastroenteritis as well as the oral reference strain C. concisus ATCC33237. Neutrophils were tested for the expression of adherence molecule CD11b by immunoflourescence and for oxidative burst response by chemiluminescence. The opsonic activity in a chemiluminescence assay was assessed with heat treated serum from patients with C. concisus infection.

Results

A strong and dose-dependent activation of neutrophil adherence molecule CD11b and oxidative burst response was demonstrated with all six C. concisus isolates. Bacteria opsonised in heat treated serum induced an increased chemiluminescence response. Heat treated serum from patients with C. concisus infection did not have a higher opsonic activity than heat treated serum from healthy volunteers.

Conclusion

C. concisus has the capability to activate the innate immune system by stimulating neutrophil cells to increased adherence molecule expression and oxidative burst response, both crucial for acute inflammation. In a chemiluminescence assay the opsonic activity of heat treated serum from patients was not increased compared to heat treated control serum suggesting a weak systemic IgG response to infection.
The Putzig partners DREF, TRF2 and KEN are involved in the regulation of the Drosophila telomere retrotransposons, HeT-A and TART
Authors: Silva-Sousa Rute , Varela Míriam Díaz , Casacuberta Elena
Published: July 2013

Background

Telomere maintenance in Drosophila relies on the targeted transposition of three very special non-LTR retrotransposons, HeT-A, TART, and TAHRE (HTT). The sequences of the retrotransposon array build up the telomere chromatin in this organism. We have recently reported the role of the chromosomal protein Putzig/Z4 in maintaining a proper chromatin structure at the telomere domain of Drosophila. Because the Putzig protein has been found in different cellular complexes related with cell proliferation, development, and immunity, we decided to investigate whether the previously described Putzig partners, DREF/TRF2 and KEN, could also be involved in the telomere function in this organism.

Results

We have found that mutant alleles for Dref/Trf2 and Ken show alterations in HeT-A and TART expression, suggesting a possible role of these protein complexes in the regulation of the telomere retrotransposons. In agreement, both HeT-A and TART contain the specific DNA binding sequences for the DREF and the KEN protein proteins.

Conclusions

We have identified three new negative regulators involved in the control of the expression of the telomeric retrotransposons, Dref, Trf2, and Ken. Our results offer some clues on which other chromatin-related proteins might be involved in telomere regulation and retrotransposon control.
Severe everolimus-induced steatohepatis: a case report
Authors: Schieren Gisela , Bölke Edwin , Scherer Axel , Raffel Andreas , Gerber Peter Arne , Kröpil Patric , Schott Matthias , Hamilton Jackson , Hayman Anne , Knoefel Wolfram Trudo , Budach Wilfried , Matuschek Christiane
Published: July 2013

The mammalian target of rapamycin inhibitors are normally favored as immunosuppressant agents for solid organ transplantation such as kidney, liver or heart. Only in recent years have they been increasingly administered for the treatment of neuroendocrine tumors. Even though mammalian target of rapamycin inhibitors are known to exhibit specific side effects, everolimus-related severe hepatic steatosis has not as yet been described in the literature. We report the case of a 76-year-old man who developed severe hepatic steatosis within four weeks of treatment with everolimus as concomitant tumor therapy for a progressively growing neuroendocrine carcinoma of the ileum. A diagnosis of hepatic steatosis was established using computer tomography and fibroscan©. Other underlying causes for steatosis hepatis could be excluded. Further studies are warranted to explain the underlying mechanisms.
Anaerobic slurry co-digestion of poultry manure and straw: effect of organic loading and temperature
Authors: Babaee Azadeh , Shayegan Jalal , Roshani Anis
Published: July 2013

In order to obtain basic design criteria for anaerobic digestion of a mixture of poultry manure and wheat straw, the effects of different temperatures and organic loading rates on the biogas yield and methane contents were evaluated. Since poultry manure is a poor substrate, in term of the availability of the nutrients, external supplementation of carbon has to be regularly performed, in order to achieve a stable and efficient process. The complete-mix, pilot-scale digester with working volume of 70 L was used. The digestion operated at 25°C, 30°C and 35°C with organic loading rates of 1.0, 2.0, 2.5, 3.0, 3.5 and 4.0 kg Volatile solid/m3d and a HRT of 15 days. At a temperature of 35°C, the methane yield was increased by 43% compared to 25°C. Anaerobic co-digestion appeared feasible with a loading rate of 3.0 kg VS/m3d at 35°C. At this state, the specific methane yield was calculated about 0.12 m3/kg VS with a methane content of 53–70.2% in the biogas. The volatile solid (VS) removal was 72%. As a result of volatile fatty acid accumulation and decrease in pH, when the loading rate was less than 1 or greater than 4 kg VS/m3d, the process was inhibited or overloaded, respectively. Both the lower and higher loading rates resulted in a decline in the methane yield.
Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events
Authors: Gustbée Emma , Anesten Charlotte , Markkula Andrea , Simonsson Maria , Rose Carsten , Ingvar Christian , Jernström Helena
Published: July 2013

Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from questionnaires, pathology reports, and patients’ charts from 592 patients without preoperative treatment. Breast-feeding duration ≤12 months of the first child was associated with higher frequency of ER+/PgR+ tumors (P=0.02). Median follow-up time was 4.9 years. Higher risk for early events was observed for breast-feeding duration of first child >12 months (LogRank P=0.001), total breast-feeding duration >12 months (LogRank P=0.008), as well as ‘excessive milk production’ during breast-feeding of the first child (LogRank P=0.001). Patients with ‘almost no milk production’ had no events. In a multivariable model including both ‘excessive milk production’ and breast-feeding duration of the first child >12 months, both were associated with a two-fold risk for early events, adjusted HRs 2.33 (95% CI: 1.25-4.36) and 2.39 (0.97-5.85), respectively, while total breast-feeding duration was not. ‘Excessive milk production’ was associated with a two-fold risk of early distant metastases, adjusted HR 2.59 (1.13-5.94), but not duration. In conclusion, ‘excessive milk production’ during breast-feeding was associated with higher risk for early events independent of tumor characteristics, stressing the need to consider host factors in the evaluation of prognostic markers.
Succinate dehydrogenase expression in breast cancer
Authors: Kim Sewha , Kim Do Hee , Jung Woo-Hee , Koo Ja Seung
Published: July 2013

The aim of this study was to investigate succinate dehydrogenase (SDH) expression in breast cancer according to breast cancer molecular subtype using immunohistochemistry and to assess the clinical implications of SDH expression. Immunohistochemical staining for ER, PR, HER-2, Ki-67, HIF-1α, SDHA, and SDHB was performed on tissue microarrays of 721 breast cancers. According to the immunohistochemistry results for ER, PR, HER-2, and Ki-67 and fluorescence in situ hybridization (FISH) results for HER-2, breast cancer molecular subtypes were classified into luminal A, luminal B, HER-2, and triple-negative breast cancer (TNBC). HER-2 subtype breast cancers most frequently showed high-level expression of SDHA in tumor cells, while the luminal A subtype most frequently showed low or negative expression of SDHA in tumor cells (P = 0.032). Stromal SDHB expression rate was highest in HER-2 subtype and lowest in TNBC (P < 0.001). SDHA-negative breast cancers were associated with younger age at diagnosis (P = 0.012), and SDHB-negative breast cancers with lower histologic grade (P = 0.044) and lower Ki-67 labeling index (LI) (P = 0.046). Tumor phenotypes according to the SDH status were SDHA(+)/SDHB(+) > SDHA(–)/SDHB(–) > SDHA(–)/SDHB(+) > SDHA(+)/SDHB(–) in order of frequency. The stromal phenotypes were SDHA(–)/SDHB(–) > SDHA(+)/SDHB(+) > SDHA(–)/SDHB(+) > SDHA(+)/SDHB(–). In conclusion, loss of SDHA or SDHB expression was observed in about 3% of breast cancers in this study. Low SDH expression status in breast tumor cells was associated with younger age at diagnosis and low-grade histology.
Cohort profile: mental health following extreme trauma in a northern Ugandan cohort of W ar-A ffected Y outh S tudy (The WAYS Study)
Authors: Amone-P’Olak Kennedy , Jones Peter B , Abbott Rosemary , Meiser-Stedman Richard , Ovuga Emilio , Croudace Tim J
Published: July 2013

War experiences are associated with the risk of long-term mental health problems. The War-affected Youths (WAYS) Study comprises a cohort of 539 youths (61% male) aged between 18 to 25 (at baseline) randomly sampled from the population of war-affected youths in northern Uganda. The study aims to chart the trajectory of long-term mental health consequences of war and the roles of individual, family, and community contextual risk and protective factors in influencing the course of mental health using Social Ecology Model, thus, addressing both the individual and its social ecology. Knowledge of postwar contexts may inform policy and guide interventions on postwar psychosocial adjustment and reintegration in conflict-prone Great Lakes region of Africa (Rwanda, Burundi, DR Congo, Uganda, Central African Republic, and South Sudan). Two waves of data collection have been conducted and more data collection is planned. At baseline, information on demographic characteristics, pre-war experiences, psychosocial outcomes, coping, stigma/discrimination, family and community acceptance and relationship, family functioning, and post-war experiences were obtained. At follow-up, information on general health, gender-based violence, PTSD, social skills, trauma memory quality, rumination, self-esteem, and psychosocial outcomes were collected. Approval to access the data can be obtained on application to the Principal Investigator upon submission of a research proposal with ethical approval from the applicant's institution. This research is funded by Wellcome Trust and Gulu University.
Fuel Economy and Safety: The Influences of Vehicle Class and Driver Behavior
Authors: Jacobsen Mark R
Published: July 2013

Fuel economy standards change the composition of the vehicle fleet, influencing accident safety. The direction and size of the effect depend on the combination of vehicles in the fleet. I provide empirical estimates of vehicle safety across classes, accounting for unobserved driving behavior and selection. I apply the model to the present structure of US fuel economy standards, accounting for shifts in the composition of vehicle ownership, and estimate an adverse safety effect of 33 cents per gallon of gasoline saved. I show how two alternative regulatory provisions fully offset this effect, producing a nearzero change in accident fatalities. (JEL D12, L51, L62, Q48, R41)
Teaching Practices and Social Capital
Authors: Algan Yann , Cahuc Pierre , Shleifer Andrei
Published: July 2013

In cross-country data, teaching practices (such as copying from the board versus working on projects together) are related to various dimensions of social capital. In micro-data from three datasets, teaching practices are also strongly correlated with student beliefs about cooperation across schools within countries. To address omitted variable and reverse causality concerns, we show that, within schools, teaching practices also have an independent and sizeable effect on student beliefs. The evidence supports the idea that progressive education promotes the formation of social capital. (JEL D83, I21, Z13)
The Coalbed Methane (CBM) Potential and CO2 Storage Capacity of the Santa Terezinha Coalfield, Paraná Basin, Brazil – 3D Modelling, and Coal and Carbonaceous Shale Characteristics and Related Desorption and Adsorption Capacities in Samples from Exploration Borehole CBM001-ST-RS
Authors: Kalkreuth W. , Holz M. , Levandowski J. , Kern M. , Casagrande J. , Weniger P. , Krooss B.
Published: July 2013

This study investigates the CBM generation and CO2 storage capacity of the coal-bearing Permian age Rio Bonito Formation in the Santa Terezinha Coalfield, Paraná Basin, Brazil. In order to assess the volumetrics of the coal seams a fourth-order sequence stratigraphic framework of the coal-bearing succession was established based on parasequence boundaries. A 3D geometric model based on data from 36 well logs was developed, and enabled subdivision of the study area into regions with very different CBM potential, due to variable cumulative coal thickness, depths and presence/absence of diabase. Strata of the coal-bearing Rio Bonito Formation were penetrated in well CBM001-ST-RS at a depth of 575.70 to 638.35 m, from which twelve coal seams and carbonaceous shales, ranging in thickness from 0.15 to 1.77 m, were retrieved for analysis. Gas desorption values range from 0.3 to 2.2 cm3/g. Gas composition is dominated by methane (> 94 Vol%). Gas isotopic analyses suggest a mixed biogenic and thermogenic origin. Vitrinite reflectance indicate a rank of high volatile A bituminous coal, with semi-anthracite occurring in contact with igneous rocks. The majority of the samples has vitrinite group contents > 50 Vol%, mineral matter-free basis. Ash yields range from 42.1 to 92.8 wt.%, whereas sulphur contents range from 0.1 to 7.7 wt.%. Volatile matter and calorific values (dry ash-free) range from 37.6 to 79.4 wt.%, and 2352 to 8107 kcal/kg, respectively. Mineral composition of the samples is dominated by quartz and kaolinite, whereas major element analyses show that SiO2 is most abundant. The 3D model allowed volumetric calculation for the coal seams and formed the basis for calculations of gas content and CO2 storage capacity. According to the 3D model the four coal-bearing parasequences of the study area contain a coal volume on the order of 3212 × 10 6 m3 suggesting a resource base of 5.5 × 109 m3 of methane associated with the coal seams and carbonaceous shales of the study area. The methane and carbon dioxide sorption capacities show a high positive correlation with TOC content. The coal seams appear to be undersaturated, since sorption capacity is significantly higher than the desorbed gas volume. The CO2 sorption capacity at mean reservoir pressure was up to 7 times higher than the methane sorption capacity. Based upon sorption capacities and reservoir conditions, a storage potential of 13.8 Gt CO2 in coal seams and carbonaceous shales of the study area is estimated.
Play Model and Hydrocarbon Transport of Carbonate Reservoirs in Lower Ordovician on Northern Slope of Tazhong Area
Authors: Jiao Weiwei , Yang Haijun , Cheng Lijun , Zhao Yue , Liu Dandan
Published: July 2013

The Northern Slope of the Tazhong area is one of the important areas to increase reserve and production in carbonate reservoirs in the Tarim Basin, west China. But in the complex superimposed basin, multiple-stage charging from multiple-sources, and mixed sources in different proportions have resulted in the complexity of oil-water relationship. Major controlling factors and play models are not clear, which has brought great difficulties to exploration. Therefore, it is necessary to study hydrocarbon generation, migration, accumulation and distribution, and recognize the dynamic process of hydrocarbon accumulation. Our research on geology, petrology and geochemistry of trace elements indicated that controlled by the key elements of cap rock, karsted weathering crust reservoir bed and strike-slip faults, accumulation of hydrocarbons in the lower Ordovician on the Northern Slope of the Tazhong area is characterized by vertical zonation and horizontal section-wise distribution. Transport framework of fault-unconformity-karsted fracture and void was established by our research on the static characteristics of faults, unconformity and karstification. Hydrocarbon migration parameters of V/Ni ratio and physical properties of oil indicated that strike-slip faults developed in the lower Ordovician were important migration pathways in the vertical direction. Hydrocarbons migrated up to the unconformity and then were charged towards both sides of the fault, like letter T. Through the analysis of matching between play elements and reservoir formation, the play model “Letter T charging through strike-slip faults, and multiple-stage reservoiring with earlier oil and later gas” was established. According to the model, the deeper formations under the Yingshan formation could be a new worthy exploration target.
Ternary Diagram of Fluorenes, Dibenzothiophenes and Dibenzofurans: Indicating Depositional Environment of Crude Oil Source Rocks
Authors: Li Meijun , Wang Tieguan , Zhong Ningning , Zhang Weibiao , Sadik Akbar , Li Hongbo
Published: July 2013

Fluorene (FL), dibenzothiophene (DBT) and dibenzofuran (DBF) and their alkylated homologues are important polycyclic aromatic compounds in crude oils and source rock extracts. They share the similar chemical structure and may have genetic relationships. The parent compounds (unsubstituted), methyl-, dimethyl- and ethyl-substituted isomers are identified by comparison with retention indices reported in literatures and correlation with co-injection of internal standards in gas chromatography-mass spectrometry (GC-MS) analysis. Therefore, their relative concentrations can be determined. Based on the large data sets, this paper preliminarily establishes a ternary diagram to interpret the depositional environment/lithology for oils and related source rocks. Five typical depositional environments/lithologies are distinguished on this ternary diagram. Data points from typical marine carbonate, fluvial/deltaic/fresh lacustrine shale and swamp fall into the DBTs, FLs and DBFs end-members, respectively. Oils from marine shale have subequal contents of FLs and DBFs and lie between the zones of fluvial/deltaic/fresh lacustrine shale and swamp, but have a little higher abundance of DBTs. The oils from brackish/saline lacustrine have intermediate contents of DBTs with a wide variety and some degree overlap with that of marine shale. On the basis of the ternary diagrams, two petroleum systems in the cratonic region of the Tarim basis are defined. The majority of discovered oils were derived from the Middle-Upper Ordovician carbonate source rocks. Whereas, some oils from wells TD2, T904, LK1 and TZ62 originated from the Cambrian and Lower Ordovician source rocks. Therefore, the ternary diagram of FLs, DBTs and DBFs is a useful method to interpret depositional environment/lithology for oils and related source rocks and to definite petroleum systems as well.
A CO2-Oil Minimum Miscibility Pressure Model Based on Multi-Gene Genetic Programming
Authors: Rezaei Mehdi , Eftekhari Mahdi , Schaffie Mahin , Ranjbar Mohammad
Published: July 2013

Over the last decades, great attention has been devoted to the CO2 injection to enhance oil recovery. Recycling CO2 into oil reservoirs provides an excellent option to store this gas in subsurface formations and also improves oil recovery. Successful design of a miscible CO2 flooding project mostly depends on accurate determination of Minimum Miscibility Pressure (MMP). In the present study, using multi-gene genetic programming together with a comprehensive sensitivity analysis, a model was developed that provides an accurate estimation of MMP for a wide range of reservoir temperatures and oil compositions. This model utilizes temperature, molecular weight of C5+ compounds, and ratio of volatile to intermediate oil fractions as input parameters. Accuracy of correlation was tested versus experimental data and those of other correlations. Results show that the new model assumes a lower error than other published correlations. Based on the results of the present study, it can be asserted that the proposed model is able to predict CO2-oil MMP with a high accuracy when the experimental data are not available.
Trace Elements in Peat Bogs of Tomsk Region (South Siberia, Russia)
Authors: Mezhibor A.M. , Arbuzov S.I. , Arkhipov V.S.
Published: July 2013

16 peat bogs of Tomsk region (in Siberia) were used to study trace elements concentrations in ombrotrophic peat. The calculations of concentration coefficient in relation to the sedimentary rocks allowed us to determine some elements which tend to accumulate in ombrotrophic peat of Tomsk region. They are Au, Br, Sr, Ba, Fe, and Cr. For selective trace elements we considered spacial variability of their mean contents in the ombrotrophic peat of Tomsk region. Together with the study of vertical distribution of trace elements in the studied peat bogs we outlined factors influencing their accumulation in peat. Lithological and mineral composition of surrounding territories plays role in the accumulation of Cr, Sc, Br, Au, and lanthanides, climatic conditions and necessity for living plants cause Ca variations. Cr, Sc, lanthanides and U are also actively accumulated in the peat near industrial cities in the south of Tomsk region.