bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling the ancestral sequence distribution and model frequencies in context-dependent models for primate non-coding sequences
Authors: Baele Guy , Van de Peer Yves , Vansteelandt Stijn
Published: August 2010

Background

Recent approaches for context-dependent evolutionary modelling assume that the evolution of a given site depends upon its ancestor and that ancestor's immediate flanking sites. Because such dependency pattern cannot be imposed on the root sequence, we consider the use of different orders of Markov chains to model dependence at the ancestral root sequence. Root distributions which are coupled to the context-dependent model across the underlying phylogenetic tree are deemed more realistic than decoupled Markov chains models, as the evolutionary process is responsible for shaping the composition of the ancestral root sequence.

Results

We find strong support, in terms of Bayes Factors, for using a second-order Markov chain at the ancestral root sequence along with a context-dependent model throughout the remainder of the phylogenetic tree in an ancestral repeats dataset, and for using a first-order Markov chain at the ancestral root sequence in a pseudogene dataset. Relaxing the assumption of a single context-independent set of independent model frequencies as presented in previous work, yields a further drastic increase in model fit. We show that the substitution rates associated with the CpG-methylation-deamination process can be modelled through context-dependent model frequencies and that their accuracy depends on the (order of the) Markov chain imposed at the ancestral root sequence. In addition, we provide evidence that this approach (which assumes that root distribution and evolutionary model are decoupled) outperforms an approach inspired by the work of Arndt et al., where the root distribution is coupled to the evolutionary model. We show that the continuous-time approximation of Hwang and Green has stronger support in terms of Bayes Factors, but the parameter estimates show minimal differences.

Conclusions

We show that the combination of a dependency scheme at the ancestral root sequence and a context-dependent evolutionary model across the remainder of the tree allows for accurate estimation of the model's parameters. The different assumptions tested in this manuscript clearly show that designing accurate context-dependent models is a complex process, with many different assumptions that require validation. Further, these assumptions are shown to change across different datasets, making the search for an adequate model for a given dataset quite challenging.
Landscape features influence gene flow as measured by cost-distance and genetic analyses: a case study for giant pandas in the Daxiangling and Xiaoxiangling Mountains
Authors: Zhu Lifeng , Zhan Xiangjiang , Meng Tao , Zhang Shanning , Wei Fuwen
Published: August 2010

Background

Gene flow maintains genetic diversity within a species and is influenced by individual behavior and the geographical features of the species' habitat. Here, we have characterized the geographical distribution of genetic patterns in giant pandas (Ailuropoda melanoleuca) living in four isolated patches of the Xiaoxiangling and Daxiangling Mountains. Three geographic distance definitions were used with the "isolation by distance theory": Euclidean distance (EUD), least-cost path distance (LCD) defined by food resources, and LCD defined by habitat suitability.

Results

A total of 136 genotypes were obtained from 192 fecal samples and one blood sample, corresponding to 53 unique genotypes. Geographical maps plotted at high resolution using smaller neighborhood radius definitions produced large cost distances, because smaller radii include a finer level of detail in considering each pixel. Mantel tests showed that most correlation indices, particularly bamboo resources defined for different sizes of raster cell, were slightly larger than the correlations calculated for the Euclidean distance, with the exception of Patch C. We found that natural barriers might have decreased gene flow between the Xiaoxiangling and Daxiangling regions.

Conclusions

Landscape features were found to partially influence gene flow in the giant panda population. This result is closely linked to the biological character and behavior of giant pandas because, as bamboo feeders, individuals spend most of their lives eating bamboo or moving within the bamboo forest. Landscape-based genetic analysis suggests that gene flow will be enhanced if the connectivity between currently fragmented bamboo forests is increased.
Association of HPA axis-related genetic variation with stress reactivity and aggressive behaviour in pigs
Authors: Muráni Eduard , Ponsuksili Siriluck , D'Eath Richard B , Turner Simon P , Kurt Esra , Evans Gary , Thölking Ludger , Klont Ronald , Foury Aline , Mormède Pierre , Wimmers Klaus
Published: August 2010

Background

Stress, elicited for example by aggressive interactions, has negative effects on various biological functions including immune defence, reproduction, growth, and, in livestock, on product quality. Stress response and aggressiveness are mutually interrelated and show large interindividual variation, partly attributable to genetic factors. In the pig little is known about the molecular-genetic background of the variation in stress responsiveness and aggressiveness. To identify candidate genes we analyzed association of DNA markers in each of ten genes (CRH g.233C>T, CRHR1 c.*866_867insA, CRHBP c.51G>A, POMC c.293_298del, MC2R c.306T>G, NR3C1 c.*2122A>G, AVP c.207A>G, AVPR1B c.1084A>G, UCN g.1329T>C, CRHR2 c.*13T>C) related to the hypothalamic-pituitary-adrenocortical (HPA) axis, one of the main stress-response systems, with various stress- and aggression-related parameters at slaughter. These parameters were: physiological measures of the stress response (plasma concentrations of cortisol, creatine kinase, glucose, and lactate), adrenal weight (which is a parameter reflecting activity of the central branch of the HPA axis over time) and aggressive behaviour (measured by means of lesion scoring) in the context of psychosocial stress of mixing individuals with different aggressive temperament.

Results

The SNP NR3C1 c.*2122A>G showed association with cortisol concentration (p = 0.024), adrenal weight (p = 0.003) and aggressive behaviour (front lesion score, p = 0.012; total lesion score p = 0.045). The SNP AVPR1B c.1084A>G showed a highly significant association with aggressive behaviour (middle lesion score, p = 0.007; total lesion score p = 0.003). The SNP UCN g.1329T>C showed association with adrenal weight (p = 0.019) and aggressive behaviour (front lesion score, p = 0.029). The SNP CRH g.233C>T showed a significant association with glucose concentration (p = 0.002), and the polymorphisms POMC c.293_298del and MC2R c.306T>G with adrenal weight (p = 0.027 and p < 0.0001 respectively).

Conclusions

The multiple and consistent associations shown by SNP in NR3C1 and AVPR1B provide convincing evidence for genuine effects of their DNA sequence variation on stress responsiveness and aggressive behaviour. Identification of the causal functional molecular polymorphisms would not only provide markers useful for pig breeding but also insight into the molecular bases of the stress response and aggressive behaviour in general.
Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa
Authors: Huang Yukan , Zhang Jing , Li Chang , Yang Guohua , Liu Mugen , Wang Qing K , Tang Zhaohui
Published: August 2010

Background

Retinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.

Methods

Linkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of EYS was used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.

Results

A single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.

Conclusions

The EYS gene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue of Drosophila spacemaker. To date, there are only eight mutations in EYS that have been identified to cause arRP. Here we report one novel homozygous nonsense mutation of EYS in a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations in EYS cause arRP. Additionally, this is the first EYS mutation identified in the Chinese population.
Burden of paediatric Rotavirus Gastroenteritis (RVGE) and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain
Authors: Diez-Domingo Javier , Suriñach Nuria Lara , Alcalde Natalia Malé , Betegón Lourdes , Largeron Nathalie , Trichard Mélanie
Published: August 2010

Background

Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain.

Methods

A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005) and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children). Health outcomes included home care cases, General Practioner (GP)/Paediatrician, emergency department visits, hospitalisations and nosocomial infections.

Results

The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate) would reduce the rotavirus gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: €22 million from the national health system perspective and €38 million from the societal perspective.

Conclusions

A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.
Comparison of glucose derivatives effects on cartilage degradation
Authors: Phitak Thanyaluck , Pothacharoen Peraphan , Kongtawelert Prachya
Published: August 2010

Background

Glucosamine (GlcN) is a well-recognized candidate for treatment of osteoarthritis. However, it is currently used in derivative forms, such as glucosamine-hydrochloride (GlcN-HCl) or glucosamine sulfate (GlcN-S). However, the molecular mode of action remains unclear. In this study, we compared the effects of Glucose (Glc), Glucuronic acid (GlcA), Glucosamine hydrochloride (GlcN-HCl) and Glucosamine sulfate (GlcN-S) on cartilage degradation.

Methods

Porcine cartilage explants were co-cultured with recombinant human IL-1β and each tested substance for 3 days. HA, s-GAG and MMP-2 releases to media were measured using ELISA, dye-binding assay and gelatin zymography, respectively. Similar studies were performed in a human articular chondrocytes (HAC) monolayer culture, where cells were co-treated with IL-1β and each reagent for 24 hours. Subsequently, cells were harvested and gene expression measured using RT-PCR. All experiments were carried out in triplicate. Student's t-tests were used for statistical analysis.

Results

In cartilage explants treated with IL-1β, GlcN-S had the highest chondroprotective activity of all four chemicals as shown by the inhibition of HA, s-GAG and MMP-2 released from cartilage. The anabolic (aggrecan core protein; AGG, SOX9) and catabolic (MMP-3, -13) genes in HACs treated with IL-1β and with/without chemicals were studied using RT-PCR. It was found that, GlcN-HCl and GlcN-S could reduce the expression of both MMP-3 and -13 genes. The IL-1β induced-MMP-13 gene expression was decreased maximally by GlcN-S, while the reduction of induced-MMP-3 gene expression was greatest with GlcN-HCl. Glc and GlcA reversed the effect of IL-1β on the expression of AGG and SOX9, but other substances had no effect.

Conclusion

This study shows that glucosamine derivatives can alter anabolic and catabolic processes in HACs induced by IL-1β. GlcN-S and GluN-HCl decreased induced MMP-3 and -13 expressions, while Glc and GlcA increased reduced-AGG and SOX9 expression. The chondroprotective study using porcine cartilage explant showed that GlcN-S had the strongest effect.
Different mutation patterns of Plasmodium falciparum among patients in Jimma University Hospital, Ethiopia
Authors: Eshetu Teferi , Berens-Riha Nicole , Fekadu Sintayehu , Tadesse Zelalem , Gürkov Robert , Hölscher Michael , Löscher Thomas , Miranda Isabel Barreto
Published: August 2010

Background

The emergence of drug resistance is a major problem in malaria control. Combination of molecular genotyping and characterization of mutations or single nucleotide polymorphisms (SNPs) correlated with drug resistance can provide information for subsequent surveillance of existing and developing drug resistance patterns. The introduction of artemether/lumefantrine (AL) as first-line treatment, never used before in Ethiopia, allowed the collection of baseline data of molecular polymorphisms before a selection due to AL could occur.

Method

97 patients with uncomplicated falciparum malaria were recruited from April to June 2006 and treated with either AL, quinine (Q) or atovaquone/proguanil (AP) in Jimma University Hospital, Ethiopia. Mutations or SNPs associated with resistance to these drugs were analysed by RFLP (pfdhfr, pfmdr1) and sequencing of the target genes (pfcytb, pfserca ).

Results

SNPs previously reported to be associated with resistance to the study drugs were identified in recrudescent and treatment sensitive isolates. A total of seven recrudescences were obtained. The pfmdr1 N86Y mutation was found in 84.5% of isolates. The triple mutation 51I,59R,108N of the pfdhfr gene occured in high frequency (83.3%) but no pfcytb mutation was detected. Sequencing showed a variety of previously described and new mutations in the pfserca gene.

Conclusion

The prevalence of mutations was in accordance with the expected patterns considering recent drug regimens. The broad introduction of AL and the cessation of former drug regimens might probably change the current distribution of polymorphisms, possibly leading to decreased sensitivity to AL in future. Continuous surveillance of molecular patterns in this region is, therefore, recommended.
Recurrent retroperitoneal Schwannomas displaying different differentiation from primary tumor: Case report and literature review
Authors: Li Zhong-qi , Wang Hai-yong , Li Jun , Teng Lisong
Published: August 2010

Background

Retroperitoneal Schwannomas are uncommonly found in the retroperitoneum and few of them show malignant transformation and invasion. Local recurrence are common in malignant Schwannomas with very few reports of tumor distinct differentiation at recurrences.

Case presentation

We report here a rare case of retroperitoneal schwannoma with multiple origins from retroperitoneum and pelvic wall. Pathological examination confirmed the case as a schwannoma with malignant transformation. Radical dissection of the tumors along with the sacrifice of adjacent sigmoid colon and left kidney failed to provide a cure for this patient. Due to tumor recurrence, a second and a third surgery of radical excision were performed 6 months and 17 months later after the first surgery, respectively. Histopathologic analysis identified that the recurrent tumors were different from the original schwannoma because of their smooth muscle-like differentiation.

Conclusion

Malignant schwannomas are uncommon sarcomas with a high incidence of local recurrence. Distinct immunohistochemical staining results of the tumors at recurrence indicate their potential of smooth-muscle like differentiation. Radical excision of the tumors may provide benefit for their local recurrences.
Secondary infection with Streptococcus suis serotype 7 increases the virulence of highly pathogenic porcine reproductive and respiratory syndrome virus in pigs
Authors: Xu Min , Wang Shujie , Li Linxi , Lei Liancheng , Liu Yonggang , Shi Wenda , Wu Jiabin , Li Liqin , Rong Fulong , Xu Mingming , Sun Guangli , Xiang Hua , Cai Xuehui
Published: August 2010

Background

Porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis are common pathogens in pigs. In samples collected during the porcine high fever syndrome (PHFS) outbreak in many parts of China, PRRSV and S. suis serotype 7 (SS7) have always been isolated together. To determine whether PRRSV-SS7 coinfection was the cause of the PHFS outbreak, we evaluated the pathogenicity of PRRSV and/or SS7 in a pig model of single and mixed infection.

Results

Respiratory disease, diarrhea, and anorexia were observed in all infected pigs. Signs of central nervous system (CNS) disease were observed in the highly pathogenic PRRSV (HP-PRRSV)-infected pigs (4/12) and the coinfected pigs (8/10); however, the symptoms of the coinfected pigs were clearly more severe than those of the HP-PRRSV-infected pigs. The mortality rate was significantly higher in the coinfected pigs (8/10) than in the HP-PRRSV- (2/12) and SS7-infected pigs (0/10). The deceased pigs of the coinfected group had symptoms typical of PHFS, such as high fever, anorexia, and red coloration of the ears and the body. The isolation rates of HP-PRRSV and SS7 were higher and the lesion severity was greater in the coinfected pigs than in monoinfected pigs.

Conclusion

HP-PRRSV infection increased susceptibility to SS7 infection, and coinfection of HP-PRRSV with SS7 significantly increased the pathogenicity of SS7 to pigs.
Sarcoidosis in a dental surgeon: a case report
Authors: Checchi Luigi , Nucci Maria C , Gatti Antonietta M , Mattia Daniele , Violante Francesco S
Published: August 2010

Introduction

Although the causes of sarcoidosis are still unknown, past and current studies have provided evidence that this disease may be associated with occupational exposure to specific environmental agents. We describe a case of sarcoidosis in a dental surgeon with long exposure to inorganic dusts. To the best of our knowledge, this is the first report of this kind in the literature.

Case presentation

At the beginning of 2000, a 52-year-old Caucasian man, who worked as a dental surgeon, presented with shortness of breath during exercise, cough and retrosternal pain. After diagnosis of sarcoidosis, a scanning electronic microscopy with X-ray microanalysis of biopsy specimens was used in order to determine whether the disease could be traced to an occupational environmental agent. Results showed the presence of inorganic dust particles within sarcoidotic granulomas, and demonstrated that the material detected was identical to that found in a powder used by our patient for several years.

Conclusions

Although these results cannot be considered as definitive proof, they do however provide strong evidence that this disease may be associated with material used by dental surgeons.
Achievements and challenges in bioartificial kidney development
Authors: Tasnim Farah , Deng Rensheng , Hu Min , Liour Sean , Li Yao , Ni Ming , Ying Jackie Y , Zink Daniele
Published: August 2010

Bioartificial kidneys (BAKs) combine a conventional hemofilter in series with a bioreactor unit containing renal epithelial cells. The epithelial cells derived from the renal tubule should provide transport, metabolic, endocrinologic and immunomodulatory functions. Currently, primary human renal proximal tubule cells are most relevant for clinical applications. However, the use of human primary cells is associated with many obstacles, and the development of alternatives and an unlimited cell source is one of the most urgent challenges. BAKs have been applied in Phase I/II and Phase II clinical trials for the treatment of critically ill patients with acute renal failure. Significant effects on cytokine concentrations and long-term survival were observed. A subsequent Phase IIb clinical trial was discontinued after an interim analysis, and these results showed that further intense research on BAK-based therapies for acute renal failure was required. Development of BAK-based therapies for the treatment of patients suffering from end-stage renal disease is even more challenging, and related problems and research approaches are discussed herein, along with the development of mobile, portable, wearable and implantable devices.
Transactivation of PDGFRβ by dopamine D4 receptor does not require PDGFRβ dimerization
Authors: Chi Sum Shing , Vetiska Sandra M , Gill Robin S , Hsiung Marilyn S , Liu Fang , Van Tol Hubert HM
Published: August 2010

Growth factor-induced receptor dimerization and cross-phosphorylation are hallmarks of signal transduction via receptor tyrosine kinases (RTKs). G protein-coupled receptors (GPCRs) can activate RTKs through a process known as transactivation. The prototypical model of RTK transactivation involves ligand-mediated RTK dimerization and cross-phosphorylation. Here, we show that the platelet-derived growth factor receptor β (PDGFRβ) transactivation by the dopamine receptor D4 (DRD4) is not dependent on ligands for PDGFRβ. Furthermore, when PDGFRβ dimerization is inhibited and receptor phosphorylation is suppressed to near basal levels, the receptor maintains its ability to be transactivated and is still effective in signaling to ERK1/2. Hence, the DRD4-PDGFRβ-ERK1/2 pathway can occur independently of a PDGF-like ligand, PDGFRβ cross-phosphorylation and dimerization, which is distinct from other known forms of transactivation of RTKs by GPCRs.
Parthenolide induces proliferation inhibition and apoptosis of pancreatic cancer cells in vitro
Authors: Liu Jun-Wei , Cai Min-Xia , Xin Ying , Wu Qing-Song , Ma Jun , Yang Po , Xie Hai-Yang , Huang Dong-Sheng
Published: August 2010

Background

To explore the anti-tumor effects of parthenolide in human pancreatic cancer.

Methods

BxPC-3 cell, a human pancreatic cancer, was treated with parthenolide at different concentrations. The MTT assay was used to analyze cell viability. Flow cytometry and DNA fragmentation analysis were applied to evaluate apoptosis after parthenolide treatment. The wound closure and cell invasion assay were also employed in the study. Western blotting was used to demonstrate Bad, Bcl-2, Bax, caspase-9 and pro-caspase-3 expression.

Results

The MTT assay indicated that the pancreatic cancer growth could be dose-dependently inhibited by parthenoolide. This phenomenon was confirmed by flow cytometry and DNA fragmentation analysis. The wound closure assay and cell invasion assay showed that BxPC-3 cell was significantly suppressed by parthenolide at 7.5 μM and 15 μM. Western Blotting demonstrated the Bcl-2 and pro-caspase-3 were down-regulated while the Bax and caspase-9 were up-regulated. No alteration in Bad expression was found after treatment.

Conclusions

The parthenolide can inhibit the cell growth, migration, and induce the apoptosis in human pancreatic cancer. These findings may provide a novel approach for pancreatic cancer treatment.
Bone events and evolution of biologic markers in Gaucher disease before and during treatment
Authors: Stirnemann Jérôme , Belmatoug Nadia , Vincent Corine , Fain Olivier , Fantin Bruno , Mentré France
Published: August 2010

Introduction

Known biomarkers of Gaucher-disease activity are platelets, chitotriosidase, angiotensin-converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP) and ferritin. The aim of this study was to retrospectively evaluate the frequency of bone events (BE) and biomarker changes during two periods: diagnosis to first enzyme-replacement therapy (ERT) and the latter to the closing date.

Methods

BE of 62 treated patients, among the 73-patient cohort followed at Beaujon Hospital, Clichy, France, were described with Kaplan-Meier curves, and linear-mixed models were used to analyze their biomarker changes and the influence of several covariates (splenectomy, diagnosis year, genotype, age at diagnosis and sex).

Results

BE occurred before (54 events in 21 patients), but also during, ERT (12 events in 10 patients), with respective frequencies (95% confidence interval) at 10 years of 22.4% (13.3 to 36.3) and 20.0% (10.2 to 36.9). Biomarker slope changes before and during ERT differed significantly for platelets (+190/mm3/year and 7,035/mm3/year, respectively; P < 0.0001) and ferritin (+4% and -14%; P < 0.0001). High ferritin levels and low platelet counts at ERT onset were significantly associated with BE during ERT (P = 0.019 and 0.039, respectively). Covariates significantly influenced biomarker changes (baseline and/or slope): splenectomy affected platelets (baseline and changes), TRAP changes and chitotriosidase changes; diagnosis date influenced ACE and TRAP baseline values; and genotype influenced chitotriosidase baseline and changes.

Conclusions

Platelet counts and ferritin levels and their slope changes at ERT onset seem to predict BE during treatment. Biomarker baseline values and changes are dependent on several covariables.
Role of 3D seismic for quantitative shallow hazard assessment in deepwater sediments
Authors: Dutta Nader C. , Utech Randal W. , Shelander Dianna
Published: August 2010

Increased drilling activities in deep water since 1985, especially in the Gulf of Mexico (GOM), have revealed numerous hazards in the shallow sediments below the seabed, such as fault scarps, gas vents, unstable slopes, and reefs and shallow subsurface geologic hazards such as faults, gas-charged sediments, buried channels, abnormally pressured sands, and gas hydrates. Drilling risks associated with shallow aquifer-pressured sands or shallow water flow (SWF) sands and gas hydrates have received the most attention. These are global problems. In the GOM alone, more than US$250 million has been lost due to SWF. While the industry has matured in handling these problems, it is estimated that the losses associated with SWF sands continue to be nearly $1.7 million per well in the GOM alone.
Subsurface resistivity changes and triggering influences detected by continuous geoelectric monitoring
Authors: Niesner E.
Published: August 2010

During a project to analyze the internal structure of landslides and identify and isolate their trig-gering factors, repeated geoelectric measurements in intervals of 1–2 years showed significant resistivity changes inside landslide-prone areas (Niesner and Weidinger, 2008). Changing water saturation was recognized as the most influential factor on these time-lapse resistivity profiles. Therefore repeated resistivity measurements should be able to observe the internal regime and dynamics of subsurface water. And, in turn, as changing water saturation is in most cases directly correlated with slope stability, a major factor influencing slope stability could be deduced from repeated resistivity measurements.
GEOPHYSICS BRIGHT SPOTS
Authors: Mahrer K.
Published: August 2010

I opened the last Bright Spots column talking about geophysics' broad diversity. As geophysicists we can and do play in a lot of arenas. The July–August issue of GEOPHYSICS supports this. In addition to its normal span of topics, July–August contains the supplement “Hydrogeophysics—Electric and Electromagnetic Methods.” Evert Slob writes that the supplement contains “more than 20 hydrogeophysics papers revealing properties and monitoring processes in the vadose zone and aquifers using ERT, SP, IP, ATEM, FDEM, NMR, and GPR (if you don't know these acronyms, more reason to open up the issue). The supplement discusses new methods and techniques and several case studies showing pitfalls, problems, limitations, and benefits.”
Role of Vitamin and Mineral Supplementation and Aspirin Use in Cancer Survivors
Authors: Giovannucci Edward , Chan Andrew T.
Published: August 2010

Multivitamins and multiminerals are widely used in the United States, but their efficacy and, perhaps more importantly, the potential for harm in individuals who have cancer have received relatively little study. Beyond their general effects on health, the use of vitamins and minerals by patients with cancer has unique implications because of their potential direct effects on existing cancers, effects on factors that may influence carcinogenesis, such as immunity, and interactions with treatment. Some evidence suggests that vitamin D at higher than standard doses may improve cancer-specific and overall survival for several cancer sites. Besides vitamin D, there is little evidence that nutritional supplements lower the risk of recurrence or improve survival from cancer, although some benefits may be possible in specific subgroups. Some data suggest that higher than standard doses of some vitamins or minerals could even enhance carcinogenesis or worsen survival in patients with cancer. For example, evidence suggests that although folate supplementation administered in preneoplastic stages may lower the risk of colorectal cancer, excessive folic acid in patients with established cancer may be harmful. For prostate cancer, some preliminary evidence indicates that excess consumption of one or a combination of components in a multivitamin/multimineral may accelerate cancer progression and increase fatality. Use of aspirin is proven to lower risk of colorectal cancer, and recent evidence suggests that aspirin use in patients with colorectal cancer improves cancer-specific and overall survival, especially in patients with tumors that express cyclooxygenase-2 (COX-2). The potential beneficial or adverse effects of dietary supplements and aspirin in survivors of cancer warrant further study.
TP53 Mutation and Survival in Chronic Lymphocytic Leukemia
Authors: Zenz Thorsten , Eichhorst Barbara , Busch Raymonde , Denzel Tina , Häbe Sonja , Winkler Dirk , Bühler Andreas , Edelmann Jennifer , Bergmann Manuela , Hopfinger Georg , Hensel Manfred , Hallek Michael , Döhner Hartmut , Stilgenbauer Stephan
Published: August 2010

Purpose

The precise prognostic impact of TP53 mutation and its incorporation into treatment algorithms in chronic lymphocytic leukemia (CLL) is unclear. We set out to define the impact of TP53 mutations in CLL.

Patients and Methods

We assessed TP53 mutations by denaturing high-performance liquid chromatography (exons 2 to 11) in a randomized prospective trial (n = 375) with a follow-up of 52.8 months (German CLL Study Group CLL4 trial; fludarabine [F] v F + cyclophosphamide [FC]).

Results

We found TP53 mutations in 8.5% of patients (28 of 328 patients). None of the patients with TP53 mutation showed a complete response. In patients with TP53 mutation, compared with patients without TP53 mutation, median progression-free survival (PFS; 23.3 v 62.2 months, respectively) and overall survival (OS; 29.2 v 84.6 months, respectively) were significantly decreased (both P < .001). TP53 mutations in the absence of 17p deletions were found in 4.5% of patients. PFS and OS for patients with 17p deletion and patients with TP53 mutation in the absence of 17p deletion were similar. Multivariate analysis identified TP53 mutation as the strongest prognostic marker regarding PFS (hazard ratio [HR] = 3.8; P < .001) and OS (HR = 7.2; P < .001). Other independent predictors of OS were IGHV mutation status (HR = 1.9), 11q deletion (HR = 1.9), 17p deletion (HR = 2.3), and FC treatment arm (HR = 0.6).

Conclusion

CLL with TP53 mutation carries a poor prognosis regardless of the presence of 17p deletion when treated with F-based chemotherapy. Thus, TP53 mutation analysis should be incorporated into the evaluation of patients with CLL before treatment initiation. Patients with TP53 mutation should be considered for alternative treatment approaches.
Consolidation Therapy With Subcutaneous Alemtuzumab After Fludarabine and Rituximab Induction Therapy for Previously Untreated Chronic Lymphocytic Leukemia: Final Analysis of CALGB 10101
Authors: Lin Thomas S. , Donohue Kathleen A. , Byrd John C. , Lucas Margaret S. , Hoke Eva E. , Bengtson Elizabeth M. , Rai Kanti R. , Atkins James N. , Link Brian K. , Larson Richard A.
Published: August 2010

Purpose

To determine if alemtuzumab consolidation improves response rate and progression-free survival (PFS) after induction chemoimmunotherapy in previously untreated symptomatic patients with chronic lymphocytic leukemia.

Patients and Methods

Patients (n = 102) received fludarabine 25 mg/m2 intravenously days 1 to 5 and rituximab 50 mg/m2 day 1, 325 mg/m2 day 3, and 375 mg/m2 day 5 of cycle 1 and then 375 mg/m2 day 1 of cycles 2 to 6; fludarabine plus rituximab (FR) administration was repeated every 28 days for six cycles. Three months after completion of FR, patients with stable disease or better response received subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg three times per week for 5 weeks.

Results

Overall response (OR), complete response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR, respectively; 15% of patients were minimal residual disease (MRD) negative. Of 102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after FR attained CR after alemtuzumab. By intent to treat (n = 102), OR and CR rates were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD negative. With median follow-up of 36 months, median PFS was 36 months, 2-year PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR, alemtuzumab was associated with five deaths resulting from infection (viral and Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis pneumonias), which occurred up to 7 months after last therapy. The study was amended to exclude CR patients from receiving alemtuzumab.

Conclusion

Alemtuzumab consolidation improved CR and MRD-negative rates after FR induction but caused serious infections in patients who had already achieved CR after induction and did not improve 2-year PFS or survival.
The Quality and Distribution of Teachers under the No Child Left Behind Act
Authors: Hanushek Eric A , Rivkin Steven G
Published: August 2010

The main effects of No Child Left Behind on the quality of teaching are likely to come through two provisions of the act. First, NCLB establishes benchmarks based on test score pass rates that schools must meet in order to remain in good standing and avoid sanctions. Since teachers are central to student performance, this accountability component of NCLB is likely to have direct effects on both the demand for and supply of teachers and therefore on both the composition of the stock of public school teachers and the distribution of those teachers among schools. Second, NCLB explicitly requires districts to have “highly qualified” teachers, and the enunciation and enforcement of such a standard might have an additional effect on the composition of teachers. We will discuss three avenues by which these requirements might affect the quality of teachers. First, we will argue that the requirements for “highly qualified” teachers are unlikely to have had any perceptible effect on the performance of students. Second, the combination of quality requirements and the more-stringent testing environment could make teaching appear more costly and risky as a profession and thus alter the composition of new entrants, but at least so far, we find no evidence of such effects. Finally, the accountability provisions might change the dynamics of the labor market for teachers, including decisions about hiring and job separation. While not completely understood, this channel might be quite important, especially at low-performing schools where the stress of the accountability requirements is highest. We will provide new evidence from Texas on the relationship between school accountability ratings and teacher transitions both out of schools and out of grades three through eight, the grades subject to NCLB testing requirements. Finally, we offer some observations about potential policy implications and a future research agenda.
Emmanuel Saez: 2009 John Bates Clark Medalist
Authors: Bernheim B. Douglas
Published: August 2010

Emmanuel Saez, winner of the 2009 John Bates Clark Medal, has distinguished himself by making fundamental contributions concerning critical theoretical and empirical issues within the field of public economics. He is one of those exceptional scholars whose work reflects a broad and thoroughly integrated vision. In carefully and creatively implementing that vision, he has led a remarkable resurgence of interest in tax policy research over the last decade. Emmanuel's work can be divided into five areas: the theory of optimal taxes and transfers; the measurement of income and wealth distributions; the measurement of behavioral responses to personal taxation; the taxation of corporate dividends; and retirement saving. A great deal of his work is closely interrelated across these topics, which makes the whole considerably greater than the sum of the parts. In effect, he has bridged the chasm between theory and practical policymaking by attacking the policy design problem from both sides at once. This article provides a survey of Emmanuel's work.
Defining a longitudinal survival model to examine forced treadmill running as a countermeasure for diet-induced weight gain
Authors: Esposito Lisa M , Simpson Richard J , Strohacker Kelley , Carpenter Katie C , McFarlin Brian K
Published: August 2010

Diet-induced weight gain increases disease risk via disruption of the innate immune system. Flow cytometry is commonly used to assess the immune system; however, in mice such measurements traditionally require terminal procedures and tissue collection to generate sufficient sample. The present study refined an existing flow cytometry method to reduce the number of mice needed to longitudinally measure monocytes. CD-1 male mice were randomly assigned to one of the three groups: DS (diet-induced weight gain + sedentary), DE (diet-induced weight gain + forced treadmill running [total distance 35,755 ± 1832 m]) or NS (normal weight gain + sedentary). DS and DE consumed a 60% fat diet and NS consumed a 10% fat diet ad libitum. Saphenous vein blood samples were collected weekly for a period of six weeks and three-colour flow cytometry was used to measure changes in monocyte (CD11b+/14+) concentration and cell-surface toll-like receptor 4 (TLR4) expression. DS (18%) and DE (17%) gained more weight than NS ( P < 0.001). On a group basis, DS expressed 17% more TLR4 than DE and NS ( P = 0.005). The present study demonstrates that a longitudinal survival model can be used to reduce the number of animals needed to complete flow cytometry experiments. Exercise during diet-induced weight prevented some (decreased monocyte TLR4 expression) but not all aspects of innate immune system function.
Southward expansion: The myth of the West in the promotion of Florida, 18761900
Authors: Knight Henry
Published: August 2010

This article examines the ways in which promoters and developers of Florida, in the decades after Reconstruction, engaged with a popular myth of the West as a means of recasting and selling their state to prospective settlers in the North and Midwest. The myth envisaged a cherished region to the west where worthy Americans could migrate and achieve social and economic independence away from the crowded confines of the East, or Europe. According to state immigration agents, land-promoters and other booster writers, Florida, although a Southern ex-Confederate state, offered precisely these western opportunities for those hard-working Northerners seeking land and an opening for agrarian prosperity. However, the myth, which posited that, in the west, an individual's labour and thrift were rewarded with social and economic improvement, meshed awkwardly with the contemporary emergence of Florida as a popular winter destination for wealthy tourists and invalids seeking leisure and healthfulness away from the North. Yet it also reflected and reinforced promotional notions of racial improvement which would occur with an influx of enterprising Anglo-Americans, who would effectively displace the state's large African American population. In Florida, the myth of the West supported the linked post-Reconstruction processes of state development and racial subjugation.
Total absolute horospherical curvature of submanifolds in hyperbolic space
Authors: Buosi Marcelo , Izumiya Shyuichi , Soares Ruas Maria Aparecida
Published: August 2010

We study the horospherical geometry of submanifolds in hyperbolic space. The main result is a formula for the total absolute horospherical curvature ofM, which implies, for the horospherical geometry, the analogues of classical inequalities of the Euclidean Geometry. We prove the horospherical Chern–Lashof inequality for surfaces in 3-space and the horospherical Fenchel and Fary–Milnor's theorems.
Effective non-vanishing conjectures for projective threefolds
Authors: Broustet Amäel , Höring Andreas
Published: August 2010

Let X be a smooth projective threefold, and let A be an ample line bundle such that KX
+ A is nef. We show that if KX
or –KX
is pseudo-effective, the adjoint bundle KX
+ A has global sections. We also give a very short proof of the Beltrametti–Sommese conjecture in dimension three, recently proven by Fukuma: if A is an ample line bundle such that KX
+ 2A is nef, the adjoint bundle KX
+ 2A has global sections.
Addendum to the synoptic review of red algal genera
Authors: Wynne Michael J. , Schneider Craig W.
Published: August 2010

An addendum to Schneider and Wynne's A synoptic review of the classification of red algal genera a half century after Kylin's “Die Gattungen der Rhodophyceen” (2007; Bot. Mar.
50: 197–249) is presented, with an updating of names of new taxa at the generic level and higher. In the last few years, the names of several new orders and families of red algae have been validated; these are cited and referenced below.
New macroalgal records for the Aegean Sea (Greece, eastern Mediterranean Sea)
Authors: Tsiamis Konstantinos , Verlaque Marc , Panayotidis Panayotis , Montesanto Barbara
Published: August 2010

Nine macroalgal taxa are reported for the first time from Greece (Aegean Sea and nearby areas): the chlorophyte Cladophora nigrescens, the phaeophyceans Cystoseira susanensis and Dictyopteris lucida, and the rhodophytes Centroceras gasparrinii, Ophidocladus simpliciusculus, Peyssonnelia coriacea, Porphyrostromium ciliare, Radicilingua thysanorhizans and Rodriguezella ligulata. Peyssonnelia stoechas, a species recently reported from Greece (Karpathos Island), is described for the first time from the Gulf of Korinthiakos. Several of the species are rare in the Mediterranean Sea, and five are new to the eastern basin, thus extending their known distribution ranges. Our results indicate that the biodiversity of the eastern Mediterranean marine flora is probably richer than originally thought. A description, illustrations, habitat, geographic distribution and taxonomic remarks are provided for each taxon.
Use of Miniature Specimen Test and Finite Element Method for Evaluation of Yield Strength and Fracture Toughness in Metallic Alloys
Authors: Reddy K. Harshavardhan , Partheepan G. , Pandey R. K. , Sehgal D. K.
Published: August 2010

The present paper describes the method for evaluation of yield strength and fracture toughness of three materials, namely, linepipe steel, aluminum (Al) alloy, and gray cast iron using miniature specimen test. Conventional standard test methods consume more material and money and may damage the integrity of the in-service component. Miniature specimen tests overcome all these demerits. A method is outlined to predict the yield strength and fracture toughness from the miniature test through the empirical relations. The validation of results has been carried out by conducting standard tensile and fracture toughness tests according to ASTM standards. Further, the finite element method has been used to simulate the miniature test. A close agreement is observed between the results of the miniature test and standard tests.
Refinement of Tools for Targeted Gene Expression in Drosophila
Authors: Pfeiffer Barret D , Ngo Teri-T B , Hibbard Karen L , Murphy Christine , Jenett Arnim , Truman James W , Rubin Gerald M
Published: August 2010

A wide variety of biological experiments rely on the ability to express an exogenous gene in a transgenic animal at a defined level and in a spatially and temporally controlled pattern. We describe major improvements of the methods available for achieving this objective in Drosophila melanogaster. We have systematically varied core promoters, UTRs, operator sequences, and transcriptional activating domains used to direct gene expression with the GAL4, LexA, and Split GAL4 transcription factors and the GAL80 transcriptional repressor. The use of site-specific integration allowed us to make quantitative comparisons between different constructs inserted at the same genomic location. We also characterized a set of PhiC31 integration sites for their ability to support transgene expression of both drivers and responders in the nervous system. The increased strength and reliability of these optimized reagents overcome many of the previous limitations of these methods and will facilitate genetic manipulations of greater complexity and sophistication.
c-Type Cytochrome Assembly in Saccharomyces cerevisiae: A Key Residue for Apocytochrome c1/Lyase Interaction
Authors: Corvest Vincent , Murrey Darren A , Bernard Delphine G , Knaff David B , Guiard Bernard , Hamel Patrice P
Published: August 2010

The electron transport chains in the membranes of bacteria and organelles generate proton-motive force essential for ATP production. The c-type cytochromes, defined by the covalent attachment of heme to a CXXCH motif, are key electron carriers in these energy-transducing membranes. In mitochondria, cytochromes c and c1 are assembled by the cytochrome c heme lyases (CCHL and CC1HL) and by Cyc2p, a putative redox protein. A cytochrome c1 mutant with a CAPCH heme-binding site instead of the wild-type CAACH is strictly dependent upon Cyc2p for assembly. In this context, we found that overexpression of CC1HL, as well as mutations of the proline in the CAPCH site to H, L, S, or T residues, can bypass the absence of Cyc2p. The P mutation was postulated to shift the CXXCH motif to an oxidized form, which must be reduced in a Cyc2p-dependent reaction before heme ligation. However, measurement of the redox midpoint potential of apocytochrome c1 indicates that neither the P nor the T residues impact the thermodynamic propensity of the CXXCH motif to occur in a disulfide vs. dithiol form. We show instead that the identity of the second intervening residue in the CXXCH motif is key in determining the CCHL-dependent vs. CC1HL-dependent assembly of holocytochrome c1. We also provide evidence that Cyc2p is dedicated to the CCHL pathway and is not required for the CC1HL-dependent assembly of cytochrome c1.