bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic fields of species: cross-species patterns of phylogenetic structure and geographical coexistence
Authors: Villalobos Fabricio , Rangel Thiago F. , Diniz-Filho José Alexandre F.
Published: February 2013

Differential coexistence among species underlies geographical patterns of biodiversity. Understanding such patterns has relied either on ecological or historical approaches applied separately. Recently, macroecology and community phylogenetics have tried to integrate both ecological and historical approaches. However, macroecology is mostly non-phylogenetic, whereas community phylogenetics is largely focused on local scales. Here, we propose a conceptual framework to link macroecology and community phylogenetics by exploring the evolutionary context of large-scale species coexistence, introducing the phylogenetic field concept. This is defined as the phylogenetic structure of species co-occurrence within a focal species' geographical range. We developed concepts and methods for analysing phylogenetic fields and applied them to study coexistence patterns of the bat family Phyllostomidae. Our analyses showed that phyllostomid bats coexist mostly with closely related species, revealing a north–south gradient from overdispersed to clustered phylogenetic fields. Patterns at different phylogenetic levels (i.e. all species versus close relatives only) presented the same gradient. Results support the tropical niche conservatism hypothesis, potentially mediated by higher speciation rates in the region of origin coupled with shared environmental preferences among species. The phylogenetic field approach enables species-based community phylogenetics, instead of those that are site-based, allowing the description of historical processes at more appropriate macroecological and biogeographic scales.
Population structure and cultural geography of a folktale in Europe
Authors: Ross Robert M. , Greenhill Simon J. , Atkinson Quentin D.
Published: February 2013

Despite a burgeoning science of cultural evolution, relatively little work has focused on the population structure of human cultural variation. By contrast, studies in human population genetics use a suite of tools to quantify and analyse spatial and temporal patterns of genetic variation within and between populations. Human genetic diversity can be explained largely as a result of migration and drift giving rise to gradual genetic clines, together with some discontinuities arising from geographical and cultural barriers to gene flow. Here, we adapt theory and methods from population genetics to quantify the influence of geography and ethnolinguistic boundaries on the distribution of 700 variants of a folktale in 31 European ethnolinguistic populations. We find that geographical distance and ethnolinguistic affiliation exert significant independent effects on folktale diversity and that variation between populations supports a clustering concordant with European geography. This pattern of geographical clines and clusters parallels the pattern of human genetic diversity in Europe, although the effects of geographical distance and ethnolinguistic boundaries are stronger for folktales than genes. Our findings highlight the importance of geography and population boundaries in models of human cultural variation and point to key similarities and differences between evolutionary processes operating on human genes and culture.
Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3
Authors: Schäfer Andrea , Karaulanov Emil , Stapf Ulrike , Döderlein Gabi , Niehrs Christof
Published: February 2013

Active DNA demethylation regulates epigenetic gene activation in numerous processes, but how the target site specificity of DNA demethylation is determined and what factors are involved are still poorly understood. Here we show that the tumor suppressor inhibitor of growth protein 1 (Ing1) is required for targeting active DNA demethylation. Ing1 functions by recruiting the regulator of DNA demethylation growth arrest and DNA damage protein 45a (Gadd45a) to histone H3 trimethylated at Lys 4 (H3K4me3). We show that reduced H3K4 methylation impairs recruitment of Gadd45a/Ing1 and gene-specific DNA demethylation. Our results indicate that histone methylation directs DNA demethylation.
SRC-3 coactivator regulates cell resistance to cytotoxic stress via TRAF4-mediated p53 destabilization
Authors: Yi Ping , Xia Weiya , Wu Ray-Chang , Lonard David M. , Hung Mien-Chie , O'Malley Bert W.
Published: February 2013

Steroid receptor coactivator 3 (SRC-3) is an oncogenic nuclear receptor coactivator that plays a significant role in drug resistance. Using a lentiviral cDNA library rescue screening approach, we identified a SRC-3 downstream gene—TRAF4 (tumor necrosis factor [TNF] receptor associated-factor 4)—that functions in cell resistance to cytotoxic stress. TRAF4 expression is positively correlated with SRC-3 expression in human breast cancers. Similar to that observed for SRC-3 overexpression, breast cancer cells overexpressing TRAF4 are more resistant to stress-induced death. Here, we further dissected the underlying molecular mechanism for SRC-3 and TRAF4-mediated resistance to cytotoxic agents. We observed that SRC-3 expression is inversely correlated with the expression of p53-regulated proapoptotic genes in breast cancers and further found that SRC-3 and TRAF4 overexpression diminished cytotoxic stress-induced up-regulation of the tumor suppressor p53 protein. To determine the mechanism, we showed that the TRAF domain of TRAF4 bound to the N-terminal TRAF-like region of the deubiquitinase HAUSP (herpesvirus-associated ubiquitin-specific protease; also named USP7) and blocked the access of p53 to the same region of HAUSP. This TRAF4-mediated inhibition of HAUSP then led to the loss of p53 deubiquitination and its stabilization in response to cellular stress. Consistent with this cellular function, we also found that TRAF4 overexpression in breast cancer patients was associated significantly with poor prognosis. Because of SRC-3's ability to abrogate p53 function, our results suggest that SRC-3 overexpression may be especially important in tumors in which p53 is not mutated.
Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy
Authors: Gibeaux Romain , Politi Antonio Z. , Nédélec François , Antony Claude , Knop Michael
Published: February 2013

Nuclear migration during yeast karyogamy, termed nuclear congression, is required to initiate nuclear fusion. Congression involves a specific regulation of the microtubule minus end-directed kinesin-14 motor Kar3 and a rearrangement of the cytoplasmic microtubule attachment sites at the spindle pole bodies (SPBs). However, how these elements interact to produce the forces necessary for nuclear migration is less clear. We used electron tomography, molecular genetics, quantitative imaging, and first principles modeling to investigate how cytoplasmic microtubules are organized during nuclear congression. We found that Kar3, with the help of its light chain, Cik1, is anchored during mating to the SPB component Spc72 that also serves as a nucleator and anchor for microtubules via their minus ends. Moreover, we show that no direct microtubule–microtubule interactions are required for nuclear migration. Instead, SPB-anchored Kar3 exerts the necessary pulling forces laterally on microtubules emanating from the SPB of the mating partner nucleus. Therefore, a twofold symmetrical application of the core principle that drives nuclear migration in higher cells is used in yeast to drive nuclei toward each other before nuclear fusion.
Four pillars of the S-phase checkpoint
Authors: Zou Lee
Published: February 2013

The yeast Mec1 kinase is a key regulator of the DNA damage response (DDR). In this issue of Genes & Development, Kumar and Burgers (pp. 313–321) report that Ddc1, Dpb11, and Dna2 function in concert to activate Mec1 during S phase of the cell cycle. Furthermore, the Tel1 kinase also contributes to the DDR in S phase when Mec1 activation is compromised.
Deterministic and Stochastic Three‐Sector Dynamic Growth Model with Endogenous Labour Supply
Authors: Dobrescu Loretti , Neamtu Mihaela , Opris Dumitru
Published: February 2013

This study explores the stability of the stationary state for a dynamic growth model with wealth and human capital accumulation. Knowledge is created through research and learning‐by‐doing, while the time allocation between labour and leisure is endogenised. We analyse the model in both its deterministic and stochastic versions. First, we describe the deterministic model and analyse the stationary state. Second, using the stationary state, we define the stochastic perturbation and study the squared mean values of the system states for the linearised model. Third, we prove that for certain parameters, the stationary state in the deterministic model is asymptotically stable. Similarly, we also prove that the squared mean values of the variables in the linearised stochastic model are asymptotically stable. Finally, we perform the comparative dynamic analysis for the propensities to save and to enjoy leisure, the tax rates used to finance research and the knowledge utilisation efficiency.
Using Panel Co‐Integration Methods To Understand Rising Top Income Shares
Authors: Neal Timothy
Published: February 2013

Rising top income shares in developed countries have recently generated a great deal of political and economic discussion. While many theories have been proposed to explain this increase, there has been little robust econometric testing of those explanations. Using a variety of data sources, this study will employ panel co‐integration methods, including theFMOLSandPDOLSestimators, to understand the long‐run relationship between the top 1 per cent income share and a number of explanatory variables. Our analysis finds that economic openness, the size and ideology of government, the development of financial markets, top marginal tax rates, technological progress and the strength of unions are all important determinants of top income shares. These results offer a comprehensive explanation of why top income shares have been rising in a number of developed economies in the last three decades. The implications of the findings for economic and social policy are also discussed.
Malignant hepatic epithelioid hemangioendothelioma with high‐output heart failure: Successful management of heart failure with transcatheter arterial chemoembolization
Authors: Hsu Chien‐Yi , Liu Yao‐Chung , Li Chung‐Pin , Huang Po‐Hsun , Lin Chin‐Hsuan , Chao Yee
Published: February 2013

A 73‐year‐old woman was admitted to hospital because of progressive dyspnea on exertion. Computed tomography revealed a large hepatic tumor, which was proved to be a hepatic epithelioid hemangioendothelioma (EHE). Echocardiography demonstrated high cardiac output, for which the tumor was considered to be the leading cause. A transcatheter arterial chemoembolization (TACE) was performed sequentially at 1‐month intervals to reduce the size of the hepatic tumor, and this temporarily improved the patient's cardiac condition and quality of life. In this case, we successfully used TACE in the treatment of hepatic EHE with high‐output heart failure. TACE is a reasonable choice of treatment both for managing malignant hepatic tumors and resolving low systemic vascular resistance by embolization of the abnormal neoangiogenic vessels. Nevertheless, clinicians should be aware of the potential adverse effect of hepatic decompensation induced by TACE, especially when the tumor involvement is widespread and poorly preserved hepatic function is encountered.
Challenges in Virological Diagnosis of HIV ‐1 Transmission from Sexual Abuse – HIV‐1 Genetic Links are Mandatory
Authors: Ehrnst Anneka
Published: February 2013

The purpose of this article is to set forth possible strategies and techniques of analysis to diagnose or identify the source of HIV transmission in victims of sexual abuse. Diagnosis of HIV‐1 transmission from sexual abuse is complicated. Timely blood samples are important. The right to confidentiality of the HIV diagnosis may prevent sampling from the offender. Hideous rapes occur during war, which victimize many women. Women delivering a child, seeking an abortion, or having a miscarriage may include victims of sexual abuse. HIV‐infected children, where vertical transmission has been excluded, are important for investigation. Men who have sex with men may abuse young men. HIV‐infected teenagers with signs of early infection should also be considered. Hundreds of single HIV‐1 sequences can be created from one or more blood samples from the case and the alleged abuser. The more HIV‐1 genes and sequences that are included, the better the outcomes of the phylogenetic relation. Evidence in support of transmission may be obtained from phylogenetic tree analysis and may also free someone from suspicion.
Estimating the Impact of Reducing Violence Against Female Sex Workers on HIV Epidemics in Kenya and Ukraine: A Policy Modeling Exercise
Authors: Decker Michele R. , Wirtz Andrea L. , Pretorius Carel , Sherman Susan G. , Sweat Michael D. , Baral Stefan D. , Beyrer Chris , Kerrigan Deanna L.
Published: February 2013

Problem

Female sex workers (FSWs) worldwide suffer disproportionate burdens of HIV and gender‐based violence. Despite evidence linking these threats, little is known about the potential HIV epidemic impact of reducing abuse.

Method of study

The Goals model approximated the impact of reducing violence against FSWs on HIV epidemics in Ukraine and Kenya, measured by reductions in new infections among FSWs and adults. Cumulative infections averted over a 5‐year period, in which violence declined was calculated, relative to a status quo with no reduction. Projections held HIV interventions constant at baseline levels; subsequently, scenarios adjusted for planned expansion of antiretroviral therapy (ART) coverage.

Results

An approximate 25% reduction in incident HIV infections among FSWs was observed when physical or sexual violence was reduced; cumulative infections averted were 21,200 and 4700 in Kenya and Ukraine, respectively. Similar percent reductions were observed assuming ART coverage expansion, with approximately 18,200 and 4400 infections averted among FSWs in Kenya and Ukraine. New infections were also averted in the general population.

Conclusion

Reducing violence against FSWs appears to impart significant reductions in new infections among FSWs and in the general adult population in both generalized and concentrated epidemics. Limitations provide direction to improve the precision of future estimates.
Viral invasion of the Amniotic Cavity (VIAC) in the Midtrimester of Pregnancy
Authors: Silasi Michelle
Published: February 2013

A role for microbial invasion leading to inflammation in the amniotic cavity and subsequent pre‐term delivery has been well established. For years, the role of viral infections in pregnancy has been minimized and thought of as harmless, with a few exceptions. Recent evidence now encourages us to expand our thinking and realize that viral infections during pregnancy may influence pregnancy more that we thought.
Exhuming the defeated: Civil War mass graves in 21st‐century Spain
Authors: FERRÁNDIZ FRANCISCO
Published: February 2013

The exhumations of two mass graves in a small Spanish village, conducted eight years apart, illustrate changing attitudes toward and procedures related to Civil War (1936–39) disinterments over the last decade. The sudden public visibility of skeletons of civilians executed by Francisco Franco's paramilitary has triggered heated debates both about how to handle these remains in a consolidated democratic state and what to make of related judicial and institutional initiatives. I place the particularity of Spain's “human rights outsourcing model” regarding Civil War crimes in comparative perspective within the framework of transnational human rights discourses and practices.
Cruising through uncertainty: Cell phones and the politics of display and disguise in Inhambane, Mozambique
Authors: ARCHAMBAULT JULIE SOLEIL
Published: February 2013

Cell phones play a conspicuous role in the way young people in Inhambane, Mozambique, juggle visibility and invisibility in their everyday lives. By opening up new social spaces within which individuals can engage in various pursuits with some degree of discretion, cell phone communication helps redress socioeconomic inequalities while preserving an unpleasant public secret about the workings of Mozambique's postwar economy: that young women are encouraged to exchange sexual favors for material gain. Drawing on the literature on secrecy and building on the local notion of “visão,” I propose an extended use of the idea of “social navigation” that captures concerns about appearances and the reproduction of wider epistemologies of ignorance.
Criteria for and outcomes of allogeneic haematopoietic stem cell transplant in children, adolescents and young adults with acute lymphoblastic leukaemia in first complete remission
Authors: Hochberg Jessica , Khaled Samer , Forman Stephen J. , Cairo Mitchell S.
Published: February 2013

Most children, adolescents and young adults with acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) have an excellent prognosis with multi‐agent chemotherapy in induction, consolidation, re‐induction and maintenance therapy. However, there is a subset of patients with a more guarded prognosis using this approach, who may benefit from haematopoietic allogeneic stem cell transplantation (alloHSCT). Commonly used criteria for alloHSCT in children, adolescents and young adults with ALL in CR1 include: induction failure, poor cytogenetics, persistent minimal residual disease (MRD), age, immunophenotype, white blood cell count at diagnosis and rapidity of induction response. Two‐year event‐free survival following alloHSCT in patients with ALL in CR1 ranges from 50 to 80% depending on disease status, donor source, conditioning therapy, age and other risk factors. Future studies should focus on more precisely identifying poor‐risk features, such as disease genomics and host pharmacogenomics, refining MRD measurements, improving unrelated donor matching, reducing MRD prior to alloHSCT, and developing post‐alloHSCT humoral and cellular therapy approaches.
FROM DISCRETE TO CONTINUOUS‐TIME TRANSITION MATRICES IN INTRA‐DISTRIBUTION DYNAMICS ANALYSIS: AN APPLICATION TO PER CAPITA WEALTH IN EUROPE
Authors: Hierro María , Maza Adolfo
Published: February 2013

Previous studies focusing on the intra‐distribution dynamics analysis have usually computed, in a Markov chain framework, discrete‐time transition matrices. Such an approach, however, can involve some limitations, especially when using stock variables. In order to illustrate the importance of the time‐scale issue when estimating transition matrices, this paper applies both discrete and continuous‐time approaches to a set of cross‐national European data on per capita wealth for the period 2000–10. The results reveal, on the one hand, that the continuous‐time estimation provides a most accurate estimation of transition probabilities and, on the other, that the differences between both approaches are especially remarkable in the long‐term equilibrium distribution.
Predominance of activated, clonally expanded T helper type 17 cells within the CD4+ T cell population in psoriatic lesions
Authors: Lewis B J , Rajpara S , Haggart A M , Wilson H M , Barker R N , Ormerod A D
Published: February 2013

Recent evidence points to the T helper type 17 (Th17) subset as key in the pathogenesis of psoriasis, but cells of this type in lesions remain to be fully characterized. Here we isolated, enumerated, functionally tested and clonotyped the CD4+ Th cell population ex vivo from lesional biopsies and paired peripheral blood samples from psoriasis patients. Th17 cells were over-represented dramatically in lesions from all patients, representing 49–93% of CD4+ Th cells compared with 3–18% in blood. Most lesional Th17 cells produced interleukin (IL)-17A ex vivo without further stimulation and expressed the CD45RO+ phenotype characteristic of activated or memory cells. There was no increase in ‘natural’ [CD25hiforkhead box protein 3 (FoxP3+)] regulatory T cells in lesions versus peripheral blood, but there was enrichment of ‘induced’ IL-10+ regulatory T cell numbers in biopsies from some patients. The lesional Th17 cells exhibited a bias in T cell receptor Vβ chain usage, suggestive of specific expansion by antigen. The therapeutic challenge is to overcome the dominance of overwhelming numbers of such antigen-specific Th17 cells in psoriatic lesions.
Screening colonoscopy in liver transplant candidates: risks and findings
Authors: Weismüller Tobias J. , Bleich Florian , Negm Ahmed A. , Schneider Andrea , Lankisch Tim O. , Manns Michael P. , Strassburg Christian P. , Wedemeyer Jochen
Published: February 2013

The indication for mandatory screening colonoscopies in liver transplant candidates is controversial. Since the introduction of MELD‐based allocation, patients with advanced liver disease and often severe comorbidities are prioritized for liver transplantation (LT). This study evaluated safety and outcome of colonoscopy in this high‐risk patient group. During a two‐yr period, we performed 243 colonoscopies in potential LT candidates. Endoscopic findings were registered in a standardized form, and correlations with biochemical or clinical parameters were analyzed using Mann–Whitney U‐test and chi‐square test. Only 57 patients (23.5%) had an endoscopically normal colon. Main findings were polyps (45.7%), hypertensive colopathy (24.3%), diverticulosis (21%), rectal varices (19.8%), and hemorrhoids (13.6%). In 21% of all patients, the removed polyps were diagnosed as adenomas. The prevalence of neoplastic polyps increased significantly with age: 13.6% (patients <50 yr) vs. 25% (patients ≥50 yr) (p = 0.03). Advanced neoplasia was found only in patients older than 40 yr. No major complications were observed; post‐interventional hemorrhage was observed in 1.7% and controlled by clipping or injection therapy. In conclusion, lower gastrointestinal endoscopy is safe and effective in LT candidates. Due to the age dependency of neoplastic polyps, a screening colonoscopy should be performed in LT candidates older than 40 yr or with symptoms or additional risk factors.
Clinical analysis of recurrent hepatocellular carcinoma after living donor liver transplantation
Authors: Yoon Young Chul , Hong Tae Ho , You Young Kyoung , Kim Dong Goo
Published: February 2013

This study aimed to analyze the clinical outcomes and factors influencing the outcome in the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). Between October, 1997 and September, 2010, 25 (16.0%) of 156 patients who had undergone LDLT for HCC experienced recurrence. All patients with recurrence, with a single exception, were in the high‐risk group. Among patients with recurrence, 76.0% of patients experienced recurrence within one yr after LDLT. One‐ and five‐yr survival rates of recurred patients were 56.0% and 8.6%, respectively. Among them, 32% of patients were treated with curative‐intent treatment, and their one‐ and five‐yr survival rates were 62.5% and 25.0%, respectively. Beyond the Milan criteria at liver transplantation (LT) (p = 0.032), multiple recurrence (p = 0.001), and palliative treatment for recurrent tumors (p = 0.049) were related to poor survival after recurrence. Additionally, the independent prognostic factors included multiple recurrence (p = 0.005) and the Milan criteria at LT (p = 0.047). Because almost all recurrent cases belonged to the high‐risk group and recurred within two yr, the high‐risk group should undergo close follow‐up for early detection and be treated with liver‐directed therapies. Although the prognosis of recurrent HCC after LDLT is poor, long‐term survival can be expected on a single recurrence and curative treatment.
Were the Hartz Reforms Responsible for the Improved Performance of the German Labour Market?
Authors: Akyol Metin , Neugart Michael , Pichler Stefan
Published: February 2013

From 2005 to 2011 employment rose and unemployment rates declined considerably in Germany. This favourable development followed the labour market reforms initiated in 2003, and there has been a tendency to attribute the improved labour market performance to those reforms. Causal micro‐evaluations of the various measures, however, show hardly any effects on variables that can be related to employment. Rather, it seems that employment increased in response to a process of wage moderation that had already begun in the 1990s. It is possible that this moderation was itself partially a product of the reforms, but this needs further investigation.
Do Private Prisons Really offer Savings Compared with their Public Counterparts?
Authors: Kish Richard J. , Lipton Amy F.
Published: February 2013

Private contracting of public services has been alleged to reduce costs. We address the critical question of whether private contracting really saves money, using the US prison privatisation experience as an example. Although the consensus in the literature identifies such savings, we raise economic issues of incomplete contracting, asymmetric information and moral hazard, which complicate matters. We discuss explicit, implicit, and agency costs that show that measuring the savings and quality impact of private contracting is more challenging than the literature suggests, and often inconclusive. This may suggest caution in designing solutions to cost pressures.
What Are the Lessons from Post‐Communist Transitions?
Authors: Roháč Dalibor
Published: February 2013

This paper provides a review of the literature on post‐communist transitions. It outlines the debate between the proponents of rapid reforms and the advocates of neo‐institutionalism. Providing evidence from the transitional countries, it suggests an alternative approach, explicitly acknowledging the impact of two categories of constraints on reforms.
Restoring Credible Economic Governance to the Eurozone
Authors: Herzog Bodo , Hengstermann Katja
Published: February 2013

This paper discusses new institutional rules for a stable and lasting European Monetary Union (EMU). We propose a return to a strict and sustainable economic governance framework, which is mainly driven by market forces within a smart rule‐based environment. Our recommendations are: (a) ex ante conditionalities with a tough monitoring process to avoid moral hazard in the future; (b) further enhancement of the Stability and Growth Pact; and (c) ultimo ratio punishment to be able to respond to the unique constellation of fiscal–monetary interaction and new rescue facilities. Countries violating fiscal rules for more than four years in a row will thus lose their fiscal sovereignty or will have to resign from the Eurozone. After fulfilling the ex ante conditionalities as well as all required criteria, the country either will recover its fiscal sovereignty, or, in case of exclusion, will be given the option to rejoin EMU under certain conditions.
Ethical Misconduct and the Global Financial Crisis
Authors: Sternberg Elaine
Published: February 2013

On both sides of the Atlantic, greed, the financial services industry and deregulation have been blamed for the ‘Global Financial Crisis’. The genuinely unethical conduct underlying it was actually much more fundamental, pervasive and pernicious; it was positively encouraged by lax fiscal policy and promoted by government‐generated moral hazards.
Quantitative evaluation of the combination between cytotoxic drug and efflux transporter inhibitors based on a tumour growth inhibition model
Authors: Sostelly Alexandre , Payen Léa , Guitton Jérôme , Pietro Attilio Di , Falson Pierre , Honorat Mylène , Boumendjel Ahcène , Gèze Annabelle , Freyer Gilles , Tod Michel
Published: February 2013

ATP‐Binding Cassette transporters such as ABCG2 confer resistance to various anticancer drugs including irinotecan and its active metabolite, SN38. Early quantitative evaluation of efflux transporter inhibitors‐cytotoxic combination requires quantitative drug‐disease models. A proof‐of‐concept study has been carried out for studying the effect of a new ABCG2 transporter inhibitor, MBLI87 combined to irinotecan in mice xenografted with cells overexpressing ABCG2. Mice were treated with irinotecan alone or combined to MBLI87, and tumour size was periodically measured. To model those data, a tumour growth inhibition model was developed. Unperturbed tumour growth was modelled using Simeoni's model. Drug effect kinetics was accounted for by a Kinetic–Pharmacodynamic approach. Effect of inhibitor was described with a pharmacodynamic interaction model where inhibitor enhances activity of cytotoxic. This model correctly predicted tumour growth dynamics from our study. MBLI87 increased irinotecan potency by 20% per μmol of MBLI87. This model retains enough complexity to simultaneously describe tumour growth and effect of this type of drug combination. It can thus be used as a template to early evaluate efflux transporter inhibitors in‐vivo.
Marine Rhodobacteraceae l‐haloacid dehalogenase contains a novel His/Glu dyad that could activate the catalytic water
Authors: Novak Halina R. , Sayer Christopher , Isupov Michail N. , Paszkiewicz Konrad , Gotz Dorothee , Mearns Spragg Andrew , Littlechild Jennifer A.
Published: February 2013

The putative l‐haloacid dehalogenase gene (DehRhb) from a marine Rhodobacteraceae family was cloned and overexpressed in Escherichia coli. The DehRhb protein was shown to be an l‐haloacid dehalogenase with highest activity towards brominated substrates with short carbon chains (≤ C3). The optimal temperature for enzyme activity was 55 °C, and the Vmax and Km were 1.75 μm·min−1·mg−1 of protein and 6.72 mm, respectively, when using monobromoacetic acid as a substrate. DehRhb showed moderate thermal stability, with a melting temperature of 67 °C. The enzyme demonstrated high tolerance to solvents, as shown by thermal shift experiments and solvent incubation assays. The DehRhb protein was crystallized and structures of the native, reaction intermediate and substrate‐bound forms were determined. The active site of DehRhb had significant differences from previously studied l‐haloacid dehalogenases. The asparagine and arginine residues shown to be essential for catalytic activity in other l‐haloacid dehalogenases are not present in DehRhb. The histidine residue which replaces the asparagine residue in DehRhb was coordinated by a conformationally strained glutamate residue that replaces a conserved glycine. The His/Glu dyad is positioned for deprotonation of the catalytic water which attacks the ester bond in the reaction intermediate. The catalytic water in DehRhb is shifted by ~ 1.5 Å from its position in other l‐haloacid dehalogenases. A similar His/Glu or Asp dyad is known to activate the catalytic water in haloalkane dehalogenases. The DehRhb enzyme represents a novel member within the l‐haloacid dehalogenase family and it has potential to be used as a commercial biocatalyst.

Database

The coordinates and structure factors of the crystal structures have been deposited in the Protein Data Bank with the codes 2yml, 2ymm, 2ymp, 2ymq and 2yn4. Nucleotide sequence data has been deposited in the GenBank database under the accession number JX868516.
Third Åland islands conference on vonWillebrand disease, 26–28September 2012: meeting report
Authors: Berntorp E. , Fuchs B. , Makris M. , Montgomery R. , Flood V. , O'Donnell J. S. , Federici A. B. , Lillicrap D. , James P. , Budde U. , Morfini M. , Petrini P. , Austin S. , Kannicht C. , Jiménez‐Yuste V. , Lee C.
Published: February 2013

The first meeting of international specialists in the field of von Willebrand disease (VWD) was held in the Åland islands in 1998 where Erik von Willebrand had first observed a bleeding disorder in some members of a family from Föglö and a summary of the meeting was published in 1999. The second meeting was held in 2010 and a report of the meeting was published in 2012. Topics covered included progress in understanding ofVWDover the last 50 years; multimers; classification ofVWD; pharmacokinetics and laboratory assays; genetics; treating the paediatric patient; prophylaxis; geriatrics; gene therapy and treatment guidelines. This third meeting held over 3 days covered the structure and function of von Willebrand factor (VWF); type 1VWD, the most common form of the disease; a lifespan of pharmacokinetics inVWD; detecting inhibitors inVWDpatients; and special challenges in understanding and treating the femaleVWDpatient.
Preferences for the “screen and treat” Strategy of Helicobacter pylori to Prevent Gastric Cancer in Healthy Korean Populations
Authors: Shin Dong Wook , Cho Juhee , Kim Su Hyun , Kim Young Joo , Choi Ho Chun , Son Ki Young , Park Sang Min , Park Jin Ho , Park Min Seon , Cho BeLong
Published: February 2013

Background

Helicobacter pylori (HP) eradication may reduce the risk of gastric cancer, and professional guidelines recommend eradication based on patients' preference. However, little data exist regarding individual's preference for HP eradication to prevent gastric cancer. We explored healthy Korean populations' preference for HP “screen and treat” strategy and its associated factors.

Methods

We conducted a cross‐sectional survey with 604 healthy adults expected to undergo screening esophagogastroduodenoscopy during routine health checkups. Survey packages—including a decision aid about “screen and treat” strategy for the HP eradication—were sent to the eligible people 1–3 weeks before the health checkup. Within the survey package, we first assessed people's knowledge and experience with HP test and treatment, provided the decision aid, and evaluated participants' preference for screening and treatment for HP to prevent gastric cancer.

Results

With the provision of the decision aid, most participants (73.7%) opted for the “screen and treat” strategy. Having family member(s) with gastric cancer (adjusted odds ratio (aOR) = 2.28; 95% confidence interval (CI), 1.16–4.47), previous treatment history of HP (aOR = 2.70; 95% CI, 1.38–5.29), and higher baseline knowledge (aOR = 1.16; 95% CI, 1.07–1.26) were significantly associated with accepting the strategy. Most participants (71.4%)—and even individuals who did not choose “screen and treat” strategy—agreed with the provision with the decision aid.

Conclusions

Individuals preferred to take the “screen and treat” strategy for the prevention of gastric cancer. Further intervention study is warranted to see if implementation of decisional support would improve decision quality and patient outcomes.
THE IMPLICATIONS OF ROBERT BRANDOM'S INFERENTIALISM FOR INTELLECTUAL HISTORY
Authors: MARSHALL DAVID L.
Published: February 2013

Quentin Skinner's appropriation of speech act theory for intellectual history has been extremely influential. Even as the model continues to be important for historians, however, philosophers now regard the original speech act theory paradigm as dated. Are there more recent initiatives that might reignite theoretical work in this area? This article argues that the inferentialism of Robert Brandom is one of the most interesting contemporary philosophical projects with historical implications. It shows how Brandom's work emerged out of the broad shift in the philosophy of language from semantics to pragmatics that also informed speech act theory. The article then goes on to unpack the rich implications of Brandom's inferentialism for the theory and practice of intellectual history. It contends that inferentialism clarifies, legitimizes, and informs intellectual historical practice, and it concludes with a consideration of the challenges faced by inferentialist intellectual history, together with an argument for the broader implications of Brandom's work.
1. INTRODUCTION
Authors: GRATTON BRIAN
Published: February 2013

Why were mid‐nineteenth‐century Hispanic populations so small in what is now the American Southwest, after centuries of colonization? A brilliant new literature provides a model of explanation in the authority of formidable indigenous polities, especially that great power that Pekka Hämäläinen reveals to us in his book The Comanche Empire.1 Employing an exercise in cartographic history, centered on the Pecos River Valley, we can confirm a hypothesis drawn from that theoretical model: Comanche sway was so great that European mapmakers appear to have lost knowledge about that geographical region. This new historical model deserves close attention from scholars. In this forum, four leading historians, drawn from different fields, assess the contribution of The Comanche Empire.
4. GLOBALIZING THE COMANCHE EMPIRE
Authors: TUTINO JOHN
Published: February 2013

The Comanche rose by adapting to the technological and trade opportunities brought to New Mexico by the eighteenth‐century expansion of New Spain's globally linked silver economy. They built an empire that flourished in the first half of the nineteenth century, dominating vast areas of the high plains and controlling complex trades, just as a social revolution within Mexico's wars of independence undermined the silver economy and ended its northward dynamism. Comanche power flourished between a struggling Mexico and an expanding US, until the military and industrial power of the latter combined with the ecological vulnerabilities of the Comanche economy to enable the Anglo‐American triumph in what should be called the War for North America of 1846–1848. The US claimed a continental West from an uncertain Mexican sovereignty and an assertive Comanche empire of war and trade. The expansion and collapse of New Spain, the rise and fall of the Comanche empire, and the rise of the United States all occurred within an evolving globalization. Spanish North America expanded to 1810; Comanche power rose in the eighteenth century and soared after 1810 as Mexico struggled with the challenges of nation‐making; then the United States defeated both to claim continental hegemony in the 1840s. These expansions, conflicts, and changes—all tied to larger processes of globalization—reshaped North America between 1700 and 1850.
Cement Selection for Implant‐Supported Crowns Fabricated with Different Luting Space Settings
Authors: Gultekin Pinar , Gultekin B. Alper , Aydin Murat , Yalcin Serdar
Published: February 2013

Purpose: To measure and compare the retentive strength of cements specifically formulated for luting restorations onto implant abutments and to investigate the effect of varying cement gap on retention strength of implant‐supported crowns.

Materials and Methods: Standard titanium abutments were scanned by means of a 3D digital laser scanner. One hundred and sixty standard metal copings were designed by a Computer Aided Design/Computer Aided Manufacturing (CAD/CAM) system with two cement gap values (20 and 40 μm). The copings were cemented to the abutments using the following eight cements with one being the control, zinc oxide temporary cement, while the other seven were specifically formulated implant cements (n = 10): Premier Implant Cement, ImProv, Multilink Implant, EsTemp Implant, Cem‐Implant, ImplaTemp, MIS Crown Set, and TempBond NE. The specimens were placed in 100% humidity for 24 hours, and subjected to a pull‐out test using a universal testing machine at a 0.5 mm/min crosshead speed. The test results were analyzed with two‐way ANOVA, one‐way ANOVA, post hoc Tamhane’ s T2, and student's t‐tests at a significance level of 0.05.

Results: Statistical analysis revealed significant differences in retention strength across the cement groups (p < 0.01). Resin‐based cements showed significantly higher decementation loads than a noneugenol zinc oxide provisional cement (TempBond NE) (p < 0.01), with the highest tensile resistance seen with Multilink Implant, followed by Cem‐Implant, MIS Crown Set, ImProv, Premier Implant Cement, EsTemp Implant, and ImplaTemp. Increasing the cement gap from 20 to 40 μm improved retention significantly for the higher strength cements: Multilink Implant, Premier Implant Cement, ImProv, Cem‐Implant, and MIS Crown Set (p < 0.01), while it had no significant effect on retention for the lower strength cements: EsTemp Implant, ImplaTemp, and TempBond NE (p > 0.05).

Conclusions: Resin cements specifically formulated for implant‐supported restorations demonstrated significant differences in retention strength. The ranking of cements presented in the study is meant to be an arbitrary guide for the clinician in deciding the appropriate cement selection for CAD/CAM‐fabricated metal copings onto implant abutments with different luting space settings.
Influence of Length of Occlusal Support on Masticatory Function of Free‐End Removable Partial Dentures: Short‐Term Adaptation
Authors: Sánchez‐Ayala Alfonso , Gonçalves Thaís Marques Simek Vega , Ambrosano Gláucia Maria Bovi , Garcia Renata Cunha Matheus Rodrigues
Published: February 2013

Purpose

To analyze masticatory function after a short adaptation period relative to occlusal support length reduction in free‐end removable partial denture (RPD) wearers.

Materials and Methods

Twenty‐three patients (55.2 ± 8.4 years) were rehabilitated with maxillary complete and mandibular free‐end RPDs extending to the second molars. Five occlusal support length conditions were determined by removing artificial teeth from the RPDs: full occlusal support (control); occlusal support to the first molars, second premolars, and first premolars; and no occlusal support. To explore a probable short‐term adaptation to occlusal support length reduction, participants wore their dentures at each condition for a period of 1 week before starting masticatory function assessment. For this purpose, masticatory performance, masticatory efficiency, chewing rate, selection chance, and breakage function were evaluated at each condition using the sieving method. Data were analyzed using repeated‐measures ANOVA and post hoc Dunnett tests (α = 0.05).

Results

Masticatory performance and masticatory efficiency for 2 to 4 mm particles under the condition of occlusal support to the first molars and second premolars were similar to control values (p > 0.05). Masticatory efficiency relative to particles smaller than 2 mm was also seen at the condition of support length to the first premolars (p > 0.05). Chewing rates showed adaptation only at the condition of support length to the first molars (p > 0.05). A similar trend was noted for the selection chance of 8‐mm particles, and breakage function for 8‐ and 2.4‐mm particles (p > 0.05).

Conclusion

After a 1‐week adaptation period to free‐end RPDs with occlusal support lengths reduced to the premolars, participants were able to achieve adequate masticatory function.
Penile paraffinoma
Authors: Turner Bruce , Goldstraw Emma , Pati Jhumur
Published: February 2013

This case study presents the case of a patient self‐injecting Vaseline into the penile skin to increase the size of the penis. The history of this procedure, complications and management options are presented.
Interim Prosthodontic Management of Surgery‐Induced Dental Agenesis: A Clinical Report of 8 Years of Treatment
Authors: Kotsiomiti Eleni , Kolokitha Olga Elpis , Lazaridis Nikolaos
Published: February 2013

The prosthodontic management of a 7‐year‐old girl with induced dental agenesis is described. The mandibular posterior tooth germs had been removed during surgical excision of a melanotic neuroectodermal tumor of infancy, at the age of 2 months. The ongoing prosthodontic treatment, now in its eighth year, was implemented by regular follow‐up of the operation outcome and by targeted orthodontic intervention. The treatment plan included the provision of four successive interim removable partial dentures. Care was taken to preserve the oral structures, adapt to the morphological changes, and satisfy the needs of the child. Due to the unfavorable biomechanical conditions, retention and stability problems were encountered. These were resolved by engaging the mechanism of neuromuscular adaptation through optimization of the shape of the denture base. For children and adolescents with extensive dental agenesis, prosthodontic management with interim removable dentures supports function, restores esthetics, and provides a solid basis for the definitive treatment.
An Approach to Measuring Adolescents' Perception of Complexity for Pictures of Fruit and Vegetable Mixes
Authors: Mielby Line Holler , Jensen Sidsel , Edelenbos Merete , Thybo Anette Kistrup
Published: February 2013

Complexity is an important parameter in the food industry because of its relationship with hedonic appreciation. However, difficulties are encountered when measuring complexity. The hypothesis of this study was that sensory descriptive analysis is an effective tool for deriving terms to measure adolescents' perception of complexity of pictures of fruit and vegetable mixes. A sensory panel evaluated 10 descriptive attributes, including simplicity and complexity, for 24 pictures of fruit and vegetable mixes. The descriptive analysis found strong inverse correlation between complexity and simplicity. An adolescent consumer group (n = 242) and an adult consumer group (n = 86) subsequently rated the pictures on simplicity and attractiveness. Pearson's correlation coefficients revealed strong correlations between the sensory panel and both consumer groups' usage of simplicity. This suggests that simplicity can be used to measure perceived complexity. In relation to attractiveness, different optimal levels of simplicity of pictures of fruit mixes were found for segments of the adolescent consumer group.

Practical Applications

These results potentially extend the applications of the sensory descriptive analysis procedure as it was found to be an effective tool to derive a term to measure adolescents' perception of complexity for pictures of food. This method can also be potentially extended to other types of stimuli. This method is thought to be extended to other situations where terms are needed to measure other consumer groups' perception of challenging parameters. For food practitioners, this gives new opportunities to measure important but challenging parameters.