bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomalous constitutive Src kinase activity promotes B lymphoma survival and growth
Authors: Ke Jiyuan , Chelvarajan R Lakshman , Sindhava Vishal , Robertson Darrell A , Lekakis Lazaros , Jennings C Darrell , Bondada Subbarao
Published: December 2009

Background

Previously we have shown that B cell receptor (BCR) expression and B cell receptor signaling pathways are important for the basal growth of B lymphoma cells. In particular we have shown that the activation of Syk, a non-src family protein tyrosine kinase and the mitogen activated protein kinases (MAPK), ERK and JNK that mediate BCR signals are required for the constitutive growth of B lymphoma cells. Since src family protein tyrosine kinases (SFKs) like Lyn are known to be needed for the phosphorylation of BCR co-receptors, Ig-α and Ig-β, we hypothesized that one or more SFKs will be constitutively activated in B lymphoma cells and may be necessary for B lymphoma growth.

Results

Src kinase activity was found to be constitutively high in many murine and human B lymphoma cell lines and primary lymphoma samples. The specific pharmacological inhibitors of SFKs, PP1 and PP2 inhibited the proliferation of a number of both murine and human B lymphomas in a dose-dependent manner. Importantly, dasatinib (BMS-354825), an oral dual BCR-ABL and SFK specific inhibitor inhibited the growth of B lymphomas in the nanomolar range in vitro and strongly inhibited a mouse lymphoma growth in vivo. Among the SFKs, Lyn is predominantly phosphorylated and Lyn-specific small interfering RNA inhibited the growth of B lymphomas, supporting an important role for Lyn in B lymphoma growth. Suppression of SFK activity blocks BCR mediated signaling pathways. PMA or CpG can partially reverse the growth inhibition induced by SFK inhibition. Although blocking SFK activity inhibited the growth of a number of B lymphomas, some lymphomas such as SudHL-4, SudHL-6, OCI-Ly3 and OCI-Ly10 are more resistant due to an increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL.

Conclusions

These studies further support our concept that BCR signaling pathways are important for the continued growth of established B lymphoma cells. Some of the intermediates in this BCR pathway are potential immunotherapeutic targets. In particular, inhibition of SFK activity alone or in synergy with inhibition of the prosurvival Bcl-2 proteins holds promise in developing more effective treatments for B lymphoma patients.
Relationship between carotid intima-media thickness and coronary angiographic findings: a prospective study
Authors: Coskun Ugur , Yildiz Ahmet , Esen Ozlem B , Baskurt Murat , Cakar Mehmet A , Kilickesmez Kadriye O , Orhan Lutfu A , Yildiz Seyma
Published: December 2009

Background

Since cardiovascular diseases are associated with high mortality and generally undiagnosed before the onset of clinical findings, there is a need for a reliable tool for early diagnosis. Carotid intima-media thickness (CIMT) is a non-invasive marker of coronary artery disease (CAD) and is widely used in practice as an inexpensive, reliable, and reproducible method. In the current study, we aimed to investigate prospectively the relationship of CIMT with the presence and extent of significant coronary artery narrowing in patients evaluated by coronary angiography for stable angina pectoris.

Methods

One hundred consecutive patients with stable angina pectoris and documented ischemia on a stress test were included in the study. The patients were divided into two groups according to the result of the coronary angiography: group 1 (39 patients) without a noncritical coronary lesion, and group 2 (61 patients) having at least one lesion more than 50% within the main branches of the coronary arteries. All of the patients underwent carotid Doppler ultrasound examination for measurement of the CIMT by a radiologist blinded to the angiographic data.

Results

The mean CIMT was 0.78 ± 0.21 mm in Group 1, while it was 1.48 ± 0.28 mm in Group 2 (p = 0.001). The mean CIMT in patients with single vessel disease, multi-vessel disease, and left main coronary artery disease were significantly higher compared to Group 1 (1.2 ± 0.34 mm, p = 0.02; 1.6 ± 0.32 mm, p = 0.001; and 1.8 ± 0.31 mm, p = 0.0001, respectively). Logistic regression analysis identified CIMT (OR 4.3, p < 0.001) and hypertension (OR 2.4, p = 0.04) as the most important factors for predicting CAD.

Conclusions

The findings of this study show that increase in CIMT is associated with the presence and extent of CAD. In conclusion, we demonstrated the usefulness of carotid intima-media thickness in predicting coronary artery disease but large-scale studies are required to define its role in clinical practice.
3D-conformal Accelerated Partial Breast Irradiation treatment planning: the value of surgical clips in the delineation of the lumpectomy cavity
Authors: Dzhugashvili Maia , Tournay Elodie , Pichenot Charlotte , Dunant Ariane , Pessoa Eduardo , Khallel Adel , Gouy Sébastien , Uzan Catherine , Garbay Jean-Rémy , Rimareix Françoise , Spielmann Marc , Vielh Philippe , Marsiglia Hugo , Bourgier Céline
Published: December 2009

Background

Accurate localisation of the lumpectomy cavity (LC) volume is one of the most critical points in 3D-conformal Partial breast irradiation (3D-APBI) treatment planning because the irradiated volume is restricted to a small breast volume. Here, we studied the role of the placement of surgical clips at the 4 cardinal points of the lumpectomy cavity in target delineation.

Methods

Forty CT-based 3D-APBI plans were retrieved on which a total of 4 radiation oncologists, two trainee and two experienced physicians, outlined the lumpectomy cavity. The inter-observer variability of LC contouring was assessed when the CTV was defined as the delineation that encompassed both surgical clips and remodelled breast tissue.

Results

The conformity index of tumour bed delineation was significantly improved by the placement of surgical clips within the LC (median at 0.65). Furthermore, a better conformity index of LC was observed according to the experience of the physicians (median CI = 0.55 for trainee physicians vs 0.65 for experienced physicians).

Conclusions

The placement of surgical clips improved the accuracy of lumpectomy cavity delineation in 3D-APBI. However, a learning curve is needed to improve the conformity index of the lumpectomy cavity.
Toxicity risk of non-target organs at risk receiving low-dose radiation: case report
Authors: Shueng Pei-Wei , Lin Shih-Chiang , Chang Hou-Tai , Chong Ngot-Swan , Chen Yu-Jen , Wang Li-Ying , Hsieh Yen-Ping , Hsieh Chen-Hsi
Published: December 2009

Absatract

The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy.
Restricted HIV-1 replication in placental macrophages is caused by inefficient viral transcription
Authors: García-Crespo K , Cadilla C , Skolasky R , Meléndez L M
Published: December 2009

HIV-1 infection in placental macrophages is limited as evidence by low viral mRNA and protein production.

HIV-infected PM show restricted replication as compared with MDM. We aimed to determine at what point in the viral replication cycle this restriction occurs in PM as compared with MDM. We performed Alu-LTR PCR for proviral DNA to detect differences in HIV integration, real-time RT-PCR to measure env and gag mRNA levels, and Western blot analysis to detect differences in viral protein expression. PM and MDM were infected with HIV-1 BaL, and DNA was extracted after 24 h and at 6 days p.i. for real-time PCR studies. At 6 and 12 days p.i., cells were lysed for Western blot analyses. We found no difference in viral integration between PM and MDM but significantly lower levels of viral protein gp120 in PM than in MDM. Real-time RT-PCR analyses revealed 24-fold less env mRNA and tenfold less gag mRNA in PM. These results suggest that HIV-1 restriction in PM occurs at the level of transcription. This study is significant, as it advances our understanding of HIV-1 infection in PM and its contribution to decreased in utero vertical transmission.
Mutz-3-derived Langerhans cells are a model to study HIV-1 transmission and potential inhibitors
Authors: de Jong Marein A W P , de Witte Lot , Santegoets Saskia J A M , Fluitsma Donna , Taylor Maureen E , de Gruijl Tanja D , Geijtenbeek Teunis B H
Published: December 2009

Mutz-3 derived Langerhans cells are a model to study HIV-1 transmission and to screen potential inhibitors.

Sexual transmission is the primary route of HIV-1 infection, and DC subsets are thought to be involved in viral dissemination to T cells. In the genital mucosa, two main subsets of DCs are present: epithelial LCs capture and degrade HIV-1 through C-type lectin Langerin, whereas subepithelial DCs express DC-SIGN, which facilitates HIV-1 transmission to T cells. As there is currently no HIV-1 vaccine available, microbicides provide an alternative strategy to limit HIV-1 spread. However, research into the function of LCs is hampered by the low availability and donor differences. Here, we set out to investigate whether LCs derived from the Mutz-3 cell line (Mu-LCs) provide a valuable tool to investigate the role of LCs in HIV-1 transmission and identify suitable potential microbicides. We demonstrate that Mu-LCs phenotypically resemble human primary LCs; Mu-LCs do not transmit HIV-1 efficiently, and inhibition of Langerin enhances HIV-1 transmission to T cells. We show that carbohydrate structures blocking DC-SIGN but not Langerin are potential microbicides, as they prevent HIV-1 transmission by DCs but do not affect the antiviral function of LCs. Therefore, Mu-LCs are a suitable model to investigate the role of LCs in HIV-1 transmission and to screen potential microbicides.
c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-β inhibits c-Maf-induced IL-21 production in CD4+ T cells
Authors: Hiramatsu Yukiko , Suto Akira , Kashiwakuma Daisuke , Kanari Hiroko , Kagami Shin-ichiro , Ikeda Kei , Hirose Koichi , Watanabe Norihiko , Grusby Michael J , Iwamoto Itsuo , Nakajima Hiroshi
Published: December 2009

c-Maf directly induces IL-21 expression by activating IL-21 promoter and CNS-2 enhancer through MARE site and TGF-β suppresses c-Maf-induced IL-21 expression.

Previous studies have shown that IL-6 potently induces IL-21 production in CD4+ T cells, whereas TGF-β inhibits IL-6-induced IL-21 production in CD4+ T cells. In this study, we addressed the mechanisms underlying the transcriptional regulation of IL-21 production in CD4+ T cells. We found that IL-6 induced c-Maf expression in CD4+ T cells and that the enforced expression of c-Maf induced IL-21 production in CD4+ T cells without IL-6, IL-4/STAT6 signaling, or an autocrine effect of IL-21. Moreover, we found that c-Maf directly bound to and activated IL-21P and the CNS-2 enhancer through MARE sites. On the other hand, we also found that although TGF-β up-regulated IL-6-induced c-Maf expression in CD4+ T cells, TGF-β inhibited c-Maf-induced IL-21 production in CD4+ T cells. Finally, we found that Foxp3 bound to IL-21P and the CNS-2 enhancer and inhibited c-Maf-induced IL-21 production modestly but significantly in CD4+ T cells. Taken together, these results suggest that c-Maf induces IL-21 production directly in CD4+ T cells by activating IL-21P and the CNS-2 enhancer and that TGF-β suppresses c-Maf-induced IL-21 production in CD4+ T cells.
Modeling and analysis of the response of a triaxial, frequency-domain electromagnetic induction sensor to a buried linear conductor
Authors: McKenna Sean P. , McKenna Jason R.
Published: December 2009

This paper presents analytical modeling results for a triaxial frequency-domain electromagnetic-induction (EMI) sensor over a homogeneous earth containing a long linear conductor. Although the conductor studied is intended to represent an underground wire or pipe, it can represent any subsurface, linear geologic structure that can channel current. Treating the sensor transmitter as a vertical magnetic dipole, the model combines the well-known solution for the magnetic field arising from the interaction with the earth with the solution for the induced magnetic field from the excited subsurface conductor. Expressions for the three components of the magnetic field at an arbitrary point above the earth are presented. Two types of coupled, moving transmitter-receiver configurations (coaxial and coplanar) wereconsidered, and the model is sufficiently flexible to allow for many other sensor variations to be studied. Characteristics of the sensor signals were explored through several parametric modeling studies that demonstrate the sensitivity of the signals to transmitter frequency, earth conductivity, conductor depth, sensor geometry, and crossing angle. Using simple relationships developed from analysis of the sensor signals, key parameters such as conductor depth and orientation can be estimated. The ability of the model to predict and characterize sensor output should prove helpful in distinguishing between geologic features and man-made underground infrastructure. These modeling results also are expected to facilitate frequency-domain EMI data analysis and interpretation, sensor design and operation, and the development of detection and classification algorithms.
The kiss - psychiatry in pictures
Authors: Rosen Ismond
Published: December 2009

The sculptor Ismond Rosen was a distinguished psychoanalyst and consultant psychiatrist who became a fellow to both the Royal College of Psychiatrists and the Society of Portrait Sculptors. He presented this 1947 white marble carving to the Royal Society of Medicine in 1987, where it can now be seen framed by a window on the south fac, ade. The stillness of its simple curves symbolises the importance of early attachments as a template for all subsequent relationships. In Dr Rosen's own words, ‘The two heads relate above and fuse below in a manner expressive of human loving, both in its earliest mother-child relationship and in adult sexual congress.’
Désiré Magloire Bourneville - (1840-1909)
Authors: Schuster Jean-Pierre , Strat Yann Le.
Published: December 2009

The name of Désiré Bourneville is linked with tuberous sclerosis complex, which he documented and named. He also contributed to major hospital reforms, especially in the care of children with intellectual disabilities. His medical and social work with such children made him a precursor in child and adolescent psychiatry.
From the Editor's desk
Authors: Tyrer Peter
Published: December 2009

British Made Foreign Journal

I am writing this just after returning from India and Sri Lanka and, after being exposed to a welter of cultures and religions in the past few days, I have had cause to reflect on the Journal's aspirations to be international. I think I can detect a touch of sophistry here. Professor Navendra Wig, one of the most distinguished of Indian psychiatrists, puts it better. He describes how the government excise records in India refer to locally produced spirits such as brandy and whisky as IMFL – ‘Indian Made Foreign Liquor’1 – and this made him realise that, at heart, he was an IMFD, an ‘Indian Made Foreign Doctor’, as he could never escape his cultural heritage however much he tried. Similarly, I cannot escape the conclusion that we are seen by all non-UK-born readers as a British Made Foreign Journal, with a style and substance that cannot genuinely resonate with all our readers. But we can learn much from each other, as this issue shows. Manoranjitham et al (pp. 26–30) show that even if we were successful in both identifying and treating depressive illness over in the West, it might have little impact on suicide in south India as there overt depression appears to be rare prior to suicide, and what matters much more is simple stress and isolation following loss. Why south India is different from the UK, and even Pakistan2 here, is a puzzle, but such research shows that we cannot export or import evidence derived from only one country if it is at least partly dependent on culture and setting. Fottrell et al (pp. 18–25) similarly demonstrate the tremendous value of one of the most joyous of events, childbirth, in Benin where perinatal mortality is high, so that even the trauma of a baby almost dying can be overcome triumphantly by the exuberance of successful motherhood. But it is equally important to report results that are entirely consistent with those in countries of different cultures, and Chen et al (pp. 31–35) find that recurrence of self-harm in Taiwan follows a pattern that is virtually identical to that in Western countries.3–5 Large international studies can allow for cultural and national variations and Bottomley et al (pp. 13–17) illustrate this in comparing risk factors for both onset of depression and recovery. Bisson et al (pp. 69–74) do likewise and in their guidelines for psychosocial care after disasters involved experts from 25 nations across the world – quite a feat.
Brain serotonin-2 receptors in acute mania
Authors: Yatham Lakshmi N. , Liddle Peter F. , Erez Jonathan , Kauer-Sant'Anna Marcia , Lam Raymond W. , Imperial Miguel , Sossi Vesna , Ruth Thomas J.
Published: December 2009

Background

Although 5-hydroxytryptamine (5-HT) has been implicated in mania, the precise alterations in the 5-HT system remain elusive.

Aims

To assess brain 5-HT2receptors in drug-free individuals experiencing a manic episode in comparison with healthy volunteers using positron emission tomography (PET).

Method

Participants (n= 10) with DSM–IV bipolar I disorder – manic episode and healthy controls (n= 10) underwent [18F]- setoperone scans. The differences in 5-HT2receptor binding potential between the two groups were determined using statistical parametric mapping (SPM) analysis.

Results

Age was a significant correlate with 5-HT2receptor binding potential with a similar magnitude of correlation in both groups. The SPM analysis with age as a covariate showed that the individuals with current mania had significantly lower 5-HT2receptor binding potential in frontal, temporal, parietal and occipital cortical regions, with changes more prominent in the right cortical regions compared with controls.

Conclusions

This study suggests that brain 5-HT∗2 receptors are decreased in people with acute mania.
Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials
Authors: Lieb Klaus , Völlm Birgit , Rücker Gerta , Timmer Antje , Stoffers Jutta M.
Published: December 2009

Background

Many patients with borderline personality disorder receive pharmacological treatment, but there is uncertainty about the usefulness of such therapies.

Aims

To evaluate the evidence of effectiveness of pharmacotherapy in treating different facets of the psychopathology of borderline personality disorder.

Method

A Cochrane Collaboration systematic review and meta-analysis of randomised comparisons of drug v. placebo, drug v. drug, or single drug v. combined drug treatment in adult patients with borderline personality disorder was conducted. Primary outcomes were overall disorder severity as well as specific core symptoms. Secondary outcomes comprised associated psychiatric pathology and drug tolerability.

Results

Twenty-seven trials were included in which first- and second-generation antipsychotics, mood stabilisers, antidepressants and omega-3 fatty acids were tested. Most beneficial effects were found for the mood stabilisers topiramate, lamotrigine and valproate semisodium, and the second-generation antipsychotics aripiprazole and olanzapine. However, the robustness of findings is low, since they are based mostly on single, small studies. Selective serotonin reuptake inhibitors so far lack high-level evidence of effectiveness.

Conclusions

The current evidence from randomised controlled trials suggests that drug treatment, especially with mood stabilisers and second-generation antipsychotics, may be effective for treating a number of core symptoms and associated psychopathology, but the evidence does not currently support effectiveness for overall severity of borderline personality disorder. Pharmacotherapy should therefore be targeted at specific symptoms.
Enhanced relapse prevention for bipolar disorder by community mental health teams: cluster feasibility randomised trial
Authors: Lobban F. , Taylor L. , Chandler C. , Tyler E. , Kinderman P. , Kolamunnage-Dona R. , Gamble C. , Peters S. , Pontin E. , Sellwood W. , Morriss R. K.
Published: December 2009

Background

Relapse prevention for bipolar disorder increases time to relapse but is not available in routine practice.

Aims

To determine the feasibility and effectiveness of training community mental health teams (CMHTs) to deliver enhanced relapse prevention.

Method

In a cluster randomised controlled trial, CMHT workers were allocated to receive 12 h training in enhanced relapse prevention to offer to people with bipolar disorder or to continue giving treatment as usual. The primary outcome was time to relapse and the secondary outcome was functioning.

Results

Twenty-three CMHTs and 96 service users took part. Compared with treatment as usual, enhanced relapse prevention increased median time to the next bipolar episode by 8.5 weeks (hazard ratio 0.79, 95% CI 0.45–1.38). Social and occupational functioning improved with the intervention (regression coefficient 0.68, 95% CI 0.05–1.32). The clustering effect was negligible but imprecise (intracluster correlation coefficient 0.0001, 95% CI 0.0000–0.5142).

Conclusions

Training care coordinators to offer enhanced relapse prevention for bipolar disorder may be a feasible effective treatment. Large-scale cluster trials are needed.
Prevalence and correlates of auditory vocal hallucinations in middle childhood
Authors: Bartels-Velthuis Agna A. , Jenner Jack A. , van de Willige Gerard , van Os Jim , Wiersma Durk
Published: December 2009

Background

Hearing voices occurs in middle childhood, but little is known about prevalence, aetiology and immediate consequences.

Aims

To investigate prevalence, developmental risk factors and behavioural correlates of auditory vocal hallucinations in 7- and 8-year-olds.

Method

Auditory vocal hallucinations were assessed with the Auditory Vocal Hallucination Rating Scale in 3870 children. Prospectively recorded data on pre- and perinatal complications, early development and current problem behaviour were analysed in children with auditory vocal hallucinations and matched controls.

Results

The 1-year prevalence of auditory vocal hallucinations was 9%, with substantial suffering and problem behaviour reported in 15% of those affected. Prevalence was higher in rural areas but auditory vocal hallucinations were more severe and had greater functional impact in the urban environment. There was little evidence for associations with developmental variables.

Conclusions

Auditory vocal hallucinations in 7- and 8-year-olds are prevalent but mostly of limited functional impact. Nevertheless, there may be continuity with more severe psychotic outcomes given the serious suffering in a subgroup of children and there is evidence for a poorer prognosis in an urban environment.
Comparison of risk factors for the onset and maintenance of depression
Authors: Bottomley Christian , Nazareth Irwin , Torres-González Francisco , Švab Igor , Maaroos Heidi-Ingrid , Geerlings Mirjam I. , Xavier Miguel , Saldivia Sandra , King Michael
Published: December 2009

Background

Factors associated with depression are usually identified from cross-sectional studies.

Aims

We explore the relative roles of onset and recovery in determining these associations.

Method

Hazard ratios for onset and recovery were estimated for 39 risk factors from a cohort study of 10 045 general practice attendees whose depression status was assessed at baseline, 6 and 12 months.

Results

Risk factors have a stronger relative effect on the rate of onset than recovery. The strongest risk factors for both onset and maintenance of depression tend to be time-dependent. With the exception of female gender the strength of a risk factor's effect on onset is highly predictive of its impact on recovery.

Conclusions

Preventive measures will achieve a greater reduction in the prevalence of depression than measures designed to eliminate risk factors post onset. The strength of time-dependent risk factors suggests that it is more productive to focus on proximal rather than distal factors.
National dissemination of effective parenting programmes to improve child outcomes
Authors: Scott Stephen
Published: December 2009

Although living standards have increased in the past 40 years, children's behaviour problems have become worse. Good parenting can help by maximising children's potential and promoting resilience. Effective programmes are available that improve parenting, but unfortunately ineffective approaches are still used widely. A new National Academy for Parenting Practitioners has been set up in England, which offers free training in evidence-based interventions and conducts research to increase their effectiveness.
Close Reading at a Distance: Bleak House
Authors: Hack Daniel
Published: January 2010

This essay argues that a combination of the frequently opposed methods of book history and reception studies, on the one hand, and those of formal analysis and close reading, on the other, is needed to illuminate the cultural work done by and with novels. Taking as my example the surprisingly extensive antebellum engagement with Bleak House on the part of African Americans and abolitionists, I show how such a combination of methods enables us to tease out the determinants, mechanics, and implications of readerly identification and appropriation across racial and national lines. African Americans and abolitionists found in Bleak House a material and imaginative resource for their efforts to tell the stories they wanted to tell and build the communities they sought to build. They did so even though Bleak House not only fails to imagine a community that includes Africans, African Americans, and slaves but goes so far as to consolidate the community it does imagine by means of their exclusion. I focus in particular on the reprinting of Bleak House in Frederick Douglass' Paper and its rewriting in, or as, The Bondwoman's Narrative by Hannah Crafts.
Natural History and the Novel: Dilatoriness and Length and the Nineteenth-Century Novel of Everyday Life
Authors: King Amy M.
Published: January 2010

Our canonical accounts of the novel form, arising out of formalist, psychoanalytic, structuralist, or Marxist interpretive practices, tend pervasively to occlude or ignore altogether one of its most salient elements: description. From Propp's schemas of narrative “functions” to Peter Brooks' textual “motor,” the driving energies of plot are taken as fundamental—to such an extent that a radically nondescriptive subgenre, the detective novel, is understood as a useful model for the novel per se. Such a focus is inevitably distorting—for the nineteenth-century British novel of everyday life, with its affinity for protracted descriptive pauses, more distorting still. Natural history influenced these descriptive practices; this essay argues that nineteenth-century novelistic description borrowed both a structure and an ethical justification from the observational practices of natural history and its knowing debt to natural theology. This borrowing included a delimited focus of attention on small objects or minute areas; the requirement to dilate at length upon such detail, finding much in the small and the quotidian; and the absolute value of close attention upon the detail, which yields truths inaccessible to wider gazes. The essay focuses on Gilbert White's The Natural History and Antiquities of Selborne (1789) and Mary Russell Mitford's Our Village (1824-32). It argues that we can detect the trace of a practice of close observation and a set of descriptive modes premised upon dilation of detail and delaying narrative drive, a descriptive mode that was particularly suited to the requirements of natural theology.
Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F
Authors: Gurden Mark D. J. , Holland Andrew J. , van Zon Wouter , Tighe Anthony , Vergnolle Mailys A. , Andres Douglas A. , Spielmann H. Peter , Malumbres Marcos , Wolthuis Rob M. F. , Cleveland Don W. , Taylor Stephen S.
Published: January 2010

Progression through mitosis and cytokinesis requires the sequential proteolysis of several cell-cycle regulators. This proteolysis is mediated by the ubiquitin-proteasome system, with the E3 ligase being the anaphase-promoting complex, also known as the cyclosome (APC/C). The APC/C is regulated by two activators, namely Cdc20 and Cdh1. The current view is that prior to anaphase, the APC/C is activated by Cdc20, but that following anaphase, APC/C switches to Cdh1-dependent activation. However, here we present an analysis of the kinetochore protein Cenp-F that is inconsistent with this notion. Although it has long been appreciated that Cenp-F is degraded sometime during or after mitosis, exactly when and how has not been clear. Here we show that degradation of Cenp-F initiates about six minutes after anaphase, and that this is dependent on a C-terminal KEN-box. Although these two observations are consistent with Cenp-F being a substrate of Cdh1-activated APC/C, Cenp-F is degraded normally in Cdh1-null cells. By contrast, RNAi-mediated repression of APC/C subunits or Cdc20 does inhibit Cenp-F degradation. These findings therefore suggest that the APC/C does not simply ‘switch’ upon anaphase onset; rather, our observations indicate that Cdc20 also contributes to post-anaphase activation of the APC/C. We also show that the post-anaphase, KEN-box-dependent degradation of Cenp-F requires it to be farnesylated, a post-translational modification usually linked to membrane association. Because so many of the behaviours of Cenp-F are farnesylation-dependent, we suggest that this modification plays a more global role in Cenp-F function.
Influence of number of children on cancer screening among adults in the United States
Authors: Stimpson Jim P , Wilson Fernando A , Reyes-Ortiz Carlos A
Published: January 2010

Objective

To investigate the influence of children in the household on the likelihood of reporting cancer screening among adult men and women living in the United States.

Methods

2004–2006 Medical Expenditure Panel Surveys (MEPS) were used to calculate the probability of self-reported cancer screening by number of children for adult men and women with adjustment for age, sex, marital status, race, education, current smoking status, obesity status, health insurance and having a usual health-care provider.

Results

The largest percentage of persons who had cancer screening was among respondents with no children in the household. In multivariate results, the probability of endoscopy was lower for persons with one child (24%) and two or more children (21%) in comparison with persons with no children living in the household (30%). Prostate-specific antigen (PSA) testing was lower among men with one child (17%) and two or more children (14%) in comparison with no children (22%). Pap smears were lower for women with two or more children (50%) but not different for women with one child (55%) in comparison with no children (56%). Mammograms were lower for women with one child (48%) and two or more children (42%) in comparison with no children in the household ( 55%).

Conclusion

Across several different cancer screening modalities, the probability of screening is lower as the number of children in the household increases. Children may be an additional barrier to screening beyond factors such as socioeconomic status and access to care.
Exploring the acceptability of two self-sampling devices for human papillomavirus testing in the cervical screening context: a qualitative study of Muslim women in London
Authors: Szarewski Anne , Cadman Louise , Ashdown-Barr Lesley , Waller Jo
Published: January 2010

Objectives

We explored Muslim women's attitudes to self-sampling for human papillomavirus (HPV) in the context of cervical cancer screening and their responses to two self-sampling devices.

Setting

A Muslim community centre in north-east London.

Methods

Following a talk given on the subject of cervical cancer and HPV at the community centre, 28 women were recruited to take part in three focus group discussions. The discussion covered cervical screening, self-sampling and HPV testing. Women were also asked for their responses to a swab self-sampling kit and a cervico-vaginal lavage device. Discussions were recorded and transcribed verbatim and the qualitative data were analysed using Framework Analysis.

Results

Participants were generally positive about cervical screening but acknowledged that some women in their community were reluctant to attend because of embarrassment, language difficulties, fear or because they were unmarried and did not want to communicate implicit messages about being sexually active. Self-sampling met a mixed response – women were concerned about not doing the test correctly, but thought that it might overcome barriers to screening for some women. HPV testing itself was thought to raise potentially difficult issues relating to trust and fidelity within marriages. Although most women said they would prefer to continue to have screening by a health professional, if they were to perform self-sampling, there was overwhelming preference for the swab over the lavage kit.

Conclusions

There was limited enthusiasm for self-sampling in this group of Muslim women who had mostly attended for cervical screening, but a clear preference for a swab rather than a cervico-vaginal lavage.
Barriers to cervical cancer screening attendance in England: a population-based survey
Authors: Waller Jo , Bartoszek Marta , Marlow Laura , Wardle Jane
Published: January 2010

Objectives

To explore barriers to cervical screening attendance in a population-based sample, and to compare barriers endorsed by women who were up-to-date with screening versus those who were overdue. We also tested the hypothesis that women who were overdue for screening would be more generally disillusioned with public services, as indexed by reported voting behaviour in elections.

Setting

A population-based survey of women in England.

Methods

Face-to-face interviews were carried out with 580 women aged 26–64 years, and recruited using stratified random probability sampling as part of an omnibus survey. Questions assessed self-reported cervical screening attendance, barriers to screening, voting behaviour and demographic characteristics.

Results

Eighty-five per cent of women were up-to-date with screening and 15% were overdue, including 2.6% who had never had a smear test. The most commonly endorsed barriers were embarrassment (29%), intending to go but not getting round to it (21%), fear of pain (14%) and worry about what the test might find (12%). Only four barriers showed significant independent associations with screening status: difficulty making an appointment, not getting round to going, not being sexually active and not trusting the test. We found support for our hypothesis that women who do not attend for screening are less likely to vote in elections, even when controlling for barrier endorsement and demographic factors.

Conclusions

Practical barriers were more predictive of screening uptake than emotional factors such as embarrassment. This has clear implications for service provision and future interventions to increase uptake. The association between voting behaviour and screening uptake lends support to the hypothesis that falling screening coverage may be indicative of a broader phenomenon of disillusionment, and further research in this area is warranted.
Autoregulation of Fox protein expression to produce dominant negative splicing factors
Authors: Damianov Andrey , Black Douglas L.
Published: December 2009

The Fox proteins are a family of regulators that control the alternative splicing of many exons in neurons, muscle, and other tissues. Each of the three mammalian paralogs, Fox-1 (A2BP1), Fox-2 (RBM9), and Fox-3 (HRNBP3), produces proteins with a single RNA-binding domain (RRM) flanked by N- and C-terminal domains that are highly diversified through the use of alternative promoters and alternative splicing patterns. These genes also express protein isoforms lacking the second half of the RRM (FoxΔRRM), due to the skipping of a highly conserved 93-nt exon. Fox binding elements overlap the splice sites of these exons in Fox-1 and Fox-2, and the Fox proteins themselves inhibit exon inclusion. Unlike other cases of splicing autoregulation by RNA-binding proteins, skipping the RRM exon creates an in-frame deletion in the mRNA to produce a stable protein. These FoxΔRRM isoforms expressed from cDNA exhibit highly reduced binding to RNA in vivo. However, we show that they can act as repressors of Fox-dependent splicing, presumably by competing with full-length Fox isoforms for interaction with other splicing factors. Interestingly, the Drosophila Fox homolog contains a nearly identical exon in its RRM domain that also has flanking Fox-binding sites. Thus, rather than autoregulation of splicing controlling the abundance of the regulator, the Fox proteins use a highly conserved mechanism of splicing autoregulation to control production of a dominant negative isoform.
Anti-Argonaute RIP-Chip shows that miRNA transfections alter global patterns of mRNA recruitment to microribonucleoprotein complexes
Authors: Wang Wang-Xia , Wilfred Bernard R. , Hu Yanling , Stromberg Arnold J. , Nelson Peter T.
Published: December 2009

MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to target polynucleotides. There are still uncertainties about how miRNAs interact with mRNAs. Here we employed a biochemical approach to isolate AGO-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During rigorous validation, the “RIP-Chip” assay identified target mRNAs specifically associated with AGO complexes. RIP-Chip was performed after transfecting brain-enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic control miRNA to identify miRNA targets. As expected, the miRNA transfections altered the mRNA content of the miRNPs. Specific mRNA species recruited to miRNPs after miRNA transfections were moderately in agreement with computational target predictions. In addition to recruiting mRNA targets into miRNPs, miR-107 and to a lesser extent miR-128, but not miR-124 or miR-320, caused apparent exclusion of some mRNAs that are normally associated with miRNPs. MiR-107 and miR-128 transfections also result in decreased AGO mRNA and protein levels. However, AGO mRNAs were not recruited to miRNPs after either miR-107 or miR-128 transfection, confirming that miRNAs may alter gene expression without stable association between particular mRNAs and miRNPs. In summary, RIP-Chip assays constitute an optimized, validated, direct, and high-throughput biochemical assay that provides data about specific miRNA:mRNA interactions, as well as global patterns of regulation by miRNAs.
The Valve Location Problem in Simple Network Topologies
Authors: Bodlaender Hans L. , Hendriks Albert , Grigoriev Alexander , Grigorieva Nadejda V.
Published: December 2009

To control possible spills in liquid or gas transporting pipe systems, the systems are usually equipped with shutoff valves. In case of an accidental leak, these valves separate the system into a number of pieces, limiting the spill effect. In this paper, we consider the problem, for a given edge-weighted network representing a pipe system and for a given number of valves, of placing the valves in the network in such a way that the maximum possible spill, i.e., the maximum total weight of a piece, is minimized. We show that the problem is NP-hard even if restricted to any of the following settings: (i) series-parallel graphs, and hence graphs of treewidth two; and (ii) all edge weights equal one. If the network is a simple path, a cycle, or a tree, the problem can be solved in polynomial time. We also give a pseudopolynomial-time algorithm and a fully polynomial-time approximation scheme for networks of bounded treewidth.
A Milk Collection Problem with Incompatibility Constraints
Authors: Caramia Massimiliano , Guerriero Francesca
Published: December 2009

The milk collection problem is well known in rural areas of the world. This paper considers this real-life problem for an Italian dairy company that collects raw milk from farmers. In our milk collection problem, we address the constraint that some farms are small and inaccessible by large vehicles; moreover, these farmers produce different milk types, and the tank trucks used for transporting the milk have multiple compartments. This generates the additional constraint that at most one milk type can be assigned to a tank compartment. The goal of this paper is to show how operations research techniques helped the company to improve its daily performance. In particular, we present a solution approach based on two mathematical formulations and local search, all embedded within a multiple-restart mechanism. The first mathematical formulation minimizes the number of vehicles to be routed in the network; the second minimizes the tour length. We also discuss experiments we conducted as part of our case study and compare our solution with the process that the company used previously.
Preference Markets for Innovation Ranking and Selection
Authors: Chen Li , Goes Paulo , Harris Wynd , Marsden James , Zhang John
Published: December 2009

Companies face constant challenges to appropriately rank and select innovative technologies for potential strategic investments, and they have used many methodologies to help them with this task; however, these existing processes have several limitations. This paper showcases how information preference markets can be structured and implemented to rank and select these technologies. We demonstrate the market process for a leading company in the Fortune 100 companies list. The results are encouraging and have persuaded the company to make a significant financial commitment to expand its use of preference markets. The work we present here offers readers a step-by-step illustration of how to develop and use preference markets in industry settings.
Durable Products with Multiple Used Goods Markets: Product Upgrade and Retail Pricing Implications
Authors: Yin Shuya , Ray Saibal , Gurnani Haresh , Animesh Animesh
Published: December 2009

Used goods markets are currently important transaction channels for durable products. For some durable products, such markets first appeared when retailers started buying back used products from “old” customers and selling them to new ones for a profit (retail used goods market). The growth of electronic peer-to-peer (P2P) markets opened up a second, frictionless used goods channel where new customers can buy used products directly from old customers (P2P used goods market). Both these markets compete with the original primary market where retailers sell unused products procured from the manufacturer. This paper focuses on understanding the role that the sequential emergence of the above two used goods markets plays in shaping the product upgrade strategy of the manufacturer and the pricing strategy of the primary market retailer in the context of a decentralized, dyadic channel dealing with a renewable set of consumers. Our analysis establishes that frequent product upgrades and rising retail prices in durable product sectors of our interest are due to the emergence of the P2P used goods market and how the market interacts with the retail used goods source in altering the relative powers of the channel partners. Moreover, contrary to popular belief, we show that the initial introduction of the retail used goods channel actually discourages introduction of new versions and restrains the rise in retail prices. We also comment on how the two used goods markets affect the profits of the channel partners. We then provide empirical support for our theoretical result regarding product upgrades using data from the college textbook industry, a durable product that fits our model setup.
Limited Memory, Categorization, and Competition
Authors: Chen Yuxin , Iyer Ganesh , Pazgal Amit
Published: December 2009

This paper investigates the effects of a limited consumer memory on the price competition between firms. It studies a specific aspect of memory—namely, the categorization of available price information that the consumers may need to recall for decision making. This paper analyzes competition between firms in a market with uninformed consumers who do not compare prices, informed consumers who compare prices but with limited memory, and informed consumers who have perfect memory. Consumers, aware of their memory limitations, choose how to encode the prices into categories, whereas firms take the limitations of consumers into account in choosing their pricing strategies. Two distinct types of categorization processes are investigated: (1) a symmetric one in which consumers compare only the labels of price categories from the competing firms and (2) an asymmetric one in which consumers compare the recalled price of one firm with the actual price of the other. We find that the equilibrium partition for the consumers calls for finer categorization toward the bottom of the price distribution. Thus consumers have a motivation to invest in greater memory resources in encoding lower prices to induce firms to charge more favorable prices. The interaction between the categorization strategies of the consumers and the price competition between the firms is such that small initial improvements in recall move the market outcomes quickly toward the case of perfect recall. Even with few memory categories, the expected price consumers pay and their surplus is close to the case of perfect recall. There is thus a suggestion in this model that market competition adjusts to the memory limitations of consumers.