bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of human meiotic recombination events with a parent-sibling tracing approach
Authors: Lee Yun-Shien , Chao Angel , Chen Chun-Houh , Chou Tina , Wang Shih-Yee Mimi , Wang Tzu-Hao
Published: August 2011

Background

Meiotic recombination ensures that each child inherits distinct genetic materials from each parent, but the distribution of crossovers along meiotic chromosomes remains difficult to identify. In this study, we developed a parent-sibling tracing (PST) approach from previously reported methods to identify meiotic crossover sites of GEO GSE6754 data set. This approach requires only the single nucleotide polymorphism (SNP) data of the pedigrees of both parents and at least two of children.

Results

Compared to other SNP-based algorithms (identity by descent or pediSNP), fewer uninformative SNPs were derived with the use of PST. Analysis of a GEO GSE6754 data set containing 2,145 maternal and paternal meiotic events revealed that the pattern and distribution of paternal and maternal recombination sites vary along the chromosomes. Lower crossover rates near the centromeres were more prominent in males than in females. Based on analysis of repetitive sequences, we also showed that recombination hotspots are positively correlated with SINE/MIR repetitive elements and negatively correlated with LINE/L1 elements. The number of meiotic recombination events was positively correlated with the number of shorter tandem repeat sequences.

Conclusions

The advantages of the PST approach include the ability to use only two-generation pedigrees with two siblings and the ability to perform gender-specific analyses of repetitive elements and tandem repeat sequences while including fewer uninformative SNP regions in the results.
Functional identification in Lactobacillus reuteri of a PocR-like transcription factor regulating glycerol utilization and vitamin B12 synthesis
Authors: Santos Filipe , Spinler Jennifer K , Saulnier Delphine MA , Molenaar Douwe , Teusink Bas , de Vos Willem M , Versalovic James , Hugenholtz Jeroen
Published: August 2011

Background

Lactobacillus reuteri harbors the genes responsible for glycerol utilization and vitamin B12 synthesis within a genetic island phylogenetically related to gamma-Proteobacteria. Within this island, resides a gene (lreu_1750) that based on its genomic context has been suggested to encode the regulatory protein PocR and presumably control the expression of the neighboring loci. However, this functional assignment is not fully supported by sequence homology, and hitherto, completely lacks experimental confirmation.

Results

In this contribution, we have overexpressed and inactivated the gene encoding the putative PocR in L. reuteri. The comparison of these strains provided metabolic and transcriptional evidence that this regulatory protein controls the expression of the operons encoding glycerol utilization and vitamin B12 synthesis.

Conclusions

We provide clear experimental evidence for assigning Lreu_1750 as PocR in Lactobacillus reuteri. Our genome-wide transcriptional analysis further identifies the loci contained in the PocR regulon. The findings reported here could be used to improve the production-yield of vitamin B12, 1,3-propanediol and reuterin, all industrially relevant compounds.
A whole blood monokine-based reporter assay provides a sensitive and robust measurement of the antigen-specific T cell response
Authors: Chakera Aron , Bennett Sophia C , Cornall Richard J
Published: August 2011

Background

The ability to measure T-cell responses to antigens is proving critical in the field of vaccine development and for understanding immunity to pathogens, allergens and self-antigens. Although a variety of technologies exist for this purpose IFNγ-ELISpot assays are widely used because of their sensitivity and simplicity. However, ELISpot assays cannot be performed on whole blood, and require relatively large volumes of blood to yield sufficient numbers of peripheral blood mononuclear cells. To address these deficiencies, we describe an assay that measures antigen-specific T cell responses through changes in monokine gene transcription. The biological amplification of the IFNγ signal generated by this assay provides sensitivity comparable to ELISpot, but with the advantage that responses can be quantified using small volumes of whole blood.

Methods

Whole blood or peripheral blood mononuclear cells (PBMCs) from healthy controls and immunosuppressed recipients of solid organ transplants were incubated with peptide pools covering viral and control antigens or mitogen for 20 hours. Total RNA was extracted and reverse transcribed before amplification in a TaqMan qPCR reaction using primers and probes specific for MIG (CXCL9), IP-10 (CXCL10) and HPRT. The induction of MIG and IP-10 in response to stimuli was analysed and the results were compared with those obtained by ELISpot.

Results

Antigen-specific T cell responses can be measured through the induction of MIG or IP-10 gene expression in PBMCs or whole blood with results comparable to those achieved in ELISpot assays. The biological amplification generated by IFNγ-R signaling allows responses to be detected in as little as 25 μL of whole blood and enables the assay to retain sensitivity despite storage of samples for up to 48 hours prior to processing.

Conclusions

A monokine-based reporter assay provides a sensitive measure of antigen-specific T cell activation. Assays can be performed on small volumes of whole blood and remain accurate despite delays in processing. This assay may be a useful tool for studying T cell responses, particularly when samples are limited in quantity or when storage or transportation is required before processing.
An intronic SNP in the thyroid hormone receptor β gene is associated with pituitary cell-specific over-expression of a mutant thyroid hormone receptor β2 (R338W) in the index case of pituitary-selective resistance to thyroid hormone
Authors: Alberobello Anna Teresa , Congedo Valentina , Liu Hong , Cochran Craig , Skarulis Monica C , Forrest Douglas , Celi Francesco S
Published: August 2011

Background

The syndrome of resistance to thyroid hormone (RTH) is caused by mutations in the thyroid hormone receptor β gene (THRB). The syndrome varies from asymptomatic to diffuse hypothyroidism, to pituitary-selective resistance with predominance of hyperthyroid signs and symptoms. The wide spectrum of clinical presentation is not completely attributable to specific THRB mutations. The THRB gene encodes two main isoforms, TR β1 which is widely distributed, and TR β2, whose expression is limited to the cochlea, retina, hypothalamus, and pituitary. Recent data demonstrated that in mice an intron enhancer region plays a critical role in the pituitary expression of the β2 isoform of the receptor. We thus hypothesized that polymorphisms in the human homologous region could modulate the pituitary expression of the mutated gene contributing to the clinical presentation of RTH.

Methods

Screening and in vitro characterization of polymorphisms of the intron enhancer region of the THRB gene in the index case of pituitary-selective RTH.

Results

The index case of pituitary-selective resistance is characterized by the missense R338W exon 9 mutation in cis with two common SNPs, rs2596623T and rs2596622C, located in the intron enhancer region of the THRB gene. Reporter gene assay experiments in GH3 pituitary-derived cells indicate that rs2596623T generates an increased pituitary cell-specific activity of the TR β2 promoter suggesting that rs2596623T leads to pituitary over-expression of the mutant allele.

Conclusions

The combined coding mutation and non-coding SNP therefore generate a tissue-specific dominant-negative condition recapitulating the patient's peculiar phenotype. This case illustrates the role of regulatory regions in modifying the clinical presentation of genetic diseases.
Development of a serotype colloidal gold strip using monoclonal antibody for rapid detection type Asia1 foot-and-mouth disease
Authors: Lin Tong , Shao Jun-jun , Du Jun-zheng , Cong Guo-zheng , Gao Shan-dian , Chang Huiyun
Published: September 2011

Background

In this study, we developed a rapid, one step colloid gold strip (CGS) capable of specifically detecting type Asia1 foot-and-mouth disease virus (FMDV). We have produced two monoclonal antibodies (mAb) to type Asia1 FMD (named 1B8 and 5E2). On the test strip, the purified 1B8 labelled with the colloidal gold was used as the detector, and the purified 5E2 and goat anti-mouse antibodies were wrapped onto nitrocellulose (NC) membranes as the test and the control line, respectively. The rapid colloidal gold stereotype diagnostic strip was housed in a plastic case.

Results

In specificity and sensitivity assay, there was no cross-reaction of the antigen with the other type of FMD and SVDV. The detection sensitivity was found to be as high as 10-5 dilution of Asia1/JSL/05 (1 × 107.2TCID50/50 μL). There was excellent agreement between the results obtained by CGS and reverse indirect hemagglutination assay (RIHA), and the agreement can reach to 98.75%.

Conclusion

We developed colloidal gold strips that have good qualities and does not require specialized equipment or technicians. This method provided a feasible, convenient, rapid, and effective for detecting type Asia1 FMDV in the fields.
Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity
Authors: Mesbah Latifa , Matute Raúl , Usychkin Sergey , Marrone Immacolata , Puebla Fernando , Mínguez Cristina , García Rafael , García Graciela , Beltrán César , Marsiglia Hugo
Published: August 2011

Background

Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies.

Methods

In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume.

Results

The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity.

Conclusion

HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly selected pediatric patient cohort with clinical features of poor prognosis and/or aggressive therapy needed. Despite of a dosimetrical advantage of HT technique, an exhaustive analysis of long-term follow-up data is needed to assess late toxicity, especially in this potentially sensitive to radiation population.
An unusual case of suprascapular nerve neuropathy: a case report
Authors: Economides Charalambos P , Christodoulou Loizos , Kyriakides Theodoros , Soteriades Elpidoforos S
Published: August 2011

Introduction

Suprascapular nerve neuropathy constitutes an unusual cause of shoulder weakness, with the most common etiology being nerve compression from a ganglion cyst at the suprascapular or spinoglenoid notch. We present a puzzling case of a man with suprascapular nerve neuropathy that may have been associated with an appendectomy. The case was attributed to nerve injury as the most likely cause that may have occurred during improper post-operative patient mobilization.

Case presentation

A 23-year-old Caucasian man presented to an orthopedic surgeon with a history of left shoulder weakness of several weeks' duration. The patient complained of pain and inability to lift minimal weight, such as a glass of water, following an appendectomy. His orthopedic clinical examination revealed obvious atrophy of the supraspinatus and infraspinatus muscles and 2 of 5 muscle strength scores on flexion resistance and external rotation resistance. Magnetic resonance imaging showed diffuse high signal intensity within the supraspinatus and infraspinatus muscles and early signs of minimal fatty infiltration consistent with denervation changes. No compression of the suprascapular nerve in the suprascapular or spinoglenoid notch was noted. Electromyographic studies showed active denervation effects in the supraspinatus muscle and more prominent in the left infraspinatus muscle. The findings were compatible with damage to the suprascapular nerve, especially the part supplying the infraspinatus muscle. On the basis of the patient's history, clinical examination, and imaging studies, the diagnosis was suspected to be associated with a possible traction injury of the suprascapular nerve that could have occurred during the patient's transfer from the operating table following an appendectomy.

Conclusion

Our case report may provide important insight into patient transfer techniques used by hospital personnel, may elucidate the clinical significance of careful movement of patients following general anesthesia, and may have important implications for patient safety techniques, including those outlined in the World Health Organization Surgical Safety Checklist program.
Identification of target antigens of anti-endothelial cell and anti-vascular smooth muscle cell antibodies in patients with giant cell arteritis: a proteomic approach
Authors: Régent Alexis , Dib Hanadi , Ly Kim H , Agard Christian , Tamby Mathieu C , Tamas Nicolas , Weksler Babette , Federici Christian , Broussard Cédric , Guillevin Loïc , Mouthon Luc
Published: August 2011

Introduction

Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to identify their target antigens.

Methods

Sera from 15 GCA patients were tested in 5 pools of 3 patients' sera and compared to a sera pool from 12 healthy controls (HCs). Serum immunoglobulin G (IgG) reactivity was analysed by 2-D electrophoresis and immunoblotting with antigens from human umbilical vein ECs (HUVECs) and mammary artery VSMCs. Target antigens were identified by mass spectrometry.

Results

Serum IgG from GCA patients recognised 162 ± 3 (mean ± SD) and 100 ± 17 (mean ± SD) protein spots from HUVECs and VSMCs, respectively, and that from HCs recognised 79 and 94 protein spots, respectively. In total, 30 spots from HUVECs and 19 from VSMCs were recognised by at least two-thirds and three-fifths, respectively, of the pools of sera from GCA patients and not by sera from HCs. Among identified proteins, we found vinculin, lamin A/C, voltage-dependent anion-selective channel protein 2, annexin V and other proteins involved in cell energy metabolism and key cellular pathways. Ingenuity pathway analysis revealed that most identified target antigens interacted with growth factor receptor-bound protein 2.

Conclusions

IgG antibodies to proteins in the proteome of ECs and VSMCs are present in the sera of GCA patients and recognise cellular targets that play key roles in cell biology and maintenance of homeostasis. Their potential pathogenic role remains to be determined.
β1 integrin mediates an alternative survival pathway in breast cancer cells resistant to lapatinib
Authors: Huang Catherine , Park Catherine C , Hilsenbeck Susan G , Ward Robin , Rimawi Mothaffar F , Wang Yen-chao , Shou Jiang , Bissell Mina J , Osborne C Kent , Schiff Rachel
Published: September 2011

Introduction

The overexpression of human epidermal growth factor receptor (HER)-2 in 20% of human breast cancers and its association with aggressive growth has led to widespread use of HER2-targeted therapies, such as trastuzumab (T) and lapatinib (L). Despite the success of these drugs, their efficacy is limited in patients whose tumors demonstrate de novo or acquired resistance to treatment. The β1 integrin resides on the membrane of the breast cancer cell, activating several elements of breast tumor progression including proliferation and survival.

Methods

We developed a panel of HER2-overexpressing cell lines resistant to L, T, and the potent LT combination through long-term exposure and validated these models in 3D culture. Parental and L/T/LT-resistant cells were subject to HER2 and β1 integrin inhibitors in 3D and monitored for 12 days, followed by quantification of colony number. Parallel experiments were conducted where cells were either stained for Ki-67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or harvested for protein and analyzed by immunoblot. Results were subjected to statistical testing using analysis of variance and linear contrasts, followed by adjustment with the Sidak method.

Results

Using multiple cell lines including BT474 and HCC1954, we reveal that in L and LT resistance, where phosphorylation of EGFR/HER1, HER2, and HER3 are strongly inhibited, kinases downstream of β1 integrin--including focal adhesion kinase (FAK) and Src--are up-regulated. Blockade of β1 by the antibody AIIB2 abrogates this up-regulation and functionally achieves significant growth inhibition of L and LT resistant cells in 3D, without dramatically affecting the parental cells. SiRNA against β1 as well as pharmacologic inhibition of FAK achieve the same growth inhibitory effect. In contrast, trastuzumab-resistant cells, which retain high levels of phosphorylated EGFR/HER1, HER2, and HER3, are only modestly growth-inhibited by AIIB2.

Conclusions

Our data suggest that HER2 activity, which is suppressed in resistance involving L but not T alone, dictates whether β1 mediates an alternative pathway driving resistance. Our findings justify clinical studies investigating the inhibition of β1 or its downstream signaling moieties as strategies to overcome acquired L and LT resistance.
Evolution of secure services for women in England
Authors: Sarkar Jaydip , di Lustro Mary
Published: September 2011

Patients detained at high and medium security reveal significant gender differences in the presentation of psychopathology, mental disorder and social and offending profiles. However, secure mental health services in England, like prisons, generally fail to recognise the core importance of the differing biopsychosocial development in women and the impact of life experiences on women's subsequent biopsychosocial functioning. As a consequence, women are often inadequately provided for in services dictated by the identified needs, risks and responsiveness of men. The lack of clinically appropriate facilities for women may account for the increased frequency with which women are readmitted to medium security and for their longer admissions to both high and medium secure care. New tertiary services are developing as a result of the lessons learnt while providing gender-blind care. However, further development is required to ensure that women receive services of the same quality, range and nature of those received by men.
Raising standards in relation to Section 136 of the Mental Health Act 1983
Authors: Hampson Michele
Published: September 2011

Despite the guidance published in revised Codes of Practice and by the Royal College of Psychiatrists, implementation of Section 136 of the Mental Health Act 1983 is still variable. Government funding in England to establish places of safety in psychiatric facilities has been effective but custody suites are still used excessively, especially for those who are brought in intoxicated. Patients feel criminalised by this use of custody suites and by the use of police vehicles rather than ambulance transport for conveyance to the place of safety. There is often a delay in commencing the assessment and the first doctor does not always have Section 12 approval as recommended in the Codes of Practice. The importance of the local Section 136 group tasked with developing and overseeing the implementation of local policy and monitoring is highlighted. There is a need for monitoring locally, but ideally in a form that can be used nationally for benchmarking and research.
Cross-national clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study
Authors: Haro Josep Maria , Novick Diego , Bertsch Jordan , Karagianis Jamie , Dossenbach Martin , Jones Peter B.
Published: September 2011

Background

Evidence suggests that schizophrenia may have a better outcome for individuals living in low- and middle-income countries compared with affluent settings.

Aims

To determine the frequency of symptom and functional remission in out-patients with schizophrenia in different regions of the world.

Method

Using data from the Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO) study we measured clinical and functional remission in out-patients with schizophrenia in different regions of the world, and examined sociodemographic and clinical factors associated with these outcomes. The 11 078 participants analysed from 37 participating countries were grouped into 6 regions: South Europe, North Europe, Central and Eastern Europe, Latin America, North Africa and Middle East, and East Asia.

Results

In total, 66.1% achieved clinical remission during the 3-year follow-up (range: 60.1% in North Europe to 84.4% in East Asia) and 25.4% achieved functional remission (range: 17.8% in North Africa and Middle East to 35.0% in North Europe). Regional differences were not explained by participants' clinical characteristics. Baseline social functioning, being female and previously untreated were consistent predictors of remission across regions.

Conclusions

Clinical outcomes of schizophrenia seem to be worse in Europe compared with other regions. However, functional remission follows a different pattern.
September 11, the War on Terror, and Perpetual Warfare
Authors: Atwood Paul L.
Published: September 2011

The history professor Andrew Bacevich of Boston University is a West Point graduate, a Vietnam War veteran, a self-styled conservative, and a leading critic of over-reach in U.S. foreign policy. He was interviewed in November 2010 by Paul L. Atwood of the University of Massachusetts, Boston. The interview covered the Bush administration's response to the September 11, 2001, attacks and the dynamics of U.S. overseas interventionism, including military-civilian relations. “Civilian control has been deeply compromised,” Bacevich claims, “and the policies that have resulted have been, more often than not, deeply flawed. This is a huge problem, to which most Americans remain blind.”
Can the Diaspora Speak?
Authors: Cvetkovich Ann
Published: September 2011

This article evaluates the role of oral history in the public memory of September 11, 2001, through a small cluster of interviews with Afghan Americans that form part of Columbia University's September 11, 2001, Oral History Narrative and Memory Project. The interviews, most of them with young, educated, and secular Afghan Americans whose families came to the United States after the 1979 Soviet invasion of Afghanistan, tell a different story of 9/11 than that of eyewitnesses and survivors at the World Trade Center. In addition to illuminating the impact of 9/11 on the everyday life of New Yorkers, the interviews reveal the backlash experienced by immigrants from Afghanistan (and from the Middle East and South Asia) and the transgenerational and transnational legacy of histories of violence, which manifest themselves in ordinary family stories and feelings. Moreover, this culturally literate, relatively assimilated group testifies to the challenges of making its perspectives on Afghanistan legible when they are solicited for public commentary. The article argues that these putatively minor and ordinary voices suggest the value of Columbia's 9/11 oral history archive in countering the hyperdocumentation and sensational representation of 9/11 in a range of genres.
FUZZY STUDIES
Authors: Perl Jeffrey M. , Davis Natalie Zemon , Allen Barry
Published: September 2011

In this introduction to Part 1 of the Common Knowledge symposium, “Fuzzy Studies,” the journal's editor discusses four essays from the 1980s by Richard Rorty, in which Rorty chose to associate himself with various neopragmatists, Continental thinkers, and “left-wing Kuhnians” under the rubric of the “new fuzziness.” The term had been introduced as an insult by a philosopher of science with positivist leanings, but Rorty took it up as an “endearing” compliment, arguing that “to be less fuzzy” was also to be “less genial, tolerant, open-minded, and fallibilist.” He defined the “new fuzziness” as “an attempt to blur just those distinctions between the objective and subjective and between fact and value which the critical conception of rationality has developed.” This introduction also examines W. V. Quine's essay “Speaking of Objects” (1957), which describes objects as fuzzy “half-entities”; Clifford Geertz's essay “Blurred Genres” (1980), which advises social scientists that being “taxonomically upstanding” is futile; and Lofti Zadeh's article “The Concept of a Linguistic Variable and Its Application to Approximate Reasoning” (1975), which abandons “Aristotelian, bivalent logic” in favor of a “fuzzy logic” based on Zadeh's “fuzzy set theory.” This introductory piece relates these theoretical works of the past half-century to the sorites paradox and to classical issues of vagueness raised and still unresolved in Western philosophy. Returning then to Rorty, the author questions how Rorty expected his endorsement of the “new fuzziness” to be applied, as proposed, to theology and politics. Suggesting that such applications are the natural work of historians, the author, having asked the historian Natalie Zemon Davis for comment, then quotes her response—which associates fuzzy studies, “common knowledge,” and peacemaking—at length.
Emotive computing may have a role in telecare
Authors: Ball Leslie , Bradley David , Brownsell Simon
Published: August 2011

This brief paper sets out arguments for the introduction of new technologies into telecare and lifestyle monitoring that can detect and monitor the emotive state of patients. The significantly increased use of computers by older people will enable the elements of emotive computing to be integrated with features such as keyboards and webcams, to provide additional information on emotional state. When this is combined with other data, there will be significant opportunities for system enhancement and the identification of changes in user status, and hence of need. The ubiquity of home computing makes the keyboard a very attractive, economic and non-intrusive means of data collection and analysis.
Evidence of benefit from telerehabilitation in routine care: a systematic review
Authors: Hailey David , Roine Risto , Ohinmaa Arto , Dennett Liz
Published: August 2011

We systematically reviewed the evidence on the effectiveness of telerehabilitation (TR) applications. The review included reports on rehabilitation for any disability, other than mental health conditions, and drug or alcohol addiction. All forms of telecommunications technology for TR and all types of study design were considered. Study quality was assessed using an approach that considered both study performance and study design. Judgements were made on whether each TR application had been successful, whether reported outcomes were clinically significant, and whether further data were needed to establish the application as suitable for routine use. Sixty-one scientifically credible studies that reported patient outcomes or administrative changes were identified through computerized literature searches on five databases. Twelve clinical categories were covered by the studies. Those dealing with cardiac or neurological rehabilitation were the most numerous. Thirty-one of the studies (51%) were of high or good quality. Study results showed that 71% of the TR applications were successful, 18% were unsuccessful and for 11% the status was unclear. The reported outcomes for 51% of the applications appeared to be clinically significant. Poorer-quality studies tended to have worse outcomes than those from high- or good-quality studies. We judged that further study was required for 62% of the TR applications and desirable for 23%. TR shows promise in many fields, but compelling evidence of benefit and of impact on routine rehabilitation programmes is still limited. There is a need for more detailed, better-quality studies and for studies on the use of TR in routine care.
Dual regulation of hepatitis C viral RNA by cellular RNAi requires partitioning of Ago2 to lipid droplets and P-bodies
Authors: Berezhna Svitlana Yu. , Supekova Lubica , Sever Mary J. , Schultz Peter G. , Deniz Ashok A.
Published: August 2011

The antiviral role of RNA interference (RNAi) in humans remains to be better understood. In RNAi, Ago2 proteins and microRNAs (miRNAs) or small interfering RNAs (siRNAs) form endonucleolytically active complexes which down-regulate expression of target mRNAs. P-bodies, cytoplasmic centers of mRNA decay, are involved in these pathways. Evidence exists that hepatitis C virus (HCV) utilizes host cellular RNAi machinery, including miRNA-122, Ago1-4, and Dicer proteins for replication and viral genome translation in Huh7 cells by, so far, nebulous mechanisms. Conversely, synthetic siRNAs have been used to suppress HCV replication. Here, using a combination of biochemical, transfection, confocal imaging, and digital image analysis approaches, we reveal that replication of HCV RNA depends on recruitment of Ago2 and miRNA-122 to lipid droplets, while suppression of HCV RNA by siRNA and Ago2 involves interaction with P-bodies. Such partitioning of Ago2 proteins into different complexes and separate subcellular domains likely results in modulation of their activity by different reaction partners. We propose a model in which partitioning of host RNAi and viral factors into physically and functionally distinct subcellular compartments emerges as a mechanism regulating the dual interaction of cellular RNAi with HCV RNA.
Coloring Graphs Using Two Colors While Avoiding Monochromatic Cycles
Authors: Nobibon Fabrice Talla , Hurkens Cor A. J. , Leus Roel , Spieksma Frits C. R.
Published: August 2011

We consider the problem of deciding whether a given directed graph can be vertex partitioned into two acyclic subgraphs. Applications of this problem include testing rationality of collective consumption behavior, a subject in microeconomics. We prove that the problem is NP-complete even for oriented graphs and argue that the existence of a constant-factor approximation algorithm is unlikely for an optimization version that maximizes the number of vertices that can be colored using two colors while avoiding monochromatic cycles. We present three exact algorithms—namely, an integer-programming algorithm based on cycle identification, a backtracking algorithm, and a branch-and-check algorithm. We compare these three algorithms both on real-life instances and on randomly generated graphs. We find that for the latter set of graphs, every algorithm solves instances of considerable size within a few seconds; however, the CPU time of the integer-programming algorithm increases with the number of vertices in the graph more clearly than the CPU time of the two other procedures. For real-life instances, the integer-programming algorithm solves the largest instance in about a half hour, whereas the branch-and-check algorithm takes approximately 10 minutes and the backtracking algorithm less than 5 minutes. Finally, for every algorithm, we also study empirically the transition from a high to a low probability of a YES answer as a function of the number of arcs divided by the number of vertices.
Quantifying the Trade-off Between IMRT Treatment Plan Quality and Delivery Efficiency Using Direct Aperture Optimization
Authors: Salari Ehsan , Romeijn H. Edwin
Published: August 2011

Beam-on time is an important measure of the delivery efficiency in intensity-modulated radiation therapy (IMRT). Traditionally, minimizing beam-on time has been postponed until the leaf sequencing stage, where the treatment plan quality is already determined and fixed. However, there is a trade-off between the beam-on time and the treatment plan quality. The aim of this study is to incorporate the beam-on time into the treatment plan optimization stage using a direct aperture optimization approach that allows for explicitly quantifying the trade-off. The proposed approach can provide clinicians with valuable information for each patient case so that they can design clinically attractive yet efficient treatment plans. Using the special structure of the problem, we propose an exact solution approach that sequentially characterizes segments of the Pareto-efficient frontier. In addition, an approximate solution technique that is applicable to more classes of evaluation criteria is developed. Our approximate technique is tested on clinical cancer cases, and its performance is compared with the general approximation techniques that are available for convex bicriteria optimization problems. The results of our experiments validate that our approach can achieve a more accurate representation of the Pareto-efficient frontier with less computational effort.
Online Product Opinions: Incidence, Evaluation, and Evolution
Authors: Moe Wendy W. , Schweidel David A.
Published: August 2011

Whereas recent research has demonstrated the impact of online product ratings and reviews on product sales, we still have a limited understanding of the individual's decision to contribute these opinions. In this research, we empirically model the individual's decision to provide a product rating and investigate factors that influence this decision. Specifically, we consider how previously posted ratings may affect an individual's posting behavior in terms of whether to contribute (incidence) and what to contribute (evaluation), and we identify selection effects that influence the incidence decision and adjustment effects that influence the evaluation decision.

Across individuals, our results show that positive ratings environments increase posting incidence, whereas negative ratings environments discourage posting. Our results also indicate important differences across individuals in how they respond to previously posted ratings, with less frequent posters exhibiting bandwagon behavior and more active customers revealing differentiation behavior. These dynamics affect the evolution of online product opinions. Through simulations, we illustrate how the evolution of posted product opinions is shaped by the underlying customer base and show that customer bases with the same median opinion may evolve in substantially different ways because of the presence of a core group of “activists” posting increasingly negative opinions.
Measurement of the pro-hormone of brain type natriuretic peptide (proBNP): methodological considerations and pathophysiological relevance
Authors: Clerico Aldo , Vittorini Simona , Passino Claudio
Published: August 2011

Recent studies demonstrated that large amounts of the pro-hormone peptide of brain natriuretic peptide (proBNP) can be detected in plasma of healthy subjects and in particular of patients with heart failure. As a result, a great part of B-type natriuretic peptides measured in patients with cardio-vascular disease may be devoid of biological activity. These findings stimulated the set up of specific immunoassay methods for the measurement of the intact proBNP peptide. The aim of this review article is to discuss the methodological characteristics and the possible clinical relevance of specific immunoassay methods for the measurement of the proBNP peptide. From an analytical point of view, a fully automated immunoassay of proBNP has some theoretical advantages (e.g., a more stable molecule with higher molecular weight than the derived peptides) compared to the active hormone BNP. Recent studies supported the concept that the precursor proBNP might be actually considered a circulating prohormone, which can be cleaved by specific plasma proteases in BNP, the active hormone, and NT-proBNP, an inactive peptide. The peripheral processing of circulating proBNP could likely be submitted to regulatory rules, which might be impaired in patients with heart failure, opening new perspectives in the treatment of heart failure (e.g., by studying drugs inducing the cleavage of the prohormone into active BNP). Furthermore, as a future perspective, the specific assay in the same plasma sample of the intact precursor proBNP and of the biologically active peptide BNP, could allow a more accurate estimation of the production/secretion of B-type related peptides from cardiomyocytes and of the global cardiac endocrine function.
Rate change detection of frequency modulated signals: developmental trends
Authors: Cohen-Mimran Ravit , Sapir Shimon
Published: August 2011

Background: The aim of this study was to examine developmental trends in rate change detection of auditory rhythmic signals (repetitive sinusoidally frequency modulated tones).

Methods: Two groups of children (9–10 years old and 11–12 years old) and one group of young adults performed a rate change detection (RCD) task using three types of stimuli. The rate of stimulus modulation was either constant (CR), raised by 1 Hz in the middle of the stimulus (RR1) or raised by 2 Hz in the middle of the stimulus (RR2).

Results: Performance on the RCD task significantly improved with age. Also, the different stimuli showed different developmental trajectories. When the RR2 stimulus was used, results showed adult-like performance by the age of 10 years but when the RR1 stimulus was used performance continued to improve beyond 12 years of age.

Conclusions: Rate change detection of repetitive sinusoidally frequency modulated tones show protracted development beyond the age of 12 years. Given evidence for abnormal processing of auditory rhythmic signals in neurodevelopmental conditions, such as dyslexia, the present methodology might help delineate the nature of these conditions.
Platelet-Derived Growth Factor B Chain Is a Novel Target Gene of Cocaine-Mediated Notch1 Signaling: Implications for HIV-Associated Neurological Disorders
Authors: Yao Honghong , Duan Ming , Hu Guoku , Buch Shilpa
Published: September 2011

Neuroinflammation associated with HIV-1 infection is exacerbated in cocaine-abusing, HIV+ individuals. The underlying mechanisms are, in part, attributable to disruption of the blood–brain barrier modulated by cocaine via platelet-derived growth factor B chain (PDGF-B). Since Notch signaling plays a critical role in CNS homeostasis, we hypothesized that it may have a role in cocaine-mediated induction of PDGF-B. The goal of this study was to link Notch signaling with PDGF-B. Using Western blot analysis, we demonstrate the role of Notch1 signaling in cocaine-mediated induction of PDGF-B in human brain microvascular endothelial cells. Exposure of cells to the γ-secretase inhibitor-DAPT or silencing of Notch1 resulted in abrogation of cocaine-mediated induction of PDGF-B. Reciprocally, activation of the Notch1 receptor by exposing cells to the Notch ligand Jagged-1 resulted in upregulation of PDGF-B expression. Furthermore, it was demonstrated that cocaine-mediated activation of Notch1 signaling leading to targeted expression of PDGF-B involved activation of the downstream effector CSL. Functional implication of Notch1 signaling in regulating expression of the vascular permeant PDGF-B was confirmedin vitrousing cell permeability assays.In vivorelevance was further corroborated in cocaine-treated mice that demonstrated increased permeability of the endothelial barrier as evidenced by Evans blue and sodium fluorescein extravasation. Specificity of Notch1 signalingin vivowas validated in mice exposed to DAPT, which failed to demonstrate barrier disruption following cocaine exposure. This is the first evidence of involvement of Notch1 activation in cocaine-mediated regulation of PDGF-B expression.
Effiziente Prototyp-Passung mittels Kreisbogensplines und Anwendungsbeispiele aus dem Automotive-Bereich
Authors: Maier Georg , Schindler Andreas
Published: September 2011

Die geeignete Beschreibung eines prototypischen Objekts ist ein zentraler Schritt des Reverse Engineering und der geometrischen Mustererkennung. Für den Einsatz der prototypischen Passung ist eine effiziente Repräsentation des Musterobjektes entscheidend. Vorgestellt wird ein Lösungsansatz, der auf einer Darstellung mittels Kreisbogensplines basiert und eine möglichst praxisnahe Modellierung verfolgt. An Beispielen aus dem Automotive-Bereich wird dessen praktische Relevanz aufgezeigt.
Combining Markers into Haplotypes Can Improve Population Structure Inference
Authors: Gattepaille Lucie M , Jakobsson Mattias
Published: August 2011

High-throughput genotyping and sequencing technologies can generate dense sets of genetic markers for large numbers of individuals. For most species, these data will contain many markers in linkage disequilibrium (LD). To utilize such data for population structure inference, we investigate the use of haplotypes constructed by combining the alleles at single-nucleotide polymorphisms (SNPs). We introduce a statistic derived from information theory, the gain of informativeness for assignment (GIA), which quantifies the additional information for assigning individuals to populations using haplotype data compared to using individual loci separately. Using a two-loci–two-allele model, we demonstrate that combining markers in linkage equilibrium into haplotypes always leads to nonpositive GIA, suggesting that combining the two markers is not advantageous for ancestry inference. However, for loci in LD, GIA is often positive, suggesting that assignment can be improved by combining markers into haplotypes. Using GIA as a criterion for combining markers into haplotypes, we demonstrate for simulated data a significant improvement of assigning individuals to candidate populations. For the many cases that we investigate, incorrect assignment was reduced between 26% and 97% using haplotype data. For empirical data from French and German individuals, the incorrectly assigned individuals can, for example, be decreased by 73% using haplotypes. Our results can be useful for challenging population structure and assignment problems, in particular for studies where large-scale population–genomic data are available.
Wg Signaling via Zw3 and Mad Restricts Self-Renewal of Sensory Organ Precursor Cells in Drosophila
Authors: Quijano Janine C , Stinchfield Michael J , Newfeld Stuart J
Published: August 2011

It is well known that the Dpp signal transducer Mad is activated by phosphorylation at its carboxy-terminus. The role of phosphorylation on other regions of Mad is not as well understood. Here we report that the phosphorylation of Mad in the linker region by the Wg antagonist Zw3 (homolog of vertebrate Gsk3-β) regulates the development of sensory organs in the anterior–dorsal quadrant of the wing. Proneural expression of Mad-RNA interference (RNAi) or a Mad transgene with its Zw3/Gsk3-β phosphorylation sites mutated (MGM) generated wings with ectopic sensilla and chemosensory bristle duplications. Studies with pMad-Gsk (an antibody specific to Zw3/Gsk3-β-phosphorylated Mad) in larval wing disks revealed that this phosphorylation event is Wg dependent (via an unconventional mechanism), is restricted to anterior–dorsal sensory organ precursors (SOP) expressing Senseless (Sens), and is always co-expressed with the mitotic marker phospho-histone3. Quantitative analysis in both Mad-RNAi and MGM larval wing disks revealed a significant increase in the number of Sens SOP. We conclude that the phosphorylation of Mad by Zw3 functions to prevent the self-renewal of Sens SOP, perhaps facilitating their differentiation via asymmetric division. The conservation of Zw3/Gsk3-β phosphorylation sites in vertebrate homologs of Mad (Smads) suggests that this pathway, the first transforming growth factor β-independent role for any Smad protein, may be widely utilized for regulating mitosis during development.
Phylogeny and Genetic Diversity of Flea Beetles (Aphthona sp.) Introduced to North America as Biological Control Agents for Leafy Spurge
Authors: Roehrdanz R , Bourchier R , Cortilet A , Olson D , Sears S
Published: September 2011

A molecular phylogeny is presented for the five main species of Aphthona flea beetles that were introduced to North America in conjunction with the leafy spurge (Euphorbia esula L.) biological control program. The mitochondrial genome was examined using polymerase chain reaction-restriction fragment length polymorphism (RFLP) of a 9,000-bp segment and nucleotide sequencing of a 575-bp piece of cox1-cox2. A neighbor—joining tree of the RFLP data, along with neighbor-joining and maximum parsimony trees of the sequence alignments, all had the same major branching pattern. Each of the recognized species was a well defined clade. Three within species subbranches had very limited mitochondrial DNA diversity. One was a Wolbachia-infected lineage of A. nigriscutis most likely generated by a Wolbachia sweep where the spreading Wolbachia infection brought along the infected mitochondrial haplotype. Two of three subclades of A. lacertosa also had very little genetic diversity. One of these subclades also displayed a divergence from the other two that was analogous to the divergence observed between some of the other species pairs, suggesting it may be a cryptic species. Its distribution was restricted to Canada. The other genetically depauperate A. lacertosa line was the only lineage recovered in the United States. The geographically restricted nature of some of the genetic lines could be exploited to possibly improve biological control in some habitats through redistribution to other locations. It is not obvious that either Wolbachia infection or a narrow genetic base has had any detrimental effect on biological control.
EMBEDDED PROMPTING MAY FUNCTION AS EMBEDDED PUNISHMENT: DETECTION OF UNEXPECTED BEHAVIORAL PROCESSES WITHIN A TYPICAL PRESCHOOL TEACHING STRATEGY
Authors: Heal Nicole A. , Hanley Gregory P.
Published: September 2011

This study describes an unexpected behavioral process that influenced behavior during the teaching of concepts to a 4‐year‐old girl. The efficacy of and preference for three strategies that varied in teacher directedness were assessed in a multielement design and concurrent‐chains arrangement, respectively. The strategy that involved the most teacher direction was most efficacious and preferred. In addition, embedded teacher prompts, common in child‐led teaching procedures, functioned as a punisher for the child's toy play. Implications for designing effective and preferred teaching conditions are discussed.