On January 30th, 2020 Callum Walley, a member of NeSI's Applications Support team, presented a webinar on troubleshooting. Having helped numerous people overcome job submission obstacles, Callum used this webinar to point out some common errors NeSI users face and tips on how to identify and solve them as an App Support professional would. This presentation highlighted a methodical approach to troubleshooting that, ideally, left attendees feeling curious and confident to find the root cause of the errors they encounter.To view the webinar recording click here: https://youtu.be/H_UXkj9Nmoc


SUMMARY The archetypal body plan of conchiferan molluscs is characterized by an external calcareous shell, though internalization of shells has evolved independently in a number of molluscan clades, including gastropod families. In gastropods, the developmental process of torsion is regarded as a hallmark that is associated with a new anatomical configuration. This configuration is present in extant prosobranch gastropod species, which predominantly bear external shells. Here, we show that short‐term exposure to platinum during development uncouples at least two of the processes associated with torsion of the freshwater snail Marisa cornuarietis. That is, the anus of the treated snails is located anteriorly, but the gill and the designated mantle tissue remains in a posterior location, thus preventing the formation of an external shell. In contrast to the prosobranchian archetype, platinum treatment results in the formation of a posterior gill and a cone‐shaped internal shell, which persists across the lifetime. This first finding of artificially induced snail‐slug conversion was also seen in the pulmonate snail Planorbarius corneus and demonstrates that selective alteration of embryonic key processes can result in fundamental changes of an existing body plan and—if altered regulation is inherited—may give rise to a new one.


The principal objective is to quantify the responses of the understory plant community to fire and fire surrogate treatments, specifically plant species composition, foliar cover, species richness, diversity, and evenness changes resulting from (1) fire exclusion in the untreated control, (2) prescribed fire, (3) thinning, (4) thinning plus prescribed fire, and (5) herbicide plus prescribed fire. The study should identify the individual species and groups of plants that are most affected (both positively and negatively) by the experimental treatments. The most effective treatments for mitigating the wildfire hazard and restoring the natural structure and function of longleaf pine forests appear to be the thinning+fire treatments. Both are very effective in rapidly establishing the appropriate stand architecture that then facilitates the safe application of periodic surface fires to achieve and maintain overall forest health. Application of these two treatments also enhances habitat quality by promoting the re-establishment and expansion of native grasses and forbs in the understory plant community. The only noteworthy disadvantage of the herbicide+fire treatment is the decline in understory plants during the period immediately following herbicide application. Fortunately, these resilient ecosystems rapidly recover from this transitory impact. Although the fire treatment is also of some value, it produces results that appear to be less consistently beneficial across the full range of plant groups. While thinning was thought to perhaps serve as a surrogate for prescribed fire, it is now recognized that its effects and benefits are ephemeral and easily lost once woody vegetation regrows to occupy an even greater proportion of the site. Thus, thinning that is not rapidly followed up (in perhaps no more than one year) with prescribed fire is of little value in mitigating wildfire danger or contributing to the aims of ecological restoration.


Focusing on Bram Stoker's Dracula (1897) and Henry James's In the Cage (1898), this paper examines the eroticising of the female typist and telegraphist during the fin de siecle and the linkages between female sexuality and the female labourer's textual productions. I aim to trouble the easy connections made by theorists such as Friedrich Kittler between the advent of the typewriter and female emancipation. To conjoin the two unproblematically is to overlook the ways in which such female figures are erotically staged when working. Both Dracula and In the Cage highlight this relationship, as well as the intersections between the female worker and her roles as wife and mother. This paper also suggests a reading of the typist and telegraphist as new types of authors, and concludes by examining the multifarious ways in which the female worker's body is presented in both texts in relation to their writing machines.


ABSTRACT What causes variation in the foreign policies of U.S. allies regarding their desired U.S. military role in their region and their troop commitments to U.S. military interventions? This paper addresses this question through documenting and explaining the sources of variation in Australia's foreign policies regarding these issues over four decades. Treating the two major political parties in Australia and their respective leaders who self-select into them as endogenous, the paper argues that Australian foreign policy, whilst always supportive of the U.S. alliance, has systematically varied. This variation has correlated with the political party in power while the late Cold War and post-Cold War balances of power remained constant. While the Labor party has only been willing to send combat troops to large U.S. military interventions when the latter have a supporting United Nations Security Council Resolution, the conservative Liberal party has been willing to military intervene without this multilateral support. The Labor party, unlike the Liberal party, has also frequently proposed the formation and consolidation of multilateral regional institutions. These preferences render the U.S. to have been necessary for the Labor Party but sufficient for the Liberal party. Future Sino-U.S. armed conflict would provide a harder test of these hypotheses.


This book completes a trilogy which started in 1973 with Jesus the Jew and continued ten years later with the appearance of Jesus and the World of Judaism, by a leading Jewish expert on the history and literature of Jesus' time whose name is especially associated with work on the Dead Sea Scrolls. Like its predecessors, it is one man's reading of the Synoptic Gospels of Mark, Matthew and Luke. It does not offer a survey of scholarly views or a discussion of competing theories but focusses on the New Testament material and what can be understood from it. It is primarily addressed to readers whose expertise lies outside the Bible, the New Testament and theology, namely those interested in ancient religions, history and culture, and especially in Judaism, though of course biblical scholars and theologians will find much that is fascinating in it. Christians ignorant or unconcerned about the historical reality behind their faith may, however, find many of its pages, and above all the final chapter, disturbing. For Professor Vermes argues that Jesus, enthusiastic herald of the imminent Kingdom of God, could not have entertained the idea of founding and setting into motion an organized society intended to endure for. ages to come. He died in despair, with his heart broken, for having done the wrong thing in the wrong place at the wrong time. The genuine message of Jesus confronts Christianity with its greatest challenge and at the same time constitutes a powerful appeal to those outside the fold of organized religion. Geza Vermes is a Fellow of the British Acad6my and Professor Emeritus of Jewish Studies in the University of Oxford.


This review estimated the effectiveness of behavior change interventions to increase physical activity (PA) among rural adult cancer survivors. PubMed Medline, CINAHL, and PsychINFO were systematically searched through July 2020. Two independent investigators screened citations to identify studies to increase PA in adults residing in rural areas who had received any cancer diagnosis. Meta-analyses were conducted to assess proportion of participants achieving PA goal, paired mean difference (MD) in aerobic PA and strength training, and retention from baseline to post-intervention. Seven studies met inclusion criteria encompassing a total of 722 participants (591 in intervention and 131 controls). Overall quality of evidence was low to medium. The pooled proportion of participants achieving PA goals (150–225 min/wk) was 39% [95% confidence interval (CI), 18%–62%]. The mean time spent engaging in aerobic PA increased from baseline to post-intervention (range, 6–52 weeks) by 97.7 min/wk (95% CI, 75.0–120.4), and the MD in time spent on strength training was 12.2 min/wk (95% CI, −8.3–32.8). The pooled retention rate was 82% (95% CI, 69%–92%) at 6 to 78 weeks. Because of the modest intervention effects, low quality of evidence, and small number of studies, further rigorously designed behavior change interventions, including randomized controlled trials with long-term follow up, are needed to confirm efficacy for increasing PA in rural cancer survivors and to test innovative implementation strategies to enhance reach and effectiveness.


To confront the philosophical system of Rene Descartes is to contemplate a magnificently laid out map of human cognitive endeavour. In following Descartes arguments, the reader is drawn into some of the most fundamental and challenging issues in all of philosophy. In this dictionary, John Cottingham presents an alphabetied guide to this most stimulating and widely-studied of philosophers. He examines the key concepts and ideas in Cartesian thought and places them in the context both of the seventeenth-century intellectual climate and of subsequent interpretation. The entries range over a wide variety of areas including cosmology, physics, theology, psychology and ethics. The book is designed to appeal to the newcomer to Descartes, whether student or general reader, while also providing detailed critical comment and precise textual references for the more advanced reader. Also included are a general introduction describing Descartes' life and works, and bibliographic guide to the Cartesian texts and the mass of interpretative literature on Descartes.


Abstract Background Candidemia and Clostridium difficile infection (CDI) are two common healthcare-associated infections (HAIs) and share risk factors such as antibiotic use and prolonged hospitalization. CDI and CDI treatment disrupt gut microbial diversity, allowing Candida overgrowth and translocation to the bloodstream. We describe CDI co-infection among patients with candidemia. Methods Population-based surveillance for candidemia was conducted through CDC's Emerging Infections Program during 2014–2016. A case of candidemia was defined as a blood culture positive for Candida species collected from a surveillance area resident. Demographic and medical information, including occurrence of CDI was collected. We defined co-infection as CDI within 90 days of candidemia and performed bivariable analysis to assess factors associated with co-infection. Results Among 2129 cases of candidemia, 190 (9%) had CDI co-infection; 116 (5%) had CDI in the 90 days before candidemia (median: 10 days) and 60 (3%) had CDI following candidemia (median: 8 days). The median age of those with CDI-candidemia co-infection was 61 years and 100 (53%) were male. Compared with candidemia alone, the odds of CDI-candidemia co-infection was significantly greater for patients of black race (OR 1.41, 95% CI 1.05–1.90), those with diabetes (OR 1.68, 1.24–2.27), pancreatitis (OR 1.91, 1.01–3.61), or solid organ transplant (OR 4.15, 2.09–8.22). Those with co-infection had higher odds of certain healthcare exposures: hemodialysis (OR 2.27, 1.57–3.28), hospital stay in the past 90 days (OR 1.9, 1.37–2.64), ICU admission in the past 14 days (OR 1.78, 1.20–2.66), and central venous catheter (CVC) at the time of candidemia (OR 1.71, 1.19–2.46). There were no significant differences in 30-day mortality or in type of Candida species, although C. parapsilosis was less common in the co-infection group (8% vs. 13%). Conclusion Nearly one in ten patients with candidemia also had CDI co-infection. Black race, certain underlying conditions, hemodialysis, previous hospitalization, ICU stay, and the presence of a CVC were associated with co-infection. Clinicians should be vigilant for coinfection of CDI and candidemia, particularly in situations with associated risk factors. Disclosures W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee


I. INTRODUCTION Today's appellate courts are being called upon to carry out their responsibilities with fewer and fewer resources. To attack their backlogs and still maintain the quality of published decisions, courts have adopted expedited dockets and other fast-track procedures. Until December 2000, the New Hampshire Supreme Court had no expedited docket. Litigants in New Hampshire appeal to the state supreme court by certiorari, not by right. (1) The five justices, however, review each case individually before they meet to determine whether the case will be accepted for briefing and further review or whether the trial court decision should stand. Regular screening meetings are scheduled each month at which justices discuss the cases. Any justice disqualified leaves the room while that case is discussed. All felony convictions are accepted for full briefing, and most are scheduled for full oral argument. Except by unanimous vote of the justices screening the case with at least three justices participating, no other case is declined. A case is accepted if one judge believes it should be. No case is declined for lack of resources or lack of time to consider the issues presented. II. THE 3JX DOCKET In December 2000, the supreme court instituted a three-judge expedited docket, referred to as the "3JX" docket. (2) The three-judge panels alternate from month to month, and the judges on each panel are not disclosed until oral argument, to eliminate the temptation to judge shop. Cases for the first 3JX dockets were initially selected from pending cases, but the court now identifies, at the time of screening, cases appropriate for future expedited dockets. In 2001, 358 of the 766 cases appealed were accepted by the court for full briefing and oral argument. Ninety-seven of those cases were decided by three-justice panels following argument on the 3JX docket. Even though the docket is expedited, the three justices read all the briefs and conduct the usual conference following the oral argument. Decisions must be unanimous, and a written decision is issued in each case. (3) In addition, the court has established a goal of issuing decisions in these cases within two to three weeks of argument. This goal is realistic because it is not necessary to put each order through the formal process that a full decision requires. Finally, 3JX decisions are not published and do not carry precedential value. If the three justices cannot reach a unanimous decision on all the issues, they may order the parties to file additional briefs. Alternatively, they may decide some issues and order reargument before the full court of other issues or the entire case. While it might be ideal for the supreme court to write a full decision in every case accepted for argument, there are many cases which lend themselves to decision by this expedited procedure. By court rule, with consent of the parties, the three-judge panel may recommend to the full court that a published opinion be issued in the case. (4) If the court accepts the referral, the two justices not on the panel may participate in the opinion by reading the briefs and listening to the tapes of oral argument. (5) The rule establishes criteria for selection of cases for the 3JX docket, including but not limited to appeals: * involving claims of error in the application of settled law; * claiming an unsustainable exercise of discretion where the law governing that discretion is settled; [or] * claiming insufficient evidence or a result against the weight of the evidence. (6) The court rule also provides several significant features. Counsel are limited to five minutes of uninterrupted oral argument, supplemented by whatever time is necessary for counsel to answer questions from the justices, rather than the usual fifteen minutes. (7) This change allows the court to schedule up to twelve cases on a single day. …


In the regulatory state, agency leaders face a fundamental choice: should they "consume" or should they "invest?" "Consume" means launching high profile cases and rule-making. "Invest" means developing and nurturing the necessary infrastructure for the agency to handle whatever the future may bring. The former brings headlines, while the latter will be completely ignored. Unsurprisingly, consumption is routinely prioritized, and investment is deferred, downgraded, or overlooked entirely. This essay outlines the incentives for agency leadership to behave in this way and explores the resulting agency costs (pun intended). The U.S. Federal Trade Commission's health care portfolio provides a useful case study of how one agency managed and minimized these costs. Our essay concludes with several proposals that should help encourage agency leadership to strike a better balance between consumption and investment.


Three earthquake sequences, each with two main earthquakes of almost the same magnitudes (ML from 5.9 to 7.0 with differences less than 0.1), have recently been observed in Taiwan. The two largest earthquakes in each sequence occurred with a short delay time between them, were strikingly similar in terms of magnitude, location and/or focal mechanism and are referred to as doublets. They were markedly distinct from typical single mainshock sequences. Our estimated static stress field generated by the first shock in the doublet shows that the second shock and most of their aftershocks were located within a region where static stress increased substantially. Thus, a possible explanation for earthquake doublet is that seismic energy for each shock had accumulated independently within adjacent crustal volumes, separated by an asperity, and that the second shock is triggered by the increased static stress after the first one. An important implication of doublet sequence is that works by emergency response teams after the first earthquake could be made more hazardous by the second.


The winemaking industry produces large volumes of wastewater that pose an environmental threat if not treated correctly. The increasing numbers of wineries and the demand for wine around the world are adding to the growing problem. The vinification process includes all steps of the winemaking process, from the receipt of grapes to the final packaged product in the bottle. To fully understand all the aspects of winery wastewater it is important to know the winemaking processes before considering possible treatments. Winemaking is seen as an art and all wineries are individual, hence treatment solutions should be different. Furthermore, wastewater also differs from one winery to another regarding its volume and composition and therefore is it vital for a detailed characterisation of the wastewater to fully understand the problem before managing it. However, prevention is better than cure. There are a number of winemaking practices that can help lower the volume of the wastewater produced to decrease the work load of the treatment system and increase the efficiency of treatment.


Background Several intravascular diagnostic techniques provide detailed information regarding the narrowing (stenosis) of the lumen of coronary arteries. They are increasingly used in addition to angiography during coronary artery stenting. Purpose To systematically review the comparative effectiveness of intravascular diagnostic techniques versus angiography alone in patients with coronary artery disease who are undergoing percutaneous coronary interventions for the following objectives: (a) to decide whether a coronary lesion needs to be stented; (b) to guide and optimize stent deployment; (c) to assess whether stent placement was successful; and (d) to evaluate the factors influencing the diagnostic techniques' effect on outcomes. Data sources MEDLINE®, Cochrane Central Register of Controlled Trials, recent conference proceedings, and ClinicalTrials.gov . Study selection We included studies of any design and duration of followup, without any language or sample size restriction. We excluded studies that did not directly compare the use of an intravascular diagnostic technique with angiography alone or another intravascular diagnostic technique to decide whether to stent or to guide coronary artery stenting. Data extraction We extracted details on study population characteristics and results, and assessed studies for risk of bias. We evaluated therapeutic decisionmaking outcomes, intermediate outcomes, and patient-centered outcomes. We appraised strength of evidence primarily based on studies rated as having a low or medium risk of bias. Data synthesis In total, 37 eligible studies evaluated two of the intravascular diagnostic techniques, namely fractional flow reserve (FFR) and intravascular ultrasound (IVUS). There is a moderate strength of evidence (drawn from one randomized controlled trial [RCT] and one nonrandomized study) that the use of FFR, as compared with angiography alone, supports the following: (a) FFR is effective in helping to decide whether intermediate coronary lesions (defined as 50% to 70% stenosis) require stenting; (b) FFR confers a lower risk of the composite endpoint of death or myocardial infarction (MI) or of major adverse cardiac events; and (c) FFR leads to fewer stents implanted and reduces the cost of the procedure. Regarding the comparison of IVUS-guided stenting and stent placement guided by angiography alone, there is a moderate strength of evidence (drawn from 9 RCTs and 22 nonrandomized studies) that supports no significant difference between the two approaches in mortality or MI, but a significant reduction in repeat revascularizations and restenosis with IVUS-guided stenting. There is insufficient evidence concerning the use of intravascular diagnostic techniques immediately after percutaneous coronary interventions to evaluate the success of stenting compared with angiography or for direct comparisons between intravascular diagnostic techniques. There is a moderate strength of evidence (on the basis of one large nonrandomized study) that sex, diabetes mellitus status, lesion length, and reference diameter among those undergoing IVUS- and angiography-guided stent placement had no significant association with major adverse cardiac events or its individual components. There is insufficient evidence to evaluate the comparative effect of intravascular diagnostic techniques other than FFR and IVUS. Limitations Studies evaluating FFR and IVUS were limited by incomplete outcome reporting, heterogeneity in outcome definitions, infrequent enrollment of women, and a lack of data on patients with left main coronary artery disease or acute MI. The evidence for FFR was derived from trials that focused on patients with lower grade angina or those with nonischemic intermediate coronary stenosis. The majority of the IVUS trials were conducted before 2000, a particularly important limitation given the rapid pace of technological advancement in this domain. Conclusions There is a moderate strength of evidence that the use of FFR (as compared with angiography alone) to decide whether or not to stent an intermediate coronary lesion confers a lower risk of composite endpoint of death or MI, or of major adverse cardiac events; leads to fewer stents being implanted; and reduces procedural costs. There is a moderate strength of evidence that the use of IVUS (as compared with angiography alone) to guide optimal stent placement reduces repeat revascularization and restenosis, but does not affect mortality or MI. Future studies will need to focus on women and on patients with more severe coronary artery disease, and to evaluate longer term (on the order of years) patient outcomes to better appreciate real world effectiveness. Stenting low-risk lesions may lead to additional invasive tests or treatments that could adversely impact long-term outcomes. Further research is also needed to evaluate the use of hybrid and novel intravascular diagnostic techniques.


Excised castor bean ('Ricinus communis' L) endosperm tissue supplied with (14 C) galactose or (14 C) mannose incorporated radioactivity into particulate cell components. The protein constituents of these organelles, when separated electrophoretically, contain radioactive sugars. That these organellar proteins contain bound carbohydrate was confirmed using gas liquid chromatography of the cleaved sugars. Three of the sugars detected, mannose, N-acetyl glucosamine and galactose, were found to be incorporated into glycoprotein via lipid-linked intermediates. Mannose is transferred from GDP mannose to an oligo saccharide-lipid via dolicol monophosphate mannose, this oligo saccharide is composed of both mannose and N-acetyl glucosamine, which is itself donated from the nucleotide-sugar via a lipid disaccharide. Oligo saccharide is then transferred from the lipid carrier to a nascent polypeptide acceptor en bloc. Galactose is added to previously core glycosylated protein via a lipid-linked intermediate in monosaccharide units. Although all enzymes catalysing these steps are exclusively housed in the endoplasmic reticulum (ER), glycoprotein products do not accumulate in the ER, but are exported to other parts of the cell, in particular the glyoxysome. The importance of post-translational glycosylation with respect to protein segregation and membrane assembly is discussed..


Chapter I presents an overview of mass spectrometry on double focusing instruments. Special attention is paid to ionisation methods which may be of use in mixture analysis.

In chapter II, following a brief introduction to chemometrics, results of the application of factor analysis to the problem of determining the components of a mixture from mass spectra of simple mixtures are given. After applying the technique to simulated data, the results of applying the technique to simple mixtures and to the deconvolution of overlapping GC/MC spectra are given. It is concluded that provided the pure compounds have 'unique' peaks in their mass spectra, and that the statistical variations in the intensities of peaks due to different mixtures are not correlated, then the technique will yield good results.

Chapter III deals with the application of CI techniques and factor analysis to the analysis of engine oils.

Attempts to use the factor analysis technique to yield a meaningful 'type' analysis of engine oil fractions was not successful.

The use of proton transfer reagents and charge transfer reagents for CI spectra of engine oil fractions was also unsuccessful. It is concluded that the complexity of engine oil mixtures and the chemical similarity of the constituent molecules makes them difficult to differentiate by CI mass spectrometry.

In the final chapter, details are gave of an investigation into the use of CI mass spectrometry and FAB mass spectrometry for the analysis of engine oil additives. The additives studied were calcium 2,2'-bis (4-alkylphenyl) sulphides.

The FAB mass spectrometry of these sulphurised phenates gave poor results with glycerol, triethanolamine, triethanolamine / sodium sulphate or squalane used as FAB matrix.

Of the CI techniques used, electron capture ionisation of the hydrolysed sample gave the most promising results. The molecular ion peak intensities were higher than those encountered in the EI spectra. In addition, the fragmentation in the EC spectra was simpler than the fragmentation in the EI spectrum.

Metastable ion studies of the EI and EC spectra of the sulphurised phenols, using the technique of metastable mapping, gave some useful results, but the poor mass resolving power and the long run times were a major drawback. It is concluded that the technique of metastable mapping is of no use where mass resolution is important, and the use of inlet systems, such as an AGHIS, which allow long sample lifetimes is recommended.

Where possible, the use of tandem mass spectrometry or Fourier transform mass spectrometry for metastable ion studies for mixture analysis, is also recommended.


OBJECTIVE
To assess agreement and trending ability of transpulmonary thermodilution (TPTD), calibrated pulse contour (PiCCO), and pulse power (PulseCO) methods compared to pulmonary artery thermodilution (PATD) for determination of cardiac output (CO) in anesthetized dogs.

DESIGN
Experimental, prospective study.

SETTING
University teaching hospital.

ANIMALS
Six adult Beagle dogs.

INTERVENTIONS
Dogs were anesthetized with sevoflurane and instrumented with pulmonary and femoral artery thermodilution catheters. CO was measured at baseline and at 5, 15, 30, 45, 60, 120, 180, and 240 minutes after IV administration of ketamine or s-ketamine. Baseline PATD and TPTD calibrated PulseCO and PiCCO, respectively. Agreement and trending ability was analyzed with Bland-Altman, concordance, and polar plot methodology.

MEASUREMENTS AND MAIN RESULTS
Median (range) CO values of 2.27 (0.98-3.4) L/min were measured with PATD, and 2.8 (1.9-4.04) L/min with TPTD, which resulted in a mean bias (± standard deviation) of -0.66 (± 0.36) L/min. Concordance rate was 91% and radial limits of agreement (RLOA) were ±35°. PATD against PiCCO resulted in a mean bias of -0.71 (± 0.62) L/min and PATD against PulseCO in a mean bias of 0.13 (± 0.46) L/min. The continuous techniques resulted in concordance rates of 77% for PATD-PiCCO and 74% for PATD-PulseCO and RLOA of ±57° and ±60°, respectively.

CONCLUSIONS
Intermittent TPTD showed marginal trending ability, while continuous pulse contour and pulse power methods showed poor trending ability over a 4-hour period. The poor performance and possible side effects of the methods tested in this study suggest that they should not be recommended for use in critical patients.


Abstract:According to cross-national research, Protestantism has significantly contributed to global democratization. While Protestantism does not inevitably cause democratization, it often generates social dynamics that favor it. Some of the most important of these are: 1) the rise of religious pluralism; 2) the development of democratic theory and practice; 3) the development of civil society; 4) the spread of mass education; 5) printing and the origins of a public sphere; 6) the reduction of corruption; and 7) economic development. The article explores how Protestant groups, including Protestant missionaries, have promoted these dynamics in the past. It also argues that contemporary Protestant movements—particularly Pentecostalism—are continuing to do so in the present, though with less dramatic results.


Are bodies sexy? How? In what sorts of ways? Sexy Bodies investigates the production of sexual bodies and sexual practices, of sexualities which are dyke, bi, transracial, and even hetero. It celebrates lesbian and queer sexualities but also explores what runs underneath and within all sexualities, discovering what is fundamentally weird and strange about all bodies, all carnalities. Looking at a pleasurable variety of cultural forms and texts, the contributors consider the particular charms of girls and horses, from National Velvet to Marnie; discuss figures of the lesbian body from vampires to tribades to tomboys; uncover 'virtual' lesbians in the fiction of Jeanette Winterson; track desire in the music of legendary Blues singers; and investigate the ever-scrutinised and celebrated body of Elizabeth Taylor. The collection includes two important pieces of fiction by Mary Fallon and Nicole Brossard. Sexy Bodies makes new connections between and amongst bodies, cruising the borders of the obscene, the pleasurable, the desirable and the hitherto unspoken rethinking sexuality anew as deeply and strangely sexy.


The Fortress Commentary on the Bible: The New Testament presents a balanced synthesis of current scholarship, enabling readers to interpret Scripture for a complex and pluralistic world. The contributors bring a rich diversity of perspectives to the task of connecting solid historical critical analysis of Scripture with sensitivity to theological, cultural, and interpretive issues arising in our encounter with the text. The contributors represent a broad array of theological commitment - Protestants, Catholics, Jews, and others. The introductory articles and section introductions in the volume discuss the dramatic challenges that have shaped contemporary interpretation of the New Testament. Individual book articles provide an introduction and commentary on key sense units that are explored through the lenses of three critical questions: The Text in its Ancient Context. What did the text probably mean in its original historical and cultural context? The Text in the Interpretive Tradition. How have centuries of reading and interpreting shaped our understanding of the text? The Text in Contemporary Discussion. What are the unique challenges and interpretive questions the text addresses for readers and hearers today?


OBJECTIVE
To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the urinary bladder epithelium of clinically normal dogs and in transitional cell carcinoma cells of dogs.

ANIMALS
21 dogs with transitional cell carcinoma of the urinary bladder and 8 dogs with clinically normal urinary bladders.

PROCEDURE
COX-1 and COX-2 were evaluated by use of isoform-specific antibodies with standard immunohistochemical methods.

RESULT
COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs. Also, COX-1 was expressed in the neoplastic cells.

CONCLUSIONS AND CLINICAL RELEVANCE
Lack of expression of COX-2 in normal bladder epithelium and its substantial expression in transitional cell carcinoma cells suggest that this isoform may be involved in tumor cell growth. Inhibition of COX-2 is a likely mechanism of the antineoplastic effects of non steroidal antiinflammatory drugs.


Using an intertemporal model of saving and capital accumulation with two types of agents (workers and capitalists) we demonstrate that it is impossible for any binding minimum wage to increase the after-tax incomes of workers if the production function is Cobb-Douglas with constant returns to scale, or if there are no differences in ability among workers. We also show that it is not possible to increase the incomes of employed workers through minimum wage legislation, even under decreasing returns to scale and heterogeneity of ability among workers, unless the welfare support provided to unemployed workers is far below what they would earn in the absence of minimum wages. Moreover, we establish that in the absence of a separate class of agents (i.e. capitalists) minimum wages cannot increase the incomes of employed workers even when there are decreasing returns to scale and no welfare support is provided to the unemployed.


ABSTRACT The Mycobacterium avium complex (MAC) is an important group of opportunistic pathogens for birds, cattle, swine, and immunosuppressed humans. Although invasion of epithelial cells lining the intestine is the chief point of entry for these organisms, little is known about the mechanisms by which members of the MAC are taken up by these cells. Studies with M. avium have shown that cytoskeletal rearrangement via activation of the small G-protein Cdc42 is involved and that this activation is regulated in part by the M. avium fadD2 gene. The fadD2 gene indirectly regulates a number of genes upon exposure to HEp-2 cells, including transcriptional regulators, membrane proteins, and secreted proteins. Overexpression of two fadD2-associated regulators (MAV_5138 and MAV_3679) led to increased invasion of HEp-2 cells, as well as altered expression of other genes. The protein product of one of the regulated genes, named CipA, has domains that resemble the PXXP motif of human Piccolo proteins, which bind SH3 domains in proteins involved in the scaffold complex formed during cytoskeletal rearrangement. Although CipA was not detected in the cytoplasm of HEp-2 cells exposed to M. avium, the recombinant protein was shown to be potentially expressed on the surface of Mycobacterium smegmatis incubated with HEp-2 cells and, possibly, to interact with human Cdc42. The interaction was then confirmed by showing that CipA activates Cdc42. These results suggest that members of the M. avium complex have a novel mechanism for activating cytoskeletal rearrangement, prompting uptake by host epithelial cells, and that this mechanism is regulated in part by fadD2, MAV_5138, and MAV_3679.


BACKGROUND
The positive relationship between problem behaviours of children with additional complex needs and psychological distress in their caregivers has been widely evidenced. Fewer studies, however, have assessed the relationship between care recipients' problem behaviours and key physiological processes, relevant for the physical health status of their care providers. This study examined the psychological, endocrine and health corollaries of child problem behaviours in caregivers of children with autism and attention deficit hyperactivity disorder.

METHODS
Caregivers (n = 18) completed self-report measures of psychological distress, child problem behaviours and incidences of commonly occurring ailments. To capture important parameters of the basal diurnal cortisol pattern, caregivers collected saliva samples at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays.

RESULTS
Data revealed a positive relationship between caregivers' perceived levels of stress and problems with child conduct behaviours. In addition, caregivers who reported more problems with child emotional and hyperactivity behaviours displayed atypical cortisol patterns characterised by flatter diurnal cortisol slopes and reduced cortisol awakening response magnitude. Subjective reports of commonly occurring ailments were also greater in caregivers experiencing more problems with child emotional behaviours.

CONCLUSIONS
These findings have implications for interventions that aim to improve the psychophysiological well-being of the caregiver by targeting problem behaviours of the care recipient.


Hydroisomerization of long chain paraffins for the production of branched alkanes has recently been intensively studied due to a large availability of these compounds. The most interesting research topics have been the development of novel bifunctional catalysts to maximize the yield of isomers and to suppress the cracking reactions. Since both of these reactions are catalyzed by Brønsted acid sites, the optimum catalyst exhibits equal amounts of metal and acid sites, and it facilitates rapid mass transfer. Thus, several hierarchical and nano-shaped zeolites have been developed, in addition to composite catalysts containing both micro- and mesoporous phases. In addition to catalyst development, the effect of the reactant structure, optimal reaction conditions, catalyst stability and comparison of batch vs continuous operations have been made.


Pressures rippling through the universe of international development aid over the last fifteen years are transforming overseas development aid from a top-down, government-only endeavor into a multi-layered, multi-party endeavor which engages governments and citizens at every level. In addition, aid priorities now reflect the reality that global problems (such as climate change and HIV Aids) need serious attention and that developing countries need grant finance to address these problems and other problems that stem from abject poverty. For the reasons described in this Article, these changes have made overseas development aid heavily dependent on grants channeled through the World Bank (referred to, throughout this article as "World Bank grants"). This dependence poses challenges for an institution set up to provide loans, not grants, and accustomed to thinking of a grant as a form of gentleman's agreement rather than a binding commitment which may range from millions to hundreds of dollars and which, whatever the amount, reflects a host of interests and voices that clamor to be heard. These challenges set the context for this Article's inquiry. This Article begins by describing the changes that recent trends in international development aid have wrought and the reasons those changes have placed the World Bank at center stage of development grant finance. It then focuses on the legal framework governing World Bank grants. Its key inquiry is the extent to which that framework facilitates and effectuates the goals and values that development grant finance aims to achieve. The article is not about whether grants for development aid achieve their targets (for example a reduction of greenhouse gas emissions in a recipient country or in the number of Aids-related deaths), an important question but one for another day. Rather, it is about whether such grants are negotiated, agreed to and delivered in a way that promotes the inclusive, participatory and collaborative approaches that recent trends in development aid hold paramount. As a starting premise, this Article concedes that the legal framework governing development grant finance is unclear (an inevitable state of affairs given the legal of clarity surrounding the legal status of a grant in the national jurisdictions of most developed countries, and, therefore, in an international legal system built on principles drawn from them). In the face of this lack of clarity the terms of the grant agreements pursuant to which development grants are made, become the operative legal framework. And so, this Article looks to those terms to determine whether such grants comport with current thinking on optimal development approaches. But not all terms of an agreement are created equal. This Article posits that in the world of development grant finance, the key elements of a grant agreement to evaluate in order to determine whether the agreement reflects an inclusive, participatory and collaborative approach are the elements that deal with the right of the grantor to cancel or suspend a grant and the provisions that apply when things go, or appear to have gone, wrong; namely the dispute resolution arrangements. The grantor is always in a position of power; dispute resolutions arrangements set the parameters within which such power may be exercised. For this reason, this Article examines the dispute resolution arrangements in World Bank grant agreements. That examination reveals that World Bank grant agreements reflect a top-down, take it or leave it relationship that does not promote or facilitate inclusion, participation and grantor/grantee collaboration. This Article concludes with some suggestions for the principles that should guide the redress of these deficiencies and the re-design of the dispute resolution arrangements that is required.


The justification of psychiatric specialization among undergraduate nursing students is examined. The data highlight how students are able to produce a positive view of their initial entry into nursing and then later create a positive and distinctive specialist occupational identity through negative comparisons with general nursing. Their experience in both psychiatric and general settings is drawn upon to add credibility to their claims. Contrasts based on the work schedules, patient focus, professional autonomy, opportunity for professional development, and required skills are considered.


Background and aims : More than 40 percent of deaths of pedestrians in traffic accidents happen in Tehran. The aim of this study was to determine the impact of human factors was associated with an increased intensity of pedestrian traffic. Methods : In this cross-sectional study, 6323 traffic injuries and 99 traffic deaths resulted from traffic accidents in pedestrian during 2013 in Tehran were investigated. Data was extracted from traffic police databases and in Tehran. In analytical analysis, logistic regression model was used to control for possible confounders Results : In studied accidents, 4070 (63.5%) and 2335 (36.5%) of injured or died pedestrians were male and female, respectively. The mean age of injured pedestrians was 39.15±19.47 years and the mean age of guilty drivers was 34.75±12.38 years. The final model showed that gender, age, pedestrian position and fault, and type of driver's license are correlated to the dependent variable. The events leading to the death was significantly higher in men, pedestrians standing next to the roadway, pedestrians fault and drivers with grade 1 of driver license. Conclusion : Human factors had much role in the severity of traffic accidents related to pedestrians in Tehran. These factors have a high correlation with environmental factors, and vehicles. More researches is needed to specifying mechanisms of effect of these factors in traffic accidents related to the pedestrians and designing strategies for promotion of traffic culture and safe behaviors in drivers and pedestrians.


Agricultural systems are geographically extensive, have profound significance to society, and affect regional energy, climate, and water cycles. Since most suitable lands worldwide have been cultivated, there is a growing pressure to increase yields on existing agricultural lands. In tropical and subtropical regions, multicropping is widely used to increase food production, but regional-to-global information related to multicropping practices is poor. The high temporal resolution and moderate spatial resolution of the MODIS sensors provide an ideal source of information for characterizing cropping practices over large areas. Relative to studies that document agricultural extensification, however, systematic assessment of agricultural intensification via multicropping has received relatively little attention. The goal of this work was to help close this information gap by developing methods that use multitemporal remote sensing to map multicropping systems in Asia. Image time-series analysis is especially challenging in this part of the world because atmospheric conditions including clouds and aerosols lead to high frequencies of missing or low-quality observations, especially during the Asian Monsoon. The methodology that we developed builds upon the algorithm used to produce the MODIS Land Cover Dynamics product (MCD12Q2), but uses an improved methodology optimized for crops. We assessed our results at the aggregate scale using state, district, and provincial level inventory statistics reporting total cropped and harvested areas, and at the field scale using survey results for 191 field sites in Bangladesh. While the algorithm highlighted the dominant continental-scale patterns in agricultural practices throughout Asia, and produced reasonable estimates of state and provincial level total harvested areas, field-scale assessment revealed significant challenges in mapping high cropping intensity due to abundant missing data.


Formulating nanoparticle based cosmetics with medicinal values to protect skin from environmental stress is a challenging task nowadays. In our work, we have prepared an emulsion of bluish pigmented cerium oxide nanoparticles (nanoceria) with potent free radical scavenging activity. The nanoceria were prepared by conventional thermal decomposition, and encapsulated by the amine-containing polyethylenimine. Characterizations such as Nuclear Magnetic Resonances (NMR), Dynamic Light Scattering (DLS), Atomic Force Microscope (AFM), Transmission Electron Micrographs (TEM) and X-ray Diffractograms (XRD) showed that the nanoceria were near spherical, monodispersed and sized 3–10 nm. UV-vis analysis confirmed that the particles were pigmented whereas circular dichroism revealed that the secondary structure of collagen, a fibrillar protein present in skin, was not affected by the presence of these pigmented nanoceria. In vitro anti-oxidant assays showed that the pigmented nanoceria were more effective than non-pigmented nanoceria against nitrile and peroxy radicals, with their activity depending on the concentration of CeO2. Thus, the emulsion of pigmented nanoceria can be evaluated, in future, as a medicinal cosmetic for protecting the skin.


During a recent expedition to the Burgers Mountains and Mt. Kegum, Papua New Guinea, several collections were made of a Vaccinium that appeared to be undescribed. With Sleumer's revision (1967) the new Vaccinium keys out to the section Oarianthe Schltr. and then to V. oranjense J. J. S. (p. 767, lead 41). It may be fitted in the key as follows: 41. Leaves coriaceous and ± stiff, margin markedly revolute. — Corolla ventricose-urceolate or ovoid-globose, (6 —)6.5— 10 by 5-8 mm O. 41a. Small epiphyte or terrestrial, then creeping and ascending to 10 cm with rooting branchlets. Leaves when dry white-glaucous above, veins and veinlets obscure. Calyx distinctly lobed to nearly its base. Corolla pale pink to red, ventricose-urceolate, 5 — 6 mm O. Filaments laxly long-hairy below. Anthers with an obliquely transverse pore. Mt. Wilhelmina. 58. V. oranjense var. oranjense 41a. Sizable sprawling shrub, epiphytic or terrestrial, c. 2 m high, branchlets not rooting. Leaves when dry glossy dark green above, beneath with raised midrib and less distinct veins. Calyx at first shortly lobed, soon salvershaped and inconspicuously dentate. Corolla pinkish purple to purple, ovoid-globose, 6 — 8 mm O. Filaments adaxially long-hairy over their entire length. Anthers with a transverse terminal pore. Burgers Mountains, Mt. Kegum V. altiterrae 41. Leaves chartaceous to subcoriaceous, margin flat or but slightly revolute. — Leaves beneath generally with visibly raised veins and veinlets. (to 42.).


Antibiotics or antibacterial are a type of antimicrobial drug. Used to treat infections caused by germs (bacteria and certain parasites).They may either kill or inhibit the growth of those organism. Several types of antibiotics also possess antiprotozoal activity. In each year all over the world, millions of patients become infected with bacteria that are resistant to antibiotics and thousands of people die each year as a direct result of these infections. Prompting the researchers to find new antibiotics to confrontation like this challenge. So for the first time in this project we evaluate the effect of New complexes of VO +2 , Co +2 , Ni +2 , Cu +2 and Ag + with 1-benzylbenzimidazole (Bbz) were synthesized by reaction of the ligand with suitable metal sources against several selected human pathogenic bacterial species for both Gram-positive ( + v e) and negative ( v e) bacteria isolated from surgical wounds. By using of disk diffusion technique our findings demonstrated that New complexes of VO +2 , Co +2 , Ni +2 , Cu +2 and Ag + with 1-benzylbenzimidazole (Bbz) showed inhibition for both Gram-positive ( + v e) and negative ( v e) bacteria but varying effects of each compound.


Extension estimates based on palinspastic restoration of only the largest faults in a deformed terrane may be significantly deficient due to neglect of "small" faults (i.e., unsampled faults, most of which have smaller displacements than do sampled faults). Small faults individually account for little extension, but there may be large numbers of them. The cumulative extension on small faults can be calculated from the fractal size distributions of fault displacements. Independent extension estimates support the inference from fault population statistics that small faults account for significant amounts of extension. For example, restorations of Mesozoic faults interpreted from seismic reflection profiles across the Viking graben in the North Sea yield extension estimates that are only 40%-75% of independent estimates. The fractal size distribution of fault displacements in the Viking graben is consistent with the hypothesis that the remaining 25%-60% of extension resulted from displacements on small faults.


This work discusses how a flexible body formalism, specifically, the Absolute Nodal Coordinate Formulation (ANCF), is combined with the Discrete Element Method (DEM) and the Newmark implicit integration method to address many-body dynamics problems; i.e., problems with hundreds of thousands of rigid and deformable bodies. DEM is used to model friction and contact between elements, while the Newmark implicit integration method allows constraints to be created between nodes and allows for large integration time steps. Since the computational effort associated with these problems is significant, the analytical framework is implemented to leverage the computational power available on the Graphical Processing Unit (GPU) cards. The developed code is validated against existing commercial and research finite element analysis software and its efficiency is compared against that of a serial implementation. Several applications are simulated to demonstrate the capabilities of the implementation.


In recent years, there has been growing interest in a range of transport policy initiatives which are
now widely described as 'soft measures'. Soft measures usually seek to give better information and
opportunities which affect the free choices made by individuals, mostly by facilitating attractive,
relatively uncontroversial, and relatively cheap alternatives. They include initiatives such as school
and workplace travel plans, personalised journey planning, car clubs, public transport information
and marketing and teleworking.
This paper will provide an overview of the evidence for a recent DfT study of soft factors (Cairns et
al 2004) which concluded that 'sufficient evidence now exists to have confidence that soft factor
interventions can have a significant effect on individual travel choices'. Indeed, the headline finding
of the review is that, 'given a fair wind from national and local government policy, and a serious but
not unrealistic commitment of effort, the voluntary changes in car use brought about by soft
measures could amount to a reduction in the order of 11% of traffic at the national level'.
Projections for peak period traffic reduction at the local level ranged between 14% and 21%.
The evidence used to inform these conclusions will be outlined in this paper. The paper will then
outline the projections of the impacts of soft factors and address the following:
- How much do soft factors cost and what value of money do they represent?
- Are soft measures introduced in combination greater than the sum of their parts?
- What constitutes a 'supportive policy environment' for soft factors?
Finally some conclusions will be drawn as to whether soft factors are indeed a 'softer option' and,
in the light of the evidence, what role they have in transport policy in the future.


Electronic ballast is basically a choke without a starter. It is a device used for stabilizing current in an electric circuit i.e. in a tube lamp supply circuit. It provides just the required amount of voltage to start the lamp by regulating the current. It is made to replace the conventional choke in fluorescent lamps as it has more advantage in lifetime operation. It has higher efficiency since it uses the power semiconductor devices with better switching methods. The main component is Ballast Controller IC IR2156. Also, PFC IC L6562 is used to manage the power factor correction while achieving high efficiency over a wide load range. Electronic Ballast, in short, is a device made to increase efficiency, thereby reducing electricity bill. There have been other projects made related to Electronic ballast but without the use of Ballast Control IC. By using IC IR2156, the efficiency can be increased greatly. The ballast being made is primarily for T8 40W tube.


Context: Spinal anesthesia is a time-tested method for orthopedic surgeries of the lower limb while peripheral nerve block is a comparatively newer method and still under controversy. Aims: The aim of this study was to compare efficacy of spinal bupivacaine and fentanyl with combined lumbar plexus and sciatic nerve block in lower limb orthopedic procedures. Settings and Design: A randomized single-blinded prospective study conducted at orthopedic operation theater and perioperative area. Subjects and Methods: Sixty patients were randomly allocated into two groups, Group A received spinal anesthesia with 12.5 mg bupivacaine and 25 μg fentanyl, Group B received lumbar plexus block with 30 ml (0.25%) bupivacaine and sciatic nerve block with 25 ml (0.25%) bupivacaine. In Group B, three patients were converted to general anesthesia due to failure of development of block. In postoperative period, visual analog scale (VAS) score was assessed, and pethidine was used as rescue analgesic. Statistical Analysis Used: IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY, USA). Results: Faster onset of sensory and motor block was found in Group A. In the intraoperative period, incidence of hypotension and bradycardia was found to be higher in Group A although statistically insignificant. In the postoperative period, the VAS score difference between the two groups was found to be significantly higher in Group B till 6 h postoperative. The total duration of analgesia was significantly higher in Group B (690.00 ± 108.344 min) than in Group A (264.67 ± 25.962 min). The total dose of analgesic required in first 24 h was significantly less in Group B (200.00 ± 57.17 mg) than in Group A (371.67 ± 28.416 mg). Conclusion: Combination of lumbar plexus and sciatic nerve block provided effective unilateral analgesia for a prolonged time into the postoperative period.


In liberal thought, slavery is imagined as reducing the human being to nothing but a body, while the free and equal political subjects of modern liberal democracies are held to be abstract, universal and disembodied individuals. In theory, bodies are also unimportant in the wage labour exchange. Though traditional models of worker citizenship insist on state and employers' duty to protect the human worth of worker citizens, they also assume the disembodied, thing-like nature of commodified labour power. Because bodies are so obviously important in the exchange between prostitute and customer, sex work is difficult to reconcile with liberal fictions of disembodiment, and one strand of feminist debate on prostitution is preoccupied by the question of whether prostitutes are like slaves or wage labourers. Protagonists on both sides of this debate often reproduce liberal understandings of labour power as a 'thing' that can be detached from the person. And yet labour power is also a contested commodity, and wage labour has historically been likened to slavery by activists struggling against the commodification of labour power. This article argues that stepping outside liberal fictions of disembodiment and recognising the parallels between prostitution, wage labour and slavery would allow greater scope for establishing a common political subjectivity amongst prostitutes, other wage workers and all those who have an interest in halting and reversing the current global trend towards the commodification of everything. In this way, common political ground between prostitutes and other wage workers is more visible when we step outside liberal assumptions about embodiment, slavery, work and citizenship.


The Jarbidge Mountains are a remote and little-visited desert mountain range at the northern edge of the Great Basin in Elko County, NV, 110 km north of Elko and 115 km southwest of Twin Falls, ID. The forest is dominated by subalpine fir (Abies lasiocarpa) at lower elevations and whitebark pine (Pinus albicaulis) at higher elevations; limber pine (P. flexilis) occurs along streams in canyons at lower elevations (2). P. albicaulis and P. flexilis are hosts for the blister rust fungus, Cronartium ribicola. In the late 1990s, a survey across the Intermountain West reported no evidence of C. ribicola in the Jarbidge Mountains or elsewhere in the central Great Basin (3). However, unpublished observations by D. A. Charlet in 1988 and 2001 indicate that blister rust has been present in the Jarbidge Mountains for at least 16 years. In September 2002, D. R. Vogler visited the Jarbidge Mountains over a 2-week period, examining whitebark pines along the unpaved route through the Humboldt-Toiyabe National Forest connecting Highway 225 and Jarbidge, NV. Blister rust-infected whitebark were found in two locations: (i) Coon Creek Summit (2,575 m elevation), atop the divide between the Great Basin to the south and the Columbia Plateau to the north, and (ii) Bear Creek drainage (2,315 to 2,405 m elevation), 6.7 km northeast of Coon Creek Summit. At Coon Creek Summit, three whitebark pines ranging in diameter from 10 to 30 cm at breast height (dbh) were infected (evidenced by spindle-shaped branch swellings, aecia, and aeciospores), with the oldest infection occurring on wood produced in 1975. Assuming a mean needle retention of 10 years, the first pine infection likely occurred between 1975 and 1984. Ribes montigenum and an unknown Ribes sp. were common at Coon Creek Summit but were not infected. In the Bear Creek drainage north of the divide, 27 whitebark pines ranging in size from under 0.3 m high to 12 cm dbh were found infected, with the oldest infection on 1976 wood indicating an origin between 1976 and 1985. Most pines there, however, appeared to have been infected between 1994 and 1998. At Bear Creek, infection on Ribes spp. was common, with R. cereum the most frequently infected species. Voucher specimens of R. cereum (KPK-948 and KPK-949) are archived in the fungal herbarium at the Institute of Forest Genetics, Placerville, CA. On pine, fresh spermatia and aeciospores were abundant even though it was late in the season. Late sporulation has also been observed above 2,500 m on western white (P. monticola) and whitebark pine northeast of Lake Tahoe in Nevada (4). To our knowledge, our report marks the first recorded intrusion by C. ribicola into the north-central Great Basin. Recently, the first report of C. ribicola on Rocky Mountain bristlecone pine (P. aristata) was documented in southern Colorado (1). Now, Great Basin bristlecone (P. longaeva), which is restricted in Nevada to higher elevations in the eastern and southern parts of the state (2), may also be at risk; the northernmost occurrence of this last whitepine holdout from blister rust is in the Ruby Mountains, 135 km south of our findings in the Jarbidge Mountains. References: (1) J. T. Blodgett and K. F. Sullivan. Plant Dis. 88:311, 2004. (2) D. A. Charlet. Atlas of Nevada Conifers. University of Nevada Press, Reno, 1996. (3) J. P. Smith and J. T. Hoffman. Western North American Naturalist 60:165, 2000. (4) J. P. Smith et al. Plant Dis. 84:594. 2000.


The United States only accounts for 0.2% of the global offshore wind installed capacity despite a potential technical resource four orders of magnitude greater. A cumbersome permitting process is one of the challenges in implementing new projects. Part of this process requires biological data in order to inform assessments of environmental impacts; yet these data may be lacking for particular taxa at the required scale. Marine spatial planning (MSP) is a process that often includes data identification, collection, collation and analyses components. In this paper, we conduct a collective case study of three areas with offshore wind projects located in waters managed by marine spatial plans, focusing on how data efforts inform MSP and offshore wind development. Our study finds that MSP can facilitate data efforts during the permitting phase of offshore wind projects, but that other initiatives, particularly renewable energy policies and zoning, appear critical towards establishing offshore wind.


This article explores how greater engagement with industry and end users has influenced the University Technology Transfer Business Model. In order to achieve this, they adopted a qualitative methodology which draws upon case study evidence of two case universities located in a particular region. The findings, represented in a conceptual framework depict a hybrid University Technology Transfer Business Model which is in a state of permanent disequilibrium as a result of path dependency and organisational culture. This permanent disequilibrium was found to cause challenges in relation to scarce resource allocation and also impacted upon the willingness and ability of academics to engage with industry and end users throughout the technology transfer process. This article contributes to an emerging stream of research on hybrid business models by identifying the challenges of permanent disequilibrium where multiple and conflicting stakeholder goals compete for legitimacy and scarce resources. From a policy and practitioner viewpoint, this research draws attention to the complexities of university, government, industry and end user (Quadruple Helix stakeholders) engagement and the implications of such on university strategy where conflicting dominant logics can cause challenges with alignment of organisational processes and mechanisms.


Coming with the ever growing computational power of mobile devices, mobile visual search have undergone an evolution in techniques and applications. A significant trend is low bit rate visual search, where compact visual descriptors are extracted directly over a mobile and delivered as queries rather than raw images to reduce the query transmission latency. In this article, we introduce our work on low bit rate mobile landmark search, in which a compact yet discriminative landmark image descriptor is extracted by using location context such as GPS, crowd-sourced hotspot WLAN, and cell tower locations. The compactness originates from the bag-of-words image representation, with an offline learning from geotagged photos from online photo sharing websites including Flickr and Panoramio. The learning process involves segmenting the landmark photo collection by discrete geographical regions using Gaussian mixture model, and then boosting a ranking sensitive vocabulary within each region, with an "entropy" based descriptor compactness feedback to refine both phases iteratively. In online search, when entering a geographical region, the codebook in a mobile device are downstream adapted to generate extremely compact descriptors with promising discriminative ability. We have deployed landmark search apps to both HTC and iPhone mobile phones, working over the database of million scale images in typical areas like Beijing, New York, and Barcelona, and others. Our descriptor outperforms alternative compact descriptors (Chen et al. 2009; Chen et al., 2010; Chandrasekhar et al. 2009a; Chandrasekhar et al. 2009b) with significant margins. Beyond landmark search, this article will summarize the MPEG standarization progress of compact descriptor for visual search (CDVS) (Yuri et al. 2010; Yuri et al. 2011) towards application interoperability.


The paper summarizes the current understanding of the evolution and diversification of birds. New insights into this field have mainly come from two fundamentally different, but complementary sources of information: the many newly discovered Mesozoic bird fossils and the wealth of genetic analyses of living birds at various taxonomic levels. The birds have evolved from theropod dinosaurs from which they can be defined by but a few morphological characters. The early evolutionary history of the group is characterized by the extinctions of many major clades by the end of the Cretaceous, and by several periods of rapid radiations and speciation. Recent years have seen a growing consensus about the higher-level relationships among living birds, at least as can be deduced from genetic data.


In order to take advantage of the narrow time window for optimal treatment efficacy, highly sensitive disease monitoring is critical in the successful management of cancer. Currently, treatment efficacy is assessed by using a combination of protein cancer biomarkers and imaging. However, both methods present limitations with regard to specificity or sensitivity due to their dependency on tumor size. Recently, a number of studies have suggested that monitoring cell free DNA (cfDNA) may provide a more specific alternative for tracking cancer treatment with greatly improved sensitivity. Here we introduce a novel next-generation sequencing based mutation detection system aimed at improving the sensitivity, reliability, and clinical utility of cancer treatment monitoring. Our system, comprised of Nebula, a whole genome amplification technology that is capable of amplifying nanogram quantities of cfDNA >1000-fold, and Firefly, a proprietary technology combining molecular biology and computational algorithm for error-suppression, has reduced the rate of random sequencing errors to 10-6. As a result, we are able to detect 1.5 variant copies from 10ng of input cfDNA with a detection rate of 46%. We have validated the Nebula-Firefly assay on a patient cohort with either colorectal (CRC) or lung cancer. Here we report the successful detection of drug resistant mutations and various genomic alterations associated with minimal residual detection (MRD) in sample cfDNA. These initial findings have led to the exploration of Nebula-Firefly as the technological backbone for a noninvasive, scalable approach for the early detection, treatment, and monitoring of cancer. Citation Format: Grace Zhao, Li Weng, Paul Tang, Johnny Sun, Yi Huang, Lingchen Guo, Hongyan Wang, Xiaozheng Kang, Wei Shen, Kang Ying, Shengrong Lin. An ultra-sensitive cell free DNA liquid biopsy assay for cancer treatment monitoring. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1375.


ABSTRACT Pakistan claims to maintain neutrality in the Iran–Saudi rift. Sustaining this approach, however, has been problematic against a backdrop of intensifying Iran–Saudi rivalry. Pakistan's choices suggest a tilt towards Saudi Arabia. Based on extensive fieldwork in Islamabad, this paper focuses on the meanings and uses of neutrality in Pakistan's foreign policy. The paper argues that Pakistan cannot be neutral due to its stronger cultural, economic and defence ties with Saudi Arabia but it promotes this rhetoric due to a combination of demographic, geographic and geopolitical factors. Islamabad's claim of neutrality serves the dual purpose of the national interests in relation to domestic and foreign affairs. Based on its economic, sectarian and geopolitical realities, Pakistan desires a neutrality in the Iranian-Saudi rivalry but it is very difficult because it has strong and multifaceted relations with Saudi Arabia. Based on the assessment of Pakistan's foreign policy choices, we argue that Pakistan continues to lean away from Iran towards Saudi Arabia.


Engineered biosensors accurately report the kinetics of EGFR activation. Building better biosensors The accuracy of a biosensor used to measure signaling events in live cells depends on both the specificity of the biosensor for its intended target and the absence of interference with the signaling pathway. Phosphotyrosine-binding SH2 domains have been used as biosensors for receptor tyrosine kinase activation. Tiruthani et al. showed that a paired SH2 domain biosensor for monitoring phosphorylation of the epidermal growth factor receptor (EGFR) at Tyr992 was not specific for EGFR and was not recruited to the membrane in a manner that accurately reflected the kinetics of EGFR signaling. Hence, the authors used two different mutagenesis and screening approaches to engineer new biosensors, mSH2 and SPY992, that exhibited greater specificity for EGFR Tyr992 and more accurately reported EGFR signaling kinetics. These approaches were extended to develop SPY1148, a biosensor for phosphorylation of EGFR at Tyr1148, and could be extended to generate phospho-specific biosensors for various targets. Live-cell fluorescence microscopy is broadly applied to study the dynamics of receptor-mediated cell signaling, but the availability of intracellular biosensors is limited. A biosensor based on the tandem SH2 domains from phospholipase C–γ1 (PLCγ1), tSH2-WT, has been used to measure phosphorylation of the epidermal growth factor receptor (EGFR). Here, we found that tSH2-WT lacked specificity for phosphorylated EGFR, consistent with the known promiscuity of SH2 domains. Further, EGF-stimulated membrane recruitment of tSH2-WT differed qualitatively from the expected kinetics of EGFR phosphorylation. Analysis of a mathematical model suggested, and experiments confirmed, that the high avidity of tSH2-WT resulted in saturation of its target and interference with EGFR endocytosis. To overcome the apparent target specificity and saturation issues, we implemented two protein engineering strategies. In the first approach, we screened a combinatorial library generated by random mutagenesis of the C-terminal SH2 domain (cSH2) of PLCγ1 and isolated a mutant form (mSH2) with enhanced specificity for phosphorylated Tyr992 (pTyr992) of EGFR. A biosensor based on mSH2 closely reported the kinetics of EGFR phosphorylation but retained cross-reactivity similar to tSH2-WT. In the second approach, we isolated a pTyr992-binding protein (SPY992) from a combinatorial library generated by mutagenesis of the Sso7d protein scaffold. Compared to tSH2-WT and mSH2, SPY992 exhibited superior performance as a specific, moderate-affinity biosensor. We extended this approach to isolate a biosensor for EGFR pTyr1148 (SPY1148). This approach of integrating theoretical considerations with protein engineering strategies can be generalized to design and evaluate suitable biosensors for various phospho-specific targets.


Linear programming (LP) decoding for low-density parity-check codes (and related domains such as compressed sensing) has received increased attention over recent years because of its practical performance-coming close to that of iterative decoding algorithms-and its amenability to finite-blocklength analysis. Several works starting with the work of Feldman showed how to analyze LP decoding using properties of expander graphs. This line of analysis works for only low error rates, about a couple of orders of magnitude lower than the empirically observed performance. It is possible to do better for the case of random noise, as shown by Daskalakis and Koetter and Vontobel. Building on work of Koetter and Vontobel, we obtain a novel understanding of LP decoding, which allows us to establish a 0.05 fraction of correctable errors for rate-½ codes; this comes very close to the performance of iterative decoders and is significantly higher than the best previously noted correctable bit error rate for LP decoding. Our analysis exploits an explicit connection between LP decoding and message-passing algorithms and, unlike other techniques, directly works with the primal linear program. An interesting byproduct of our method is a notion of a "locally optimal" solution that we show to always be globally optimal (i.e., it is the nearest codeword). Such a solution can in fact be found in near-linear time by a "reweighted" version of the min-sum algorithm, obviating the need for LP. Our analysis implies, in particular, that this reweighted version of the min-sum decoder corrects up to a 0.05 fraction of errors.


"The Lord's Librarians" describes in new detail the activities of the American Seamen's Friend Society in distributing loan libraries to merchant and naval ships for over 130 years. Based on the archives of the Society in the G.W. Blunt White Library at the Mystic Seaport Museum, the study examines the history of the Society in its efforts towards moral improvement of seamen, fostering temperance, reducing licentiousness, encouraging Sabbath worship and observation, countering swearing, and promoting thrift and financial responsibility among sailors. It examines the largely evangelical collection development policies for these compact 40-45 volume library boxes, and attempts to locate the surviving boxes and surviving books from these libraries. It ends with some unanswered questions which deserve further study.


Recent efforts to restore America's tallgrass prairie are challenged by the introduction of invasive species that can monopolize resources and suppress the growth of native plants. Our experiment studied the effects of a new method, goat grazing, on the invasive plant Lespedeza cuneata and soil conditions in order to determine the value of goats as an invasive plant control mechanism. The study was conducted at the Conard Environmental Research Area of Grinnell College, near Kellogg, Iowa. We collected and tested plant and soil data in October, 2009 from test plots that had never been grazed and plots that were grazed by goats at two different times during the summers, L. cuneata's primary growing period, of 2008 and 2009. We found L. cuneata in grazed plots to have significantly lower mean density, biomass, and height; however, soil conditions did not vary among treatments. These results show that goat grazing is an effective eliminator of the invasive species and has minimal impact on the soil. Thus, this treatment may be useful for future restoration efforts that involve species elimination.


In this work I will focus my attention on a specific manga, Cream Soda by Adachi Mitsuru (1996). As suggested by Eco (1999), I will analyze this single work keeping in mind that it belongs to a medium and some genre practiced through this medium, but focusing my attention on the specific syntax of the speech of Adachi. This means that in this work I won't talk about manga in general or in itself, at least, not in the foreground and in the first instance, but I will consider Adachi's specific execution of the art of manga. This work will start from the analysis of single panels, and their relationship with each other inside the page layout, following the critical path indicated by Thierry Groensteen (1999), and will be then accompanied by the analysis of images and texts contained inside those panels, with special regard to their relationship with each other and with images and texts contained in other panels, following the lead of Barbieri (1995) and Pellitteri (1998). The analysis of the elements that this text brings together to create a coherent narrative, and those elements it will not, will show that to properly understand Adachi's manga the reader must recognize the fictional nature of what he is reading and his function as co-author of the story. Obviously this reflection is based on a first level or narrative interpretation of the text because it is starting from this basic layer that all the other layers can be explored. This is also the reason why this work provides a punctual examination of the single panels. The analysis here proposed will also demonstrate that, despite many panels open up to different levels of readings, the activation of the second or third level of reading is not a given. It will also become evident, though, that if one stops at a first level reading, the most obvious one, the text in question isn't really fulfilled according to its author's expectations: the reader's high engagement with the text and how, as a result, he is able to better understand it, forms the heart of Adachi's style and language. Disseminating his work with clues, spoilers, symbolic objects and inside jokes, Adachi invites, in fact, his reader not only to re-read the text but also to read between the lines. As it will be demonstrated through this work, with his stylistic solutions and meta-narrative approach, Adachi often brings into question the art of manga and its specific language, and therefore I believe that the analysis of his peculiar execution of this art and language can represent a good starting off point for a more general discourse on the manga language.p { margin-bottom: 0in; text-align: justify; }


Agricultural intensification has contributed to the degradation of freshwaters in the UK, through enhanced delivery of fine sediment and associated contaminants, leading to sedimentation and eutrophication. European legislation (Water Framework Directive 2000/60/EC) and subsequent UK government initiatives such as Catchment Sensitive Farming (CSF) and Demonstration Test Catchments (DTC), aim to improve the quality of freshwaters. The DTC programme aims to find cost-effective ways to reduce agricultural diffuse water pollution.

This study aimed to monitor rivers in the Hampshire Avon DTC with existing and planned mitigation measures, to measure the effectiveness of the mitigation measures, and to develop an experimental design for wider application for pollution mitigation. The methods used and tested in this study were a combination of affordable, replicable and sustainable methods (in-stream sediment collection and water quality monitoring), more complicated, expensive, analytical laboratory methods (particle size, loss-on-ignition, geochemistry, mineral magnetism, environmental radionuclides), and sediment source fingerprinting. The mitigation measures were: improvement to farm infrastructure, a wooded and a grassed riparian buffer, and a constructed wetland and in-stream pond treatment train.

The improved farm infrastructure (resurfacing of a farm track, installation of a retention pond, improvements to a drainage ditch) effectively reduced inputs of sediment and associated contaminants to the river, however, this had little positive impact on the river due to greater importance of inputs from other sources. The riparian buffers were reducing fine sediment and associated contaminant inputs laterally and from upstream, however, the effectiveness of the riparian buffers was undermined by a lack of riparian buffers upstream and by sub-surface field drains. Combined analysis of the river from the farm infrastructure in the headwaters (farm scale) to the wooded riparian buffer downstream (sub-catchment scale) showed a change in the dominant source of sediment. This highlighted that an experimental design would require monitoring at varying spatial scales, as individual farm scale mitigation measures may have little impact on an entire sub-catchment due to the importance of other sources from a larger drainage area. The constructed wetland and instream pond were not effective at reducing longitudinal delivery of fine sediment and associated contaminants due to issues related to maintenance and design, emphasising the importance of appropriate targeting, design, and maintenance of mitigation measures.

The results from this study showed that the methods used would be suitable as part of an experimental design for wider application. Although complex and expensive, sediment source fingerprinting is essential for determining appropriate and cost-effective mitigation at farm and sub-catchment scales. Monitoring of the sediment and water quality using the affordable, replicable and sustainable methods could be managed by farmers and landowners across a dense spatial area, at a high temporal frequency, to ensure sustainable effectiveness of mitigation. There is a need for more co-working between policy makers and scientists to ensure appropriate funding and timescales for research are provided, and with farmers and landowners to improve understanding and vested interest in the contribution of agriculture to the degradation of water quality.


The present study examined spell checker software for both spelling recognition and production among college students. Sixty-four participants identified and corrected spelling in a prewritten story and produced spelling by writing a story. Both were completed with or without spell checker access. Results demonstrated differences between the performance of good and poor spellers (as defined using a baseline spelling test). When compared to good spellers, poor spellers corrected a greater percentage of spelling errors with spell checker than without. Spell checker helped all participants produce fewer spelling errors, but not fewer homophone errors. Additionally, more often than good spellers, poor spellers reported placing less effort into spelling words correctly when using spell checker. These findings suggest that poor spellers may have a greater need for spell checker than good spellers, and may be at a greater risk for relying on the software as the only step in the proofreading process.


Abstract Gross primary productivity (GPP) is a key component of ecosystem carbon fluxes and the carbon balance between the biosphere and the atmosphere. Accurate estimation of GPP is essential for quantifying plant production and carbon balance for grasslands. Satellite-derived vegetation indices (VIs) are often used to approximate GPP. The widely used VIs include atmospherically resistant vegetation index, enhanced vegetation index (EVI), normalized difference greenness index, normalized difference vegetation index, reduced simple ratio, ratio vegetation index, and soil-adjusted vegetation index (SAVI). The evaluation of the performance of these VIs for approximating GPP, however, has been limited to one or two VIs and/or using GPP observations from one or two sites. In this study, we examined the relationships between the nine VIs derived from the moderate resolution imaging spectroradiometer (MODIS) and tower-based GPP at five eddy covariance flux sites over the grasslands of northern China. Our results showed that the nine VIs were generally good predictors of GPP for grasslands of northern China. Overall, EVI was the best predictor. The correlation between EVI and GPP also declined from the south to the north, indicating that EVI and GPP exhibited closer relationships in more southerly sites with higher vegetation cover. We also examined the seasonal influence on the correlation between VIs and GPP. SAVI exhibited the best correlation with GPP in spring when the grassland canopy was sparse, while EVI exhibited the best correlation with GPP in summer when the grassland cover was dense. Our results also showed that VIs could capture variations in observed GPP better in drought period than in nondrought period for an alpine meadow site because of the suppression of vegetation growth by drought.


This study sought to provide evidence for the existence of specific grammatical features which one could definitely say are characteristic of Kenyan English. Using a questionnaire, it gauged the extent of acceptability of twenty-six features by between 75 and 188 respondents. The twenty-six features appeared in sentences that would be considered as deviant in standard international English, and informants were instructed to correct errors in them. The sample of respondents was drawn, over a two-year period, from eight classes of students specializing in either linguistics or communication at the University of Nairobi. The target features covered "grammar" in its widest sense: from punctuation marks and spelling to morphological, syntactic and lexical aspects. The results showed that fourteen (i.e. 54%) of the twenty-six structures scored acceptability ratings of at least 60%. These could be argued to be indeed characteristic of at least written Kenyan English. But, with acceptability ratings for some other structures being as low as only two and eighteen percent, the results equally suggest that some apparently very common features of Kenyan English would only be accepted in spoken, rather than written language.


SnBi based solder alloys become an interesting alternative for standard SnAgCu as they can be used to solder components at much lower temperature. The typically 50°C lower solder reflow temperature is less damaging for PCB and components, and also prevents hot tear and head-in-pillow failures for large fine pitch BGA components. A reasonable concern for these low-melting temperature solders is the thermal cycling reliability performance, in particular for harsh conditions such as automotive products. In this work, thermal cycling testing and failure analysis have been performed on 9 × 9 mm size QFN components and large chip components (2010 and 2512) which are typically sensitive to thermal fatigue. The results are benchmarked to standard SAC alloy. Also the process advantages from the low temperature solder alloys are depicted in this paper. Finally, the effect of Pb contamination on this SnBi based solder is investigated.


We present an experimental study of the flapping instability which appears when a coaxial liquid jet is atomized by a cocurrent fast gas stream. When primary atomization does not lead to a total break-up of the liquid jet, it undergoes a large-wavelength instability, characterized by very large amplitude oscillations, and can break into large liquid fragments whose typical size is the jet diameter. These large liquid fragments, and consequently the flapping instability, are to be avoided in applications related to combustion where liquid droplets need to be as small as possible. We carried out experiments with air and water coaxial jets, with a gas/liquid velocity ratio of order 50. We studied the consequence of the flapping instability on the break-up of the liquid jet. Measurements of the frequency of the instability were carried out. We suggest a mechanism where the flapping instability could be triggered by non axisymmetrical KH modes.Copyright © 2010 by ASME


Dr Peach recently drew the writer's attention to the occurrence of a dyke of unusual characters in Lauderdale. This dyke has proved to be a monchiquite, and is apparently distinct petrographically from all other intrusions described from south-east Scotland. It occurs on the left bank of the Earnscleugh Burn (a tributary of the Leader Water) three-quarters of a mile south of the farm of Earnscleugh, its outcrop making a prominent scar on the grassy hillside. Though contacts with the surrounding sediments are not exposed, the dyke is clearly seen to have a north-east trend. The length and breadth of the outcrop are about 50 yards and 10 yards respectively. The grits of Upper Old Red Sandstone age, into which the dyke has been intruded, do not appear to have undergone much alteration. Petrography.—In the hand specimen the rock is seen to be strikingly porphyritic, large phenocrysts of unaltered biotite and hornblende being imbedded in a decomposed purple groundmass of very fine grain. The prophyritic constituents are not abundant, but their large size makes them exceedingly conspicuous. The biotite forms well-shaped hexagonal plates up to 1 inch in diameter, while the hornblende prisms are usually corroded and are seldom more than ½ inch across. The marginal portions of the dyke are crowded with xenoliths. Owing to the decomposed nature of the groundmass it was found exceedingly difficult to retain the large phenocrysts in thin sections during grinding, and a separate microscopic examination was therefore made of the biotite and hornblende. The


Current treatment for hemophilic bleeding episodes is limited to the intravenous infusion of intravenous purified and recombinant factor protein. While this is generally effective, it is transient due to the brief lifespan of the proteins. Aside from this, factor protein treatment is costly, constrains the prophylactic use of factors and can potentially lead to degenerative joint disease as well as susceptibility to infectious agents, including HIV virus [1]. Hence, for many years now, attention has been focused on gene therapy as a potential cure for hemophilia. Nevertheless, clinical trials that have been undertaken in this direction have shown that this cure will not be easily achieved. This paper discusses the progress done in the field of research in the context of gene therapy for hemophilia, as well as the challenges that have emerged and how these could possibly be resolved based on research.


One of welfare reform's most significant consequences is the devolution of policy‐making authority from the federal government and states to local governments and frontline workers. What is perhaps less often appreciated is that devolution of authority to state governments has been accompanied by a significant decentralization of policy‐making authority within states. As a result, prior research has not given sufficient attention to local political context as a factor shaping program implementation. This article examines the effect of local political values on the use of sanctions to penalize welfare recipients. Analyzing administrative data from the Florida Department of Children and Families for over 60,000 welfare clients, we find that there is a statistically significant amount of local variation in sanctioning rates across the state of Florida, even after controlling welfare clients' characteristics. Local sanctioning patterns are systematically related to selected characteristics of local communities, including their ideological orientations.


Abstract Homœopathy, once an accepted form of medicine, is currently under attack in Australia, so much so that its very existence is threatened. To illustrate techniques of marginalisation of homœopathy in Australia, the Australian National Health and Medical Research Council's (NHMRC) report of 2015 is examined. As there is no standard framework or classification of marginalisation techniques, boundary work ideas were used to suggest techniques used in the process of marginalisation. To condemn homœopathy, the NHMRC used at least eight techniques: authority, asserting protection of autonomy, exclusion, double standards, normalisation, denigration, censorship, expansion and diversion. The NHMRC report is a revealing example of how biomedicine uses various tactics to marginalise alternative therapies, thereby maintaining biomedicine's dominant position.


Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.